ABSTRACT Introduction: The clinical manifestations of sickle cell disease (SCD) result from an inherited mutation in the beta-globin chain of hemoglobin (Hb) that causes Hb tetramers to polymerize when deoxygenated. The resulting erythrocyte deformation causes mechanical obstruction of blood flow by sickled cells, hemolysis, anemia and end-organ injury. While pain is the hallmark symptom of SCD, chronic organ injury as a result of anemia, inflammation and progressive vasculopathy play a major role in morbidity and mortality. Due to the complex pathophysiology of SCD, the need for an individualized, multi-modal pharmacologic approach is apparent. Until 2018, hydroxyurea was the only disease-modifying pharmacologic therapy approved for use in SCD. Since then, three new agents have been approved including voxelotor, the subject of this review.Areas covered: Published pre-clinical and clinical data are reviewed. Voxelotor is a first-in-class small-molecule agent that binds to Hb and increases oxygen affinity, preventing polymerization. Recent clinical trials have shown that it increases Hb concentration and reduces hemolysis in patients with SCD. This increase in Hb concentration may significantly impact morbidity and mortality from chronic organ injury.Expert opinion: The mechanism of action, published studies and current opinions on the clinical use of voxelotor in SCD are presented.


Alzheimer's Disease affects millions of people worldwide, but till today, the gold standard
for definitive diagnosis of this disease is a biopsy. Nevertheless, with the progress
of the disease, a volume loss in the Hippocampus can be observed. Therefore, good
segmentation methods are crucial to facilitate quantification of this loss.
The focus of this work is on the development of a Machine Learning algorithm, more
precisely a Generative Adversarial Network, for the automated segmentation of the
human Hippocampus and its substructures in Magnetic Resonance Images. In particular,
the task is to determine if the integration of a pre-trained network that generates
segmentations into a Generative Adversarial Network scheme can improve generated
segmentations. In this context, a segmentation network in form of a U-net corresponds
to the generator. The discriminator is developed separately and merged in a second
step with the generator for combined training.
With a literature review regarding the automated segmentation of the Hippocampus,
current methods in this field and their medical and technological basics were identified.
The datasets were preprocessed to make them suitable for the use in a neural
network. In the training process, the generator was trained first until convergence.
Then, the Generative Adversarial Network including the pre-trained generator was
trained. The outcomes were evaluated via cross-validation in two different datasets
(Kulaga-Yoskovitz and Winterburn). The Generative Adversarial Network scheme
was tested regarding different architectural and training aspects, including the usage
of skip-connections and a combined loss function.
The best results were achieved in the Kulaga-Yoskovitz dataset with a Dice coefficient
of 90.84 % after the combined training of generator and discriminator with a joined
loss function. This improves the current state of the art method in the same task and
dataset with a Dice index of 88.79 % by Romero [Rom17]. Except of two cases in the
Winterburn dataset, the proposed combined method could always improve the Dice
results after the training of only the generator, even though only by a small amount.


This perspective paper explores the choice of psychotherapy for psilocybin-assisted psychotherapy for treatment-resistant depression. There is evidence to support the use of some psychotherapies in treating 'treatment-resistant' depression, and emerging evidence for the efficacy of psilocybin. The next step which is the focus of this paper is to identify psychotherapies that are both effective and congruent with the psilocybin experience. The evidence for the efficacy of the psychotherapies is drawn from a Cochrane review and the analysis of their congruence with the psilocybin experience is drawn from a qualitative meta-synthesis of the experience of psilocybin. The paper will examine whether three one-to-one psychotherapies identified as effective in the treatment of treatment-resistant depression are compatible with the psilocybin experience. Each psychotherapy will be examined in relation to its congruence with the qualitative evidence that suggests the choice of psychotherapy needs to give priority to the subjective experience, facilitate emotional processing, support connectedness with others, acceptance of the self as emotional and support change based on the person's insights into their relationships with others and the world in which they live. We conclude that interpersonal psychotherapy and intensive short-term dynamic psychotherapy align with that experience, although others are currently being trialled.


The magnetic circular dichroism of III-V diluted magnetic semiconductors, calculated within a theoretical framework suitable for highly disordered materials, is shown to be dominated by optical transitions between the bulk bands and an impurity band formed from magnetic dopant states. The real-space Green's functions incorporate spatial correlations in the disordered conduction band and valence-band electronic structure, and include extended and localized states on an equal basis. Our findings reconcile unusual trends in the experimental magnetic circular dichroism in III-V diluted magnetic semiconductors with the antiferromagnetic p-d exchange interaction between a magnetic dopant spin and its host.


The tree of life is highly reticulate, with the history of population divergence buried amongst phylogenies deriving from introgression and lineage sorting. In this study, we test the hypothesis that there are regions of the oak (Quercus, Fagaceae) genome that are broadly informative about phylogeny and investigate global patterns of oak diversity. We utilize fossil data and restriction-site associated DNA sequencing (RAD-seq) for 632 individuals representing ca. 250 oak species to infer a time-calibrated phylogeny of the world's oaks. We use reversible-jump MCMC to reconstruct shifts in lineage diversification rates, accounting for among-clade sampling biases. We then map the > 20,000 RAD-seq loci back to a recently published oak genome and investigate genomic distribution of introgression and phylogenetic support across the phylogeny. Oak lineages have diversified among geographic regions, followed by ecological divergence within regions, in the Americas and Eurasia. Roughly 60% of oak diversity traces back to four clades that experienced increases in net diversification due to climatic transitions or ecological opportunity. The support we find for the phylogeny contrasts with high genomic heterogeneity in phylogenetic signal and introgression. Oaks are phylogenomic mosaics, and their diversity may in fact depend on the gene flow that shapes the oak genome.


Small molecule inhibitors of hepatitis C virus (HCV) are being developed to complement or replace treatments with pegylated interferons and ribavirin, which have poor response rates and significant side effects. Resistance to these inhibitors emerges rapidly in the clinic, suggesting that successful therapy will involve combination therapy with multiple inhibitors of different targets. The entry process of HCV into hepatocytes represents another series of potential targets for therapeutic intervention, involving viral structural proteins that have not been extensively explored due to experimental limitations. To discover HCV entry inhibitors, we utilized HCV pseudoparticles (HCVpp) incorporating E1-E2 envelope proteins from a genotype 1b clinical isolate. Screening of a small molecule library identified a potent HCV-specific triazine inhibitor, EI-1. A series of HCVpp with E1-E2 sequences from various HCV isolates was used to show activity against all genotype 1a and 1b HCVpp tested, with median EC50 values of 0.134 and 0.027 µM, respectively. Time-of-addition experiments demonstrated a block in HCVpp entry, downstream of initial attachment to the cell surface, and prior to or concomitant with bafilomycin inhibition of endosomal acidification. EI-1 was equally active against cell-culture adapted HCV (HCVcc), blocking both cell-free entry and cell-to-cell transmission of virus. HCVcc with high-level resistance to EI-1 was selected by sequential passage in the presence of inhibitor, and resistance was shown to be conferred by changes to residue 719 in the carboxy-terminal transmembrane anchor region of E2, implicating this envelope protein in EI-1 susceptibility. Combinations of EI-1 with interferon, or inhibitors of NS3 or NS5A, resulted in additive to synergistic activity. These results suggest that inhibitors of HCV entry could be added to replication inhibitors and interferons already in development.


The Quantum well structures have exhibited significant utility in the fabrication of advanced laser devices. The Gallium nitride semiconductor and its alloy particularly AlGaN based quantum structures are having important applications in optical data storage systems and the visible displays. Due to tailoring of wide band gap energy the spectrum obtained is from visible to ultraviolet wavelength range. We had thoroughly investigated the influence of Aluminum mole fraction variation in AlxGa1-xN under a biased condition for GaN/AlGaN based quantum heterostructure optical properties. Here, we had used 6X6 Hamiltonian to realize these properties. The 6X6 Hamiltonian has been chosen to include the many body effect in the calculation and to enhance the accuracy of the optimized results. The paper is focused to reveal the Aluminum mole fraction dependence of near and far filed intensities, peak optical gain, carrier concentration, and optical confinement factor. The effective index method has been used in determination of the optical field intensity in the near and far regimes. The variation in Aluminum mole fraction produces disparity in carrier concentration; hence, we have obtained the spontaneous emission and optical gain as a function of photon energy for different carrier density. The piezoelectric effect on GaN quantum well due to AlGaN barriers has been included through Poisson equation. This Poisson equation has been solved in a self-consistent manner along with Schrödinger and subsequently carrier concentrations have been deduced with a high accuracy using our simulation tools developed in MATLAB.


Eleftherios Venizelos loved books. He collected them, read them, and annotated them. With few exceptions, the most important being his translation of Thucydides into modern Greek, he did not write them. Books were an important part of his life, and he continued until the end to buy them. His collection of books is of historical and psychological interest. After his death in 1936, the books were transferred from his apartment in Paris and his wife's house in Athens to the Venizelos family house in Halepa, near Chania in Crete. After many vicissitudes, especially during the German occupation of Crete, they came to rest in Chania Municipal Library, where they remain today. This paper explores Venizelos' reading habits and preferences through this collection, showing that he used books both for professional information, for pleasure, and to improve his knowledge of foreign languages, in particular English. He was familiar with the great authors from Homer to Shakespeare; with philosophy from Aristotle to Bergson; with poetry, fiction, but especially with political thought, history and literature. It is good that the collection remains in the hands in the Municipal Library in the city where Venizelos lived and worked.


States are states, in part, because they persist through time. Knowing is one such state, and it often persists beyond the time when evidence is first apprehended. The consequences for epistemology of this persistence are explored, including what are termed 'unearned knowledge,' and 'one-sided knowledge.' Knowing that you are not dreaming is one (important) example of unearned and one-sided knowing. The author contends that arguments for scepticism and for knowing as a purley mental state are undermined when this persistence is properly understood.


