Multiple sclerosis (MS) is one of the most common neurological disabilities of the central nervous system. Immune-modulatory therapy with Interferon-β (IFN-β) is a commonly used first-line treatment to prevent MS patients from relapses. Nevertheless, a large proportion of MS patients on IFN-β therapy experience their first relapse within 2 years of treatment initiation. Feature selection, a machine learning strategy, is routinely used in the fields of bioinformatics and computational biology to determine which subset of genes is most relevant to an outcome of interest. The majority of feature selection methods focus on alterations in gene expression levels. In this study, we sought to determine which genes are most relevant to relapse of MS patients on IFN-β therapy. Rather than the usual focus on alterations in gene expression levels, we devised a feature selection method based on alterations in gene-to-gene interactions. In this study, we applied the proposed method to a longitudinal microarray dataset and evaluated the IFN-β effect on MS patients to identify gene pairs with differentially correlated edges that are consistent over time in the responder group compared to the non-responder group. The resulting gene list had a good predictive ability on an independent validation set and explicit biological implications related to MS. To conclude, it is anticipated that the proposed method will gain widespread interest and application in personalized treatment research to facilitate prediction of which patients may respond to a specific regimen.


Better access to knowledge and knowledge production has to be reconsidered as key to successful individual and social mitigation and adaptation strategies for global change. Indeed, concepts of sustainable development imply a transformation of science towards fostering democratisation of knowledge production and the development of knowledge societies as a strategic goal. This means to open the process of scientific knowledge production while simultaneously empowering people to implement their own visions for sustainable development. Advocates of sustainability science support this transformation. In transdisciplinary practice, they advance equity and accountability in the access to and production of knowledge at the science–society interface. UNESCO points to advancements, yet Northern dominance persists in knowledge production as well as in technology design and transfer. Further, transdisciplinary practice remains experimental and hampered by inadequate and asymmetrically equipped institutions in the North and South and related epistemological and operational obscurity. To help identify clear, practicable transdisciplinary approaches, I recommend examining the institutional route – i.e., the learning and adaptation process – followed in concrete cases. The transdisciplinary Eastern and Southern Africa Partnership Programme (1998–2013) is a case ripe for such examination. Understanding transdisciplinarity as an integrative approach, I highlight ESAPP's three key principles for a more democratised knowledge production for sustainable development: (1) integration of scientific and "non-scientific" knowledge systems; (2) integration of social actors and institutions; and (3) integrative learning processes. The analysis reveals ESAPP's achievements in contributing to more democratic knowledge production and South ownership in the realm of sustainable development.


17 yrs. old boy presented with low back pain and progressive deformity with no history of trauma or tuberculosis. Clinically there was tender knuckle formation at L2 level. X-rays showed vertebra plana (concentric collapse) at L2 level along with skull involvement. While being investigated patient developed partial collapse at L3 level and pelvis involvement within a week. On biopsy from L3 vertebra the lesion was found to be eosinophilic granuloma. This is a case report of a rare instance in which acute progression of eosinophilic granuloma occurred involving multiple skeletal sites in an adult.


The antigenicity of the so-called scarlet fever anatoxin which was produced by detoxifying scarlet fever toxin with formol and heat is due to the presence of toxoid. Rabbits can be used for the determination of antigenicity of scarlet fever anatoxin. The antigenicity of the purified and concentrated scarlet fever anatoxin described has been demonstrated by animal and human test. The antigenicity of the anatoxin prepared from scarlet fever toxin which was produced in a semi-synthetic medium has been demonstrated. The addition of alum seems to increase the antigenicity of scarlet fever anatoxin. The degree of immunity conferred on rabbits by immunization with conbined scarlet fever and diphtheria anatoxin is as high as that conveyed by a single anatoxin.


OBJECTIVE
To investigate incidence and causes of complete failed fertilization after intracytoplasmic sperm injection (ICSI) in a tertiary care facility.

METHODS
A total of 1,779 cycles between February 1994 and December 2003 were analyzed. Study parameters were female age, infertility diagnosis, ovarian stimulation protocol, estradiol level on day of hCG administration, number of follicles, number of oocytes retrieved, number of oocytes injected, and semen parameters.

RESULTS
Complete failed fertilization occurred in 23 cycles (1.29%) involving a total of 85 oocytes injected. Infertility causes among patients with failed fertilization included unexplained (43.6%), male factor (26%), presence of more than one factor (17.4%), hysterectomy (4.4%), premature ovarian failure (4.3%), and advanced age (4.3%). In 12 cycles (52%), fewer than 5 follicles were present. In three (13%) cycles, no mature (MII) oocyte was available and in 61% (14/23) fewer than 3 MII oocytes were available for ICSI. Immotile sperm was used for ICSI in 5 cycles (21.7%). The source of sperm in 17 (74%) cycles was from ejaculate, in 4 cycles from testicular aspiration (TESA), one from percutaneous epididymal sperm aspiration (PESA) and one from retrograde ejaculation.

CONCLUSIONS
Our data indicate that major contributing factors to failed fertilization after intracytoplasmic sperm injection are number of MII oocytes retrieved and availability of viable sperm for injection. Although the incidence of complete failed fertilization is not remarkable, it may increase with increasing patient age and a lower number of follicles.


Abstract Multispectral imaging is a new technology that is being deployed to assess seed quality parameters. Examples of applications in the detection and identification of fungi on seeds are presented, together with an example of the technology used for maturity determination in sugar beet seed. Results from multispectral imaging are compared with reference methods, and a high correlation is found. Applications of the technique for varietal discrimination and insect damage are also presented. There is a need for non-destructive, reliable and fast techniques, and it is concluded that multispectral imaging has potential for seed quality assessment, in particular for those components associated with surface structure and chemical composition, seed colour, morphology and size.


Many researchers, managers, and companies are currently dealing with digital transformation. Yet, there exists a research gap on the exact meaning and scope of this transformation. In this paper, an in-depth literature study was performed and synthesized to inductively construct a conceptual framework that reconciles the distinct definitions and aspects of digital transformation. From the framework, we derived a novel and comprehensive definition of digital transformation which was validated against the literature and shown to be exhaustive. Furthermore, our definition explicitly explains why digital transformation is happening and accelerating. Researchers and practitioners can use the framework to position their work and to gain a better understanding of its wide scope and impacts. This work can be among the first steps towards a unified understanding of digital transformation.


Worldwide, antibiotic use is increasing, but many infections against which antibiotics are applied are not even caused by bacteria. Over‐the‐counter and internet sales preclude physician oversight. Regional differences, between and within countries highlight many potential factors influencing antibiotic use. Taking a systems perspective that considers pharmaceutical commodity chains, we examine antibiotic overuse from the vantage point of both sides of the therapeutic relationship. We examine patterns and expectations of practitioners and patients, institutional policies and pressures, the business strategies of pharmaceutical companies and distributors, and cultural drivers of variation. Solutions to improve antibiotic stewardship include practitioners taking greater responsibility for their antibiotic prescribing, increasing the role of caregivers as diagnosticians rather than medicine providers, improving their communication to patients about antibiotic treatment consequences, lessening the economic influences on prescribing, and identifying antibiotic alternatives.


The objective o f the present study is the analysis of the effect of core and face sheet anisotropy on the natural frequencies of plane and doubly curved sandwich structures with laminated composite face sheets and an anisotropic core. For the analysis, a h igher-order sandwich shell theory is adopted. For the special case of a sandwich shell with rectangular projection, an analytical solution is obtained by means of an extended Galerkin procedure. Assuming a harmonic time-dependent response, the problem is transformed into an eigenvalue problem, which can be solved in a nu merically rather efficient manner. The numerical scheme is applied to an analysis of the effect of the face sheet anisotropy induced by fibre angle variations in laminated face sheets consisting of unidirectionally infinite fibre reinforced carbon epoxy plies. Further anisotropy effects derive from the use of honeycomb cores with anisotropy transverse shear moduli. It is observed that anisotropy of core and face sheets may have distinct effects on the lower natural frequencies.


BACKGROUND
Disease-causing mutations in CACNA1D gene occur in aldosterone-producing adenomas and familial hyperaldosteronism. We determined whether single nucleotide polymorphisms in CACNA1D gene associate with higher aldosterone resulting in salt sensitivity of blood pressure (BP) and increased BP in men and women.

METHODS
Data were obtained from the HyperPATH (International Hypertension Pathotypes) cohort, where participants completed a cross-over intervention of liberal and restricted sodium diets. Multi-Ethnic Genotyping Array identified 104 CACNA1D single nucleotide polymorphisms that met quality control. Single nucleotide polymorphism is rs7612148 strongly associated with systolic BP and was selected for study in 521 Whites in 3 scenarios ([1] hypertensives; [2] normotensives; [3] total population=hypertensives+normotensives) using multivariate regression analysis.

RESULTS
In the total population and hypertensives, but not normotensives, risk allele carriers (CC, GC), as compared with nonrisk allele homozygotes (GG), exhibited higher salt sensitivity of BP and, on liberal sodium diet, higher systolic BP, lower baseline and angiotensin II-stimulated aldosterone, and lower plasma renin activity. On restricted sodium diet, BP was similar across genotypes, suggesting sodium restriction corrected/neutralized the genotype effect on BP. Because increased aldosterone did not seem to drive the increased salt sensitivity of BP and increased BP on liberal sodium diet, we assessed renal plasma flow. Renal plasma flow increase from restricted to liberal sodium diets was blunted in risk allele homozygotes in the total population and in hypertensives. A replication study in another cohort HyperPATH B (International Hypertension Pathotypes Cohort B) confirmed BP-genotype associations.

CONCLUSIONS
CACNA1D rs7612148 risk allele associated with increased BP and salt sensitivity of BP, likely due to an impaired ability to increase renal plasma flow in response to a liberal sodium diet and not to excess aldosterone.


