Flux Discharge Cascades in Various Dimensions

We study the dynamics of electric flux discharge by charged particle pair or spherical string or membrane production in various dimensions. When electric flux wraps at least one compact cycle, we find that a single "pair" production event can initiate a cascading decay in real time that "shorts out" the flux and discharges many units of it. This process arises from local dynamics in the compact space, and so is invisible in the dimensionally-reduced truncation. It occurs in theories as simple as the Schwinger model on a circle, and has implications for any theory with compact dimensions and electric flux, including string theories and the string landscape.Comment: 19+8 pages, 3 figures, 3 appendice

Combined 18F-FDG PET/CT Imaging for the Initial Evaluation of Glottic Cancer

ObjectivesThe primary aim of this study was to determine whether 18F-FDG-PET/CT (PET/CT) scans provide additional diagnostic information in addition to the direct laryngoscopic examination (L/E) and contrast-enhanced CT (CT) in patients with glottic cancer during the initial evaluation.MethodsFifty-five consecutive patients with glottic cancer of the larynx that had L/E, CT and PET/CT were enrolled. The diagnostic value of each modality was compared for their accuracy in predicting the extent of the primary tumors on sub-site based analysis and the final tumor staging. The reference standards were either the surgical pathology findings or clinical/radiological follow-up outcome. Changes in patient care based on PET/CT results were compared with the treatment decisions based on L/E with CT.ResultsFor primary tumor sub-site based analysis, the sensitivity was significantly higher for L/E (92.8%) than for PET/CT (79.4%, P=0.028). The comparisons between L/E vs. CT and CT vs. PET/CT did not reach statistical significance. As an initial tumor-staging method the L/E had a diagnostic accuracy of 76.4%, compared to 61.8% for CT and 41.8% for PET/CT. The L/E and CT were better than the PET/CT (P=0.0009 and 0.049) for the initial TNM staging. PET/CT scanning changed the clinical decision-making based on the L/E with CT results in 12.7% of cases, of whom 5.5% had no additional PET/CT related benefit.ConclusionThe results of this study showed that PET/CT imaging added no clinical information benefit compared to the L/E and CT for the initial evaluation of patients with glottic cancer

Stimulus-dependent maximum entropy models of neural population codes

Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. To be able to infer a model for this distribution from large-scale neural recordings, we introduce a stimulus-dependent maximum entropy (SDME) model---a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. The model is able to capture the single-cell response properties as well as the correlations in neural spiking due to shared stimulus and due to effective neuron-to-neuron connections. Here we show that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. As a result, the SDME model gives a more accurate account of single cell responses and in particular outperforms uncoupled models in reproducing the distributions of codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like surprise and information transmission in a neural population.Comment: 11 pages, 7 figure

Plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum</it>, has developed resistance to many of the drugs in use. The recommended treatment policy is now to use drug combinations. The atovaquone-proguanil (AP) drug combination, is one of the treatment and prophylaxis options. Atovaquone (ATQ) exerts its action by inhibiting plasmodial mitochondria electron transport at the level of the cytochrome bc1 complex. <it>Plasmodium falciparum in vitro </it>resistance to ATQ has been associated with specific point mutations in the region spanning codons 271-284 of the <it>cytochrome b </it>gene. ATQ -resistant <it>Plasmodium yoelii </it>and <it>Plasmodium berghei </it>lines have been obtained and resistant lines have amino acid mutations in their CYT <it>b </it>protein sequences. <it>Plasmodium chabaudi </it>model for studying drug-responses and drug-resistance selection is a very useful rodent malaria model but no ATQ resistant parasites have been reported so far. The aim of this study was to determine the ATQ sensitivity of the <it>P. chabaudi </it>clones, to select a resistant parasite line and to perform genotypic characterization of the <it>cytb </it>gene of these clones.</p> <p>Methods</p> <p>To select for ATQ resistance, <it>Plasmodium. chabaudi chabaudi </it>clones were exposed to gradually increasing concentrations of ATQ during several consecutive passages in mice. <it>Plasmodium chabaudi cytb </it>gene was amplified and sequenced.</p> <p>Results</p> <p>ATQ resistance was selected from the clone AS-3CQ. In order to confirm whether an heritable genetic mutation underlies the response of AS-ATQ to ATQ, the stability of the drug resistance phenotype in this clone was evaluated by measuring drug responses after (i) multiple blood passages in the absence of the drug, (ii) freeze/thawing of parasites in liquid nitrogen and (iii) transmission through a mosquito host, <it>Anopheles stephensi</it>. ATQ resistance phenotype of the drug-selected parasite clone kept unaltered. Therefore, ATQ resistance in clone AS-ATQ is genetically encoded. The Minimum Curative Dose of AS-ATQ showed a six-fold increase in MCD to ATQ relative to AS-3CQ.</p> <p>Conclusions</p> <p>A mutation was found on the <it>P. chabaudi cytb </it>gene from the AS-ATQ sample a substitution at the residue Tyr268 for an Asn, this mutation is homologous to the one found in <it>P. falciparum </it>isolates resistant to ATQ.</p