The medical records of 12 dogs with multilobular osteochondrosarcoma (MLO) and examined at the Veterinary Teaching Hospital, Colorado State University from August 1979 to January 1987 were reviewed. Medical records of 1 dog with MLO and 3 dogs with MLO examined at the Ontario Veterinary College, University of Guelph and the Veterinary Medical Teaching Hospital, University of California, Davis, respectively, were also reviewed and included in the study. The mean age of affected dogs was 7.5 years, a single breed did not appear to be overrepresented, and males were affected as frequently as were females. All of the primary lesions affected either the mandible, maxilla, or cranium. Excision was the only treatment in 11 dogs, 2 dogs had radiotherapy in addition to excision, and 1 dog had radiotherapy and chemotherapy after excision. Twelve treated dogs had follow-up information available. Of the 12 treated dogs, 7 (58%) had local recurrence, with median time to recurrence of 14 months. Seven dogs (58%) developed metastatic disease after treatment, with median time to metastasis of 14 months. The median disease-free interval was 12 months, and the median survival time was 21 months. Excision with histologically complete surgical margins appeared to offer good opportunity for long-term tumor control. The role of adjuvant chemotherapy and radiotherapy in the management of MLO remains unclear.


Background: Little is known about the distribution of diagnoses that account for fatigue in patients in primary care. We evaluated the diagnoses established within 1 year after presentation with fatigue in primary care that were possibly associated with the fatigue. Methods: We conducted a prospective observational cohort study with 1-year follow-up. We included adult patients who presented with a new episode of fatigue between June 2004 and January 2006. We extracted data on diagnoses during the follow-up period from the patients' medical records as well as data on pre-existing chronic diseases. Results: Of the 571 patients for whom diagnostic data were available, 268 (46.9%) had received one or more diagnoses that could be associated with fatigue. The diagnoses were diverse and mostly included symptom diagnoses, with main categories being musculoskeletal (19.4%) and psychological problems (16.5%). Clear somatic pathology was diagnosed in 47 (8.2%) of the patients. Most diagnoses were not made during the consultation when fatigue was presented. Interpretation: Only a minority of patients were diagnosed with serious pathology. Half of the patients did not receive any diagnosis that could explain their fatigue. Nevertheless, because of the wide range of conditions and symptoms that may explain or co-occur with the fatigue, fatigue is a complex problem that deserves attention not only as a symptom of underlying specific disease.


Purpose Although imatinib-induced hepatotoxicity may aggravate the patient's clinical condition and alter the treatment plan, the underlying mechanism of and factors influencing imatinib-induced hepatotoxicity have rarely been investigated. The purpose of this study was to investigate factors affecting on the incidence of hepatotoxicity within 90 days after starting imatinib treatment and time to onset of imatinib-induced hepatotoxicity. Materials and Methods We retrospectively evaluated the records of 177 patients receiving imatinib from October 2012 to September 2017. The analyzed factors included sex, age, body weight, body surface area, underlying disease, and concomitant drugs. Results The proportion of patients with hepatotoxicity within 90 days after imatinib administration was 33.9%. Proton pump inhibitors (PPIs) increased the incidence of hepatotoxicity approximately 3.8-fold and doubled the hazard of time to reach hepatotoxicity. Patients with liver disease or hepatitis B virus (HBV) carriers had a more than 8-fold higher risk of hepatotoxicity and a 5.2-fold increased hazard of hepatotoxicity compared to those without liver disease or HBV. Patients with body weight under 55 kg had a 2.2-fold higher risk for occurrence of hepatotoxicity. Patients with an imatinib dose > 400 mg had a 2.3-fold increased hazard of time to reach hepatotoxicity compared to those with an imatinib dose ≤ 400 mg. Conclusion The findings of this study suggest that the use of PPIs and presence of liver disease or HBV were associated with imatinib-induced hepatotoxicity. Thus, close liver function monitoring is recommended, especially in patients with liver impairment or using PPIs.


All physicians performing surgery while the patient is under general anesthesia must be aware of the existence of idiopathic malignant hyperthermia. A young adult had a malignant hyperthermic reaction despite four prior uneventful administrations of general anesthetics. To my knowledge, this is the first report of a patient who survived following a hyperthermic reaction, having sustained considerable residual brain damage. There is a great need for continuous body-temperature monitoring during general anesthesia.


Formulation of transient skin effect problems in terms of potentials are presented. In case of a prescribed voltage, a magnetic vector potential and an electric scalar potential and, if the current is given, a current vector potential and a magnetic scalar potential are used. The boundary value problems are numerically solved by means of edge finite element techniques. The analysis of a complicated high power bus bar arrangement is presented as a numerical example.


Sensor nodes in wireless sensor networks are provided with limited battery power so power conservation is one of the most important issues in WSN. An energy efficient approach can be achieved for data gathering by distributing energy consumption in Wireless Sensor Networks (WSN) by employing sink mobility. Existing data gathering schemes require the sink to periodically update its location to the network to ensure multi-hop connectivity as well as to specify the sinks trajectory in advance which makes it unsuitable for applications consisting of changing field situations such as precision agriculture. The purposed scheme combines approach of Sinktrail with aggregation. Gathering of data is done using Sinktrail i.e., proactive data reporting protocol which is passed further for data aggregation, that is base on slicing and mixing technique, which results into low power consumption for data reporting. Thus proposed work based on a combination of both Sinktrail and aggregation to improve the energy efficiency of data gathering.


"A Down Brother," looks at the role Earvin "Magic" Johnson played in the redevelopment of South Central Los Angeles in the wake 1992 civic unrest. Johnson famously teamed up with several multi-national brands to build a series of movie theaters, coffee shops, and restaurants in the area. While his business moves have been well chronicled, almost no one has taken seriously his ideas. Johnson claimed that recycling black dollars, not state action, was the best way to rebuild. His actions placed him in a long line of nationalist-tinged race men. But more than that, they reflected the thinking of many South Central residents, who themselves adhered in the wake of the riots to a broad, and sometimes vague, set of nationalist ideas. In the end, Johnson's schemes didn't rebuild South Central, and he eventually walked away from the area, raising questions about in his particular notion of black capitalist development with its reliance on service jobs and outside dollars. Yet, Johnson's very popularity and the popularity of his ideas highlight the enduring importance of nationalist ideas in California's Long Civil Rights Movement.


Electron transport coefficients have been determined in the W7-AS stellarator. The diffusion and convection coefficients were obtained by modulating the gas feed into the plasma and by measuring the propagation of the density perturbation. The experiments were carried out at a variety of plasma densities, heating powers and magnetic fields. The results are summarized in the form of a scaling expression for the diffusion coefficient. Transient inward convection was found in the boundary plasma. This convection plays a minor role in the core plasma except with higher heating power, where outward convection was observed. The results are compared with earlier W7-AS transport results.


This paper intends a comparative analysis of personality traits likely to be found in two groups of subjects, namely people happy, or unhappy with the use they make of their spare time. The random-selected, quota sampling sample involved 300 Argentine subjects (37% male subjects, 63% female subjects) aged 15 to 22, from different social-economic levels. All subjects were living in the city of Buenos Aires. The technique of profile analysis for 2 independent groups was applied. Once the hypothesis of parallelism was refuted, it was decided that the simple variance technique should be resorted to. From the 16 variance analysis performed (i.e. one for each personality factor), statistically significant differences--with a 5% risk level--were found out among the groups as regards the following factors only: Factor C (Emotional instability, or Ego weakness-Higher ego strength), Factor H (Threctia-Parmia), Factor O (Untroubled adequacy-Guilt proneness), and Factor Q4 (Low ergic tension-High ergic tension).


Childhood Obesity and Depression By Leslie Horton Obesity is a commonly experienced health issue. Children who suffer from obesity may experience medical concerns such as type 2 diabetes and hypertension (American Obesity Association, 2006). Obese children may also face psychological consequences. An overweight child may experience criticism from peers while finding it difficult to participate in age-related activities. Considering this fact, one can understand why psychological effects of childhood obesity are of concern. The purpose of this study is to examine the links between obesity and childhood depression, rated by the Childhood Depression Inventory (CDI-2). Twenty-nine children were administered the CDI-2. Activity level and age of children was collected. Current weight and height was also collected. The results of this study indicated that there was no relationship between CDI2 scores and weight. Furthermore, surprisingly there was no relationship between exercise, time spent watching TV/computer time verses CDI-2 scores. There was a relationship between weight and sports participation.


