bluuebunny/crossref_metadata_2025 huggingface dataset:
Signatures of slope failures and river‐delta collapses in a perialpine lake (Lake Lucerne, Switzerland)
Authors: Hilbe Michael , Anselmetti Flavio S.
Published: March 2014

Historical reports from the 17th Century document two destructive tsunamis with run‐ups exceeding 5 m, affecting proximal basins of Lake Lucerne (Switzerland). One event in ad 1601 is coeval with a strong nearby earthquake (MW ca 5·9) which caused extensive slope failures in many parts of the lake. The second event in ad 1687 is associated with an apparently spontaneous partial collapse of the Muota river delta. This study combines high‐resolution bathymetry, reflection seismic and lithological data to document the sedimentary and morphological signatures of the two subaqueous mass movements that probably generated the observed tsunamis. Such mass movements are significant as a common sedimentation process and as a natural hazard in fjord‐type lakes and similar environments. The deposits, covering large parts of the basins with thicknesses reaching >10 m, consist of two subunits: A lower ‘massflow deposit’ contains variably deformed sediments from the source areas. Its emplacement affected pre‐existing sediments, incorporating thin sediment slices into the deposit and increasing its volume. Deep‐reaching deformation near basin margins is expressed as bulges on the lake floor. An overlying ‘megaturbidite’, featuring a graded, sandy base and a thick homogeneous muddy part, was deposited from suspended particles. The source area for the ad 1601 event, gently dipping lateral slopes with an unconsolidated hemipelagic sediment cover, hosts a pronounced slide scar with sharp escarpments and sliding surfaces. The source area for the ad 1687 event on an active delta slope has been overprinted by continued sedimentation and does not show an unambiguous scar. The case studies are exemplary for end‐member types of source areas (lateral versus delta slopes) and trigger mechanisms (seismic versus aseismic); they show that morphological mapping and reconstructions of past events are key components of a hazard assessment for mass movement‐generated tsunamis.
Spatial distribution of dust deposition within a small drainage basin: Implications for loess deposits in the Negev Desert
Authors: Kidron Giora J. , Zohar Motti , Starinsky Abraham
Published: March 2014

Loessial colluvial sediments and aeolian aprons are common deposits in the Negev Desert Highlands. In an attempt to monitor the amounts and distributional pattern of loess, monthly dust measurements were carried out during 2004 to 2006 in 10 cm diameter traps located at 18 stations along four slopes, north‐facing, south‐facing, east‐facing and west‐facing in a second‐order drainage basin near Sede Boqer, Negev Desert Highlands, Israel. Annual total dust depositions ranged between 110 g and 178 g m−2 with an average of 151·1 g m−2. The average annual dust deposition in the catchment was 23·5% higher than the average amount recorded at the hilltops (122·4 g m−2) and may be a consequence of sheltering opportunities in the hilly topography. When analysed according to season and aspect, significantly higher monthly amounts were received during the wet rainy season of December to March (17·0 g m−2), in comparison with the rest of the year (8·1 g m−2). As for the aspect, while no significant differences characterized north‐facing and south‐facing slopes, east‐facing slopes received significantly higher amounts (by 43·3%) than west‐facing slopes, pointing to preferential dust deposition at the leeward slope. Concurring with the classical model that anticipates higher dust deposition at the leeside slope, but in disagreement with some reports published in the literature, the findings of this study were also supported by a field survey that showed preferential loess accumulation at the eastern and north‐eastern aspects. These findings may shed light on distributional patterns of colluvial sediments and aeolian aprons in the Negev, on soil‐forming processes and on past cycles of dust deposition.
Planform architecture, stratigraphic signature and morphodynamics of an exhumed Jurassic meander plain (Scalby Formation, Yorkshire, UK)
Authors: Ielpi Alessandro , Ghinassi Massimiliano
Published: March 2014

Modern fluvial meander plains exhibit complex planform transformations in response to meander‐bend expansion, downstream migration and rotation. These transformations exert a fundamental control on lithology and reservoir properties, yet their stratigraphic record has been poorly evaluated in ancient examples due to the lack of extensive three‐dimensional exposures. Here, a unique exhumed meander plain exposed to the north of Scarborough (Yorkshire, UK) is analysed in terms of architecture and morphodynamics, with the aim of developing a comprehensive model of facies distribution. The studied outcrop comprises tidal platforms and adjacent cliffs, where the depositional architecture of un‐tilted deposits was assessed on planform and vertical sections, respectively. In its broader perspective, this study demonstrates the potential of architectural mapping of extensive planform exposures for the reconstruction of ancient fluvial morphodynamics. The studied exhumed meander plain is part of the Scalby Formation of the Ravenscar Group, and originally drained small coastal incised valleys within the Jurassic Cleveland Basin. The meander plain is subdivided into two storeys that contain in‐channel and overbank architectural elements. In‐channel elements comprise expansional and downstream‐migrating point bars, point‐bar tails and channel fills. Overbank elements comprise crevasse complexes, levées, floodplain fines and lake fills. The evolution of the point bars played a significant role in dictating preserved facies distributions, with high flood‐stage nucleation and accretion of meander scrolls later reworked during waning flood‐stages. At a larger scale, meander belt morphodynamics were also a function of valley confinement and contrasts in substrate erodibility. Progressive valley infilling decreased the valley confinement, promoting the upward transition from prevalently downstream migrating to expansional meander belts, a transition associated with enhanced preservation of overbank elements. Strikingly similar relations between valley confinement, meander‐bend transformations and overbank preservation are observed in small modern meandering streams such as the Beaver River of the Canadian prairies and the Powder River of Montana (USA).
Viscoelastic response of the lateral side of the ankle to cyclic inversion: A time course analysis
Authors: Malmir K. , Olyaei G. R. , Talebian S. , Jamshidi A. A.
Published: March 2014