Vascular Endothelial Growth Factor (VEGF) is a key factor for tumor progression through induction of angiogenesis and other actions including immune alteration. Myeloid-derived suppressor cells (MDSC) are a major type of immune-suppressing cell that appear in cancer or inflammation and that have been reported to express the VEGF-receptor and to be activated by VEGF. To study the clinical importance of VEGF and MDSC for cancer, peripheral blood was collected from patients with gastrointestinal, ovarian, breast, thyroid and pulmonary cancers. Peripheral blood mononuclear cells (PBMC) were separated using a Ficoll-density gradient and were used for the detection of MDSC (CD11b+CD14-CD33+) using flow cytometry and for cytokine-production assays. For these assays, PBMC were stimulated with PHA and the production of cytokines including IL-12 (Th1 inducer), IL-10, (anti-inflammatory cytokine) and IL-17, (pro-inflammatory cytokine), were measured over 24 h using ELISAs. Serum concentrations of IL-10 and VEGF were also measured using ELISAs. The serum levels of both VEGF and MDSC were significantly increased in almost all types of cancer tested and significantly correlated with each other. Their levels also significantly correlated with neutrophil/lymphocyte ratios (NLR) (inflammation marker) and CRP levels, and were inversely correlated with the PHA-stimulation index (SI) (cell mediated immune responses marker) and serum concentrations of rapid-turnover protein (RTP) (nutrition marker). VEGF levels also correlated with serum concentrations of IL-10 and VEGF, and production of IL-17, and inversely correlated with production of IL-12. The prognosis of stage IV colorectal cancer with high VEGF was significantly worse than that with low VEGF. In thyroid cancer, the number of MDSC was significantly higher, NLR and CRP levels were higher, and RTP levels were lower in patients with undifferentiated carcinoma than in those with differentiated carcinoma including papillary and follicular carcinomas. Thus VEGF was increased in cancer and correlated with immune suppression driven by MDSC, inflammation and malnutrition. Although cancer immunotherapy is currently in use for a number of cancers, MDSC have been reported to be a major inhibitor of cancer immunotherapy even in cases in which an immune checkpoint inhibitor was used. An anti-VEGF treatment strategy has now been established in combination with chemotherapy for many types of cancer. Among various types of anti-MDSC trials, anti-VEGF treatment seems to be an effective adjuvant therapy of cancer immunotherapy. Citation Format: Masahiko Shibata, Kenji Gonda, Takahiro Nakajima, Koji Kono, Hiroyuki Suzuki, Seiichi Takenoshita. VEGF-A is increased and correlates with MDSC-driven immune suppression, systemic inflammation, nutritional impairment and poor prognosis in patients with cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3679. doi:10.1158/1538-7445.AM2017-3679


Background Some mutations in the HIV-1 Gag gene are known to confer resistance to ritonavir-boosted protease inhibitors (PI/r), but their clinical implications remain controversial. This review aims at summarizing current knowledge on HIV-1 Gag gene mutations that are selected under PI/r pressure and their distribution according to viral subtypes. Materials and methods Randomized and non-randomized trials, cohort and cross-sectional studies evaluating HIV-1 Gag gene mutations and protease resistance associated mutations, will all be included. Searches will be conducted (from January 2000 onwards) in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILAC), Web of Science, African Journals Online, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Hand searching of the reference lists of relevant reviews and trials will be conducted and we will also look for conference abstracts. Genotypic profiles of both Gag gene and the protease region as well as viral subtypes (especially B vs. non B) will all serve as comparators. Primary outcomes will be the "prevalence of Gag mutations" and the "prevalence of PI/r resistance associated mutations". Secondary outcomes will be the "rate of treatment failure" and the distribution of Gag mutations according to subtypes. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permits, random effects models will be used where appropriate. This study will be reported according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta Analyses. Discussion This systematic review will help identify HIV-1 Gag gene mutations associated to PI/r-based regimen according to viral subtypes. Findings of this review will help to better understand the implications of the Gag gene mutations in PI/r treatment failure. This may later justify considerations of Gag-genotyping within HIV drug resistance interpretation algorithms in the clinical management of patients receiving PI/r regimens. Systematic review registration PROSPERO: CRD42019114851.


The primum non nocere letter by Boon et al. urged caution and careful examination of the evidence and logistics of low-dose radiotherapy in COVID-19 patients. This is exactly what was requested in March and what has occurred since late April 2020 when the first phase I/II clinical trial was approved at the Winship Cancer Institute, Emory University Hospital. The preprint of day-7 interim results by the investigators concluded, "In a small pilot trial of 5 oxygen-dependent patients with COVID-19 pneumonia, low-dose whole-lung radiation led to rapid improvement in clinical status, encephalopathy, and radiographic infiltrates without acute toxicity or worsening the cytokine storm. Low-dose whole-lung radiation appears to be safe, shows early promise of efficacy, and warrants larger prospective trials." Preliminary results from another clinical trial gave similar results. In conclusion, the authors believe it would be unethical not to investigate radiotherapy as a potential remedy against COVID-19 induced pneumonia


A simple and accurate method to determine the content of fluoride in non-volatile organofluoro compounds or in biological samples has been developed. The method includes the metallic sodium fusion followed by quantitative estimation of fluoride using fluoride-sensitive electrode.


Paederia foetida L. is an important medicinal herb harboring lots of essential drug producing metabolites and the plant has been going to be endangered due to lack of proper strategies for conservation. Since, indirect organogenesis by tissue culture is considered as the valuable tools for rapid multiplication and improvement of plant genetic resources, application of this technique should be very imperative for the conservation of this valuable and rare medicinal plant. Hence, the research effort was made to develop a suitable protocol for indirect organogenesis in-vitro using nodal explants of P. foetida. After surface sterilization, the explants were submitted to MS medium supplemented with different concentrations and combinations of plant growth regulators for showing the performance in terms of callus induction, shoot proliferation and root initiation. Among the surface sterilants used, 0.1% HgCl2 treated for 2 minutes and 3% NaOCl treated for 10 minutes showed better performance and maintained 100% and 80% survivability respectively. MS medium supplemented with 2, 4-D at 1.5 mg L-1 showed better performance than others in terms of initiation of callus from nodal explants. In contrast, NAA at 0.5 mg L-1 and BAP 0.2 mg L-1 showed highest rate of callus proliferation with somatic embryos from proliferated callus. During shoot organogenesis, MS medium supplemented with BAP 2 mg L-1 showed better results for the regeneration of shoots from embryogenic calli. The shoots derived from callus produced roots by half strength MS medium supplemented with IAA. After acclimatization, the plantlets were allowed to ambient condition for further establishment. Our findings claim the establishment of a suitable protocol for indirect organogenesis of P. foetida that could be employed for rapid multiplication, conservation and sustainable utilization of P. foetida as valuable genetic resource.


Objectives: Torquetenovirus (TTV) and Redondovirus (ReDoV) are the most prevalent viruses found in the human respiratory virome in viral metagenomics studies. A large-scale epidemiological study was performed to investigate their prevalence and loads in saliva samples according to SARS-CoV-2 status. Methods: Saliva samples from 448 individuals (73% SARS-CoV-2 negative and 27% SARS-CoV-2 positive) aged 23–88 years were tested. SARS-CoV-2 and TTV were determined in saliva by specific qualitative and quantitative real-time PCRs, respectively. A sub-cohort of 377 subjects was additionally tested for the presence and load of ReDoV in saliva, and a different sub-cohort of 120 subjects for which paired saliva and plasma samples were available was tested for TTV and ReDoV viremia at the same timepoints as saliva. Results: TTV in saliva was 72% prevalent in the entire cohort, at a mean DNA load of 4.6 log copies/mL, with no difference regardless of SARS-CoV-2 status. ReDoV was found in saliva from 61% of the entire cohort and was more prevalent in the SARS-CoV-2-negative subgroup (65% vs. 52%, respectively). In saliva, the total mean load of ReDoV was very similar to the one of TTV, with a value of 4.4 log copies/mL. The mean viral loads in subjects infected with a single virus, namely, those infected with TTV or ReDoV alone, was lower than in dually infected samples, and Tukey's multiple-comparison test showed that ReDoV single-infected samples resulted in the only true outlier (p = 0.004). Differently from TTV, ReDoV was not detected in any blood samples. Conclusions: This study establishes the prevalence and mean value of TTV and ReDoV in saliva samples and demonstrates the existence of differences between these two components of the human virome.


Abstract. Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic air pollutants. The dispersion of PAHs in the atmosphere is influenced by gas–particle partitioning and chemical loss. These processes are closely interlinked and may occur at vastly differing timescales, which complicates their mathematical description in chemical transport models. Here, we use a kinetic model that explicitly resolves mass transport and chemical reactions in the gas and particle phases to describe and explore the dynamic and non-equilibrium interplay of gas–particle partitioning and chemical losses of PAHs on soot particles. We define the equilibration timescale τeq of gas–particle partitioning as the e -folding time for relaxation of the system to the partitioning equilibrium. We find this metric to span from seconds to hours depending on temperature, particle surface area, and the type of PAH. The equilibration time can be approximated using a time-independent equation, τ eq ≈ 1 k des + k ads , which depends on the desorption rate coefficient kdes and adsorption rate coefficient kads , both of which can be calculated from experimentally accessible parameters. The model reveals two regimes in which different physical processes control the equilibration timescale: a desorption-controlled and an adsorption-controlled regime. In a case study with the PAH pyrene, we illustrate how chemical loss can perturb the equilibrium particulate fraction at typical atmospheric concentrations of O3 and OH . For the surface reaction with O3 , the perturbation is significant and increases with the gas-phase concentration of O3 . Conversely, perturbations are smaller for reaction with the OH radical, which reacts with pyrene on both the surface of particles and in the gas phase. Global and regional chemical transport models typically approximate gas–particle partitioning with instantaneous-equilibration approaches. We highlight scenarios in which these approximations deviate from the explicitly coupled treatment of gas–particle partitioning and chemistry presented in this study. We find that the discrepancy between solutions depends on the operator-splitting time step and the choice of time step can help to minimize the discrepancy. The findings and techniques presented in this work not only are relevant for PAHs but can also be applied to other semi-volatile substances that undergo chemical reactions and mass transport between the gas and particle phase.