Thrombosis is the major cause of morbidity and mortality in Chuvash erythrocytosis (CE), caused by a hypomorphic R200W mutation of the Von Hippel-Lindau (VHL) gene, a negative regulator of hypoxia inducible factors (HIFs). This mutation augments HIF activity even in normoxia. High hematocrit associated with hyperviscosity has been considered a risk factor for thrombosis suggesting that maintaining normal hematocrit may prevent thrombosis. However, our prospective controlled study reported that phlebotomies, but not the high hematocrit, are associated with increased risk of thrombosis (PMID 289208) by a mechanism that remains to be elucidated.
 Phlebotomies lead to iron deficiency. We explored the potential role of iron deficiency as a cause of thrombosis. Iron deficiency induces HIF activity by inhibiting prolyl hydroxylase domain 2 (PHD2), an inhibitor of HIFs that requires iron as a co-factor (PMID 18066546). The expression of certain prothrombotic genes regulated by HIFs is modestly increased in CE mononuclear cells (PMID 23993337). We hypothesized that further augmentation of already high HIF activity by iron deficiency might further increase expression of prothrombotic genes leading to increased risk of thrombosis in phlebotomized subjects.
 We reported that, in polycythemia vera (PV) and essential thrombocythemia (ET), the pattern of increase in prothrombotic and inflammatory gene expression differs between granulocytes and platelets (PMID: 32203583), suggesting cell-specific contributions to thrombosis in these disorders. We analyzed the whole transcriptome of the platelets of 10 CE patients, 6 with iron deficiency (ferritin <20 ng/ml) and 4 with normal ferritin: 2,412 genes were upregulated and 670 were downregulated (p <0.05 and Log2 fold change >1). Dysregulated genes as analyzed by Ingenuity Pathway Analysis (Qiagen) were associated with platelet binding, hemostasis and thrombus signaling and decreased bleeding time. To explore our hypothesis further, we quantitated the mRNA of these HIF-regulated prothrombotic genes: THBS1 (thrombospondin 1), SERPINE1 (plasminogen activator inhibitor-1 [PAI-1]), ITGA2B (integrin alpha-IIb), PTGS2 (prostaglandin-endoperoxide synthase 2), SELP (P-selectin), PDGFA (platelet derived growth factor subunit A), and ITGB3 (integrin beta-3). We analyzed granulocytes from 16 CE subjects (8 iron deficient) and platelets from 12 CE subjects (7 iron deficient). In platelets, THBS1, SELP, SERPINE1, and PDGFA mRNA levels were higher in iron deficient CE subjects than those with normal ferritin (p=0.015-0.088). In all CE subjects, the mRNA levels of these four genes correlated inversely with ferritin (figure 1). PTGS2 (known to be down regulated in thrombosis) was down regulated in iron deficient CE patients and correlated positively with ferritin. ITGB3 and ITGA2B mRNA levels were not different between the two groups. In granulocytes, SELP mRNA was augmented in CE patients with iron deficiency and both SELP and ITGB3 mRNA levels correlated inversely with ferritin. We did not find a difference in expression of KLF2, a regulator of thrombotic genes, in iron deficient versus iron sufficient CE patients; see this meeting Song J et al.
 We then tested our hypothesis of augmentation of thrombosis risk by iron deficiency in granulocytes from 50 PV and ET patients (9 with iron deficiency) and platelets from 41 patients (5 with iron deficiency). In granulocytes, THBS1, SELP, and IRAK1 (Interleukin 1 Receptor Associated Kinase 1) mRNA levels were higher in patients with iron deficiency, and IRAK1, THBS1, and SERPINE1 mRNA levels correlated inversely with ferritin. In platelets, THBS1, and SERPINE1 mRNA were higher in patients with iron deficiency and SELP, THBS1, and SERPINE1 mRNA levels correlated inversely with ferritin. JAK2V617F allele burden also correlated inversely with ferritin.
 Our study demonstrates that iron deficiency is associated with increased expression of HIF-regulated prothrombotic genes in CE platelets and granulocytes in a pattern that differs between these two cell types. We also report increased expression of prothrombotic genes in PV and ET patients with iron deficiency. These results underline the potential danger of phlebotomies in attempts to control high hematocrit. We caution against indiscriminate use of therapeutic phlebotomy for treatment of patients with PV and other erythrocytoses.
 VG &JTP contributed equally
 Figure

 Gordeuk: Ironwood: Research Funding; Novartis: Consultancy; CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding.


Both Semi-Supervised Leaning and Active Learning are techniques used when unlabeled data is abundant, but the process of labeling them is expensive and/or time consuming. In this paper, those two machine learning techniques are combined into a single nature-inspired method. It features particles walking on a network built from the data set, using a unique random-greedy rule to select neighbors to visit. The particles, which have both competitive and cooperative behavior, are created on the network as the result of label queries. They may be created as the algorithm executes and only nodes affected by the new particles have to be updated. Therefore, it saves execution time compared to traditional active learning frameworks, in which the learning algorithm has to be executed several times. The data items to be queried are select based on information extracted from the nodes and particles temporal dynamics. Two different rules for queries are explored in this paper, one of them is based on querying by uncertainty approaches and the other is based on data and labeled nodes distribution. Each of them may perform better than the other according to some data sets peculiarities. Experimental results on some real-world data sets are provided, and the proposed method outperforms the semi-supervised learning method, from which it is derived, in all of them.


In international marketing, Information Sharing (ISh) is essential between a buyer and a seller to build and improve a relationship of Export Supply Chain Management (ExSCM). While ISh has been discussed as a granular dimension in the previous research, this research places ISh as a focal underpinning in the ExSCM. ISh in exporter-producer relationship is investigated to understand ISh creation and theoretical perspectives in order to combine different theoretical dimensions in unified model and analyze interrelations among ISh's antecedents, ISh creation, and ISh's consequences. Based on a literature review, experts interviews, and quantitative analyses, a sequence of hypotheses is tested empirically in Fresh Fruit and Vegetable (FFV)-export industry. Expected contributions are an understanding the theoretical perspectives, namely relationship, network, and transaction perspectives to generate new insights and theoretical dimensions in ExSCM and an investigating the impact of the theoretical dimensions on ISh, which impacts on the export chain performance. In addition, new practical insights are provided to managers in how to develop export business of FFV from Jordan to European markets.


As billion transistor system-on-chips (SoC) become commonplace and design complexity continues to increase, designers are faced with the daunting task of meeting escalating design requirements in shrinking time-to-market windows, and have begun using an IP-based SoC design methodology that permits reuse of key SoC functional components. Since the communication architectures connecting components in these SoC designs significantly impact system performance, it is imperative that designers explore the communication design space efficiently, quickly and early in the design flow. Transaction level modeling (TLM) is an emerging abstraction that facilitates early exploration of SoC architectures. This paper outlines a typical IP-based SoC design flow, and presents the cycle count accurate at transaction boundaries (CCATB) modeling abstraction which is a fast, efficient and flexible approach for exploring bus-based communication architectures in SoC designs. The CCATB models not only take less time to model but are also faster to simulate than existing modeling abstractions for communication architecture exploration such as pin-accurate BCA (PA-BCA) and transaction based BCA (T-BCA). Experimental results on several industrial SoC subsystem case studies show that CCATB models are faster than PA-BCA by as much as 120% on average and by 67% on average when compared to T-BCA, demonstrating the advantages of CCATB-based TLM abstraction for exploring bus-based SoC communication architectures.


Background Area-based inequalities in mortality are well known in UK and elsewhere, with poorer areas having higher mortality than more affluent areas. Despite area level measures of deprivation being used extensively in research and also to inform policy, they are not without problems. The modifiable areal unit problem occurs when data are combined into units for analysis and this can result in biassed results. A further issue is area sizes can differ in population. Both phenomena have implications for the size of inequality between most deprived and least deprived areas. This analysis examines inequalities in mortality by area deprivation using three administrative geographic levels with different population sizes. Methods Carstairs scores are a measure of material disadvantage derived from four variables from the 2011 Census in Scotland. Carstairs was calculated for postcode sectors (PS: average population 5,233); data zones (DZ: average population 815); and Census output areas (OA: average population 114). Mortality data for 2010–2012 for Scotland were combined with population data from the 2011 Census for men and women aged 0–64 years. Poisson regression was used to assess age adjusted inequalities in all cause mortality and mortality due to ischaemic heart disease (IHD) and cancer. Results There were 44,048 deaths at ages 0–64 between 2010–2012 in a population of 4,666,267. Rate ratios (RR) tended to increase as the geographic areas became smaller. For all-cause mortality the RR for men for PS was 3.08 [95% confidence interval (2.95–3.22)]; DZ 4.34 (4.15–4.53); and OA 5.01 (4.19–5.24). For women the corresponding RR (95% CI) were PS 2.51 (2.38–2.64); DZ 3.39 (3.21–3.57); OA 3.77 (3.57–3.98). For IHD mortality the RR for men for PS was 3.59 (3.21–4.00); DZ 5.34 (4.78–5.97); and OA 6.08 (5.43–6.80). The corresponding RR for women: PS 3.99 (3.29–4.84); DZ 6.72 (5.50–8.20); and OA 7.46 (6.09–9.13). For cancer mortality the RR for men for PS was 2.08 (1.93–2.25); DZ 2.57 (2.38–2.77); and OA 2.83 (2.62–3.06). The corresponding RR for women: PS 1.74 (1.61–1.88); DZ 2.03 (1.88–2.20); and OA 2.20 (2.03–2.38). Conclusion Inequalities increase for all-cause mortality and cause-specific mortality as geographies get smaller. One possible reason is pockets of deprivation are easier to identify when using smaller areas – small areas tend to be more internally homogenous than large areas. Alternatively, it could be individual deprivation driving the relationship with health and the smaller the area, the closer deprivation captures individual status. Focusing interventions on the smallest geographic areas may help to reduce widening health inequalities.


The triumph of neoliberalism globally signifies what one might term the poverty of (critical) theory, as does the phenomenon known as 'post-theory', with its cynical rejection of the claims of theory. Here I do not wish to retrace the steps of Adorno and Horkheimer in Dialectic of Enlightenment to remind ourselves of the fatal dialectical intertwinement of enlightenment with obfuscation and domination; rather, I wish to follow the trail suggested by critical motifs in the work of various thinkers to demonstrate the 'poverty of (critical) theory', that is, its incapacity to effect the crucial transition from theoretical insight in, and exposition of, the sources of alienation, oppression and ideological obfuscation, to emancipatory action. The work of Gil Germain on technology and consumerism highlights the extent to which contemporary humans' world has been constructed as one 'minus desire', where all needs have supposedly been satisfied, and which tends to produce self-satisfied beings, incapable of 'acting' in accordance with the demands of freedom. With Kant's famous motto, 'Sapere aude', as a point of departure, Hardt and Negri's corrective in terms of the need to act, and not only 'think' critically, is pursued. This is followed by an elaboration on Arendt's vita activa, to unpack what action amounts to, and whether the conditions for its enactment exist today. What becomes clear is that critical theory is incapable, by itself, of guaranteeing emancipatory action. By way of analogy, first the importance of (critical) 'thinking' according to Stiegler, and then that of distinguishing between theory and what Parker describes as potentially effecting a 'revolution in subjectivity' at the psychoanalytical clinic is emphasised; that is, the subject's re-articulation of her or his relationship with power. The point is that this amounts to a 'preparation' for possible commensurate transformative action in social reality, and similarly, it is argued, 'thinking' as well as critical theory can merely prepare the subject for emancipatory action, which is something irreducibly different from theory. To illustrate the difference between critical theory and emancipatory action, a glimpse is afforded of instances of such action reported in the work of Foster and Klein, before demonstrating (with reference to Nietzsche) what is at stake to move from the level of the individual to that of the collective.


