Diagnostic and therapeutic considerations in idiopathic hypereosinophilia with warm autoimmune hemolytic anemia.

Hypereosinophilic syndrome (HES) encompasses numerous diverse conditions resulting in peripheral hypereosinophilia that cannot be explained by hypersensitivity, infection, or atopy and that is not associated with known systemic diseases with specific organ involvement. HES is often attributed to neoplastic or reactive causes, such as chronic eosinophilic leukemia, although a majority of cases remains unexplained and are considered idiopathic. Here, we review the current diagnosis and management of HES and present a unique case of profound hypereosinophilia associated with warm autoimmune hemolytic anemia requiring intensive management. This case clearly illustrates the limitations of current knowledge with respect to hypereosinophilia syndrome as well as the challenges associated with its classification and management

Uncertainty in parameterizing floodplain forest friction for natural flood management, using remote sensing

One potential Natural Flood Management (NFM) option is floodplain reforestation or manage existing riparian forests, with a view to increasing flow resistance and attenuate flood hydrographs. However, the effectiveness of floodplain forests as resistance agents, during different magnitude overbank floods, has yet to be appropriately parameterized for hydraulic models. Remote sensing offers high-resolution datasets capable of characterizing vegetation structure from a variety of platforms, but they contain uncertainty. For the first time, we demonstrate uncertainty propagation in remote sensing derivations of complex vegetation structure through roughness prediction and floodplain flow for extreme flows and different forest types (young and old Poplar plantations, young and old Pine plantations, and an unmanaged riparian forest). The lowest uncertainties resulted from terrestrial and airborne lidar, where airborne lidar is currently best at defining canopy leaf area, but more research is needed to determine wood area. Mean literature uncertainties in stem density, trunk diameter, wood, and leaf area indices (20, 10, 30, 20%, respectively) resulted in a combined Manning’s n uncertainty from 11–13% to 11–17% at 2 m to 8 m flow depths. This equates to 7–8% roughness uncertainty per 10% combined forest structure uncertainty. Individually, stem density and trunk diameter uncertainties resulted in the largest Manning’s n uncertainty at all flow depths, especially for flow though Pine plantations. For deeper flows, leaf and woody areas become much more important, especially for unmanaged riparian forests with low canopy morphology. Forest structure errors propagated to flow depth demonstrate that even small flows can change by a decimeter, while deeper flows can change by 40 cm or more. For flow depth, errors in canopy structure are deemed more severe in flows depths beyond 4–6 m. This study highlights the need for lower uncertainty in all forest structure components using remote sensing, to improve roughness parameterization and flood modeling for NFM

Terrestrial structure-from-motion: spatial error analysis of roughness and morphology

Structure-from-Motion (SfM) photogrammetry is rapidly becoming a key tool for morphological characterisation and change detection of the earth surface. This paper demonstrates the use of Terrestrial Structure-from-Motion (TSfM) photogrammetry to acquire morphology and roughness data at the reach-scale in an upland gravel-bed river. We quantify 1) spatially-distributed error in TSfM derived Digital Elevation Models (DEMs) and 2) identify differences in roughness populations acquired from TSfM photogrammetry versus TLS. We identify an association between local topographic variation and error in the TSfM DEM. On flatter surfaces (e.g. bar and terrace surfaces), the difference between the TSfM and TLS DEMs are generally less than ±0.1 m. However, in areas of high topographic variability (>0.4 m) such as berm or terrace edges, differences between the TSfM and TLS DEMs can be up to ±1 m. Our results suggest that grain roughness estimates from the TSfM point cloud generate values twice those derived from the TLS point cloud on coarse berm areas, and up to four-fold those derived from the TLS point cloud over finer gravel bar surfaces. This finding has implications when using SfM data to derive roughness metrics for hydrodynamic modelling. Despite the use of standard filtering procedures, noise pertains in the SfM DEM and the time required for its reduction might partially outweigh the survey efficiency using SfM. Therefore, caution is needed when SfM surveys are employed for the assessment of surface roughness at a reach-scale

Ozone effects on blood biomarkers of systemic inflammation, oxidative stress, endothelial function, and thrombosis: The Multicenter Ozone Study in oldEr Subjects (MOSES).

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p<0.01. There were no effects of ozone on the three primary markers of systemic inflammation and a prothrombotic state: C-reactive protein, monocyte-platelet conjugates, and microparticle-associated tissue factor activity. However, among the secondary endpoints, endothelin-1, a potent vasoconstrictor, increased from pre- to post-exposure with ozone concentration (120 vs 0 ppb: 0.07 pg/mL, 95% confidence interval [CI] 0.01, 0.14; 70 vs 0 ppb: -0.03 pg/mL, CI -0.09, 0.04; p = 0.008). Nitrotyrosine, a marker of oxidative and nitrosative stress, decreased with increasing ozone concentrations, with marginal significance (120 vs 0 ppb: -41.5, CI -70.1, -12.8; 70 vs 0 ppb: -14.2, CI -42.7, 14.2; p = 0.017). GSTM1 status did not modify the effect of ozone exposure on any of the outcomes. These findings from healthy older adults fail to identify any mechanistic basis for the epidemiologically described cardiovascular effects of exposure to ozone. The findings, however, may not be applicable to adults with cardiovascular disease