Malaria prevalence in Nias District, North Sumatra Province, Indonesia

BACKGROUND: The Nias district of the North Sumatra Province of Indonesia has long been known to be endemic for malaria. Following the economic crisis at the end of 1998 and the subsequent tsunami and earthquake, in December 2004 and March 2005, respectively, the malaria control programme in the area deteriorated. The present study aims to provide baseline data for the establishment of a suitable malaria control programme in the area and to analyse the frequency distribution of drug resistance alleles associated with resistance to chloroquine and sulphadoxine-pyrimethamine.\ud METHODS: Malariometric and entomology surveys were performed in three subdistricts. Thin and thick blood smears were stained with Giemsa and examined under binocular light microscopy. Blood blots on filter paper were also prepared for isolation of parasite and host DNA to be used for molecular analysis of band 3 (SAO), pfcrt, pfmdr1, dhfr, and dhps. In addition, haemoglobin measurement was performed in the second and third surveys for the subjects less than 10 years old.\ud RESULTS: Results of the three surveys revealed an average slide positivity rate of 8.13%, with a relatively higher rate in certain foci. Host genetic analysis, to identify the Band 3 deletion associated with Southeast Asian Ovalocytosis (SAO), revealed an overall frequency of 1.0% among the 1,484 samples examined. One hundred six Plasmodium falciparum isolates from three sub-districts were successfully analysed. Alleles of the dhfr and dhps genes associated with resistance to sulphadoxine-pyrimethamine, dhfr C59R and S108N, and dhps A437G and K540E, were present at frequencies of 52.2%, 82.5%, 1.18% and 1.18%, respectively. The pfmdr1 alleles N86Y and N1042D, putatively associated with mefloquine resistance, were present at 31.4% and 2%, respectively. All but one sample carried the pfcrt 76T allele associated with chloroquine resistance. Entomologic surveys identified three potential anopheline vectors in the area, Anopheles barbirostris, Anopheles kochi and Anopheles sundaicus.\ud CONCLUSION: The cross sectional surveys in three different sub-districts of Nias District clearly demonstrated the presence of relatively stable endemic foci of malaria in Nias District, North Sumatra Province, Indonesia. Molecular analysis of the malaria parasite isolates collected from this area strongly indicates resistance to chloroquine and a growing threat of resistance to sulphadoxine-pyrimethamine. This situation highlights the need to develop sustainable malaria control measures through regular surveillance and proper antimalarial drug deployment

The influence of extra-cellular matrix and stroma remodeling on the productivity of long-term human bone marrow cultures