The increasing interest around imaging and microsurgery techniques based on the photoacoustic effect has boosted active research into the development of exogenous contrast agents that may enhance the potential of this innovative approach. In this context, plasmonic particles as gold nanorods are achieving resounding interest, owing to their efficiency of photothermal conversion, intense optical absorbance in the near infrared region, inertness in the body and convenience for conjugation with ligands of molecular targets. On the other hand, the photoinstability of plasmonic particles remains a remarkable obstacle. In particular, gold nanorods easily reshape into nanospheres and so lose their optical absorbance in the near infrared region, under exposure to few-ns-long laser pulses. This issue is attracting much attention and stimulating ad-hoc solutions, such as the addition of rigid shells and the optimization of multiple parameters. In this contribution, we focus on the influence of the shape of gold nanorods on their photothermal behavior and photostability. We describe the photothermal process in the gold nanorods by modeling their optical absorption and consequent temperature dynamics as a function of their aspect ratio (length / diameter). Our results suggest that increasing the aspect ratio does probably not limit the photostability of gold nanorods, while shifting the plasmonic peak towards wavelengths around 1100 nm, which hold more technological interest.


The difference in the prevalence of periodontitis degrees between ischemic stroke with diabetes mellitus and prediabetes mellitus Nanik Sulistyowati1*, Retnaningsih2, Widiastuti2, Rendy Sumali3, Amin Husni2, Endang Kustiowati2, Jimmy Eko Budi Hartono2, Dwi Pudjanarko2 Background: Stroke is a cerebrovascular disease caused by atherosclerosis. Oral health and atherosclerosis may be associated with cerebrovascular disease. Some studies proved the association between chronic infectious diseases, including periodontal tissue disease with stroke risk factors. Diabetes Mellitus has a risk of microvascular complications that are pathologically related to periodontal disease. This study compares the degree of periodontitis between ischemic stroke with diabetes mellitus and ischemic stroke with prediabetes mellitus. Methods: This study is an observational analytic study with a cross-sectional design. The subjects of this study were infarct stroke patients with diabetes mellitus and prediabetes mellitus in the inpatient ward of Kariadi Hospital Semarang, who met the inclusion and exclusion criteria. The study was conducted from January to March 2020. Infarct stroke was assessed by using head CT scan, while diabetes mellitus using blood glucose with 2 hours postprandial blood glucose and HbA1c, and periodontal disease using MMI (Miller's Mobility Index). The data were analyzed with chi-square correlation test and logistic regression test. The results were significant if the p-value <0.05. Results: This study was conducted to 42 ischemic stroke patients with diabetes mellitus and prediabetes mellitus. All of the cases also had hypertension. The prevalence of severe periodontitis in DM-hypertension was (OR=0.66; 95% CI=0.120.354) compared to prediabetes-hypertension. The chances of severe periodontitis in the age of 61-70 years (OR=2.626; 95% CI=0.473-14.587) compared to the age 51-60 years, dyslipidemia (OR=0.392; 95% CI=0.076-2.016) compared to non dyslipidemia, obesity (OR=2.346; 95% CI=0.382-14.428) compared to non-obesity, smoking (OR=1.768; 95% CI=0.3718.425) compared to non-smokers. Conclusion: in this study, all cases of diabetes mellitus and prediabetes mellitus were suffered along with hypertension. The prevalence of severe periodontitis in prediabetes-hypertension patients increased compared to hypertensive-DM patients. There was an increased possibility of severe periodontitis in the risk factors groups of age 61-70 years, obesity, and smoking.


This paper suggests a hotspot identification method based on crash severity using Continuous Risk Profile (CRP) approach which is a recently introduced method for identifying high collision concentration locations. The process of selecting hotspots is an essential step for road safety improvement projects since it provides decision makers with reasonable evidence for the allocation of budgets in a cost-effective manner. Therefore roadway sections that could maximize the reduction of crash costs are needed to be investigated as target sites for treatments. In this study, two types of crash severity weights are applied to each collision and then, CRP diagrams are illustrated by the values of crash frequency, equivalent property damage only (EPDO) and severity weighted frequency based on the number of fatalities and injuries. Top seven sites which include high peak locations in each CRP are selected and grouped by the approaches, and accident costs per unit length are compared to evaluate the potential cost reduction of the three groups. As a result, the EPDO group is expected to lead the most cost savings if safety improvement projects are performed. Findings from the paper will contribute to both enhancing accuracy for identifying hotspots and saving social costs caused by traffic accidents.


Parkinson's disease (PD) patients progressively accumulate intracytoplasmic inclusions formed by misfolded α-synuclein known as Lewy bodies (LBs). LBs also contain other proteins that may or may not be relevant in the disease process. To identify proteins involved early in LB formation, we performed proteomic analysis of insoluble proteins in a primary neuron culture model of α-synuclein pathology. We identified proteins previously found in authentic LBs in PD as well as several novel proteins, including the microtubule affinity-regulating kinase 1 (MARK1), one of the most enriched proteins in this model of LB formation. Activated MARK proteins (MARKs) accumulated in LB-like inclusions in this cell-based model as well as in a mouse model of LB disease and in LBs of postmortem synucleinopathy brains. Inhibition of MARKs dramatically exacerbated α-synuclein pathology. These findings implicate MARKs early in synucleinopathy pathogenesis and as potential therapeutic drug targets. SIGNIFICANCE STATEMENT Neurodegenerative diseases are diagnosed definitively only in postmortem brains by the presence of key misfolded and aggregated disease proteins, but cellular processes leading to accumulation of these proteins have not been well elucidated. Parkinson's disease (PD) patients accumulate misfolded α-synuclein in LBs, the diagnostic signatures of PD. Here, unbiased mass spectrometry was used to identify the microtubule affinity-regulating kinase family (MARKs) as activated and insoluble in a neuronal culture PD model. Aberrant activation of MARKs was also found in a PD mouse model and in postmortem PD brains. Further, inhibition of MARKs led to increased pathological α-synuclein burden. We conclude that MARKs play a role in PD pathogenesis.


We report a molecular mechanism that controls brain response to stress and regulates adaptive behavior. In a mouse model under subacute stress, activation of the nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade occurs selectively in cortical microglia. This stress response causally underlies cognitive inflexibility in mouse behaviors, which is proven by pharmacological intervention or microglia-specific genetic intervention targeting the initial steps of the N-GAPDH cascade. We performed ChIP-Seq against N-GAPDH and for the first time demonstrate how N-GAPDH influences the genome-wide transcriptional landscape under stress. Through this analysis, we obtained evidence that High-Mobility Group Box (HMGB) downstream of the N-GAPDH cascade, connected with the NMDA receptor, is responsible for the regulation of the adaptive behavior. Furthermore, the activation of this N-GAPDH-HMGB cascade is reflected by augmented autofluorescence in peripheral blood cells. Consistent with these observations, we clinically demonstrated an association between augmented lymphoblast autofluorescence and impaired cognitive flexibility in patients with schizophrenia.


Ruminations on death recur throughout Job. Equally, language of the non-human world is prevalent. This article examines the coalescence of these tropes in the implicit "necro-ecology" of the book. As though observing the decomposition of a corpse, it focusses on four Joban images, each expressing human death in non-human terms: maggots colonise the cadaver; scavengers consume it. The body disintegrates into dust; plants grow and wither there. At each stage, the article shows how death and life are entangled together, the one requiring and enabling the other. Equally, beings are entangled with each other, challenging the human pretence to self-contained individuality. The article thus fits into a broader trend in the (post)humanities to cultivate scholarship conducive to multi-species flourishing, showing how Job provides fertile compost for symbiotic inter-species alliances of living and dying together.


The requirements for a practical module for an undersea system1 are high coupling efficiency, good stability with respect to temperature variation, high reliability, and easy fabrication. We have developed for transatlantic transmission (TAT 8) the module shown in Fig. 1, designed to satisfy these requirements. We use a buried heterostructure laser2 selected for a submarine system. High coupling efficiency (−4 dB) is achieved using a tapered single-mode fiber with a spherical tip. The optical power levels are checked by a germanium photodetector which monitors the rear laser diode output.


A simple, environmentally and economically benign, scalable synthesis was developed for the production of micrometer long hexagonal cerium phosphate nanowires, complex urchin-like nanostructures and their terbium-doped counterparts. It was proven that neither sophisticated equipment nor structure directing agents or pH adjustment or tedious procedures are necessary, because the precise regulation of precursor addition rate is sufficient to control the morphology of the product nanostructures. Nanowires and nanourchins can be obtained by the instantaneous vs. drop-wise addition of phosphoric acid to an aqueous cerium nitrate solution, respectively. Terbium doping is readily achieved by dissolving a calculated amount of terbium nitrate in the precursor solution. Spherulitic lanthanide phosphate nanostructure formation mechanisms offered in the literature were critically reviewed and assessed against our experimental findings obtained by studying the sonochemical disintegration of nanourchins. Terbium doping introduced green luminescence and slowed down the temperature induced hexagonal to monoclinic phase transition of cerium phosphate.


Animal venoms are theorized to evolve under the significant influence of positive Darwinian selection in a chemical arms race scenario, where the evolution of venom resistance in prey and the invention of potent venom in the secreting animal exert reciprocal selection pressures. Venom research to date has mainly focused on evolutionarily younger lineages, such as snakes and cone snails, while mostly neglecting ancient clades (e.g., cnidarians, coleoids, spiders and centipedes). By examining genome, venom-gland transcriptome and sequences from the public repositories, we report the molecular evolutionary regimes of several centipede and spider toxin families, which surprisingly accumulated low-levels of sequence variations, despite their long evolutionary histories. Molecular evolutionary assessment of over 3500 nucleotide sequences from 85 toxin families spanning the breadth of the animal kingdom has unraveled a contrasting evolutionary strategy employed by ancient and evolutionarily young clades. We show that the venoms of ancient lineages remarkably evolve under the heavy constraints of negative selection, while toxin families in lineages that originated relatively recently rapidly diversify under the influence of positive selection. We propose that animal venoms mostly employ a 'two-speed' mode of evolution, where the major influence of diversifying selection accompanies the earlier stages of ecological specialization (e.g., diet and range expansion) in the evolutionary history of the species–the period of expansion, resulting in the rapid diversification of the venom arsenal, followed by longer periods of purifying selection that preserve the potent toxin pharmacopeia–the period of purification and fixation. However, species in the period of purification may re-enter the period of expansion upon experiencing a major shift in ecology or environment. Thus, we highlight for the first time the significant roles of purifying and episodic selections in shaping animal venoms.