As trade unions have declined, a representation gap has appeared in British workplaces over the past two decades. In examining the nature of this gap and assessing current attempts to close it, this book draws on original research from the ESRC's prestigious Future of Work Programme. In this edited collection, some of the UK's leading employment relations researchers present insightful evidence of new developments in trade union and worker representation, focusing on key themes such as partnership, gender, and worker attitudes and organization in the 'knowledge economy'.


This cross-sectional study analyses determinants of condom-use behaviour among patients attending dedicated STD clinics in South Africa. A structured interviewer-administered survey was conducted among 1473 patients. Patients' beliefs and attitudes towards condom use in general, as well as their personal condom-use behaviour were measured. Their perceptions, regarding the social influence of their partners and friends on their condom use, and of their selfefficacy in using condoms, while infected with an STD were also measured. Condom use, as a dependent variable, was examined and patients were placed in a pre-contemplation stage if they had never used a condom, contemplation if they had seriously thought of using a condom, some action stage if they sometimes used a condom and regular action stage if they used a condom every time. The relationships between the stages of change, as dependent variables, and the independent variables were investigated for both those patients with steady partners and those with outside partners. This was performed by stepwise multiple regression analyses. The variables that significantly explained stages of change were similar for patients with steady partners and those with outside partners. In both partner groups communication was the variable most strongly associated with the use of condoms. General self-efficacy in condom use, self-efficacy in condom use with a partner and attitudes towards the use of condoms played a role in determining patients' different stages of change.


In the past decade there has been a dramatic growth in UK student numbers, with students from non-traditional and under-represented groups being encouraged to participate in higher education. However, levels of withdrawal in those higher education institutions that have a greater proportion of non-traditional students have also been increasing. Higher education institutions have introduced various strategies in an effort to cope with this problem, but unfortunately current models offer little in the way of explaining the causes of (and little justification for the strategies used to reduce) withdrawal. It is proposed that in attending to the explanations of withdrawal, consideration must be given to discovering the underlying characteristics of the teaching and learning environment and the manner in which a student's perceptions and expectations of that environment may impact on their decision to withdraw. An ethnographical study using grounded theory is used to capture these underlying characteristics. This study provides an explanation of the teaching and learning environment as it relates to the student's beliefs, the actions between the student and staff and the intentions of the institution. The results of this initial study are presented. These results represent a preliminary 'grounded' model of the teaching and learning environment of the Technology Faculty at Southampton Institute.


ABSTRACT Background: Paratonia is one of the associated movement disorders characteristic of dementia. The aim of this study was to develop an assessment tool (the Paratonia Assessment Instrument, PAI), based on the new consensus definition of paratonia. An additional aim was to investigate the reliability and validity of the PAI. Methods: A three-phase cross-sectional survey was conducted. In the first two phases, the PAI was developed and validated. In the third phase, the inter-observer reliability and feasibility of the instrument was tested. Results: The original PAI consisted of five criteria that all needed to be met in order to make the diagnosis. On the basis of a qualitative analysis, one criterion was reformulated and another was removed. Following this, inter-observer reliability between the two assessors resulted in an improvement of Cohen's κ from 0.532 in the initial phase to 0.677 in the second phase. This improvement was substantiated in the third phase by two independent assessors with Cohen's κ ranging from 0.625 to 1. Conclusion: The PAI is a reliable and valid assessment tool for diagnosing paratonia in elderly people with dementia that can be applied easily in daily practice.


ABSTRACT This article presents the results of a study conducted to quantify the seasonal variation of coherence in synthetic aperture radar (SAR) interferograms in Kiruna, Northern Sweden. In SAR interferometry (InSAR), coherence is an important concept that provides a good indication of the phase stability of the scatterers. Therefore, in this study, the degree of coherence is used as a parameter to identify the seasonal variation interferograms. For this study, 34 Radarsat-2 ultra-fine beam mode (U6D) images of the Kiruna area (67°51ʹN, 20°14ʹE) and the improved digital elevation model (DEM) created by merging the Radarsat-2 DEM and ASTER DEM were used to produce 561 differential interferograms. The interferograms were arranged in three different ways for the analysis, with the first including common master interferograms (with the summer master image), the second including the sequential interferograms that have the shortest temporal baseline, and the third accounting for all possible combinations of the interferograms (full network of interferograms). Following this step, the variation of coherence for forest areas, urban areas, and flat waste rock areas was studied. This study shows that interferograms generated for the Kiruna region exhibit seasonal variations in coherence due to the ground snow layer in winter. Furthermore, when there is water on the ground due to the melting of the snow layer (in the spring) or due to rains in autumn, the coherence is reduced considerably. Another significant feature is that there is a significant change in summer-to-summer coherence for some regions even over the course of a few years. Based on this study, it is clear that the winter Radarsat-2 U6D beam mode images are not suitable for differential interferometric SAR (DInSAR) deformation measurements in flat waste rock regions in Kiruna. It is expected that even with winter images, PSInSAR or CTM techniques will be able to provide better deformation measurements, but, in this study, those techniques were not assessed. The next step will be to study the seasonal variations in coherence in natural or man-made targets/persistent scatterers using persistent scatter InSAR (PSInSAR) or coherence target monitoring (CTM) techniques.


Open Distance Learning is gaining popularity as a successful alternative for on-campus higher education especially with the emergence of web based platforms which enable the online delivery of courses worldwide. This emerging educational pedagogy can successfully be employed as means of capacity building of the people living in the less fortunate parts of the world where higher education especially at master level are scarce. This paper presents a two-year collaborative master study programme in sustainable energy engineering offered in synchronous with an on-campus study programme conducted by the KTH Royal Institute of Technology of Sweden, to students of Sri Lanka, which was facilitated by the Open University of Sri Lanka. The paper describes the need of such a programme, the format of course delivery and assessment thereof, plus the benefits gained. This programme has produced 72 post graduates in Sri Lanka alone and more than 200 distant postgraduates worldwide in the field of sustainable energy engineering during last 10 years period. In terms of capacity building in the energy sector in Sri Lanka this is considered a great achievement. The experience gained by the local staff in the role of local facilitators who engaged in some of the academic related activities such as evaluation of students' presentation and co-supervision of thesis projects have been greatly appreciated as being additional benefits to the staff in terms of their own academic development and capacity building. Finally, conclusions are made on how remote programmes of study could successfully be delivered to places where such know-how is scarce by adapting appropriate technologies in training personnel at postgraduate level to meet the needs of the industry.


Pedestrian trajectory prediction is an important but difficult task in self-driving or autonomous mobile robot field because there are complex unpredictable human-human interactions in crowded scenarios. There have been a large number of studies that attempt to understand humans' social behavior. However, most of these studies extract location features from previous one time step while neglecting the vital velocity features. In order to address this issue, we propose a novel feature-cascaded framework for long short-term network (CF-LSTM) without extra artificial settings or social rules. In this framework, feature information from previous two time steps are firstly extracted and then integrated as a cascaded feature to LSTM, which is able to capture the previous location information and dynamic velocity information, simultaneously. In addition, this scene-agnostic cascaded feature is the external manifestation of complex human-human interactions, which can also effectively capture dynamic interaction information in different scenes without any other pedestrians' information. Experiments on public benchmark datasets indicate that our model achieves better performance than the state-of-the-art methods and this feature-cascaded framework has the ability to implicitly learn human-human interactions.


In order to get rid of health hazard of asbestos fiber, a new kind of non-asbestos fiber reinforce composite by beater-addition process, which is used for sealing and gasket, has been developed to replace traditional asbestos gasket materials. The mechanical properties of the new composite were tested, and the performance between it and asbestos sheet paper were contrasted. Results show that the density, cross direction tensile strength, machine direction tensile strength and ignition loss at temperature of 300°C of the new composite are 1.19g/cm3, 2.62MPa, 3.15MPa and 15.61% respectively, while the performances of asbestos paper produced under the same condition are 1.26g/cm3, 2.87MPa, 3.24MPa and 12.03% respectively. Excellent performance, low cost and simple manufacture process of the new composite make it is possible to substitute traditional asbestos paper and apply widely.


Experiments were performed to determine whether visna/maedi virus (VMV), a small ruminant lentivirus (SRLV), could infect sheep via ocular tissues. The EV1 strain of VMV was administered into the conjunctival space of uninfected sheep, and the animals monitored for the presence of provirus DNA and anti-VMV antibodies in blood. The results showed that provirus DNA appeared in peripheral blood mononuclear cells of all animals within a few weeks of receiving either 10(6) TCID50 or 10(3) TCID50 of VMV. Of the animals receiving the higher dose of virus via the conjunctival space, two seroconverted by 7 and 10 weeks post-infection, one seroconverted 8 months post-infection, and one had not seroconverted by 15 months post-infection. With the lower virus dose, the animals infected via the trachea seroconverted by 4 and 14 weeks, respectively. After ocular infection with this dose, one animal showed a transitory seroconversion with low levels of antibody, peaking at 2 weeks post-administration. The remaining three of the animals infected via the eyes did not seroconvert over a period of 13 months. At post-mortem, evidence for the presence of proviral DNA was obtained from ocular tissue, lungs or mediastinal lymph node in both groups of animals. Histological analysis of lung tissue from animals receiving the lower dose of virus showed the presence of early inflammatory lesions. The results thus show for the first time that transmission of VMV can occur via ocular tissues, suggesting that the conjunctival space may be an additional route of natural transmission.


