Influenza surveillance during the post-pandemic influenza 2010/11 season in Greece, 04 October 2010 to 22 May 2011.

In this manuscript, we summarise the experience of Greece during the post-pandemic influenza season 2010/11 from 04 October 2010 to 22 May 2011. The spread of the disease and its impact were monitored using multiple surveillance systems, such as sentinel surveillance, virological surveillance and all-cause mortality surveillance. We also focus on the characteristics of laboratory-confirmed severe influenza cases who required admission to an intensive care unit (ICU) (n=368), and/or with a fatal outcome (n=180). The influenza-like illness rate reported from sentinel surveillance started rising in early January 2011 and peaked between 31 January and 6 February 2011. The total number of ICU admissions was higher in the post-pandemic influenza season than during the pandemic period causing a lot of pressure on ICUs. The overall population mortality rate due to influenza A(H1N1)2009 was higher than during the pandemic period (15.9 vs 13.2 fatal cases per million, p=0.087). Our data suggest that the severity of clinical illness in the first post-pandemic influenza season was comparable or even higher than during the pandemic.

Interpretability methods of machine learning algorithms with applications in breast cancer diagnosis.

Early detection of breast cancer is a powerful tool towards decreasing its socioeconomic burden. Although, artificial intelligence (AI) methods have shown remarkable results towards this goal, their "black box" nature hinders their wide adoption in clinical practice. To address the need for AI guided breast cancer diagnosis, interpretability methods can be utilized. In this study, we used AI methods, i.e., Random Forests (RF), Neural Networks (NN) and Ensembles of Neural Networks (ENN), towards this goal and explained and optimized their performance through interpretability techniques, such as the Global Surrogate (GS) method, the Individual Conditional Expectation (ICE) plots and the Shapley values (SV). The Wisconsin Diagnostic Breast Cancer (WDBC) dataset of the open UCI repository was used for the training and evaluation of the AI algorithms. The best performance for breast cancer diagnosis was achieved by the proposed ENN (96.6% accuracy and 0.96 area under the ROC curve), and its predictions were explained by ICE plots, proving that its decisions were compliant with current medical knowledge and can be further utilized to gain new insights in the pathophysiological mechanisms of breast cancer. Feature selection based on features' importance according to the GS model improved the performance of the RF (leading the accuracy from 96.49% to 97.18% and the area under the ROC curve from 0.96 to 0.97) and feature selection based on features' importance according to SV improved the performance of the NN (leading the accuracy from 94.6% to 95.53% and the area under the ROC curve from 0.94 to 0.95). Compared to other approaches on the same dataset, our proposed models demonstrated state of the art performance while being interpretable.

Respiratory health of municipal solid waste workers.

BACKGROUND: There is an increasing evidence that the incidence of work-related pulmonary problems is greater in waste collectors than in the general workforce. AIMS: To evaluate the respiratory health of municipal solid waste workers (MSWWs). METHODS: One hundred and eighty-four municipal employees of Keratsini (104 MSWWs and 80 controls) participated in a cross-sectional study. All participants were asked to fill in a slightly modified version of the Medical Research Council questionnaire. Lung function was evaluated by spirometry. RESULTS: Spirometry revealed reduced mean forced vital capacity (FVC) and forced expiratory volume in 1 s (as a percentage of predicted values) in MSWWs compared with controls. After adjustment for smoking status, only the decline in FVC was statistically significant (P < 0.05). Prevalence of all respiratory symptoms was higher in MSWWs than in controls. After adjustment for confounding factors, the difference reached statistical significance (P < 0.05) for morning cough, cough on exertion and sore throat. CONCLUSIONS: The results of this cross-sectional study indicate a higher prevalence of respiratory symptoms and a greater decrease in lung function in MSWWs. A number of limitations such as the relatively small size of population and the 'healthy worker' effect should be taken into account.

Optical polarization properties of (11-22) semi-polar InGaN LEDs with a wide spectral range.