The present industry update covers the period 1 October-31 October 2017, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature. While the corporate news in October was traditionally dominated by the announcement of the third quarter results, with most of them showing market and revenue growth but also an increasing number of initial public offerings after years of slower financial development, we also saw trends continuing toward an increasing number of convergences of drugs with nanotechnology, devices and 21st century information technology. Whether it is using E Ink's 'Smart Patch', AstraZeneca's autoinjector, Elektrofi's Elektroject suspensions or NanOlogy's NanoPac, there is an ever increasing number of combinations dof devices, drugs and applications reaching, more and more the clinic and the market. Controlled release is another feature increasingly addressed by many of the above innovations. For example, the drug-loaded x-ray imageable microscopic beads that have been developed by researchers at UCL Cancer Institute (London, UK) take this one step further in order to pursue local, controlled and in situ validated local delivery.


Lateral Flow Immunoassays (LFIAs) are among the most successful Point of Care (POC) tests. However, factors like reagent stability, reaction rates, and binding kinetics limit the performance and robustness of LFIAs. One of the factors that affects the overall performance of LFIA is the fluid flow rate, and hence, it is desirable to maintain a predictable fluid velocity in porous media. The main objective of this study is to build a statistical model that estimates the fluid velocity in porous media for any given ambient condition to enable us to determine the optimal design parameters for achieving a desired fluid velocity in porous media.


Background Too-frequent screening for cervical cancer can increase costs, lead to unnecessary invasive procedures associated with overtreatment, and shift resources away from the one in five women who do not receive recommended routine screening. Context A large, US-based integrated healthcare system with centralised evidence services and eight independent regions developed and implemented an evidence-based guideline for cervical cancer screening. Novel implementation strategies and performance monitoring in one region in Southern California led to significant improvements and are described below. Description of Best Practice Graded evidence summaries were conducted by a centralised analytic unit, and recommendations developed by a guideline team with representation from each region. In one large region with more than 3 million patients, interventions aimed at the practitioner, patient and systems levels were implemented for routine Pap and HPV co-testing. Practitioner interventions included electronic distribution of guidelines, point-of-care electronic prompts, and workflow support. Patient-level interventions included point-of-care education, and in-reach/outreach activities. System-level interventions focused on centralised patient outreach letters and reminder calls, computerised decision support, and unscreened cancer lists for panel management. Monthly performance monitoring on a measure of "overpopulation" was reported at medical centre, department and provider levels. In a five-year period, over 100,000 fewer unnecessary Pap tests were performed, while screening rates increased by 7%. Lessons for Guideline Developers, Adaptors, Implementers, and/or Users Centralised guideline development, coupled with coordinated implementation and performance monitoring, can reduce unnecessary screening and invasive procedures, focus resources on appropriate routine screening in underscreened populations, improve patient access and reduce costs.


In this case, a 27-year-old nulliparous woman with a pelvic multiple cystic mass was treated and found with ovarian mature cystic teratoma associated with port-site metastasis (PSM). Suspecting recurrence of mature cystic teratoma, a second laparoscopic surgery found a small mass, on the right under abdomen's peritoneal membrane, at the laparoscopic port sites of the initial operation. Pathological report of the peritoneal mass and left ovarian tumor confirmed a mature cystic teratoma. To the best of the authors' knowledge, this is the first reported PSM in associated with benign ovarian tumor.


At the close of the Second World War, modernist poets found themselves in an increasingly scientific world, where natural and social sciences claimed exclusive rights to knowledge of both matter and mind. Following the overthrow of the Newtonian worldview and the recent, shocking displays of the power of the atom, physics led the way, with other disciplines often turning to the methods and discoveries of physics for inspiration. In Physics Envy, Peter Middleton examines the influence of science, particularly physics, on American poetry since World War II. He focuses on such diverse poets as Charles Olson, Muriel Rukeyser, Amiri Baraka, and Rae Armantrout, among others, revealing how the methods and language of contemporary natural and social sciences—and even the discourse of the leading popular science magazine Scientific American—shaped their work. The relationship, at times, extended in the other direction as well: leading physicists such as Robert Oppenheimer, Werner Heisenberg, and Erwin Schrodinger were interested in whether poetry might help them explain the strangeness of the new, quantum world. Physics Envy is a history of science and poetry that shows how ultimately each serves to illuminate the other in its quest for the true nature of things.


Purpose Regulation of ocular blood flow might be impaired in glaucoma patients. We compared the reaction of retinal vessels to a short-term increase of intraocular pressure (IOP), using a retinal vessel analyzer (RVA), in normal volunteers, ocular hypertensive patients (OH) and primary open angle glaucoma patients (POAG). Methods Ten healthy subjects (56 ± 8 years, IOP 13.7 ± 1.6 mmHg), 10 OH patients (55 ± 12 years, IOD 23.4 ± 4.1 mmHg) and 11 POAG patients (60 ± 11 years, IOP 23.3 ± 1.95 mmHg) were evaluated. Arterial and venous retinal vessel diameter was measured continuously before, during and after raising IOP to suprasystolic values by the suction cup method, described as ocular oscillo-dynamography. Results The change in vessel diameter after the IOP rise differed in its temporal sequence and in absolute values depending on the group examined. In the retinal branch veins the reduction of vessel diameter during the IOP rise was significantly different in POAG (0% ± 6.7) and volunteers (-6.7% ± 8.5; p = 0.06) and in POAG and OH (-6.7% ± 7.0; p = 0.04). At 70–130 sec after IOP increase a dilatation occurred, again differing significantly in POAG (+5.8% ± 3.9) and volunteers (+9.7% ± 4.3; p = 0.03). Systemic blood pressure did not show any significant differences between groups or during the course of the examination. Discussion At short-term rise in IOP leads to less retinal vessel reaction in POAG patients than in volunteers and OH. This might be due to impaired autoregulation to ocular perfusion changes in POAG patients.


These practice parameters review the current state of knowledge about posttraumatic stress disorder (PTSD) in children and adolescents. The parameters were written to aid clinicians in the assessment and treatment of children and adolescents with PTSD symptoms. A literature search and extensive review were conducted in order to evaluate the existing empirical and clinical information in this regard. Expert consultation was also solicited. The main findings of this process were that a wide variety of stressors can lead to the development of PTSD symptoms in this population; that the specific PTSD symptoms manifested may vary according to the developmental stage of the child and the nature of the stressor, and for this reason, the diagnostic criteria for PTSD in adults may not adequately describe this disorder in children and adolescents; that several factors seem to mediate the development of childhood PTSD following a severe stressor; and that most of the therapeutic interventions recommended for children with PTSD are trauma-focused and include some degree of direct discussion of the trauma. Controversies and unresolved issues regarding PTSD in children are also addressed.


Percolation thresholds for solvent diffusion within hydrated model polymeric membranes are derived from dissipative particle dynamics in combination with Monte Carlo (MC) tracer diffusion calculations. The polymer backbones are composed of hydrophobic A beads to which at regular intervals Y-shaped side chains are attached. Each side chain is composed of eight A beads and contains two identical branches that are each terminated with a pendant hydrophilic C bead. Four types of side chains are considered for which the two branches (each represented as [C], [AC], [AAC], or [AAAC]) are splitting off from the 8th, 6th, 4th, or 2nd A bead, respectively. Water diffusion through the phase separated water containing pore networks is deduced from MC tracer diffusion calculations. The percolation threshold for the architectures containing the [C] and [AC] branches is at a water volume fraction of ∼0.07 and 0.08, respectively. These are much lower than those derived earlier for linear architectures of various side chain length and side chain distributions. Control of side chain architecture is thus a very interesting design parameter to decrease the percolation threshold for solvent and proton transports within flexible amphiphilic polymer membranes.


A review of Jung's writing on the 'feeling-toned complex' shows that he considered it to comprise independent, split-off, psychic elements. Modern advances in scientific thinking and technology, namely Dynamic Systems Theory and neuro-imaging, allow us to better define and explore this psychic phenomenon. Considering the constellation of the complex as a hierarchy of dynamic systems allows for a prediction of the timing of brain activity. This has been confirmed by two independent studies using fMRI and QEEG while administering the Word Association Experiment, the tool Jung used to investigate brain/psychic functioning over a century ago. Using as a framework the stages of the constellation of a complex viewed as a hierarchy of dynamic systems, I review the neuro-imaging studies reported by Petchkovsky et al. (2013, 2017) and Escamilla et al. (2018), concluding that quantitative theoretical predictions and experimental results are in agreement within an order of magnitude. The change in attention caused by the constellation of the complex can also be conceived as the switching from a default neuro-network, a startle response activating executive functioning in the frontal cortex of either the ego-complex or an autonomous complex.


We have conducted a variability survey of the local group galaxy M33 using g ′ , r ′ , and i ′ observations from 27 nights spanning 17 months made with the MegaPrime/MegaCam instrument on the 3.6 m CFHT telescope. We identify more than 36000 variable sources with g ′ , r ′ , i ′ . 24 out of approximately 2 million point sources in a one square degree field of view. This increases the number of known variables in this galaxy by more than a factor of 20. In this paper we provide a brief description of the data and a general overview of the variable star population which includes more than 800 candidate variable blue and red supergiant stars, more than 2000 Cepheids, and more than 19000 long period variable AGB and RGB stars.


The ad hoc network may play an important part in future wireless communication systems. However, system synchronization of the ad hoc network is a big challenge due to the lack of a fixed infrastructure and the dynamically changing topology. A novel self synchronization algorithm is proposed for the ad hoc network based on TDMA; the network topology structure information is gathered in some assigned time slots to build a connected domain set and broadcast the system synchronization messages over the whole network. The system time slot cost of synchronization is about 16.7%, and the probability of a node being successfully synchronized is higher than 95% in typical network environments, as shown by simulation.