The stromal cell layer is believed to play an important role in long-term human bone marrow cultures (LTHBMCs). At present, neither the role that the stromal cell extra-cellular matrix (ECM) plays in influencing stroma behavior is well understood nor are the effects of stroma aging. Rapid medium exchanged LTHBMCs were established on surfaces precoated with human natural fibronectin and type 1 rat tail collagen. Although initial adhesion of hematopoietic cells was improved by the presence of both ECMs, the overall progenitor and nonadherent cell productivity was not improved nor did the stroma grow to confluency faster. Thus, the ECMs used did not significantly influence the cell productivity of LTHBMCs. To examine the influence of stromal cell layer aging, conditioned medium was obtained from the first two weeks of LTHBMCs that was subsequently concentrated and used as a medium supplement in a second set of slowly exchanged LTHBMCs. The presence of the concentrated conditioned medium (conCM) enhanced the production of nonadherent cells three-fold compared with control over an eight week culture period. Control cultures that were exposed to conCM after 4 weeks in culture significantly improved their cell productivity during the latter 4 weeks of culture compared with control. The productivity of cultures exposed to conCM for 4 weeks dropped significantly when unsupplemented medium was used for the latter 4 weeks of culture. Interestingly, phytohemagglutin-stimulated leukocyte-conditioned medium stimulated LTHMBCs in a similar fashion, as did conditioned medium from early LTHBMCs. Taken together, these results strongly suggest that the stromal cell layer does produce important factors for active hematopoiesis during its growth to confluence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42613/1/10616_2004_Article_BF00146672.pd

Do parents who smoke underutilize health care services for their children? A cross sectional study within the longitudinal PIAMA study

Background. A higher prevalence of respiratory symptoms and an associated increase in health care utilization among children with parents who smoke is to be expected. From previous studies however, it appears that parents who smoke may underutilize health services for their children, especially with respect to respiratory care. This study explores the validity and generalizability of the previous assumption. Methods. Data were obtained from a Dutch birth-cohort study; the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) project. Information regarding parental smoking, the child's respiratory symptoms and health care use and potential confounders were obtained by postal questionnaires. Multivariate logistic models were used to relate parental smoking to the child's respiratory symptoms and health care use. Results. The study comprised 3,564, 4-year old children. In the crude analysis, respiratory symptoms were more frequent among children with a parent who smoked, while health care utilization for respiratory symptoms was not significantly different between children with or without a parent who smoked. In the multivariate analyses, maternal smoking had a larger impact on the child's respiratory symptoms and health care use as compared to paternal smoking. Maternal smoking was positively associated with mild respiratory symptoms of the child, adjusted odds ratio [AOR] 1.50 (1.19-1.91), but not with severe respiratory symptoms AOR 1.03 (0.75-1.40). Among children with mild respiratory symptoms, children with a mother who smoked were less likely to be taken to the general practitioner (GP) for respiratory symptoms, than children with mothers who did not smoke, AOR 0.58 (0.33-1.01). This finding was less pronounced among children with severe respiratory symptoms AOR 0.86 (0.49-1.52). Neither GP visits for non-respiratory symptoms nor specialized care for respiratory disease were significantly associated with parental smoking. Conclusion. Mothers who smoke appear to underutilize health care for their children with mild respiratory symptoms. Health care workers should be informed about this phenomenon. Inquiring after the respiratory health of the children during regular visits to healthy baby clinics may help to tr

CpG oligonucleotide activates Toll-like receptor 9 and causes lung inflammation in vivo

Background Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-ODN) initiate an innate immune response mediated by the pattern recognition receptor Toll-like receptor 9 (TLR9). This leads in particular to the expression of proinflammatory mediators such as tumor necrosis factor (TNF-alpha) and interleukin-1beta (IL-1beta). TLR9 is expressed in human and murine pulmonary tissue and induction of proinflammatory mediators has been linked to the development of acute lung injury. Therefore, the hypothesis was tested whether CpG-ODN administration induces an inflammatory response in the lung via TLR9 in vivo. Methods Wild-type (WT) and TLR9-deficient (TLR9-D) mice received CpG-ODN intraperitoneally (1668-Thioat, 1 nmol/g BW) and were observed for up to 6 hrs. Lung tissue and plasma samples were taken and various inflammatory markers were measured. Results In WT mice, CpG-ODN induced a strong activation of pulmonary NFKB as well as a significant increase in pulmonary TNF-alpha and IL-1beta mRNA/protein. In addition, cytokine serum levels were significantly elevated in WT mice. Increased pulmonary content of lung myeloperoxidase (MPO) was documented in WT mice following application of CpG-ODN. Bronchoalveolar lavage (BAL) revealed that CpG-ODN stimulation significantly increased total cell number as well as neutrophil count in WT animals. In contrast, the CpG-ODN-induced inflammatory response was abolished in TLR9-D mice. Conclusion This study suggests that bacterial CpG-ODN causes lung inflammation via TLR9