Electroluminescence polarization measurements have been performed on a series of semi-polar InGaN light emitting diodes (LEDs) grown on semi-polar (11-22) templates with a high crystal quality. The emission wavelengths of these LEDs cover a wide spectral region from 443 to 555 nm. A systematic study has been carried out in order to investigate the influence of both indium content and injection current on polarization properties, where a clear polarization switching at approximately 470 nm has been observed. The shortest wavelength LED (443 nm) exhibits a positive 0.15 polarization degree, while the longest wavelength LED (555 nm) shows a negative -0.33 polarization degree. All the longer wavelength LEDs with an emission wavelength above 470 nm exhibit negative polarization degrees, and they further demonstrate that the dependence of polarization degree on injection current enhances with increasing emission wavelength. Moreover, the absolute value of the polarization degree decreases with increasing injection current. In contrast, the polarization degree of the 443 nm blue LED remains constant with changing injection current. This discrepancy can be attributed to a significant difference in the density of states (DOS) of the valence subbands.

Monolithically integrated white light LEDs on (11-22) semi-polar GaN templates.

Carrier transport issues in a (11-22) semi-polar GaN based white light emitting diode (consisting of yellow and blue emissions) have been investigated by detailed simulations, demonstrating that the growth order of yellow and blue InGaN quantum wells plays a critically important role in achieving white emission. The growth order needs to be yellow InGaN quantum wells first and then a blue InGaN quantum well after the growth of n-type GaN. The fundamental reason is due to the poor hole concentration distribution across the whole InGaN quantum well region. In order to effectively capture holes in both the yellow InGaN quantum wells and the blue InGaN quantum well, a thin GaN spacer has been introduced prior to the blue InGaN quantum well. The detailed simulations of the band diagram and the hole concentration distribution across the yellow and the blue quantum wells have been conducted, showing that the thin GaN spacer can effectively balance the hole concentration between the yellow and the blue InGaN quantum wells, eventually determining their relative intensity between the yellow and the blue emissions. Based on this simulation, we have demonstrated a monolithically multi-colour LED grown on our high quality semi-polar (11-22) GaN templates.

Polarized white light from hybrid organic/III-nitrides grating structures.

Highly polarised white light emission from a hybrid organic/inorganic device has been achieved. The hybrid devices are fabricated by means of combining blue InGaN-based multiple quantum wells (MQWs) with a one-dimensional (1D) grating structure and down-conversion F8BT yellow light emitting polymer. The 1D grating structure converts the blue emission from unpolarised to highly polarised; Highly polarised yellow emission has been achieved from the F8BT polymer filled and aligned along the periodic nano-channels of the grating structure as a result of enhanced nano-confinement. Optical polarization measurements show that our device demonstrates a polarization degree of up to 43% for the smallest nano-channel width. Furthermore, the hybrid device with such a grating structure allows us to achieve an optimum relative orientation between the dipoles in the donor (i.e., InGaN/GaN MQWs) and the diploes in the acceptor (i.e., the F8BT), maximizing the efficiency of non-radiative energy transfer (NRET) between the donor and the acceptor. Time-resolved micro photoluminescence measurements show a 2.5 times enhancement in the NRET efficiency, giving a maximal NRET efficiency of 90%. It is worth highlighting that the approach developed paves the way for the fabrication of highly polarized white light emitters.

Monolithically multi-color lasing from an InGaN microdisk on a Si substrate.

An optically pumped multi-color laser has been achieved using an InGaN/GaN based micro-disk with an undercut structure on a silicon substrate. The micro-disk laser has been fabricated by means of a combination of a cost-effective microsphere lithography technique and subsequent dry/wet etching processes. The microdisk laser is approximately 1 µm in diameter. The structure was designed in such a way that the vertical components of the whispering gallery (WG) modes formed can be effectively suppressed. Consequently, three clean lasing peaks at 442 nm, 493 nm and 522 nm have been achieved at room temperature by simply using a continuous-wave diode laser as an optical pumping source. Time-resolved micro photoluminescence (PL) measurements have been performed in order to further confirm the lasing by investigating the excitonic recombination dynamics of these lasing peaks. A three dimensional finite-difference-time-domain (FDTD) simulation has been used for the structure design.

Ets and retroviruses - transduction and activation of members of the Ets oncogene family in viral oncogenesis.