Although important, viscoelastic behavior of the ankle's lateral side has rarely been studied. The present study assesses the viscoelastic behavior during cyclic inversions. Eighteen recreationally active healthy males underwent 40 passive cyclic inversions using a Biodex dynamometer at 5 °/s through 80% of maximum range of motion. Energy absorption and restitution and dissipation coefficient were calculated for each repetition. Changes in the mean of the dependent variables for repetitions 1 (R1), R5, R10, R15, R20, R25, R30, R35 and R40 were compared by three one‐way analyses of variance with repeated measures. There was a significant difference between the means of energy absorption for the selected repetitions from R1 to R20 (P < 0.01), but there was no significant difference between them from R20 to R40 (P > 0.05). There was no significant difference between the means of energy restitution for the selected repetitions (P > 0.05). Whereas there was no significant difference consecutively between the means of dissipative coefficient for the selected repetitions (P > 0.05), there was a significant difference between the means of R30 or R40 relative to the baseline (P < 0.005). The decrease in the energy absorbed and the dissipation coefficient following repeated inversions may be due to the slippage of collagen fibers. The decrease in the shock absorbing ability of the tissues may expose them to injury.
HLA‐alleles associated with increased risk for extra‐pulmonary involvement in sarcoidosis
Authors: Darlington P. , Gabrielsen A. , Sörensson P. , Tallstedt L. , Padyukov L. , Eklund A. , Grunewald J.
Published: March 2014

Genetic factors influence the risk for disease as well as the clinical picture seen in sarcoidosis and especially the genes localized to the human leukocyte antigen (HLA) region on chromosome 6 are of importance. The aim of this study was to further investigate associations between HLA‐DRB1 alleles and the risk for extra‐pulmonary manifestations (EPMs), i.e. engagement of the skin, superficial lymph nodes, eyes, nervous system, kidneys, hypercalcemia, parotid and salivary glands, heart, liver, spleen and bone marrow in Scandinavian sarcoidosis patients. One thousand patients with together with a group of 2000 healthy individuals, matched for sex and age. HLA‐DRB1 alleles were determined for all patients and controls. Excluding erythema nodosum and ankle arthritis, we found 288 of 1000 patients to have EPMs. There were 383 patients with Löfgren's syndrome (LS), and among them EPM were relatively uncommon and diagnosed in only 31 (8.1%) of the patients. In contrast, among the 617 non‐LS patients, 257 (41.6%) had EPM (P < 0.0001). In LS patients, the absence of HLA‐DRB1*03 substantially increased the risk factor for EPM (erythema nodosum and ankle arthritis excluded) (P < 0.0001). A distinct HLA allele combination, HLA‐DRB1*04/*15, was identified as a risk factor for EPM in all patients (25 of 50 with DRB1*04/15 had EPM). In conclusion, EPM are common in non‐LS sarcoidosis. Furthermore, HLA‐typing of sarcoidosis patients can be used in the clinic to identify patients with an increased risk for EPM.
Tumor antigen‐specific CD4+ T cells in cancer immunity: from antigen identification to tumor prognosis and development of therapeutic strategies
Authors: Protti M. P. , Monte L. D. , Lullo G. D.
Published: March 2014

CD4+ T cells comprise a large fraction of tumor infiltrating lymphocytes and it is now established that they may exert an important role in tumor immune‐surveillance. Several CD4+ T cell subsets [i.e. T helper (Th)1, Th2, T regulatory (Treg), Th17, Th22 and follicular T helper (Tfh)] have been described and differentiation of each subset depends on both the antigen presenting cells responsible for its activation and the cytokine environment present at the site of priming. Tumor antigen‐specific CD4+ T cells with different functional activity have been found in the blood of cancer patients and different CD4+ T cell subsets have been identified at the tumor site by the expression of specific transcription factors and the profile of secreted cytokines. Importantly, depending on the subset, CD4+ T cells may exert antitumor versus pro‐tumor functions. Here we review the studies that first identified the presence of tumor‐specific CD4+ T cells in cancer patients, the techniques used to identify the tumor antigens recognized, the role of the different CD4+ T cell subsets in tumor immunity and in cancer prognosis and the development of therapeutic strategies aimed at activating efficient antitumor CD4+ T cell effectors.
Growth of accretionary wedges and pulsed ophiolitic mélange formation by successive subduction of trench‐parallel volcanic elevations
Authors: Hajná Jaroslava , Žák Jiří , Kachlík Václav
Published: March 2014