Outdoor particulate matter and childhood asthma admissions in Athens, Greece: a time-series study

<p>Abstract</p> <p>Background</p> <p>Particulate matter with diameter less than 10 micrometers (PM₁₀) that originates from anthropogenic activities and natural sources may settle in the bronchi and cause adverse effects possibly via oxidative stress in susceptible individuals, such as asthmatic children. This study aimed to investigate the effect of outdoor PM₁₀concentrations on childhood asthma admissions (CAA) in Athens, Greece.</p> <p>Methods</p> <p>Daily counts of CAA from the three Children's Hospitals within the greater Athens' area were obtained from the hospital records during a four-year period (2001-2004, n = 3602 children). Mean daily PM₁₀concentrations recorded by the air pollution-monitoring network of the greater Athens area were also collected. The relationship between CAA and PM₁₀concentrations was investigated using the Generalized Linear Models with Poisson distribution and logistic analysis.</p> <p>Results</p> <p>There was a statistically significant (95% CL) relationship between CAA and mean daily PM₁₀concentrations on the day of exposure (+3.8% for 10 μg/m³increase in PM₁₀concentrations), while a 1-day lag (+3.4% for 10 μg/m³increase in PM₁₀concentrations) and a 4-day lag (+4.3% for 10 μg/m³increase in PM₁₀concentrations) were observed for older asthmatic children (5-14 year-old). High mean daily PM₁₀concentration (the highest 10%; >65.69 μg/m³) doubled the risk of asthma exacerbations even in younger asthmatic children (0-4 year-old).</p> <p>Conclusions</p> <p>Our results provide evidence of the adverse effect of PM₁₀on the rates of paediatric asthma exacerbations and hospital admissions. A four-day lag effect between PM₁₀peak exposure and asthma admissions was also observed in the older age group.</p

Analysis of the dihydrofolate reductase-thymidylate synthase gene sequences in Plasmodium vivax field isolates that failed chloroquine treatment

<p>Abstract</p> <p>Background</p> <p>To use pyrimethamine as an alternative anti-malarial drug for chloroquine-resistant malaria parasites, it was necessary to determine the enzyme's genetic variation in dihydrofolate reductase-thymidylate syntase (DHFR-TS) among Korean strains.</p> <p>Methods</p> <p>Genetic variation of <it>dhfr-ts </it>genes of <it>Plasmodium vivax </it>clinical isolates from patients who did not respond to drug treatment (<it>n </it>= 11) in Korea were analysed. The genes were amplified using the polymerase chain reaction (PCR) with genomic DNA as a template.</p> <p>Results</p> <p>Sequence analysis showed that the open reading frame (ORF) of 1,857 nucleotides encoded a deduced protein of 618 amino acids (aa). Alignment with the DHFR-TS genes of other malaria parasites showed that a 231-residue DHFR domain and a 286-residue TS domain were seperated by a 101-aa linker region. This ORF shows 98.7% homology with the <it>P. vivax </it>Sal I strain (XM001615032) in the DHFR domain, 100% in the linker region and 99% in the TS domain. Comparison of the DHFR sequences from pyrimethamine-sensitive and pyrimethamine-resistant <it>P. vivax </it>isolates revealed that nine isolates belonged to the sensitive strain, whereas two isolates met the criteria for resistance. In these two isolates, the amino acid at position 117 is changed from serine to asparagine (S117N). Additionally, all Korean isolates showed a deletion mutant of THGGDN in short tandem repetitive sequences between 88 and 106 amino acid.</p> <p>Conclusions</p> <p>These results suggest that sequence variations in the DHFR-TS represent the prevalence of antifolate-resistant <it>P. vivax </it>in Korea. Two of 11 isolates have the Ser to Asn mutation in codon 117, which is the major determinant of pyrimethamine resistance in <it>P. vivax</it>. Therefore, the introduction of pyrimethamine for the treatment of chloroquine-resistant vivax malaria as alternative drug in Korea should be seriously considered.</p