Studies of retroviral-induced oncogenesis in animal systems led to the initial discovery of viral oncogenes and their cellular homologs, and provided critical insights into their role in the neoplastic process. V-ets, the founding member of the ETS oncogene family, was originally identified as part of the fusion oncogene encoded by the avian acute leukemia virus E26 and subsequent analysis of virus induced leukemias led to the initial isolation of two other members of the ETS gene family. PU.1 was identified as a target of insertional activation in the majority of tumors induced by the murine Spleen Focus Forming virus (SFFV), while fli-1 proved to be the target of Friend murine leukemia virus (F-MuLV) in F-MuLV induced erythroleukemia, as well as that of the 10A1 and Graffi viruses. The common features of the erythroid and myeloid diseases induced by these viruses provided the initial demonstration that these and other members of the ETS family play important roles in hematopoietic development as well as disease. This review provides an overview of the role of ETS genes in retrovirally induced neoplasia, their possible mechanisms of action, and how these viral studies relate to current knowledge of the functions of these genes in hematopoiesis.

The Gag-Myb-Ets fusion oncogene alters the apoptotic response and growth factor dependence of interleukin-3 dependent murine cells.

Expression of the avian E26-derived Gag-Myb-Ets fusion oncogene in interleukin-3(IL3)-dependent murine hematopoietic cell lines results in a pattern of cell line dependent changes in growth factor-induced proliferation and apoptosis. A drug-selectable retrovirus expressing p135Gag-Myb-Ets induced an erythropoietin(Epo)-responsive phenotype in the cell lines FDC-P2, BaF3 and 32Dc123. Gag-Myb-Ets expression alone did not increase expression of GATA-1 or the Epo receptor(EpoR) in the presence of IL3, and infected cell lines express increased GATA-1 and EpoR only when IL3 was replaced by Epo in the culture media. Indicative of Epo-induced erythroid differentiation, these cells also began to express beta-globin after 3-5 days growth in Epo. Unlike control cells, infected FDC-P2 cells failed to undergo programmed cell death (apoptosis) when transferred from IL3- to Epo-containing media, although a fraction of the cells failed to proliferate following the media shift. Three other IL3-dependent cell lines showed no changes in growth behavior when induced to express the fusion oncogene. Our data shows that Gag-Myb-Ets can have different affects on growth factor pathways depending on the cell background, suggesting a model in which the p135gag-myb-ets fusion oncogene promotes these different responses through its affect on apoptosis.

FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells.

The FLI-1 oncogene, a member of the ETS family of transcription factors, is associated with both normal and abnormal hematopoietic cell growth and lineage-specific differentiation. We have previously shown that overexpression of FLI-1 in pluripotent human hematopoietic cells leads to the induction of a megakaryocytic phenotype. In this report we show that FLI-1 also acts as an inhibitor of erythroid differentiation. Following the induction of erythroid differentiation, pluripotent cells express reduced levels of FLI-1. In contrast, when FLI-1 is overexpressed in these cells, the levels of erythroid markers are reduced. The ability of FLI-1 overexpressing cells to respond to erythroid-specific inducers such as hemin and Ara-C is also inhibited, and the uninduced cells show a reduced level of the erythroid-associated GATA-1 transcription factor mRNA. Furthermore, expression of a GATA-1 promoter-driven reporter construct in K562 cells is inhibited by co-transfection with a construct expressing FLI-1. Our results support the hypothesis that FLI-1 can act both positively and negatively in the regulation of hematopoietic cell differentiation, and that inhibition of GATA-1 expression may contribute to FLI-1-mediated inhibition of erythroid differentiation.

ETS-1 induces increased expression of erythroid markers in the pluripotent erythroleukemic cell lines K562 and HEL.

Members of the ETS gene family are known to be expressed in hematopoietic tissues and cell lines, and there is increasing evidence that ETS proteins may play a role in normal hematopoietic cell development. We demonstrate that ETS-1 can contribute to the development of an erythroid phenotype in vitro. The pluripotent erythroleukemic K562 and HEL cell lines express messages for a number of ETS genes, but only c-ETS-1 levels are elevated in response to treatment with hemin or cytosine arabinofuranoside (Ara-C), agents which induce erythroid differentiation. Furthermore, ETS-1 antisense oligonucleotides inhibit hemoglobinization of cells treated with Ara-C or hemin, and K562 and HEL cells infected with retrovirus expressing the c-ETS-1 gene exhibit a significant increase in erythroid character (as indicated by benzidine staining for hemoglobin (Hb) and surface marker analysis), a dramatic increase in responsiveness to hemin or Ara-C, and a decreased rate of proliferation (20-40% of control rates). In contrast, infection with virus expressing ETS-2 or vector sequences only causes no detectable changes in the proliferation or erythroid character of either the HEL or K562 cell lines. These data indicate a role for ETS-1 in erythroid differentiation.