Fault‐bounded coherent belts alternating with belts of mélanges are common in accretionary wedges and are usually interpreted as a result of imbrication along subduction zone megathrusts. Using the Neoproterozoic/early Cambrian Blovice accretionary complex (BAC), Bohemian Massif, as a case example, we present a new model for the origin of alternating belts through the repetition of several cycles of (1) offscraping and deformation of trench‐fill sediments to form the coherent units, interrupted by (2) arrival and subduction of linear, trench‐parallel volcanic elevations. The latter process leads to an increase in the wedge taper, triggering mass‐wasting and formation of olistostromes. At the same time, ophiolitic mélanges form by disruption of an upper part of the volcanic ridge and incorporation of the disrupted ocean‐floor succession into the olistostromes. Specifically, the BAC represents a complete section across an accretionary wedge and records three such major pulses of ophiolitic mélange formation through subduction of an outboard back‐arc basin.
Toys and toilets: cross‐sectional study using children's toys to evaluate environmental faecal contamination in rural Bangladeshi households with different sanitation facilities and practices
Authors: Vujcic Jelena , Ram Pavani K. , Hussain Faruqe , Unicomb Leanne , Gope Partha Sarathi , Abedin Jaynal , Mahmud Zahid Hayat , Sirajul Islam M. , Luby Stephen P.
Published: March 2014

Objective

To evaluate household faecal contamination using children's toys among 100 rural Bangladeshi households categorised as ‘cleaner’ (toilet that reliably separates faeces from the environment and no human faeces in/around living space) or ‘less clean’ (no toilet or toilet that does not reliably separate faeces from the environment and human faeces in/around living space).

Methods

We distributed toy balls to each household and rinsed each study toy and a toy already owned by the household in 200 ml of Ringer's solution. We enumerated faecal coliforms and faecal streptococci from each rinse using membrane filtration methods.

Results

Study toys from 39 cleaner households had lower mean faecal coliform contamination than toys from 61 less clean households (2.4 log10 colony‐forming units (CFU)/200 ml vs. 3.2 log10 CFU/200 ml, P = 0.03). However, wealth measures explained a portion of this relationship. Repeat measures were moderately variable [coefficient of variation (CV) = 6.5 between two toys in the household at the same time, CV = 37.6 between toys in the household at two different times 3–4 days apart]. Too few households owned a non‐porous toy to compare groups without risk of bias.

Conclusion

In rural Bangladesh, improved sanitation facilities and practices were associated with less environmental contamination. Whether this association is independent of household wealth and whether the difference in contamination improves child health merit further study. The variation found was typical for measures of environmental contamination, and requires large sample sizes to ascertain differences between groups with statistical significance.
Foreign Ownership and the Extensive Margins of Exports: Evidence for Manufacturing Enterprises in Germany
Authors: Raff Horst , Wagner Joachim
Published: March 2014

We examine how foreign ownership of a firm affects the variety of goods that the firm exports and the number of countries it trades with. We construct a simple theoretical model of how foreign ownership may affect these extensive margins of exports and take this model to data from Germany, one of the leading actors on the world market for goods. In line with theoretical predictions we find that foreign‐owned firms do export more goods to more countries after controlling for firm size, productivity and industry affiliation. These differences between foreign‐owned firms and domestically controlled firms are highly statistically significant, and they are large from an economic point of view, with foreign‐owned firms exporting up to 39 per cent more goods to up to 31 per cent more countries.
Internal and External Knowledge and Introduction of Export Varieties
Authors: Johansson Börje , Johansson Sara , Wallin Tina
Published: March 2014

Firms in local industries maintain their capability to generate new export varieties by simultaneously exploiting internal and external knowledge resources. The paper introduces the notion ‘variety triplet’ to distinguish individual export varieties, where a triplet is a unique combination of a firm, a product code and a destination country. For each date, the set of variety triplets in each local industry records all remaining export varieties introduced in the past. In view of this, the paper examines how internal and external knowledge of local industries influence the industry's scope and value of export varieties. First, the paper contributes by considering a local industry's internal and external knowledge, as well as the conjunction of its internal and external knowledge sources. Second, the knowledge sources are shown to influence both the stock and the dynamics of a local industry's variety triplets, using firm‐level data from Sweden.
Study of Far-Field Pyroshock Responses of Composite Panels
Authors: Velmurugan R. , Mohamed Najeeb E.
Published: March 2014

The experimental and numerical studies on far-field pyroshock responses of composite panels are presented in this paper. The purpose of this study is to find out the region of composite panel where the pyroshock response is high and thereby the panel can be used as a testing bed to examine tiny elements such as electronic parts used in spacecraft. Experiments based on bi-plate technology are conducted on different combination of e-glass/epoxy composite panel parameters. The structural responses are analyzed using panel parameters as well as shock response spectrums (SRSs) computed from the acceleration-time histories. The experiments are carried out for a low range of chamber pressure with projectiles of varying length to get the far-field response of the test panel. The accelerations of the panel at selected locations are measured by the PCB Piezotronics (Depew, NY) accelerometers and National Instruments-Data Acquisition (NI-DAQ) system (National Instruments, Austin, TX) with labview software. Finite element analysis (FEA) for the pyroshock environment is done using abaqus/Explicit software. Due to the symmetry of the structure as well as the loading, only quarter portion of the panel is analyzed. From the results, it is found that acceleration increases as thickness of composite test panel increases (about 20–70%) for all the combinations of projectile length and chamber pressure at all the points considered on the laminate. Transfer of acceleration from steel plate onto composite panel through physical connections is predominant (about 90–95% of total transfer) than that through air media between the steel plate and the composite panel. Velocity with lower momentum induces lower frequency modes to be dominant whereas velocity with higher momentum induces higher frequency modes. Normally higher accelerations (about 40–90%) are experienced at the center location than any other locations under consideration. The SRSs are obtained both from FEA and experiments. The experimental study shows good agreement with the FEA results both in acceleration time history as well as in SRS.
Modeling Developmental Changes in the Yo-Yo Intermittent Recovery Test Level 1 in Elite Pubertal Soccer Players
Authors: Deprez Dieter , Valente-dos-Santos Joao , e Silva Manuel Coelho , Lenoir Matthieu , Philippaerts Renaat M. , Vaeyens Roel
Published: March 2014

Purpose:

To model the development of soccer-specific aerobic performance, assessed by the Yo-Yo Intermittent Recovery Test Level 1 in 162 elite pubertal soccer players, age 11–14 y at baseline.