Background: Blood culture is the definitive method for the diagnosis and treatment of bacteremia and fungemia. Analysis of blood cultures positive for pathogenic species and trends in antimicrobial susceptibility can help delineate appropriate and experimental treatment strategies. In this study, we investigated the incidence of pathogenic species and trends in antimicrobial susceptibility in blood cultures collected from 2003 to 2007 to help clinicians to determine the best methods of diagnosis and treatment. Changes between previously published analyses and this study were also investigated. Methods: Five-year blood culture results obtained at Kyung Hee University Hospital between 2003 and 2007 were analyzed to determine the bacterial and fungal species present and the antimicrobial susceptibility of the isolates. Antimicrobial susceptibility was tested by the broth microdilution method and the CLSI disk diffusion method. Results: Among the 66,437 blood cultures, 5,645 were positive. Of the positive blood cultures, 59.8% were positive for aerobic and facultative anaerobic gram-positive cocci. Coagulase-negative staphylococci (CoNS) were frequently isolated. The numbers of anaerobic species and fungi decreased over the years. Conclusion: CoNS were the microorganisms most commonly isolated from blood cultures at Kyung Hee University Hospital. The number of cultures positive for fungi was higher than that reported in previous studies, but the absolute isolation rate over five years decreased. Anaerobic species were much less frequently isolated than reported for other hospitals. (Korean J Clin Microbiol 2009;12:163-168)


Purpose The present study was conducted to analyze the effect of varicocelectomy on serum follicle-stimulating hormone (FSH) and testosterone. The interrelationship between seminal and hormonal variables is also investigated. Patients and Methods A prospective cohort study was conducted on patients of the urology clinic from 2012 to 2017. The study was conducted in the Security Forces Hospital, in Riyadh, Saudi Arabia. Infertile patients who had already undergone the FSH examination and testosterone twice were included in the study. Statistical Package for Social Sciences (SPSS) version 21.0 was used to analyze the data. Results A total of 186 patients were studied which reveals that the age group of 21–30 years was higher than other age groups 80 (43%), micro varicocelectomy was performed in 138 (74%) of patients and 79 (47%) patients had one-year infertility. The study assessed the effect of varicocelectomy on sperm count and motility serum FSH, testosterone, luteinizing hormone (LH), and prolactin, and it was found that none of the variables showed significant association after varicocelectomy, except for luteinizing hormone (P-value = 0.014). Testosterone levels in patients who had FSH ≤10 were also evaluated and it was found that the level of testosterone was increased with a decreased level of FSH (P-value = 0.005). Conclusion It was concluded from our results that after varicocelectomy, those patients who had FSH levels ≤10 were found to have increased testosterone levels. LH was also found to be significant; however, other hormones were not found to be significant. This may occur due to the reason that we have the majority of the participants in the age group 21–30. Further prospective studies are needed to evaluate the association with ample sample size.


Alterations in intestinal microbial communities in humans are associated with enhanced susceptibility to inflammatory diseases suggesting that signals derived from commensal bacteria may influence the development and/or function of the immune system. Supporting this, germ-free (GF) mice exhibit reduced numbers of lymphocytes in the periphery and intestinal intraepithelial compartment. However, whether alterations in the composition of commensal bacteria influence immunity to infection remains poorly defined. To test this, mice housed under conventional (CNV) or GF conditions were infected with acute LCMV and the development of antigen-specific CD8+ T cell responses were analyzed. At day 7 p.i., GF mice exhibited a significant reduction in the frequency and number of LCMV-specific CD8+ T cells in multiple tissues including the spleen and intestinal intraepithelial compartment. The diminished CD8+ T cell response was not the result of inherent developmental defects in GF mice as depletion of intestinal bacteria in CNV mice via antibiotics also resulted in diminished LCMV-specific CD8+ T cell responses and impaired viral clearance. Further, adoptive transfer of CFSE-labeled LCMV-specific CD8+ T cells revealed a delay in the activation and expansion of LCMV-specific CD8+ T cells in antibiotic-treated mice. Collectively, these studies indicate that signals derived from intestinal bacteria aid in the induction of a rapid immune response required for immunity to viral infection.


Background/Aims: After BRAF, NRAS is the most commonly mutated oncogene in melanoma. However therapies targeting NRAS remain elusive. Recent investigations have demonstrated that mutated RAS can increase glycolytic metabolism in cancer cells, and our previous work has elucidated a role for glycolysis in the sensitivity of BRAF-mutant melanoma cells to inactivation of BRAF(1). This study aims to identify the molecular pathways controlling glycolysis in NRAS-mutant melanoma in the context of therapeutic targeting of critical oncogenic pathways. Methods: A panel of NRAS and BRAF-mutant melanoma cell lines were screened for changes in viability and glycolysis following treatment with a panel of small molecule inhibitors targeting the MAPK and PI3K pathways. Glycolytic responses of melanoma cells, following MEK, ERK, selective-PI3K, AKT, mTOR or combined PI3K/mTOR inhibition (alone or in combination), were investigated by assessing cell proliferation, glucose uptake, lactate production, and known transcriptional regulators of glycolysis. Results: In NRAS-mutant melanoma, MEK and ERK inhibition resulted in a reduction in lactate production, and similar responses were observed following treatment with mTORC1/2 and PI3K/mTOR inhibitors but not AKT or selective PI3K inhibitors. Treatment with MEK or ERK inhibitors resulted in a consistent reduction in glucose uptake, with a more modest effect being observed following combined PI3K/mTOR inhibition. Treatment with a combination of MEK or ERK inhibitor with either an mTORC1/2 or PI3K/mTOR inhibitor, resulted in synergy with respect to a reduction in cell proliferation. However, synergy was not demonstrated when lactate production and glucose uptake were assessed indicating that inhibition of MEK or ERK was sufficient to inhibit glycolysis in NRAS-mutant cells. Notably, treatment with these inhibitors also resulted in altered expression of transcriptional regulators of glycolysis (reduced MYC and HIF1α, increased TXNIP protein expression via MondoA), similar to that seen in BRAF-mutant melanoma cells. The role of each individual transcriptional regulator of glycolysis in the response of NRAS-mutant cells to MEK/ERK inhibition is under investigation. Conclusion: NRAS-mutant melanoma cells demonstrate a similar glycolytic phenotype to BRAF-mutant melanoma cells, with MAPK pathway or mTOR inhibition resulting in decreased lactate production, glucose uptake and modulation of the MYC/HIF1α/MondoA network of transcriptional regulators of glycolysis. These findings identify the mechanism of oncogene-driven glycolysis in NRAS-mutant melanoma, and open new possibilities for targeting glycolysis as a therapeutic target in the treatment of patients with NRAS-mutant melanoma. References: 1. Parmenter TJ, Kleinschmidt M, Kinross KM et al. Response of BRAF mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis. Cancer Discovery, 2014;4:423-433. Citation Format: Aparna D. Rao, Lorey K. Smith, Tiffany J. Parmenter, Grant A. McArthur. Mutant NRAS regulates glycolysis in melanoma through ERK, mTOR and the MYC/HIF1α/MondoA network of transcriptional regulators. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B23.


Background: Functional neuroimaging studies of schizophrenia have identified abnormal activations in many brain regions. In an effort to interpret these findings from a network perspective, we carried out a meta-analysis of this literature, mapping anatomical locations of under- and over-activation to the topology of a normative human functional connectome. Methods: We included 314 task-based functional neuroimaging studies including more than 5000 patients with schizophrenia and over 5000 controls. Coordinates of significant under- or over-activations in patients relative to controls were mapped to nodes of a normative connectome defined by a prior meta-analysis of 1641 functional neuroimaging studies of task-related activation in healthy volunteers. Results: Under-activations and over-activations were reported in a wide diversity of brain regions. Both under- and over-activations were significantly more likely to be located in hub nodes that constitute the "rich club" or core of the normative connectome. In a subset of 121 studies that reported both under- and over-activations in the same patients, we found that, in network terms, these abnormalities were located in close topological proximity to each other. Under-activation in a peripheral node was more frequently associated specifically with over-activation of core nodes than with over-activation of another peripheral node. Conclusions: Although schizophrenia is associated with altered brain functional activation in a wide variety of regions, abnormal responses are concentrated in hubs of the normative connectome. Task-specific under-activation in schizophrenia is accompanied by over-activation of topologically central, less functionally specialized network nodes, which may represent a compensatory response.


Hypoxia promotes aggressiveness, angiogenesis and resistance in glioma. It has been reported that resveratrol has strong anti-tumor ability and can inhibit migration and invasion of varieties of tumor including glioma. However, whether resveratrol inhibits hypoxia-induced migration and invasion of glioma cells is still unknown. In this study, we found glioma U87 and U251 cells migration and invasion was reduced by resveratrol under hypoxia condition and higher doses led to stronger block, while proliferation of U87 and U251 cells was hardly effected. Mechanically, hypoxia-induced upregulation of phosphorylated signal transducer and activator of transcription 3(p-STAT3) was blocked by resveratrol. MicroRNA-34a (miR-34a) is a tumor suppressor whose promoter region has a conserved STAT3-binding site and can be negatively regulated by STAT3. Interestingly, miR-34a was downregulated under hypoxia but upregulated by resveratrol which was perhaps relevant to changes in level of p-STAT3. The effect of resveratrol on p-STAT3 and miR-34a was both time-and dose-dependent. Summarizing, resveratrol inhibits hypoxia-induced migration and invasion possibly via p-STAT3/miR-34a axis and this effect is both time-and dose-dependent.


A transition of quantum walk induced by classical randomness changes the probability distribution of the walker from a two-peak structure to a single-peak one when the random parameter exceeds a critical value. We first establish the generality of the localization by showing its emergence in the presence of random rotation or translation. The transition point can be located manually by examining the probability distribution, momentum of inertia, and inverse participation ratio. As a comparison, we implement three supervised machine learning methods, the support vector machine (SVM), multilayer perceptron neural network, and convolutional neural network with the same data and show they are able to identify the transition. While the SVM sometimes underestimates the exponents compared to the manual methods, the two neural-network methods show more deviations for the case with random translation due to the fluctuating probability distributions. Our work illustrates potentials and challenges facing machine learning of physical systems with mixed quantum and classical probabilities.


OBJECTIVE
To explore the composition characteristics of traditional Chinese medicine (TCM) syndromes in patients with acute ischemic stroke of yin or yang syndrome by investigating the characteristics of TCM syndromes at different periods after onset.