A patient with Klinefelter's syndrome and thalassemia intermedia.

Klinefelter's syndrome (KS) is associated with a wide spectrum of clinical features, such as tall stature, eunuchoid proportions, testes disproportionately small for the level of pubertal development, gynecomastia and behavioral problems. The association of KS with thalassemia intermedia has not been previously reported. A male patient with thalassemia intermedia was diagnosed with KS at the age of 14 years when endocrine evaluation for delayed puberty showed hypergonadotrophic hypogonadism. Thyroid function was normal; however, basal and GnRH-stimulated gonadotropin concentrations were raised while serum testosterone was low. Karyotype analysis revealed KS (47,XXY). Testosterone replacement therapy started soon after diagnosis and now at the age of 20 years the patient's height is 178.3 cm, the U/L ratio is 0.91. Testicular volume is 12 ml (Prader orchidometer) and his pubic hair is stage 4. To our knowledge this is the first case of a patient suffering from KS and thalassemia intermedia reported in the literature.

Suppression of the Ewing's sarcoma phenotype by FLI1/ERF repressor hybrids.

Fusion of the 5' half of the Ewing's sarcoma (ES) gene EWS with the DNA-binding domain of several transcription factors has been detected in many human tumors. The t(11;22)(q24;q12) chromosomal translocation is specifically linked to ES and primitive neuroectodermal tumors and results, in the majority of cases, in the fusion of the amino terminus of the EWS gene to the carboxyl-terminal DNA-binding domain of the FLI1 gene. The chimeric protein has been shown to be oncogenic, a potent transcriptional activator, and necessary for the maintenance of the Ewing's phenotype, making it an attractive target for gene therapy. In this study, we demonstrate that the ES transformed phenotype can be suppressed by chimeric transcriptional repressors containing the DNA-binding domain of FLI1 and the regulatory and repressor domain of ERF, a transcription suppressor and member of the ets gene family. The hybrid repressor is expressed at levels comparable with EWS/FLI1, does not affect EWS/FLI1 expression, and exhibits similar DNA-binding specificity but suppresses transcriptional activity. The FLI1/ERF repressor, like the wild-type ERF, is regulated by mitogen-activated protein kinase-dependent subcellular localization. Our data suggest that transformation by EWS/FLI1 may partially be due to activation of specific EWS/FLI1-regulated genes involved in cell proliferation.

Inhibition of cellular activities by triethyllead. Role of glutathione and accumulation of triethyllead in vitro.

We investigated the interaction of triethyllead with ATP-coupled cellular enzymatic activities and the role of GSH to reverse the observed inhibition of these enzymes. Triethyllead inhibited the membrane bound Na+-K+-ATPase from HeLa cells (IC50 12 microM) and the ATP-hydrolysing activity of the mitochondrial F0-F1-ATPase complex (IC50 17 microM). Addition of 1 mM GSH reversed both enzyme activities totally, whereas lower GSH concentrations showed a less pronounced effect. Surprisingly, in freshly isolated rat liver mitochondria the ATP-synthesizing activity was also inhibited by triethyllead (IC50 16 microM), in spite of a measured high intramitochondrial GSH concentration (up to 10 mM). Further experiments in isolated submitochondrial particles revealed that ATP-synthesis and ATP-hydrolysis were inhibited by triethyllead with similar IC50 values, and both activities could be protected in vitro from the organolead compound in the presence of 1 mM GSH. Thus in all activities tested in vitro a high excess of GSH over triethyllead (greater than or equal to 25-fold) is necessary to restore the inhibited enzymes. The intramitochondrial triethyllead concentration was further determined after incubation of intact mitochondria with 10 microM of the organolead compound. The organolead concentration measured was as high as 600 microM. This means that in intact mitochondria there exists only a ca. 16-fold excess of GSH, which has been shown to be insufficient to protect ATP-synthesizing and ATP-hydrolyzing activities of the F0-F1-ATPase from triethyllead in vitro. We concluded that in intact mitochondria the F0-F1-ATPase complex is inhibited by triethyllead due to its accumulation in the matrix.