Methods:

Longitudinal multilevel modeling analyses comprised predictors related to growth (chronological age, body size [height and weight] and composition [fat mass, fat-free mass]), and motor coordination [3 Körperkoordination Test für Kinder subtests: jumping sideways, moving sideways, backward balancing] and estimated biological-maturation groups (earliest [>percentile 33] and latest maturers [>percentile 66]).

Results:

The best-fitting model on soccer-specific aerobic performance could be expressed as –3639.76 + 369.86 × age + 21.38 × age2 + 9.12 × height – 29.04 × fat mass + 0.06 × backward balance. Maturity groups had a negligible effect on soccer-specific aerobic performance (–45.32 ± 66.28; P > .05).

Conclusion:

The current study showed that the development of aerobic performance in elite youth soccer is related to growth and muscularity and emphasized the importance of motor coordination in the talentidentification and -development process. Note that biological maturation was excluded from the model, which might endorse the homogeneity in estimated biological-maturation status in the current elite pubertal soccer sample.
Responses to Exercise in Normobaric Hypoxia: Comparison of Elite and Recreational Ski Mountaineers
Authors: Faiss Raphael , von Orelli Claudia , Dériaz Olivier , Millet Grégoire P.
Published: March 2014

Purpose:

Hypoxia is known to reduce maximal oxygen uptake (VO2max) more in trained than in untrained subjects in several lowland sports. Ski mountaineering is practiced mainly at altitude, so elite ski mountaineers spend significantly longer training duration at altitude than their lower-level counterparts. Since acclimatization in hypobaric hypoxia is effective, the authors hypothesized that elite ski mountaineers would exhibit a VO2max decrement in hypoxia similar to that of recreational ski mountaineers.

Methods:

Eleven elite (E, Swiss national team) and 12 recreational (R) ski mountaineers completed an incremental treadmill test to exhaustion in normobaric hypoxia (H, 3000 m, FIO2 14.6% ± 0.1%) and in normoxia (N, 485 m, FIO2 20.9% ± 0.0%). Pulse oxygen saturation in blood (SpO2), VO2max, minute ventilation, and heart rate were recorded.

Results:

At rest, hypoxic ventilatory response was higher (P < .05) in E than in R (1.4 ± 1.9 vs 0.3 ± 0.6 L · min−1 · kg−1). At maximal intensity, SpO2 was significantly lower (P < .01) in E than in R, both in N (91.1% ± 3.3% vs 94.3% ± 2.3%) and in H (76.4% ± 5.4% vs 82.3% ± 3.5%). In both groups, SpO2 was lower (P < .01) in H. Between N and H, VO2max decreased to a greater extent (P < .05) in E than in R (–18% and –12%, P < .01). In E only, the VO2max decrement was significantly correlated with the SpO2 decrement (r = .74, P < .01) but also with VO2max measured in N (r = .64, P < .05).

Conclusion:

Despite a probable better acclimatization to altitude, VO2max was more reduced in E than in R ski mountaineers, confirming previous results observed in lowlander E athletes.
The A4 Study: Stopping AD Before Symptoms Begin?
Authors: Sperling Reisa A. , Rentz Dorene M. , Johnson Keith A. , Karlawish Jason , Donohue Michael , Salmon David P. , Aisen Paul
Published: March 2014

A new secondary prevention trial in older people with amyloid accumulation at high risk for Alzheimer’s disease dementia should provide insights into whether anti-amyloid therapy can delay cognitive decline.
The Last Line of Defense Against Atherosclerosis
Authors: Voora Deepak
Published: March 2014

The miRNA miR-126 protects against atherosclerosis by promoting a healthy endothelium.
Salmonella enterica Serovar Typhi Impairs CD4 T Cell Responses by Reducing Antigen Availability
Authors: Atif Shaikh M. , Winter Sebastian E. , Winter Maria G. , McSorley Stephen J. , Bäumler Andreas J.
Published: March 2014

Salmonella entericaserovar Typhi is associated with a disseminated febrile illness in humans, termed typhoid fever, whileSalmonella entericaserovar Typhimurium causes localized gastroenteritis in immunocompetent individuals. One of the genetic differences between both pathogens is the presence inS. Typhi of TviA, a regulatory protein that shuts down flagellin (FliC) expression when bacteria transit from the intestinal lumen into the intestinal mucosa. Here we investigated the consequences of TviA-mediated flagellum gene regulation on flagellin-specific CD4 T cell responses in a mouse model ofS. Typhimurium infection. Introduction of theS. TyphitviAgene intoS. Typhimurium suppressed antigen presentation of dendritic cells to flagellin-specific CD4 T cellsin vitro. Furthermore, TviA-mediated repression of flagellin expression impaired the activation and proliferation of naive flagellin-specific CD4 T cells in Peyer's patches and mesenteric lymph nodes, which was accompanied by increased bacterial dissemination to the spleen. We conclude that TviA-mediated repression of flagellin expression reduces antigen availability, thereby weakening flagellin-specific CD4 T cell responses.
EspC Promotes Epithelial Cell Detachment by Enteropathogenic Escherichia coli via Sequential Cleavages of a Cytoskeletal Protein and then Focal Adhesion Proteins
Authors: Navarro-Garcia Fernando , Serapio-Palacios Antonio , Vidal Jorge E. , Salazar M. Isabel , Tapia-Pastrana Gabriela
Published: March 2014