METHODS
One thousand two hundred and forty-six patients with acute ischemic stroke were admitted in twenty hospitals. According to the "diagnostic criteria of syndrome differentiation of stroke", the characteristics of syndromes in the patients were investigated at the periods of 1-3 days, 4-10 days and 11-30 days after they had ischemic stroke. General distribution of six basic syndromes was compared between the patients with yin syndrome and the patients with yang syndrome at the three periods. The six basic syndromes were wind syndrome, pathogenic fire syndrome, phlegm syndrome, blood stasis syndrome, qi deficiency syndrome, and syndrome of yin deficiency and yang hyperactivity.

RESULTS
The percentages of wind, pathogenic fire, and phlegm syndromes in the patients were decreased at the period of 11-30 days as compared with the period of 1-3 days (87.1% vs 79.3%, 52.1% vs 38.7% and 67.1% vs 57.4% respectively, P<0.01). However, the percentages of the syndromes of blood stasis, qi deficiency, and yin deficiency and yang hyperactivity were similar at the three periods (P>0.05). There were no differences in the distribution of yin and yang syndromes among the three periods (P>0.05). The percentages of syndromes of wind, pathogenic fire, phlegm, and yin deficiency and yang hyperactivity were higher (P<0.01), and the percentages of syndromes of blood stasis and qi deficiency were lower (P<0.05, P<0.01) in patients with yang syndrome than in patients with yin syndrome. The complex of three syndromes was the most frequent composition pattern in the patients at the three periods. The percentages of complex syndromes of four or five syndromes were higher, and the percentages of single-syndromes and complex syndromes of two syndromes were lower in patients with yang syndrome than in patients with yin syndrome (P<0.05, P<0.01). The most frequent complex syndromes in patients with yin syndrome were complex syndrome of wind, phlegm, blood stasis and qi deficiency, and complex syndrome of wind, phlegm and qi deficiency; while the most frequent complex syndromes in patients with yang syndrome were complex syndrome of wind, pathogenic fire, phlegm and qi deficiency, and complex syndrome of wind, pathogenic fire and phlegm.

CONCLUSION
The main discrimination between the yin and yang syndromes is that the yang syndrome is characterized by pathogenic fire. The syndromes of phlegm, qi deficiency, and blood stasis are not associated with the diagnosis of yin or yang syndrome.


Designing a spoken language understanding system for command-and-control applications can be challenging because of a wide variety of domains and users or because of a lack of training data. In this paper we discuss a system that learns from scratch from user demonstrations. This method has the advantage that the same system can be used for many domains and users without modifications and that no training data is required prior to deployment. The user is required to train the system, so for a user friendly experience it is crucial to minimize the required amount of data. In this paper we investigate whether a capsule network can make efficient use of the limited amount of available training data. We compare the proposed model to an approach based on Non-negative Matrix Factorisation which is the state-of-the-art in this setting and another deep learning approach that was recently introduced for end-to-end spoken language understanding. We show that the proposed model outperforms the baseline models for three command-and-control applications: controlling a small robot, a vocally guided card game and a home automation task.


RIN4 is an intensively studied immune regulator in Arabidopsis and is involved in perception of microbial features outside and bacterial effectors inside plant cells. Furthermore, RIN4 is conserved in land plants and is targeted for posttranslational modifications by several virulence proteins from the bacterial pathogen Pseudomonas syringae. Despite the important roles of RIN4 in plant immune responses, its molecular function is not known. RIN4 is an intrinsically disordered protein (IDP), except at regions where pathogen-induced posttranslational modifications take place. IDP act as hubs for protein complex formation due to their ability to bind to multiple client proteins and, thus, are important players in signal transduction pathways. RIN4 is known to associate with multiple proteins involved in immunity, likely acting as an immune-signaling hub for the formation of distinct protein complexes. Genetically, RIN4 is a negative regulator of immunity, but diverse posttranslational modifications can either enhance its negative regulatory function or, on the contrary, render it a potent immune activator. In this review, we describe the structural domains of RIN4 proteins, their intrinsically disordered regions, posttranslational modifications, and highlight the implications that these features have on RIN4 function. In addition, we will discuss the potential role of plasma membrane subdomains in mediating RIN4 protein complex formations.


Besides MDR1/P‐glycoprotein (MDR1/P‐gp), glucosylceramide synthase (GCS), an enzyme, which transfers UDP–glucose to ceramide to form glucosylceramide was also related with multidrug resistance (MDR) in breast cancer. Although many research showed that GCS could affect mdr1 in cancer cells, nobody knows that whether mdr1 can affect GCS in breast cancer. Our study aims to verify that.


This paper proposes a continual tree algorithm for integrated voice/data wireless networks. The continual tree algorithm (CTA) is a new kind of reservation scheme and uses an improved continual tree algorithm to reserve slots of a channel. And based on a CTA a multimedia wireless multiple access (MWMA) is discussed. In addition to pretty good channel efficiency of a reservation scheme due to CTA, MWMA has the following three futures. 1. A tree algorithm is stable, but the contention period to reserve slots of a channel is variable in length. So they are not suitable to transmit real-time data. Improving a tree algorithm and applying it to a fixed length frame of a channel, MWMA can transmit both real-time data and non-real-time data using a common channel. 2. A fixed length frame suffers from a large average delay under low traffic. MWMA divides a frame into small frames so that real-time data is communicated with short delays. 3. The center station controls reservations centrally using verbose slots. By this centralized scheme, MWMA mitigates energy limitations of user's mobile terminals, a problem of coming and going of many terminals not given to the network, and a hidden terminal problem.


- Abstract: In this paper we propose an accelerated lifetime test model with threshold stress under a Log-logistic distribution to express the behavior of lifetimes and a general stress-response relationship. We present a sampling-based inference procedure of the model based on Markov Chain Monte Carlo techniques. We assume proper but vague priors for the parameters of interest. The methodology is illustrated on an artificial and real lifetime data set.


Purpose: Cannabinoids and their synthetic and endogenous
analogs exert not only psychoactive, but also cardiovascular
effects. These effects are complex and comprise direct
consequences on the myocardium, vasculature, and modulate also
autonomic outflow in the central and peripheral nervous system.
The aim of this study was to investigate the relationship
between certain symptoms of chronic heart failure (myocardial
infarction, plasma cholesterol concentration) to the FAAH and
CNR 1 receptor gene polymorphism. Methods: A total of 324
subjects were genotyped and stratified in case – control study.
A case group of 155 patients with a personal history of chronic
heart failure and 169 age and sex matched controls without a
personal history of cardiovascular disorder, diabetes mellitus
and obesity was collected. All of the subjects were genotyped
for FAAH 385 C/A polymorphism and CNR1 1359 G/A polymorphism
using polymerase chain reaction and restriction analysis. The
distributions of genotype and allelic frequencies were
calculated using chi-square tests. To calculate the
significance of odds ratio, Fisher's exact test was used.
Results: The homozygous CNR1 1359 A/A genotype was
significantly associated with higher plasma cholesterol
concentration in case group subjects (P=0.04). The individuals
carrying A allele have a 2,37-fold increase in the risk for the
development of myocardial infarction (odds ratio, OR=2.37, 95%
confidence interval, CI:1.36-6.93, P=0.01) Conclusions: The
study results suggest a role for FAAH 385 A/A variant as a risk
factor for myocardial infarction. The CNR1 1359 A/A
polymorphism is probably associated with higher plasma
cholesterol concentration. Thus, the pharmacological
interference with this system may change therapeutic approaches
in certain cardiovascular disorders.


With the emergence of edge computing, there is an increasing need for running convolutional neural network based object detection on small form factor edge computing devices with limited compute and thermal budget for applications such as video surveillance. To address this problem, efficient object detection frameworks such as YOLO and SSD were proposed. However, SSD based object detection that uses VGG16 as backend network is insufficient to achieve real time speed on edge devices. To further improve the detection speed, the backend network is replaced by more efficient networks such as SqueezeNet and MobileNet. Although the speed is greatly improved, it comes with a price of lower accuracy. In this paper, we propose an efficient SSD named Fire SSD. Fire SSD achieves 70.7mAP on Pascal VOC 2007 test set. Fire SSD achieves the speed of 30.6FPS on low power mainstream CPU and is about 6 times faster than SSD300 and has about 4 times smaller model size. Fire SSD also achieves 22.2FPS on integrated GPU.


ABSTRACT. A new species of Langlieria is described from the Upper Devonian (Frasnian) Irish Valley Member of the Catskill Formation. The type material was collected from a road cut exposure on the north side of the westbound lanes of Pennsylvania Route 322 west of Port Matilda, Centre County, Pennsylvania, U.S.A. The new species of Langlieria, the second from the Catskill Formation, is represented by high quality cranial material including parietal and postparietal shields, cheek, principal gular, and lower jaw; fin material; and body scales. The new species is the fourth tristichopterid to be described from the Catskill Formation (after Hyneria lindae, Langlieria radiatus, and Eusthenodon bourdoni) and the first from the Irish Valley Member. It is also the first species of Langlieria with a known record in the Frasnian. Sedimentological and stratigraphic data suggest that the discovery site represents a distal, tide-dominated location within the Catskill Delta system with a greater marine influence than has been reconstructed for the previously described Catskill Formation tristichopterids. A new phylogenetic analysis of Tristichopteridae is presented that is the first to include the new species of Langlieria described here and E. bourdoni from the Cogan House Exit Ramp locality (Famennian, Duncannon Member) along U.S. Route 15/Interstate 99. The 50% majority-rule consensus tree from the analysis supports a highly-nested clade of tristichopterids that includes all of the considered species from the Famennian, with the exception of Heddleichthys dalgleisiensis, and additionally includes the Frasnian Langlieria species that is described here.