Recurrent dislocation after reconstructive hip surgery remains a challenging problem to treat. Constrained acetabular components can provide an excellent solution, in selected patients. Failure of constrained components may still occur despite excellent component implantation and occurs at the liner-shell and shell-bone interfaces usually as a result of trauma or aseptic loosening. We describe the failure of a Trident bipolar acetabular component at its bipolar/insert interface, a previously unreported mode of failure. (Hip International 2007; 17: 241-4)


The concentrations of amino acids (AA), stroke index and infarct area were determined in 26 gerbils which were divided into 3 groups: RSM-treated (n = 8), Saline-treated (n = 10) and sham-operated (n = 8). The levels of AA were measured with microdialysis technique in cerebral cortex. The concentrations of neurotransmitter AA, as Glu and GABA and Asp, were significantly increased during the first 60 min after CCA ligation, while the concentrations of non-neurotransmitter AA, as Thr and Ser, had no significant changes. In RSM-treated gerbils, the level of Glu was significantly lower than that of the saline-treated, but the GABA in RSM-treated was significantly higher than that of the saline-treated. The ratio of Glu/GABA was significantly decreased after ischemia. The RSM could improve the reduction of ratio of Glu/GABA during 0-30 min and 91-120 min after cerebral ischemia. There were statistically significant decrease in terms of stroke index in RSM-treated group when compared with saline-treated group at 24 h and 16 h after CCA ligation respectively. The RSM has a tendency to decrease the size of infarct area, but no statistical difference. The results suggest that the neurotransmitter AA involve in the pathophysiological procedures of cerebral ischemia and the RSM can attenuate dysfunctions of EAA and IAA. Furthermore, the results also imply that there may be an alternate way to treat cerebral ischemia by inhibiting the presynaptic releasing of Glu and stimulating the releasing of GABA.


Pluripotent hematopoietic stem cells have been studied extensively, but the events that occur during their differentiation remain largely uncharted. To develop a system that allows the differentiation of cultured multipotent progenitors by time-lapse fluorescence microscopy, myelomonocytic cells were labeled with green fluorescent protein (GFP) in vivo. This was achieved by knocking the enhanced GFP (EGFP) gene into the murine lysozyme M (lys) locus and using a targeting vector, which contains a neomycin resistant (neo) gene flanked by LoxP sites and "splinked" ends, to increase the frequency of homologous recombination. Analysis of the blood and bone marrow of the lys-EGFP mice revealed that most myelomonocytic cells, especially mature neutrophil granulocytes, were fluorescence-positive, while cells from other lineages were not. Removal of the neo gene through breeding of the mice with the Cre-deleter strain led to an increased fluorescence intensity. Mice with an inactivation of both copies of the lys gene developed normally and were fertile. (Blood. 2000;96:719-726)


Background: The ultimate goal of AntiRetroViral Treatments (ART) is to achieve complete immune restoration and lasting viral suppression in the infected patient. In order to ensure the efficacy, safety and accessibility of antiretroviral drugs (ARVs), it is recommended that they should be prescribed according to national guidelines; which are evolving with the various recommendations of the World Health Organization (WHO) and the arrival of newer, more effective and safer molecules. Objective: The objective of this study was to assess the rational use of Antiretrovirals in patients treated in Kinshasa before the use of Dolutegravir within the national program in order to assess the correct use of these molecules. Methods: This work is a descriptive cross-sectional study to assess the rational use of first-line ARVs among People Living with HIV (PLHIV) in different Centers of Treatment (ATCs) in Kinshasa before the introduction of Dolutegravir. The records of patients on ARVs were randomly and rationally selected in 12 different ATCs for HIV in Kinshasa according to three centers per district in the period from June to September 2018. Information on use and consumption of ARVs, compliance with guidelines, change of therapeutic combination as well as their reasons were consulted for the present study. Results: 507 files of PLHIV were collected in the various ATCs. 274 (54.1%) were from female patients. The most represented age group was 26 to 35 years with 192 patients (37.9%). The mean duration of first-line treatment for all patients included was 16.30 ± 5.85 months. The most widely used combination of ARVs overall was TDF + 3TC + EFV at 45.4%. 305 (60.2%) PLHIV kept the same first-line treatment molecule throughout the treatment period with an average treatment duration of 12.9 ± 2.77 months. The most common combination found in this population was TDF + 3TC + EFV (69.2%). 202 (39.8%) PLHIV changed treatment molecule yet respecting the first-line combinations. The average duration of treatment for those who changed molecules was 21.43 ± 7.25 months. Before the change, 112 (55.5%) of these patients were using the ZDV + 3TC + EFV combination. After switching, 105 (52%) of the patients used the TDF + 3TC + NVP combination. The first reason for changing molecules was its unavailability (53.3%) in the ATCs. Conclusion: Although some banned molecules are still available in some treatment centers, the guidelines on first-line treatments are respected in different centers in Kinshasa.


Abstract : This paper presents a method to mitigate high latency in the teleoperation of unmanned ground systems through display prediction and state estimation. Specifically, it presents a simulation environment which models both sides of the teleoperation system in the laboratory. The simulation includes a teleoperated vehicle model to represent the dynamics in high fidelity. The sensors and actuators are modeled as well as the communication channel. The latency mitigation approach is implemented in this simulation environment, which consists of a feed-forward vehicle model as a state estimator which drives a predictive display algorithm. These components work together to help the operator receive immediate feedback regarding his/her control actions. The paper contains a technical discussion of the design as well as specific implementation. It concludes with the presentation of some experimental data which demonstrate significant improvement over the unmitigated case.


There is a saying, 'do not paint the devil on the wall', which is commonly taken to mean that one should, for all intents and purposes, avoid portraying something in an overly negative or exaggerated way. The German origin of the proverb is even more interesting. It says: 'One should not paint the devil on the wall, since he will enter the room anyway'[1]. Rather than referring to a moral virtue (don't be overly pessimistic, don't exaggerate), the original proverb is, in itself, a pessimistic view on the world. In short, you don't need to evoke the devil, since he is already here. Or, perhaps, you don't need to exaggerate, since the world is already exaggerated. This special issue started out as an attempt to pursue this idea: If the world is exaggerated, wouldn't this require us to use exaggerated examples to describe it? ...

[1] Man braucht den Teufel nicht an die Wand zu malen, er kommt auch ohne das herein


This paper presents in detail the design of a linearly-polarized electronically reconfigurable unit-cell for transmitarray antennas with a 2-bit phase resolution in Ka-band. The size of the proposed unit-cell is 5.1×5.1×1.3 mm3. It is implemented on a dielectric stack-up composed of six metal layers, three dielectric substrates and two bonding films. The radiating elements are printed on both external metallic layers and are loaded by two PIN diodes controlling the transmission phase. This unit-cell is used to design a 196-element transmitarray with 784 PIN diodes. The performance of this 2-bit transmitarray has been evaluated numerically using our in-house simulation tool and compared to a transmitarray with a 1-bit phase quantization. A maximum gain of 22.9 dBi, an aperture efficiency of 32.3%, and a side-lobe level equal to −18.1 dB at broadside have been obtained at 29 GHz.


Recent work suggests that the human ear varies significantly between different subjects and can be used for identification. In principle, therefore, using ears in addition to the face within a recognition system could improve accuracy and robustness, particularly for non-frontal views. The paper describes work that investigates this hypothesis using an approach based on the construction of a 3D morphable model of the head and ear. One issue with creating a model that includes the ear is that existing training datasets contain noise and partial occlusion. Rather than exclude these regions manually, a classifier has been developed which automates this process. When combined with a robust registration algorithm the resulting system enables full head morphable models to be constructed efficiently using less constrained datasets. The algorithm has been evaluated using registration consistency, model coverage and minimalism metrics, which together demonstrate the accuracy of the approach. To make it easier to build on this work, the source code has been made available online.


Introduction Globally, approximately half of the estimated 6.3 million under-5 deaths occur in the neonatal period (within the first 28 days of life). Kenya ranks among countries with the highest number of neonatal deaths, at 20 per 1000 live births. Improved identification and management of neonates with potentially life-threatening illness is critical to meet the WHO's target of ≤12 neonatal deaths per 1000 live births by 2035. We developed an interactive (two-way) short messaging service (SMS) communication intervention, Mobile Solutions for Neonatal Health (Mobile women's and children's health (WACh) NEO), focused on the perinatal period. Mobile WACh NEO sends automated tailored SMS messages to mothers during pregnancy and up to 6 weeks post partum. Messages employ the Information-Motivation-Behaviour Skills framework to promote (1) maternal implementation of essential newborn care (ENC, including early, exclusive breast feeding, cord care and thermal care), (2) maternal identification of neonatal danger signs and care-seeking, and (3) maternal social support and self-efficacy. Participants can also send SMS to the study nurse, enabling on-demand remote support. Methods and analysis We describe a two-arm unblinded randomised controlled trial of the Mobile WACh NEO intervention. We will enrol 5000 pregnant women in the third trimester of pregnancy at 4 facilities in Kenya and randomise them 1:1 to receive interactive SMS or no SMS (control), and conduct follow-up visits at 2 and 6 weeks post partum. Neonatal mortality will be compared between arms as the primary outcome. Secondary outcomes include care-seeking, practice of ENC and psychosocial health. Exploratory analysis will investigate associations between maternal mental health, practice of ENC, care-seeking and SMS engagement. Ethics and dissemination This study received ethical approval from the University of Washington (STUDY00006395), Women and Infants Hospital (1755292-1) and Kenyatta National Hospital/University of Nairobi (P310/04/2019). All participants will provide written informed consent. Findings will be published in peer-reviewed journals and international conferences. Trial registration number NCT04598165


This paper examines the interplay between exchange rate regimes and policies and commercial policy in six transition economies. In all these economies the rate of protection afforded domestic industry by the exchange rate has been eroded by high rates of inflation and insufficient growth in productivity. As a result, there has been pressure on governments to increase trade barriers and each country examined has had recourse to various means of restricting imports. We argue that more flexible management of the nominal exchange rate would be a preferable way of dealing with the real appreciation of these countries' currencies. exchange rates, trade policy, transition economies.