EspC is a non-locus of enterocyte effacement (LEE)-encoded autotransporter produced by enteropathogenic
Escherichia coli
(EPEC) that is secreted to the extracellular milieu by a type V secretion system and then translocated into epithelial cells by the type III secretion system. Here, we show that this efficient EspC delivery into the cell leads to a cytopathic effect characterized by cell rounding and cell detachment. Thus, EspC is the main protein involved in epithelial cell cytotoxicity detected during EPEC adhesion and pedestal formation assays. The cell detachment phenotype is triggered by cytoskeletal and focal adhesion disruption. EspC-producing EPEC is able to cleave fodrin, paxillin, and focal adhesion kinase (FAK), but these effects are not observed when cells are infected with an
espC
isogenic mutant. Recovery of these phenotypes by complementing the mutant with the
espC
gene but not with the
espC
gene mutated in the serine protease motif highlights the role of the protease activity of EspC in the cell detachment phenotype.
In vitro
assays using purified proteins showed that EspC, but not EspC with an S256I substitution [EspC
S256I
], directly cleaves these cytoskeletal and focal adhesion proteins. Kinetics of protein degradation indicated that EspC-producing EPEC first cleaves fodrin (within the 11th and 9th repetitive units at the Q1219 and D938 residues, respectively), and this event sequentially triggers paxillin degradation, FAK dephosphorylation, and FAK degradation. Thus, cytoskeletal and focal adhesion protein cleavage leads to the cell rounding and cell detachment promoted by EspC-producing EPEC.
Induction of Bacterial Antigen-Specific Colitis by a Simplified Human Microbiota Consortium in Gnotobiotic Interleukin-10
−/−
Mice
Authors: Eun Chang Soo , Mishima Yoshiyuki , Wohlgemuth Steffen , Liu Bo , Bower Maureen , Carroll Ian M. , Sartor R. Balfour
Published: March 2014

We evaluated whether a simplified human microbiota consortium (SIHUMI) induces colitis in germfree (GF) 129S6/SvEv (129) and C57BL/6 (B6) interleukin-10-deficient (IL-10
−/−
) mice, determined mouse strain effects on colitis and the microbiota, examined the effects of inflammation on relative bacterial composition, and identified immunodominant bacterial species in “humanized” IL-10
−/−
mice. GF wild-type (WT) and IL-10
−/−
129 and B6 mice were colonized with 7 human-derived inflammatory bowel disease (IBD)-related intestinal bacteria and maintained under gnotobiotic conditions. Quantification of bacteria in feces, ileal and colonic contents, and tissues was performed using 16S rRNA gene selective quantitative PCR. Colonic segments were scored histologically, and gamma interferon (IFN-γ), IL-12p40, and IL-17 levels were measured in supernatants of unstimulated colonic tissue explants and of mesenteric lymph node (MLN) cells stimulated by lysates of individual or aggregate bacterial strains. Relative bacterial species abundances changed over time and differed between 129 and B6 mice, WT and IL-10
−/−
mice, luminal and mucosal samples, and ileal and colonic or fecal samples. SIHUMI induced colitis in all IL-10
−/−
mice, with more aggressive colitis and MLN cell activation in 129 mice.
Escherichia coli
LF82 and
Ruminococcus gnavus
lysates induced dominant effector
ex vivo
MLN TH1 and TH17 responses, although the bacterial mucosal concentrations were low. In summary, this study shows that a simplified human bacterial consortium induces colitis in ex-GF 129 and B6 IL-10
−/−
mice. Relative concentrations of individual SIHUMI species are determined by host genotype, the presence of inflammation, and anatomical location. A subset of IBD-relevant human enteric bacterial species preferentially stimulates bacterial antigen-specific TH1 and TH17 immune responses in this model, independent of luminal and mucosal bacterial concentrations.
The Iron-Sensing Fur Regulator Controls Expression Timing and Levels of Salmonella Pathogenicity Island 2 Genes in the Course of Environmental Acidification
Authors: Choi Eunna , Kim Hyunkeun , Lee Hwiseop , Nam Daesil , Choi Jeongjoon , Shin Dongwoo
Published: March 2014