Hepatic stellate cells (HSCs), a major component of the tumor microenvironment in liver cancer, play important roles in cancer progression as well as drug resistance. Here, we presented a microchannel plate-based co-culture model that integrated Hepa1-6 tumor spheroids with JS-1 stellate cells in three-dimensional (3D) concave microwells to mimic the in vivo tumor microenvironment by recapitulating epithelial-mesenchymal transition and chemoresistance. The expression of epithelial-mesenchymal transition (EMT)-related markers and factors was analyzed using immunofluorescent staining and the changes in viability following exposure to different concentrations of paclitaxel were measured. Cell spheroids formed 3D tumor spheroids within 3 days. Culture conditions were optimized for Hepa1-6 cells and JS-1 cells, and their appropriate interactions were confirmed by reciprocal activation. JS-1 under co-culture showed a change in cellular morphology and an increased expression of α-SMA. The expression of EMT-related markers, such as vimentin and TGF-β1, was higher in the co-cultured Hepa1-6 spheroids compared to that in mono-cultured spheroids. Following paclitaxel exposure, JS-1 cells showed significant changes in survival under both mono- and co-culture conditions, while Hepa1-6 presented negligible changes. The proposed microfluidic platform makes it possible to observe the positioned three-dimensional cell spheroids, which would be extensively used not only for well-organized spheroid creation, but also for better quantitative and qualitative understanding of the cell-cell interaction effect.


In this paper, the concept of Jordan triple higher -homomorphisms on prime
rings is introduced.  A result of Herstein is extended on this concept from the ring  into the prime ring .  We prove that every Jordan triple higher -homomorphism of ring  into prime ring  is either triple higher -homomorphism  or triple higher -anti-homomorphism of  into .


Michael Schaller supplies the historical background to show how the US transformed Japan from enemy to ally, covering the crucial years from 1945 to 1973 in which Japan emerged as a regional and global economic power. Schaller focuses on political, strategic, and economic relations, illuminating the connections between America's early trade policies toward Japan and the desire to secure the country as a bulwark against Communism in Asia.


Fresh ideas for the modern mage lie at the heart of this thought-provoking guide to magic theory. Approaching magical practice from an information paradigm, Patrick Dunn provides a unique and contemporary perspective on an ancient practice. Dunn teaches all about symbol systems, magical artifacts, sigils, spirits, elementals, languages, and magical journeys, and explains their significance in magical practice. There are also exercises for developing magic skills, along with techniques for creating talismans, servitors, divination decks, and your own astral temple.


This historical commentary describes formative events in the history of test reviewing as it has unfolded over the past 8 decades and recounts how the tradition established by Oscar Krisen Buros has continued and evolved since his death in 1978. The narrative provides the context in which psychological tests first appeared and subsequent concerns about their quality and claims made by their respective publishers. The discussion then recounts the test reviewing efforts undertaken by Oscar Buros to address these issues, discusses challenges faced during the early years of these efforts, and reviews the contributions of Luella Buros, Oscar's wife. Reference volumes in the Mental Measurements Yearbook series that Oscar Buros founded in 1938 continue to provide independent expert reviews of tests representing a wide spectrum of mental measurements that are used for a variety of purposes. The article concludes with a description of how Buros's mission to improve the science and practice of testing and assessment has been preserved and extended.


The report of the National Children's Bureau study of staff morale, qualifications and retention in England (Mainey, 2003) rightly highlighted a number of crucial issues facing providers of residential child care. Entitled Better Than You Think the key finding was that the rates of morale and job satisfaction were not low despite the adverse environment in which residential care operates. Residential care in the modern world is intended to be mainly a temporary placement for some of the most demanding young people who require out-of-home care. However, as with foster care, significant numbers of young people are spending years in out-of-home care and many residential services have to accommodate a wide variety of needs within a single unit. This general remit is challenging enough but the sector also continues to struggle with the aftermath of a number of high profile public inquiries which have identified instances of abuse of children and young people in residential care (Kent, 1997; Utting, 1997; Waterhouse, 2000).


It has been proposed that the drugs (6-hydroxydopamine, guanethidine, vinblastine) which are known to destroy sympathetic neurons in neonatal animals do so by preventing the accumulation of retrogradely transported nerve growth factor (NGF). It was found, consistent with the proposal, that administration of 6-hydroxydopamine (100 mg/kg s.c.) or vinblastine (0.4 mg/kg s.c.) 16 h prior to the administration of [125I]NGF complete prevented the accumulation of retrogradely transported [125I]NGF in superior cervical ganglia of neonatal rats. Administration of 6-hydroxydopamine or vinblastine to adult rats (where it does not cause sympathetic neuron cell death) did not completely prevent the retrograde transport of NGF, although 6-hydroxydopamine produced an alteration of the time course of accumulation (early times unaffected, later times depressed). The administration of guanethidine to adult rats (50 mg/kg/day) produced a modest decrease in the accumulation of NGF (40-60%). It would appear, however, that this decrease cannot account for the cytotoxic effects of guanethidine since: (1) sub-cytotoxic doses of guanethidine and non-cytotoxic guanidinium blocking agents also produce modest decreases in the retrograde transport in NGF; and (2) the retrograde transport of [125I]NGF is not affected in neonatal animals until after the neurons are clearly damaged. Hence, the data are entirely consistent with the hypothesis that NGF deprivation caused by 6-hydroxydopamine and vinblastine is the mechanism of the cytotoxic effects of these drugs on sympathetic neurons in neonatal animals. Guanethidine destroys sympathetic neurons by some other mechanism.


In this report, the nanopatterning method based on atomic force microscopy (AFM) with electrical bias to form the oxide patterns on silicon wafer is described. Under constant bias, 30 V, the linear pattern size is proportional to the rising humidity in the working environment. According to our experimental results, the sizes of the most circular nanopatterns are in the range from 50 nm to 70 nm depending on the applied bias and interaction time. In the results of evaluating the generation of oxidative production, the diameters and the number of oxide two dimensional nanopattern array, defaulted to 25 dots in 1 microm2, appeared in the AFM images have increasing tendency with the larger bias and the longer dwell time. Moreover, the imaging features of nanopatterns caused by bias 30 V have better performance than those by 10 V, and the dwell time only takes 0.015 s per dot.


The purpose of this study is to examine the effectiveness, or otherwise, of vector infographics on ESL students' acquisition of grammar, especially the use of tenses. After questioning college teachers about their teaching environment and main challenges, eight infographic designs were created to assist in the teaching of the simple present and simple past tenses. These designs were presented to 20 undergraduates. Mixed research methodologies including questionnaires were applied. Data were analyzed using (t-test) and refined by Wilcoxon Signed Ranks Test using IBM SPSS statistics. The significance of pre and post exam's results showed that p =0.028 (t-test) and 0.027 (Wilcoxon) < 0.05. This means that H0 is rejected and the applied infographics, as a cognitive education tool, improves student learning outcomes.


Numerous peptides (neuropeptides) have been recently found to be present in both the nervous and endocrine systems composing what is now known as the diffuse neuroendocrine system. Two immunological methods, radioimmunoassay and immunocytochemistry, have been used here in combination to study their distribution and cellular localization. A number of these neuropeptides have recently been found to be abnormal in disease state, thus providing further information as to their role in normal and pathological conditions.


Introduction: Weight management in obese subjects is suggested to improve cardiac remodelling. Little is known about the atrial electrical changes that accompany weight reduction.Methods: In a randomized-controlled trial (ANZCTR: 12610000497000), 46 subjects with BMI >27 in sinus rhythm were randomized to a comprehensive risk factor management program or general lifestyle advice, and followed-up for 12-months. Metabolic profiles, pharmacotherapy, BMI, waist circumference (WC) and body surface area (BSA) were recorded. Digital analysis of 12-lead ECGs was used to assess P-wave duration (PWD) and area (PWA) and indexed to BSA (PWD-I and PWA-I), at baseline and at completion of the study.Results: Subjects were well matched for all baseline characteristics (25 active, 21 controls). Mean follow-up was 11.6±1.6 months. Using the paired-sample t-test, significant reduction was seen in all indices at 12-months (PWD; P<0.001, PWA; P=0.001, PWD-I; P=0.014, PWA-I; P=0.016) in the active group. No significant difference was seen in the control group. Using regression analysis with intention-to-treat, active group allocation was predictive of abbreviated P-wave indices (P=0.019). Controlling for age, gender, baseline respiratory disturbance index (RDI), ΔBMI, ΔWC and ΔBSA, significant correlation remained between shortening of PWD-I and number of anti-hypertensive medication used (P=0.026). Conclusion: A structured comprehensive risk factor management program, with aggressive hypertension management and weight reduction, is associated with a favourable improvement in ECG-derived indices of atrial electrical remodelling.


GADD45b, which is associated with cellular stress response and apoptosis regulation, was frequently under‐expressed in HCC. In a previous study we found GADD45b belongs to a group of sorafenib‐regulated genes that are independent of mitogen‐activated protein kinase‐extracellular signal‐regulated kinase (MEK)/ extracellular signal‐regulated kinase (ERK) signaling pathway. The present study explored the role of sorafenib‐induced GADD45b expression in HCC cells. HCC cell lines tested included HepG2, Hep3B, Huh‐7, and Huh‐7R, a sorafenib‐resistant cell line established by continuously exposure of Huh‐7 cells to sorafenib. GADD45b expression was examined by quantitative real‐time PCR and western blotting. Control of GADD45b transcription was examined by luciferase reporter assay using a series of reporter plasmids with deletions or site‐directed mutants of the 5′‐flanking region of GADD45b promoter. Apoptosis was analyzed by measuring the subG1 fraction and annexin V staining using flow cytometry. Both the mRNA and the protein levels of GADD45b was increased after sorafenib but not after the MEK inhibitor CI‐1040 or U0126 treatment, suggesting that GADD45b induction was independent of cellular MEK/ERK activity. GADD45b induction was more prominent in sorafenib‐sensitive HCC cells (Huh‐7 and HepG2, IC50 6–7 µM) but less so prominent in sorafenib‐resistant HCC cells (Hep3B and Huh‐7R, IC50 12–15 µM). Knockdown of GADD45b expression by siRNA partially abrogated the pro‐apoptotic effects of sorafenib in Huh‐7 and HepG2 cells but not Hep3B cells. The region −339/−267 in the 5′‐flanking region of GADD45b promoter, which contained AP‐1 (−298/−292) and Sp1 (−285/−277) binding sites, was found crucial for GADD45b induction by sorafenib. Binding of c‐Jun and Sp1 to GADD45b promoter was confirmed by chromatin immunoprecipitation. Sorafenib also increased the phosphorylation of JNK in sorafenib‐sensitive but not in sorafenib‐resistant HCC cells. Sorafenib‐induced GADD45b expression can be alleviated by treatment with the specific JNK inhibitor SP600125. Our data indicated that induction of GADD45b expression, which is mediated by cellular JNK/c‐Jun signaling pathway but not MEK/ERK signaling, contributes to sorafenib‐induced apoptosis in HCC cells. Failure of GADD45b induction may confer sorafenib resistance. GADD45b may be used as a predictive biomarker for sorafenib sensitivity in HCC. (Supported by grants NSC97‐3112‐B‐002‐012, NSC98‐3112‐B‐002‐007, NSC98‐3112‐B‐002‐037) Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B226.