Modem building design is complex and involves many different disciplines operating in a fragmented manner. Appropriate computer-based decision support (DS) tools are sought that can raise the level of integration of different activities at the conceptual stage, in order to help create better designs solutions. This project investigates opportunities that exist for using techniques based upon the Genetic Algorithm (GA) to support critical activities of conceptual building design (CBD). Collective independent studies have shown that the GA is a powerful optimisation and exploratory search technique with widespread application. The GA is essentially very simple yet it offers robustness and domain independence. The GA efficiently searches a domain to exploit highly suitable information. It maintains multiple solutions to problems simultaneously and is well suited to non-linear problems and those of a discontinuous nature found in engineering design. The literature search first examines traditional approaches to supporting conceptual design. Existing GA techniques and applications are discussed which include pioneering studies in the field of detailed structural design. Broader GA studies are also reported which have demonstrated possibilities for investigating geometrical, topological and member size variation. The tasks and goals of conceptual design are studied. A rationale is introduced, aimed at enabling the GA to be applied in a manner that provides the most effective support to the designer. Numerical experiments with floor planning are presented. These studies provide a basic foundation for a subsequent design support system (DSS) capable of generating structural design concepts. A hierarchical Structured GA (SGA) created by Dasgupta et al [I) is investigated to support the generation of diverse structural design concepts. The SGA supports variation in the size, shape and structural configuration of a building and in the choice of structural frame type and floor system. The benefits and limitations of the SGA approach are discussed. The creation of a prototype DSS system, abritrarily called Designer-Pro (DPRO), is described. A detailed building design model is introduced which is required for design development and appraisal. Simplifications, design rationale and generic component modelling are mentioned. A cost-based single criteria optimisation problem (SCOP) is created in which other constraints are represented as design parameters. The thesis describes the importance of the object-oriented programming (OOP) paradigm for creating a versatile design model and the need for complementary graphical user interface (GUI) tools to provide human-computer interaction (HCI) capabilities for control and intelligent design manipulation. Techniques that increase flexibility in the generation and appraisal of concept are presented. Tools presented include a convergence plot of design solutions that supports cursor-interrogation to reveal the details of individual concepts. The graph permits study of design progression, or evolution of optimum design solutions. A visualisation tool is also presented. The DPRO system supports multiple operating modes, including single-design appraisal and enumerative search (ES). Case study examples are provided which demonstrate the applicability of the DPRO system to a range of different design scenarios. The DPRO system performs well in all tests. A parametric study demonstrates the potential of the system forDS. Limitations of the current approach and opportunities to broaden the study form part of the scope for further work. Some suggestions for further study are made, based upon newly-emerging techniques. ii


Investigation of the changes of the mouse liver cells revealed early reaction of endothelial sinusoid cells and Kupffer cells after endotoxin application. During first 60 min. after endotoxin injection there were certain bulge of nuclear zone, changes of nuclear shape, appearance of microfilaments in the cytoplasm of endothelial cells. An increase in the number of the pores and fenestrae grouped in sieve plates was discovered in the endothelial cells. Their luminal surface formed the bubbles. Such changes of the endothelial cells can be described as their activation. Reaction of the endothelial cells of hepatic sinusoids and activation of the Kupffer cells were revealed at the same time.


IMPORTANCE
Atopic dermatitis (AD) is associated with multiple potential risk factors for obesity and high blood pressure (BP), including chronic inflammation, sleep disturbance, and mental health comorbidity. Previous studies found associations between general obesity and AD. However, it is unknown whether AD is associated with central obesity and/or high BP.

OBJECTIVES
To determine whether central obesity and high BP are increased in pediatric AD.

DESIGN, SETTING, AND PARTICIPANTS
This case-control study performed in multicenter pediatric dermatology practices in the United States recruited 132 children (age range, 4-17 years) with active moderate to severe AD and 143 healthy controls from April 1, 2009, through December 31, 2012.

EXPOSURES
Diagnosis and severity of AD assessed by a pediatric dermatologist.

MAIN OUTCOMES AND MEASURES
Body mass index, waist circumference, waist to height ratio, systolic BP, and diastolic BP.

RESULTS
Moderate to severe AD was associated with body mass index for age and sex of 97th percentile or greater (logistic regression; odds ratio [OR], 2.64; 95% CI, 1.15-6.06), International Obesity Task Force obesity cutoffs (OR, 2.38; 95% CI, 1.06-5.34), waist circumference in the 85th percentile or greater (OR, 3.92; 95% CI, 1.50-10.26), and waist to height ratio of 0.5 or greater (OR, 2.22; 95% CI, 1.10-4.50). Atopic dermatitis was associated with higher BP for age, sex, and height percentiles (systolic BP: OR, 2.94; 95% CI, 1.04-8.36; diastolic BP: OR, 3.68; 95% CI, 1.19-11.37), particularly a systolic BP in the 90th percentile or higher (OR, 2.06; 95% CI, 1.09-3.90), in multivariate models that controlled for demographics, body mass index and waist circumference percentiles, and history of using prednisone or cyclosporine. Atopic dermatitis was associated with higher systolic BP in Hispanics/Latinos (general linear model; β, .23; 95% CI, .04-.43) and Asians (β, .16; 95% CI, .03-.30). Severe to very severe AD was associated with systolic BP in the 90th percentile or higher (adjusted OR, 3.14; 95% CI, 1.13-8.70). Atopic dermatitis was associated with a family history of hypertension (adjusted OR, 1.88; 95% CI, 1.14-3.10) and type 2 diabetes mellitus (adjusted OR, 1.64; 95% CI, 1.02-2.68) but not obesity or hyperlipidemia.

CONCLUSIONS AND RELEVANCE
Moderate to severe pediatric AD may be associated with central obesity and increased systolic BP.


The model reduction method introduced in [Benner, P. and Schneider, A.; Balanced Truncation Model Order Reduction for LTI Systems with many Inputs or Outputs, in A. Edelmayer: Proceedings of the 19th International Symposium on Mathematical Theory of Networks and Systems, 2010, ISBN/ISSN: 978-963311-370-7] shows how to reduce linear time-invariant (LTI) continuous-time state space systems with either many inputs or many outputs using the well-known balanced truncation approach. We call this method balanced truncation for many terminals (BTMT). In this work we generalize BTMT to descriptor systems of the form Eẋ(t) = Ax(t) +Bu(t), A,E ∈ Rn×n, B ∈ Rn×m, y(t) = Cx(t) +Du(t), C ∈ Rp×n, D ∈ Rp×m, where m ∈ O(n) and p ≪ n, or vice versa. We show how to obtain a reduced order model by solving one Lyapunov equation and using the Gauss-Kronrod quadrature to compute the needed projection matrices. In particular, we discuss the case when E is singular and show numerical results.


The time-delay (TD) mode of operation of lateral effect position sensors (LEPSD) is investigated and compared with the voltage-difference mode. A normalized dynamic equation describing the lateral photovoltage spatial and temporal distribution is derived and solved in response to a variety of beam shapes and time modulations. The normalization of the dynamic equation allows description of the characteristics of a whole group of LEPSDs having the same ratio of series to shunt resistance. Several advantageous features unique to the TD mode are found: (1) Existence of operating frequencies where the response around the midpoint becomes perfectly linear. (2) The response becomes more linear and the dynamic range increases as the optical spot size increases. (3) The dynamic range increases with the operating frequency. (4) The TD response is not affected by the existence of background illumination. (5) No need for signal normalization.


Delphinidin, a major anthocyanidin present in many pigmented fruits and vegetables, possesses antioxidant, antiinflammatory, and antiangiogenic properties. In this study, we provide evidence that it could be developed as a novel agent against human prostate cancer (PCa). We observed that delphinidin treatment to human PCa LNCaP, C4-2, 22RN1, and PC3 cells resulted in a dose-dependent inhibition of cell growth without having any substantial effect on normal human prostate epithelial cells. We selected PC3 cells as a test model system because of their highly aggressive proliferative nature. Delphinidin treatment of cells resulted in a dosedependent induction of apoptosis and arrest of cells in G2-M phase. This induction of apoptosis seems to be mediated via activation of caspases because N-benzyloxycarbonyl-Val-AlaAsp(OMe)-fluromethylketone significantly reduced apoptosis induced by delphinidin. We also observed that delphinidin treatment of cells resulted in a dose-dependent decrease in (a) phosphorylation of IKB kinase ; (NEMO), (b) phosphorylation of nuclear factor-KB (NF-KB) inhibitory protein IKBA, (c) phosphorylation of NF-KB/p65 at Ser and NF-KB/p50 at Ser, (d) NF-KB/p65 nuclear translocation, and (e) NF-KB DNA binding activity. Delphinidin administration (2 mg, i.p. thrice weekly) to athymic nude mice implanted with PC3 cells resulted in a significant inhibition of tumor growth. Analysis of tumors from delphinidin-treated mice showed significant decrease in the expression of NF-KB/p65, Bcl2, Ki67, and PCNA. Taken together, our data suggest that delphinidin could be developed as an agent against human PCa. [Cancer Res 2008;68(20):8564–72]


Purpose

Focusing on the specific context of two European old industrial regions – South Yorkshire (UK) and North Region of Portugal – this paper aims to identify and conceptualise a set of relational capabilities that business leaders perceive to play a key role in industrial rejuvenation.

Design/methodology/approach

A qualitative research design operationalised via case studies was followed for the empirical analysis. Data collection was developed through in-depth interviews with managing directors in small and medium-sized enterprises (SMEs) belonging to the metal and engineering industry and the textile and footwear sectors in the two old industrial regions. Data analysis followed the techniques of data categorisation, within case-analysis and cross-case analysis.