In order to survive inside macrophages,
Salmonella
produces a series of proteins encoded by genes within
Salmonella
pathogenicity island 2 (SPI-2). In the present study, we report that Fur, a central regulator of iron utilization, negatively controls the expression of SPI-2 genes. Time course analysis of SPI-2 expression after the entry of
Salmonella
into macrophages revealed that SPI-2 genes are induced earlier and at higher levels in the absence of the Fur regulator. It was hypothesized that Fur repressed the SPI-2 expression that was activated during acidification of the phagosome. Indeed, as pH was lowered from pH 7.0 to pH 5.5, the lack of Fur enabled SPI-2 gene expression to be induced at higher pH and to be expressed at higher levels. Fur controlled SPI-2 genes via repression of the SsrB response regulator, a primary activator of SPI-2 expression. Fur repressed
ssrB
expression both inside macrophages and under acidic conditions, which we ascribe to the direct binding of Fur to the
ssrB
promoter. Our study suggests that
Salmonella
could employ iron inside the phagosome to precisely control the timing and levels of SPI-2 expression inside macrophages.
Sialic Acid Residues Are Essential for Cell Lysis Mediated by Leukotoxin from Aggregatibacter actinomycetemcomitans
Authors: Munksgaard Peter Svenssen , Skals Marianne , Reinholdt Jesper , Poulsen Knud , Jensen Maria Risager , Yang Chuanxu , Leipziger Jens , Vorup-Jensen Thomas , Praetorius Helle A.
Published: March 2014

Leukotoxin (LtxA) fromAggregatibacter actinomycetemcomitansis known to target and lyse β2-integrin-expressing cells such as polymorphonuclear leukocytes and macrophages. LtxA is an important virulence factor that facilitates chronic inflammation and is strongly associated with a fast-progressing form of periodontitis caused by the JP2 clone of the bacterium. Here, we show that sialic acid residues are important for LtxA-induced cell lysis, regardless of whether the cell express β2-integrin or not. Clearly, removal of sialic acid groups significantly reduces a β2-integrin-specific LtxA-induced lysis. Moreover, sialic acid presented on alternative proteins, such as, for instance, on erythrocytes that do not express β2-integrin, also makes the cells more sensitive to LtxA. The data also illustrate the importance of the negative charge in order for the sialic acid to associate LtxA with the membrane. Removal of sialic acid is in itself sufficient to significantly reduce the negative charge on the erythrocytes. Moreover, we found that on human erythrocytes there is a positive association between the sensitivity to LtxA and the amount of negative charge caused by sialic acid. Interestingly, these features are not shared by all RTX toxins, since α-hemolysin fromEscherichia coliinduced cell lysis of both β2-integrin-expressing and nonexpressing cells and this lysis is independent of the presence of sialic acid residues. In conclusion, LtxA not only is cytotoxic to β2-integrin-expressing cells but can potentially initiate cell lysis in all cells that present a sufficient density of sialic acid groups on their plasma membrane.
Vesiculovirus Neutralization by Natural IgM and Complement
Authors: Tesfay Mulu Z. , Ammayappan Arun , Federspiel Mark J. , Barber Glen N. , Stojdl David , Peng Kah-Whye , Russell Stephen J.
Published: March 2014

Because of its very low human seroprevalence, vesicular stomatitis virus (VSV) has promise as a systemic oncolytic agent for human cancer therapy. However, as demonstrated in this report, the VSV infectious titer drops by 4 log units during the first hour of exposure to nonimmune human serum. This neutralization occurs relatively slowly and is mediated by the concerted actions of natural IgM and complement. Maraba virus, whose G protein is about 80% homologous to that of VSV, is relatively resistant to the neutralizing activity of nonimmune human serum. We therefore constructed and rescued a recombinant VSV whose G gene was replaced by the corresponding gene from Maraba virus. Comparison of the parental VSV and VSV with Maraba G substituted revealed nearly identical host range properties and replication kinetics on a panel of tumor cell lines. Moreover, in contrast to the parental VSV, the VSV with Maraba G substituted was resistant to nonimmune human serum. Overall, our data suggest that VSV with Maraba G substituted should be further investigated as a candidate for human systemic oncolytic virotherapy applications.

IMPORTANCEOncolytic virotherapy is a promising approach for the treatment of disseminated cancers, but antibody neutralization of circulating oncolytic virus particles remains a formidable barrier. In this work, we developed a pseudotyped vesicular stomatitis virus (VSV) with a glycoprotein of Maraba virus, a closely related but serologically distinct member of the familyRhabdoviridae, which demonstrated greatly diminished susceptibility to both nonimmune and VSV-immune serum neutralization. VSV with Maraba G substituted or lentiviral vectors should therefore be further investigated as candidates for human systemic oncolytic virotherapy and gene therapy applications.
Brevibacterium caseiisolated as a cause of relapsing peritonitis
Authors: Althaf Mohammed Mahdi , Abdelsalam Mohamed Said , Alsunaid Mohammed Sunaid , Hussein Maged Hassan
Published: March 2014

We report a case of relapsing peritonitis in a 33-year-old woman on automated peritoneal dialysis. End-stage renal disease was secondary to systemic lupus erythematosus complicated with lupus nephritis. The organism isolated wasBrevibacterium caseithat was not readily identified, delaying appropriate management with an extended antibiotic course. Definite management ofB caseiperitonitis was peritoneal dialysis catheter removal.
Acute respiratory failure in a 35-year-old woman following preterm vaginal delivery
Authors: Bhandari H M , Gorecha M , Woodman J
Published: March 2014