Neurophysiologic evaluation of long-term desferrioxamine therapy in beta-thalassemia patients.

Forty patients with beta-thalassemia major (BTM), between 11 and 19 years of age and maintained on long-term desferrioxamine (DFO) treatment, were examined by evoked potential and nerve conduction velocity studies to investigate a possible involvement of the auditory, visual, somatosensory, or peripheral nervous pathways. Pathologic findings in brainstem auditory-, visual-, and somatosensory-evoked potentials, and nerve conduction velocity studies were demonstrated in 25%, 15%, 7.5%, and 25% of the patients, respectively, whereas 15% demonstrated involvement of multiple neural pathways. Subclinical involvement of the auditory pathway was statistically associated with higher mean daily DFO dose and longer duration of DFO therapy, whereas abnormalities regarding the somatosensory pathways were related to older age, longer mean duration of DFO therapy, and lower serum copper levels. Involvement of the peripheral nervous system was related to lower serum copper levels. Multiple involvement of neural pathways was related to longer mean duration of DFO therapy. We conclude that risk factors related to long-term DFO treatment are only partly responsible for the subclinical involvement of neural pathways demonstrated in beta-thalassemia major patients.

Filial therapy: effects on two children's behavior and mothers' stress.

Due to patients' continual and natural contact with their children, as well as shortages of professionals, parents are increasingly being asked to play a significant role in treatment for the children's emotional and behavior problems. Filial therapy is a treatment that involves parents by teaching parents to conduct child-centered play therapy sessions with their children. The current study sought to examine filial therapy effectiveness by measuring changes in children's behavior and parental stress in parenting. Mothers of two preschool children were administered the Behavior Assessment for Children and the Parenting Stress Index prior to, following completion of, and 2 mo. after participating in a 10-wk. filial therapy training program. Results suggest significant decreases in externalizing behaviors and decreased parenting stress for one parent of the two children. Informal parental reports of changes suggest that parents saw improved relationships with their children, their own confidence increased, generalization of skills, and improvements with regard to behavior problems.

Room temperature continuous-wave green lasing from an InGaN microdisk on silicon.

Optically pumped green lasing with an ultra low threshold has been achieved using an InGaN/GaN based micro-disk with an undercut structure on silicon substrates. The micro-disks with a diameter of around 1 µm were fabricated by means of a combination of a cost-effective silica micro-sphere approach, dry-etching and subsequent chemical etching. The combination of these techniques both minimises the roughness of the sidewalls of the micro-disks and also produces excellent circular geometry. Utilizing this fabrication process, lasing has been achieved at room temperature under optical pumping from a continuous-wave laser diode. The threshold for lasing is as low as 1 kW/cm(2). Time-resolved micro photoluminescence (PL) and confocal PL measurements have been performed in order to further confirm the lasing action in whispering gallery modes and also investigate the excitonic recombination dynamics of the lasing.

Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia.

Schizophrenia is a strongly heritable disorder, and identification of potential candidate genes has accelerated in recent years. Genomewide scans have identified multiple large linkage regions across the genome, with fine-mapping studies and other investigations of biologically plausible targets demonstrating several promising candidate genes of modest effect. The recent introduction of technological platforms for whole-genome association (WGA) studies can provide an opportunity to rapidly identify novel targets, although no WGA studies have been reported in the psychiatric literature to date. We report results of a case-control WGA study in schizophrenia, examining approximately 500 000 markers, which revealed a strong effect (P=3.7 x 10(-7)) of a novel locus (rs4129148) near the CSF2RA (colony stimulating factor, receptor 2 alpha) gene in the pseudoautosomal region. Sequencing of CSF2RA and its neighbor, IL3RA (interleukin 3 receptor alpha) in an independent case-control cohort revealed both common intronic haplotypes and several novel, rare missense variants associated with schizophrenia. The presence of cytokine receptor abnormalities in schizophrenia may help explain prior epidemiologic data relating the risk for this illness to altered rates of autoimmune disorders, prenatal infection and familial leukemia.