As a new class of two-dimensional materials, the MXene family has triggered attention because of its unique electrical and mechanical properties. MXene's excellent electrical conductivity and hydrophilicity make it an ideal option for polymer nanocomposite fabrication. For the first time, polymer nanocomposites of polyvinyl alcohol (PVA)/Ti3C2T x (MXene) were used for charge storage applications in the X-band frequency range (8.2-12.4 GHz). By implementing solution casting and vacuum-assisted filtration (VAF), flexible thin films with exceptional dielectric properties (solution casting @ 10.0 wt % MXene: ε' = 370.5 and tan δ = 0.11 and VAF @ 10.0 wt % MXene: ε' = 3166 and tan δ = 0.09) were fabricated. The reported dielectric constants in this study are among the highest values obtained in X-band frequency with low dielectric losses. This outstanding performance originates from the high electrical conductivity of synthesized Ti3C2T x MXene (σ ≈ 1.4 ± 0.077 × 106 S/m; the highest reported value for Ti3C2T x MXene to date in the literature), great dispersion state, and the nacre-like structure of the polymer nanocomposites. Combining the exceptional properties of MXene with the effective nacre-like structure, PVA/MXene nanocomposites can be used as a novel charge storage material, fulfilling the requirements of flexible electronics and energy storage devices.


We apply text analysis approaches for a specialized search engine for 3D CAD models and associated products. The main goals are to distinguish between actual product descriptions and other text on a website, as well as to decide whether a given text is or contains a product name.
For this we use paragraph vectors for text classification, a character-level long short-term memory network (LSTM) for a single word classification and an LSTM tagger based on word embeddings for detecting product names within sentences. Despite the need to collect bigger datasets in our specific problem domain, the first results are promising and partially fit for production use.


The interactions between dimeric porphyrins, covalently linked at their peripheries, have been measured from their electronic absorption spectra and 13C nmr spectra.


On-chip networks for future system-on-chip designs need simple, high performance implementations. In order to promote system-level integrity, guaranteed services (GS) need to be provided. We propose a network-on-chip (NoC) router architecture to support this, and demonstrate with a CMOS standard cell design. Our implementation is based on clockless circuit techniques, and thus inherently supports a modular GALS-oriented design flow. Our router exploits virtual channels to provide connection-oriented GS, as well as connection-less best-effort (BE) routing. The architecture is highly flexible, in that support for different types of BE routing and GS arbitration can be easily plugged into the router.


BACKGROUND
Severe sepsis is a clinical syndrome frequently occurring in intensive care units (ICUs) when systemic infection results in multiorgan dysfunction. No Polish data concerning treatment and prognosis in this group of patients have been available to date.

MATERIAL/METHODS
The Polish Working Group for Sepsis introduced in 2003 internet registration of severe sepsis cases treated in ICUs in Poland. Information about severe sepsis were entered including the type of infection, clinical course, methods and results of treatment.

RESULTS
From 20.04.2003 to 10.01.2004, 1043 severe sepsis cases were reported by 104 ICUs. Mean age of patients was 59 years. Mean duration of treatment was 19 days, with mortality rate of 55%. In 60% dysfunction of 4 or more organs was diagnosed. In 55% the underlying disease was surgical and abdominal cavity was the primary infection site (47%). Pathogens most likely to cause severe sepsis were G- (48%) and G+ (43%) bacteria, as well as fungi (21%). Positive blood culture was obtained in 45% of patients. Treatment involved antibiotic and support of organ function. Activated protein C was used in 8.2%, causing a reduction of mortality.

CONCLUSIONS
Severe sepsis in Polish ICUs develops most frequently in the course of intra-abdominal infections. Dysfunction of 4 or more organs caused observed high mortality (55%) Internet surveillance proved to be useful method of collecting information, widely accepted by personnel of ICUs.


This study presents the results of effect of a combination of bismuth subnitrate teat canal sealant (Boviseal® -Bimeda® Animal Health, Ireland) and the antibiotic Ampicillin & Cloxacillin (Bovaclox® DC-Norbrook Laboratories Ltd-UK) when used during the dry period on occurrence of mastitis 100 days post-calving. The objectives of this study were: to determine the effect of Boviseal® teat canal sealant in combination with Bovaclox® DC in control of dairy cow mastitis 100 days after calving; to determine bacterial pathogens causing mastitis in the selected farms and to determine risk factors for occurrence of dairy mastitis in the selected farms. This controlled field trial was carried out in two Kenyan dairy farms: Chemusian Farm in Nakuru County and Gicheha Farm in Kiambu County. 156 dairy cows were used in the study. Healthy cows with no history of mastitis in their current lactation were recruited. They were randomly placed into either of the two study groups: the control and the test group. The Control group received Bovaclox® DC while the Test group received the Bovaclox® DC followed by Boviseal®. The cows were followed during the entire dry period and 100 days post-calving monitoring for mastitis occurrence. Cows in the control group were more susceptible to mastitis 100 days post-calving compared to cows in the treatment group (P<0.001, RR=4.4, OR=17.7). Of the bacterial pathogens, coagulase negative Staphylococci (CNS) were the most common pathogens isolated from mastitic milk at 34.6 % followed by Micrococcus spp. (9.0%). Other bacteria isolated were Streptococcus agalactiae (3.8%), Staphylococcus aureus (1.9%); Escherichia coli (0.6%) and various bacterial mixtures. Results of logistic regressions at P≤0.05 showed that farm, position of the quarter, type of barn floor and type of treatment were significantly associated with occurrence of mastitis. Cows in Gicheha farm whose barn floor was earthen, those cows in the control group and hindquarters were risk factors for mastitis (RR=1.5, 4.4 and 1.18 respectively). The results of this study showed that Bovaclox® DC + Boviseal® teat canal sealant combination applied during the dry period is more effective in controlling bovine mastitis 100 days post-calving compared to the use of Bovaclox® DC alone. The study thus recommends the use of Bovaclox® DC + Boviseal® dry cow combination for control of bovine mastitis.


We conducted a survey of pediatric training program directors (75% response rate) regarding program support services for house staff, directors' attitudes about stress in training, and program plans to ameliorate such stress. Support services included explicit measures to alleviate stress, policies that may minimize stress, evaluation of house staff performance, feedback regarding career concerns, and benefits (eg, medical insurance and child care). Most programs offered services to reduce stress from training, but few offered preventive services. Support policies were reported to be inadequate, especially in the areas of coverage for leaves of absence. Maternity leave represented most leaves of absences, as 10% of the female house staff and 11% of the male house staff members became parents. Program directors' terms were short, and only 30% perceived these roles to be their primary roles. Male directors believed that female house officers had a harder time adjusting to their programs. We suggest changes and present a simple way for program directors to evaluate their support services.


The objective of the study was to investigate milk yield and eating behaviour of crossbred goats, German Improved Fawn × Hair crossbred (GIF) and Saanen × Hair goats (S), in subtropical eastern Mediterranean climate of Turkey during early summer season. Eight GIF and eight S goats were individually housed in 1.5 × 1.5 m pens. Diurnal eating patterns were monitored by a system that recorded meal size and meal length. Milk yield (kg/day) was 1.77 in GIF and 2.0 in S goats, whereas milk production efficiency (kg feed/kg milk) was 1.15 in GIF and 1.07 in S goats. The differences between GIF and S goats in eating behaviour parameters were significant: the S goats had higher meal size and meal length and longer inter-meal interval, meal time, and eating rate within in each meal, but lower number of meals in comparison with GIF goats. German Improved Fawn × Hair crossbred and Saanen × Hair goats have similar lactation performance under good nutritional condition, but their eating behaviours are quite different.


Background: The stomach is a very unusual site of metastasis from melanoma. Due to the few reports, we collected a case series in order to focus their endoscopic, clinical and biological features and to explore the therapeutic outcomes.
Methods: We collected 9 consecutive cases of gastric localization of metastatic melanoma. Results: All patients presented a long, nonspecific and vague history of gastric symptoms often cured as gastritis. The endoscopic features included multiple smooth black spots, ulcerated polypoid lesions or a wide neoplastic infiltration. BRAF status was mutated in only 1 patient while an NRAS mutation was found in 3 cases. Palliative gastrectomy was performed in 4 of 9 patients resulting in a good control of symptoms. The median survival in patients underwent gastrectomy was 25 months vs 4 months in non-surgically treated patients. Conclusions: We emphasize that physicians should be aware of the possible gastric involvement in patients with a history of melanoma and should suggest to promptly perform an endoscopic evaluation in symptomatic patients. Gastrectomy should be offered to all patients for palliative intent and to allow to plan systemic therapies recently enhanced with new and more effective drugs.


OMIS1 (Operative Modular Imaging Spectrometer) is a new imaging spectrometer designed by Shanghai Institute of Technical Physics, and has eight thermal infrared bands (nos. 105–112). This paper presents the use of images obtained from these thermal infrared bands to detect and map coal fires in north-western China. According to experiments in the Rujigou area of Ningxia municipality, each thermal infrared band has high correlation (>0.939). Regression analysis of land surface temperature (LST) with the pixel value in each thermal infrared band indicates: (1) for images acquired at daytime (from 11:00 to 13:00 local time), the first four thermal infrared bands have a linear relationship, and the final four bands have an exponential relationship; (2) for images acquired in the early morning (from 06:00 to 07:30), each band has a linear relationship. In conclusion, the ground temperature map is based on the 107th band of morning time. The mapping error is greatly determined by the quantity and precision of ground data measured synchronously.