A 35-year-old woman, a non-smoker with a normal body mass index, ‘felt wheezy’ and developed profound hypoxia 30 min after preterm vaginal delivery at 24+ weeks of gestation. She denied other symptoms, had no fever but was tachycardic and tachypnoeic with normal blood pressure. Pulmonary embolism, amniotic fluid embolism, cardiomyopathy, arrhythmias, sepsis and non-cardiogenic pulmonary oedema were considered as differential diagnoses. Chest X-ray showed an increased pulmonary vasculature, but the blood tests, ECG, echocardiogram and CT pulmonary angiogram were essentially normal. She was managed on a high dependency area with high-flow oxygen and intravenous antibiotics. She improved dramatically and the oxygen requirements dropped to 2 L over the next 4 h. It is plausible that this woman had acute non-cardiogenic pulmonary oedema secondary to a combination of risk factors. This case highlights the importance of a methodical and multidisciplinary approach for a prompt diagnosis and successful treatment of an acutely ill parturient.
A case of asymptomatic renal pseudoaneurysm post partial nephrectomy treated successfully
Authors: Jalil Rozh , Mohamed Omar , Webster Jeff
Published: March 2014

Pseudoaneurysm remains one of the rare complications of partial nephrectomy with reported rates of 0.4–1.4%. We add to the literature a case of asymptomatic pseudoaneurysm post laparoscopic partial nephrectomy (LPN) that was successfully treated with embolisation.
A forensic perspective of the AFL investigation into peptides: an antidoping investigation case study
Authors: Harcourt Peter Rex , Marclay Francois , Clothier Brett
Published: March 2014

Background

The World Anti-Doping Agency (WADA) is introducing enhancements to doping investigations in its 2015 Code, which include improved sharing of information between antidoping organisations (including sporting bodies) and enhanced accountability of athlete support staff. These additions will improve the control of links between sports doping and organised crime. In February 2013 the Australian Crime Commission released a report that linked several professional sporting codes, professional athletes with links to organised crime, performance enhancing drugs and illicit substances. Following this report the Australian Football League (AFL) partnered the Australian national antidoping organisation to investigate peptide use in Australian football.

Methods

This review compared the model proposed by Marclay, a hypothetical model for anti-doping investigations that proposed a forensic intelligence and analysis approach, to use the forensic capabilities of the AFL investigation to test the model's relevance to an actual case.

Results

The investigation uncovered the use of peptides used to enhance athlete performance. The AFL investigation found a high risk of doping where athlete support staff existed in teams with weak corporate governance controls. A further finding included the need for the investigation to provide a timely response in professional team sports that were sensitive to the competition timing. In the case of the AFL the team was sanctioned prior to the finals as an interim outcome for allowing the risk of use of performance-enhancing substances. Doping violation charges are still being considered.

Discussion

Antidoping strategies should include the investigation of corporate officers in team doping circumstances, the mandatory recording of all athlete substance use during competition and training phases, the wider sharing of forensic intelligence with non-sporting bodies particularly law enforcement and collaboration between antidoping and sporting organisations in doping investigations.

Conclusions

The AFL investigation illustrated the importance of the 2015 WADA Code changes and highlighted the need for a systematic use of broad forensic intelligence activities in the investigation of doping violations.
Machine-learning prediction of cancer survival: a retrospective study using electronic administrative records and a cancer registry
Authors: Gupta Sunil , Tran Truyen , Luo Wei , Phung Dinh , Kennedy Richard Lee , Broad Adam , Campbell David , Kipp David , Singh Madhu , Khasraw Mustafa , Matheson Leigh , Ashley David M , Venkatesh Svetha
Published: March 2014

Objectives

Using the prediction of cancer outcome as a model, we have tested the hypothesis that through analysing routinely collected digital data contained in an electronic administrative record (EAR), using machine-learning techniques, we could enhance conventional methods in predicting clinical outcomes.

Setting

A regional cancer centre in Australia.

Participants

Disease-specific data from a purpose-built cancer registry (Evaluation of Cancer Outcomes (ECO)) from 869 patients were used to predict survival at 6, 12 and 24 months. The model was validated with data from a further 94 patients, and results compared to the assessment of five specialist oncologists. Machine-learning prediction using ECO data was compared with that using EAR and a model combining ECO and EAR data.

Primary and secondary outcome measures

Survival prediction accuracy in terms of the area under the receiver operating characteristic curve (AUC).

Results

The ECO model yielded AUCs of 0.87 (95% CI 0.848 to 0.890) at 6 months, 0.796 (95% CI 0.774 to 0.823) at 12 months and 0.764 (95% CI 0.737 to 0.789) at 24 months. Each was slightly better than the performance of the clinician panel. The model performed consistently across a range of cancers, including rare cancers. Combining ECO and EAR data yielded better prediction than the ECO-based model (AUCs ranging from 0.757 to 0.997 for 6 months, AUCs from 0.689 to 0.988 for 12 months and AUCs from 0.713 to 0.973 for 24 months). The best prediction was for genitourinary, head and neck, lung, skin, and upper gastrointestinal tumours.

Conclusions

Machine learning applied to information from a disease-specific (cancer) database and the EAR can be used to predict clinical outcomes. Importantly, the approach described made use of digital data that is already routinely collected but underexploited by clinical health systems.
Prevalence of obesity in attention-deficit/hyperactivity disorder: study protocol for a systematic review and meta-analysis
Authors: Cortese Samuele , Moreira Maia Carlos Renato , Rohde Luis Augusto , Morcillo-Peñalver Carmen , Faraone Stephen V
Published: March 2014

Introduction

An increasing number of clinical and epidemiological studies suggest a possible association between attention-deficit/hyperactivity disorder (ADHD) and obesity/overweight. However, overall evidence is mixed. Given the public health relevance of ADHD and obesity/overweight, understanding whether and to what extent they are associated is paramount to plan intervention and prevention strategies. We describe the protocol of a systematic review and meta-analysis aimed at assessing the prevalence of obesity/overweight in individuals with ADHD versus those without ADHD.