Findings

The study identifies relational capabilities that firms use to identify, access and leverage new knowledge: frequent meetings with customers; frequent meetings with suppliers; dialogue with government to influence policy that encourages research and technology transfer; partnership actions for the commercialisation of products and services; active membership with sector associations; immersion in science and technological parks; intentionally establishing links with entrepreneurship-supporting entities; human resources development by technical training institutions; and systematic links with the University. The relational capabilities identified require structured communication processes and alliance management practices to enable and support absorptive capacity and learning in inter-organisational networks.

Practical implications

The relational capabilities identified can help position regions in specific markets and value chains, contribute to improving regions' internal and external connections and assist in combining regions' strengths to create industrial capability in high-growth-potential areas.

Originality/value

This paper highlights the role of relational capabilities as a way to secure access to knowledge and competencies needed for firms' innovation and avoidance of competency traps. This is particularly relevant in the context of European smart specialisation policy, where key regional stakeholders collectively engage in the identification of areas of competitive strength, enhanced coordination and strategic alignment of resources. The study is not without limitations, as findings are based on case studies of SMEs operating in the manufacturing industry and the analysis of relational capabilities is focused on knowledge novelty.


Polymer-based solar cells (PSCs) are an attractive option for low-cost renewable energy, but have achieved limited success due to their poor performance. This issue is related to the lack of effective strategies to control the active layer morphology. The active layer is a mixture of semiconducting polymers and fullerene derivatives, which form a kinetically trapped nanostructure that is highly sensitive to the processing variables. In this dissertation, the methodology to quantify and improve the nanostructures of a standard PSC system consisting of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61-butyric acid methyl ester (PCBM) was developed. Small angle neutron scattering (SANS) was used as the major tool for this purpose. Firstly, we studied the effect of common processing variables on the morphology and device performance. It was concluded there are two distinct length scales in the morphology: a local phase size of about 15 nm, and a higher-ordered structure with a length scale of 22 nm to 34 nm, based on model analysis. Secondly, we proposed a novel device architecture employing silica particles to alter the aggregation state of PCBM. By analyzing the absolute scattering intensity of SANS data, we conclusively demonstrated that some PCBM will migrate away from the bulk region to the surface of the silica upon annealing and improve the device performance. The overall effect is to decrease the device series resistance and improve the power conversion efficiency by 10 % to 20 % relative to the control group. These results suggest phase separation between the polymer and fullerene can only be partially manipulated by tuning processing variables, but a greater control can be achieved by the proposed design with silica particles.


In revision total hip arthroplasty, an arthrographically loose or migrated cemented or porous ingrowth acetabular component may be found to be quite secure and difficult to remove. An acetabular component that is not loose may need to be removed because of infection or malposition. Based on a previous study of torque failure of cemented and uncemented acetabular components in vitro, a pneumatic impact wrench has been developed that delivers repetitive shear loads to the implant-cement or implant-bone interfaces. Eight acetabular components (three polyethylene, two metal backed, and three porous coated) were implanted with polymethylmethacrylate into fresh, unembalmed human anatomic specimen acetabuli. Seven components were easily removed using this new device at an average setting of 16 kg/m of torque. One polyethylene component could not be removed because the studs cut through polyethylene grooves. In one pelvis, a fracture occurred through a pubic anchoring hole when the driver was taken by error through a 40 degrees arc rather than the recommended 15 degrees arc. This device has been used in vivo in four cases, easily removing the components without damage to the surrounding bone.


The aim of this study was to evaluate the effects of a teacher training program on teacher outcomes. The teachers' knowledge and attitudes regarding inclusion, classroom management strategies, and their relationships with children both with and without disabilities were evaluated using self-report instruments. In addition, their classroom behaviors were evaluated by independent observers. The teacher education program included a variety of topics related to inclusion and effective strategies for inclusive classrooms. The data were collected prior to the education, after the completion of the program, and 6 months afterwards. The results indicated that the teacher program seemed to have moderate-to-large effects on all teacher outcomes, but the changes in their classroom behaviors were minimal.


This research was supported in part by the
Office of Water Resources Research. U.S. Department of the Interior under Project B-045-OHIO


We analyze a new type of plasmon system arising from small metal nanoparticles linked by narrow conductive molecular bridges. In contrast to the well-known charge-transfer plasmons, the bridge in these systems consists only of a narrow conductive molecule or polymer in which the electrons move in a ballistic mode, showing quantum effects. The plasmonic system is studied by an original hybrid quantum-classical model accounting for the quantum effects, with the main parameters obtained from first-principles density functional theory simulations. We have derived a general analytical expression for the modified frequency of the plasmons and have shown that its frequency lies in the near-infrared (IR) region and strongly depends on the conductivity of the molecule, on the nanoparticle-molecule interface, and on the size of the system. As illustrated, we explored the plasmons in a system consisting of two small gold nanoparticles linked by a conjugated polyacetylene molecule terminated by sulfur atoms. It is argued that applications of this novel type of plasmon may have wide ramifications in the areas of chemical sensing and IR deep tissue imaging.


Groundwater resources have great importance in arid and semi-arid areas as a major source of water supplier. Population growth, industrial development and lack of proper environmental control have led to quality decline and contamination of groundwater resources. One of the main problems in the qualitative assessment of these resources is that it is impossible to sample all points. Considering the spatial correlation of environmental variables, Geo-statistical methods extend result of the observation points to other parts and save sampling time and cost. In this study, geo-statistical methods were engaged to prepare spatial and probability maps of heavy metal contamination of arsenic, lead and cadmium concentration as well as spatial variation of qualitative parameters of electrical conductivity, TDS and total hardness in the groundwater of Qom watershed, and results of interpolation were evaluated using cross-validation method by means of MBE, RMSE and RMSSE indexes. The results showed the superiority of the exponential model (with least RSS and maximum r2) for semi-variogram for arsenic and spherical model for lead and cadmium to be used in ordinary kriging to produce spatial maps of these elements. Semi-variogram exponential model for arsenic, the spherical model for cadmium and lead showed higher estimation accuracy to provide the probability map for heavy metal pollution in indicator kriging. Due to proper correlation (r=0.994) between electrical conductivity and TDS, use of each variable as covariate to aid in the estimation of the other, increases the accuracy of estimated Co-kriging in compare with ordinary kriging method. Validation results indicate the superiority of the spherical model to estimate the total hardness in the ordinary kriging. Finally, maps produced with the GS+ software environment were transferred to GIS and were presented as spatial maps by adding the watershed borders.


Sperm migration towards an oocyte in the female reproductive tract is an important step for successful fertilization. Although several sperm-chemotactic factors have been identified in mammals, it is unclear whether these chemoattractants contribute to sperm migration towards an oocyte that is the final destination for sperm. Furthermore, chemoattractants for bovine sperm are still undiscovered even though the follicular fluid attracts sperm in cattle. Here, we demonstrated that a single bovine cumulus-oocyte complex (COC) had the ability to attract sperm, suggesting that the COC secreted sperm chemoattractants. We identified stromal cell-derived factor 1 (SDF1), which was expressed in COCs, and its receptor CXCR4 in sperm, as a candidate. Our results showed that bovine sperm preferentially migrated to the area with a high SDF1 concentration and occasionally showed turn movements by asymmetric flagellar bends during the migration. We also demonstrated that increasing the intracellular Ca2+ concentration via Ca2+ channels was related to SDF1-induced sperm chemotaxis. Finally, a CXCR4 inhibitor significantly suppressed the in vitro bovine sperm migration towards a COC. Taken together, we propose that SDF1 is a chemotactic factor for bovine sperm to regulate their migration towards an oocyte via the CXCR4 receptor.


The role of proline residues in transport catalysis mediated by GLUT3 has been investigated using site-directed mutagenesis. PCR methodology was used to construct a series of eight mutant GLUTS cDNAs in which individual proline residues were replaced with alanine. Heterologous expression of the GLUTS Pro-Ala mutants in Xenopus laevis oocytes was achieved by microinjection of in vitro transcribed mRNA and has enabled an extensive analysis of the kinetic properties of these mutants. Km values for the zero-trms influx of 2-deoxy-D-glucose into mutant-injected oocytes have been determined, and compared to the values obtained for wild type GLUTS expressed in the same system. The effect of each proline substitution on the integrity of the exofacial and endofacial binding sites was investigated by determining Ki values for the inhibition of 2-deoxy-D-glucose zero-trans influx by maltose and cytochalasin B, respectively. Although no individual proline residue was observed to be absolutely essential for GLUTS catalytic activity, mutation of Pro206, Pro381, Pro385 and Pro451 to alanine resulted in an increase in the Ki for maltose. Replacement of prolines at positions 381, 383 and 385, located within putative transmembrane helix 10 of GLUT3, resulted in a reduction in the Ki for cytochalasin B. The small but significant changes observed in the nature of exofacial substrate binding indicate that proline residues are important for transporter function. In addition, the prolines located within helix 10 are important in the conformational changes of the protein. Measurement of transporter turnover numbers in Xenopus oocytes has not previously been possible due to the lack of an accurate and reproducible method for the isolation of a pure plasma membrane fraction. In order to further characterise the kinetics of the Pro-Ala mutants, a protocol was designed, based on a number of previous attempted methods, for the isolation of a clean plasma membrane fraction from Xenopus oocytes. Results from dot blot and Western blot analysis of plasma membrane fractions isolated from GLUT3-expressing oocytes, indicated that the preparation of a plasma membrane fraction free from other cellular contaminants was extremely problematic, despite various attempts at optimisation. This was attributed to the abundance of glutinous yolk protein and to the extremely fragile nature of the plasma membrane of the oocyte. Consequently, it was concluded that this methodology was not suitable for the accurate quantitation of cell surface transporters and the subsequent determination of turnover numbers in this system. To address the problem of quantitation of cell surface transporters, stable expression of GLUT transporters in a mammalian cell-culture line was investigated as an alternative to expression in oocytes. Simple and reproducible subcellular fractionation procedures are available for this cell line which would enable measurement of transporter turnover numbers. Additionally, this system is more convenient for use in photolabelling studies using ATB- BMPA and cytochalasin B, since large amounts of plasma membranes from cultured mammalian cells can be easily obtained without the need for repeated mRNA injections.