Methods and analysis

We will include studies of any design (except case reports or case series) comparing the prevalence of obesity and/or overweight in children or adults with and without ADHD (or hyperkinetic disorder). We will search an extensive number of databases including PubMed, Ovid databases, Web of Knowledge and Thomson-Reuters databases, ERIC and CINAHL. No restrictions of language will be applied. We will also contact experts in the field for possible unpublished or in press data. Primary and additional outcomes will be the prevalence of obesity and overweight, respectively. We will combine ORs using random-effects models in STATA V.12.0. The quality of the study will be assessed primarily using the Newcastle-Ottawa Scale. Subgroup meta-analyses will be conducted according to participants’ age (children vs adults) and study setting (clinical vs general population). We will explore the feasibility of conducting meta-regression analyses to assess the moderating effect of age, gender, socioeconomic status, study setting, geographic location of the study (low-income, middle-income countries vs high-income countries), definition of obesity, method to assess ADHD, psychiatric comorbidities and medication status.

Ethics and dissemination

No ethical issues are foreseen. The results will be published in a peer-reviewed journal and presented at national and international conferences of psychiatry, psychology, obesity and paediatrics.

Registration

PROSPERO-National Institute of Health Research (NIHR) Prospective Register of Systematic Reviews (CRD42013006410).
Benefits of family planning: an assessment of women's knowledge in rural Western Kenya
Authors: Mutombo Namuunda , Bakibinga Pauline , Mukiira Carol , Kamande Eva
Published: March 2014

Background

The last two decades have seen an increase in literature reporting an increase in knowledge and use of contraceptives among individuals and couples in Kenya, as in the rest of Africa, but there is a dearth of information regarding knowledge about benefits of family planning (FP) in Kenya.

Objectives

To assess the factors associated with knowledge about the benefits of FP for women and children, among women in rural Western Kenya.

Methods

Data are drawn from the Packard Western Kenya Project Baseline Survey, which collected data from rural women (aged 15–49 years). Ordinal regression was used on 923 women to determine levels of knowledge and associated factors regarding benefits of FP.

Results

Women in rural Western Kenya have low levels of knowledge about benefits of FP and are more knowledgeable about benefits for the mother rather than for the child. Only age, spousal communication and type of contraceptive method used are significant.

Conclusions

Women's level of knowledge about benefits of FP is quite low and may be one of the reasons why fertility is still high in Western Kenya. Therefore, FP programmes need to focus on increasing women's knowledge about the benefits of FP in this region.
Evidence for the use of glomerulomegaly as a surrogate marker of glomerular damage and for alpha-linolenic acid-rich oils in the treatment of early obesity-related glomerulopathy in a diet-induced rodent model of obesity
Authors: Caligiuri Stephanie P.B. , Blydt-Hansen Tom , Love Karin , Grégoire Mélanie , Taylor Carla G. , Zahradka Peter , Aukema Harold M.
Published: March 2014

Obesity-related glomerulopathy (ORG) is a unique and emerging condition that can lead to renal failure. Early detection, aided by an earlier diagnostic marker, would improve patient outcomes; this could be facilitated by an accurate model. Such a model would be useful to examine interventions like dietary fatty acids, which are known to influence renal diseases in later stages. In this study, obese-prone rats were provided high-fat (55% of energy) diets for 12 weeks to generate a model of diet-induced obesity. The rats were subsequently provided dietary oils with various levels of alpha-linolenic acid (ALA) and linoleic acid (LA) for 8 weeks, as follows: (g ALA:LA per 100 g oil): canola/flax (20:18), canola (8:18), soy (9:53), high-oleic canola/canola (5:16), high-oleic canola (2:15), lard/soy (1:8), and safflower (0.2:73). The model developed obesity, glomerulomegaly, proteinuria, and scarce glomerular damage with an indolent course. Morphometry and histology revealed glomerulomegaly as the first renal structural alteration. The utility of this marker as a predictor for the presence of ORG and renal injury was evidenced by its correlation to visceral adiposity (p < 0.0001, r = 0.44), proteinuria (p < 0.0001, ρ = 0.55), change in proteinuria (p = 0.0092, ρ = 0.42), and glomerular damage (p < 0.0001, ρ = 0.48). Renal triglyceride ALA:LA was strongly correlated with dietary ALA:LA (p < 0.0005, ρ = 0.96), and inversely associated with mean glomerular volume (p = 0.02, ρ = –0.82). The diet-induced obese model accurately represents early ORG, and implicates glomerulomegaly as an early surrogate diagnostic marker. Early intervention with ALA-rich dietary oils slowed glomerular enlargement; these findings warrant further clinical investigation to promote optimal patient outcomes.
Small firm subsistence and market dimensionality
Authors: Bruggeman Jeroen , Péli Gábor
Published: March 2014

In many markets, large and small firms coexist. As large firms can in principle out-compete small ones, the actual presence of the latter asks for an explanation. In ours, we focus on the dimensionality of markets, which can change as a consequence of product innovations, preference elaboration or institutions. We show that increasing market dimensionality substantially enlarges the market periphery relative to the market center, which creates new potential niches for small firms. We thereby provide a parsimonious explanation for small firm subsistence.