The primary therapeutic effects of enteral nutrition in patients with Crohn's disease have been reported previously. Although the quantity and type of fat in enteral nutrition are considered to be important, it is unclear how fat modulates mucosal inflammatory responses in the intestine. In the present study, we evaluated the effects of medium-chain and long-chain fatty acids (MCFA and LCFA) on interleukin (IL)-8 secretion in a fetal intestinal epithelial cell line, intestine-407 cells. IL-8 expression was evaluated at the protein and mRNA levels. The activation of nuclear factor-kB was assessed with an electrophoretic gel mobility shift assay. The addition of oleic acid (LCFA) micelles, but not octanoic acid (MCFA) micelles, weakly but significantly enhanced basal IL-8 secretion in the intestine-407 cells. The addition of MCFA (5 mmol/L) induced a 40% increase in IL-1b–induced IL-8 secretion and a 35% increase in tumor necrosis factor (TNF)-a–induced IL-8 secretion, respectively. The addition of LCFA (5 mmol/L) induced a 140% increase in IL-1b–induced IL-8 secretion and a 110% increase in TNF-a–induced IL-8 secretion, respectively. These responses were also observed at the mRNA levels. The electrophoretic gel mobility shift assay indicated that both MCFA and LCFA enhanced IL-1b– and TNF-a–induced nuclear factor-kB activation. We demonstrated the proinflammatory activities of MCFA and especially LCFA. It is likely that medium-chain triglycerides may be more suitable than long-chain triglycerides as an energy source in enteral diets in the treatment of patients with Crohn's disease. J. Nutr. 130: 2636–2640, 2000.


To develop a novel separation technique of matrix alloys from metal matrix composite, separation experiments for various kinds of particle reinforced metal matrix composites (PRMMCs) were carried out. The Al-4mass%Cu alloy, Al-7mass%Si alloy and cast iron were used as matrix. The SiC particles (particle size: 75μm) and Al2O3 particles (particle size: 120μm) were used as reinforcement. The PRMMC specimen was placed in a silica tube container with a small nozzle (nozzle size: 0.75mm) at the bottom and was melted by H.F. induction heating. Then the molten PRMMC specimen was forced to flow out through the nozzle by applying a certain pressure of Ar gas. Most of the molten matrix alloy flowed out through the nozzle and the remainder in the container consisted of the reinforcements and a part of the matrix alloy. The amount of separated matrix alloy increased with decreasing the volume fraction of reinforcement particles in PRMMC specimens. With decreasing the fabrication temperature from 1273K to 1073K, the amount of matrix alloy separated from SiCP/Al-7mass%Si alloy composites increased. It is considered that a reaction layer formed on the surface of SiC particles at 1273K improves the wettability between the molten matrix alloy and SiC particle, which prevents the separation of molten matrix alloy from reinforcements. On the other hand, the amount of separated matrix alloy from 20vol% Al2O3P/cast iron composites was very high due to no reaction layer formed at interface between Al2O3 particle and cast iron.


Microorganisms respond to osmotic stress mostly by accumulating compatible solutes, either by uptake from the medium or by de novo synthesis. These osmotically active mol- ecules preserve the positive turgor pressure required for cell division. The diversity of compatible solutes is large but falls into a few major chemical categories; they are usually small or- ganic molecules such as amino acids or their derivatives, and carbohydrates or their derivatives. Some are widely distributed in nature while others seem to be exclusively present in specific groups of organisms. This review discusses the diversity and distribution of known classes of compatible solutes found in prokaryotes as well as the increasing knowledge of the genes and pathways involved in their synthesis. The alternative roles of some archetypal compatible solutes not subject to os- moregulatory constraints are also discussed.


It is argued in this paper that robots are just quasi-autonomous beings, which must be understood, within an emergent systems view, as intrinsically linked to and presupposing human beings as societal creatures within a technologically mediated world. Biosemiotics is introduced as a perspective on living systems that is based upon contemporary biology but reinterpreted through a qualitative organicist tradition in biology. This allows for emphasizing the differences between (1) an organism as a general semiotic system with vegetative and self-reproductive capacities, (2) an animal body also with sentience and phenomenal states, and (3) higher forms of anthroposemiotic systems such as humans, machines and robots. On all three levels, representations (or sign action) are crucial processes. The "representationalism" invoked by critiques of cognitive science and robotics tends to focus only on simplistic notions of representation, and must be distinguished from a Peircean or biosemiotic notion of representation. Implications for theorizing about the physical, biological, animate, phenomenal and social body and their forms of autonomy are discussed.


Cloud water was simultaneously collected in Teziutlan town, located in a mountainous region in the Sierra Madre Oriental, State of Puebla, Mexico, to compare three co-located cloud water collectors. Two of the collectors were passive; the first one was an omnidirectional collector known as ASRC (Atmospheric Science Research Center String Collector). The second was a metallic mesh collector with 0.041-cm diameter stainless steel wires woven on a polyethylene frame. The third one was an active collector in which air is aspirated through a duct at a rate of 3.5 m s -1 . Cloud droplets are collected on vertically strung wires on a teflon frame. Liquid water content and collector capacity were evaluated by the corresponding equations. The results indicated that there were not differences in chemical composition concentrations between the passive collectors, however, statistical differences were found between the active and passive collectors. Finally, the collection capacity was higher in the active collector than in passive collectors, due to the inherent differences in design between the active and passive collectors.


BACKGROUND
Quantitative or qualitative abnormalities of erythroid progenitors in patients with chronic renal failure (CRF) could be the major factor for recombinant human erythropoietin (rHuEPO) hyporesponsiveness and severe anemia in hemodialysis (HD) patients receiving rHuEPO therapy.

METHODS
Purified 1 x 10(4) circulating CD34+ cells isolated from rHuEPO-hyporesponsive HD patients (EPO-H; n = 10), rHuEPO-responsive non-HD patients with CRF (EPO-R; n = 8), nonanemic HD patients without rHuEPO therapy (EPO-W/O; n = 10), and healthy volunteer controls (CON; n = 10) were subjected to a methylcellulose culture system supplemented with rHuEPO, recombinant human interleukin-3 (IL-3), recombinant human stem cell factor (SCF), and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for 14 days.

RESULTS
The average number of burst-forming units of erythroids (BFU-Es) was significantly less in the EPO-H group compared with the CON and EPO-W/O groups. Furthermore, colony size also was significantly smaller in the EPO-H group. Total RNAs were extracted from approximately 100 colonies/patient and subjected to complementary DNA expression array studies of 268 growth factors, cytokines, chemokines, and their receptors. A characteristic cluster upregulated in the EPO-R and EPO-W/O groups and downregulated in the EPO-H group was identified that contained various cytokines and growth factors, including IL-6, GM-CSF, vascular endothelial growth factor B, IL-9, IL-3, leukemia inhibitory factor, and interferon alpha-2, and such receptors as thrombopoietin receptor, IL-9 receptor, and colony-stimulating factor 1 receptor.

CONCLUSION
These data suggest that the cross-talk network or autocrine/paracrine regulatory loop is critically impaired in BFU-E-derived cells in EPO-H patients, and investigation of these cluster genes would facilitate the development of novel therapeutic strategies for such patients.


The work presented in the thesis is based on the assumption that two types of cognitive processes can be differentiated, domain-specific (i.e. modular) and domain-general (i.e. central) processes. Autism and dyslexia are viewed as disorders with domain-specific deficits, while mental retardation is viewed as a disorder in central processing. Using Anderson's (1986) inspection time paradigm it was shown that central processing speed was intact in autism and dyslexia but impaired in mental retardation. The modularity status of phonological processing was investigated using the Phonological Assessment Battery. It was found that test performances did not only require intact phonological skills, but also intact domain-general functioning. The interaction between modular and central processes was studied by examining surface form retention levels for scrambled and ordered stories. The results showed that the autistic group had enhanced, the dyslexic and MLD groups suppressed surface form retention levels. It was further found that half of the subjects in the autistic group were hyperlexic, and that these subjects, in particular, represented enhanced levels of surface form. It was suggested that weak central coherence could explain this finding. Poor surface form retention in dyslexia was viewed as a secondary consequence of the phonological processing deficit. Representation of gist was examined for the same stories and in the same conditions, showing that enhanced piecemeal processing of text in the hyperlexic group was accompanied by poorer gist representation for ordered stories. The dyslexic and the MLD group were unimpaired in gist representation. These findings indicated that the abnormality in central processing in autism (i.e. weak central coherence) affected both low-level (surface form) and high-level (gist representation) central processes. In dyslexia gist representation was unaffected by modular, phonological processing deficits. The hyperlexic and non-hyperlexic subgroups were further investigated with respect to differences in the degree of weak central coherence, executive and Theory of Mind dysfunctioning. The results indicated that weak central coherence might be contributing factor in hyperlexic developments. There were no group differences in ToM, but some indication that hyperlexic subjects had greater executive function impairments.


The notion that cardiovascular disease (CVD) primarily occurs in men is slowly disappearing. More women than men die of CVD every year, and when women survive, the burden and consequences are worse than in men. Markers of stress and other psychosocial factors have been associated with poor outcomes. Multiple studies have demonstrated sex-based differences in the vascular and endothelial responses to mental stress. Psychosocial stressors were also found to be independent risk factors for the development and progression of CVD. This review arises from accumulating evidence suggesting that psychological well-being may improve cardiac-related outcomes, independent of cardiac risk factors. Despite the fact that positive physician-patient engagement is likely to play a critical role in promoting positive psychological traits and healthy behaviors, current physician awareness and advocacy are rather suboptimal, despite active awareness campaigns such as the American Heart Association's Go Red for Women®. There is a need to further study the role and management of stress as a CVD risk factor, especially in women, who are disproportionately affected.