Large-scale chromosome flip-flop reversible inversion mediates phenotypic switching of expression of antibiotic resistance in lactococci

Bacteria can gain resistance to antimicrobials by acquiring and expressing genetic elements that encode resistance determinants such as efflux pumps and drug-modifying enzymes, thus hampering treatment of infection. Previously we showed that acquisition of spectinomycin resistance in a lactococcal strain was correlated with a reversible genomic inversion, but the precise location and the genes affected were unknown. Here we use long read whole-genome sequencing to precisely define the genomic inversion and we use quantitative PCR to identify associated changes in gene expression levels. The boundaries of the inversion fall within two identical copies of a prophage-like sequence, located on the left and right replichores; this suggests possible mechanisms for inversion through homologous recombination or prophage activity. The inversion is asymmetrical in respect of the axis between the origin and terminus of the replication and modulates the expression of a SAM-dependent methyltransferase, whose heterologous expression confers resistance to spectinomycin in lactococci and that is up regulated on exposure to spectinomycin. This study provides one of the first examples of phase variation via large-scale chromosomal inversions that confers a switch in antimicrobial resistance in bacteria and the first outside of Staphylococcus aureus

Magnetic tracing of fine-sediment over pool-riffle morphology

Field studies documenting fine-sediment (< 2 mm) transport in gravel-bed rivers are rare. For the first time in a fluvial environment, a technique that enhances the magnetic susceptibility of sand is used to trace its longitudinal dispersion and storage. This paper describes the methodology behind the artificial magnetic enhancement of iron-stained sand, and presents the results from sand tracing exercises conducted on two gravel-bed channels with pool-riffle morphology; one unregulated and sinuous in nature (site A), the other regulated and straight (site B), both situated on the River Rede Northumberland, UK. Two tonnes of magnetically enhanced tracer sand was introduced to site A and four tonnes to site B, to provide information on fine-sediment storage dynamics, interaction of fines with the stream bed, and rates of movement, expressed as virtual velocity (Vi). Sand transport pathways appeared to differ between the reaches; for site A, sand storage was found on bars and riffle margins with no storage or signs of transport through pools, and in contrast pool storage of tracer was a key feature shown at site B. Topographic forcing may cause differences in sediment sorting at site A; topographic highs tend to have low sand transport rates with sand grains becoming congested in these areas, whereas topographic lows show higher transport rates resulting in greater dispersion. Supply limitation of sand on the falling limb of the hydrograph may also become an issue in the topographic lows at this site. Hydrograph differences between the regulated and unregulated reaches could also play a role; however this could not be quantified in this study. There was no evidence of sand infiltration into the bed at site A; however marginal evidence for infiltration into the near-surface (0–15 cm) substrate voids was found at site B. The general lack of evidence for significant infiltration may reflect limited availability of void space in substrate framework gravels. Tracer sand was transported over the bed surface, with little vertical interaction with the substrate, despite periods of gravel mobilisation at site A. Vi over the study duration for site A was 2.28 m day− 1, and 0.28 m day− 1 for site B. These values are greater than those calculated using existing predictive equations developed from gravel tracer data, possibly reflecting differences in the mode of transport between bedload and saltation load

Constraints on the Geological History of the Karst System in Southern Missouri, U.S.A. Provided by Radiogenic, Cosmogenic and Physical/Chemical Characteristics of Doline Fill

Območje Ozarkov v južnem Missouriju gradijo predvsem karbonatne, morske, platformne kamnine paleozojske starosti. Teren, ki vsebuje obširen kras, predstavlja kopno že od poznega Paleozojka. Da bi bolje razumeli geološko zgodovino tega kraškega sistema, smo raziskali stratigrafske podatke ohranjene v zapolnitvi velike vrtače pri največjem izviru v okolici. Vzorci zapolnitve iz naravnih izdankov in iz vrtine so bili analizirani s termoluminiscenco (TL) in 10Be kozmogeno metodo. Fizikalno-kemijske značilnosti zapolnitve so bile določene vizualno, z rentgensko metodo in merjenjem velikosti delcev. Podatki vrtine kažejo, da je debelina alohtonega materiala, ki zapolnjuje vrtačo 36,3 m. Ta material prekriva podorne bloke in sedimente debeline vsaj 15,6 m. Glede na teksturo, strukturo in barvo delimo material, ki zapolnjuje vrtačo na 7 con. Analize 10Be koncentracij kažejo, da material za celotni stolpec zapolnitve izvira iz rezidualnega materiala iz srednjega (Illinoian) in zgornjega Pleistocena (Wisconsian). Rentgenske analize glin kažejo, da zapolnitev vrtače vsebuje enake količine kaolinita in illita, kar je skladno z zemeljskim preperevanjem.The Ozark Plateaus region of southern Missouri is underlain by dominantly carbonate marine platform rocks of Paleozoic age. The region has been sub-aerially exposed since the late Paleozoic and is characterized by extensive karst. To better understand the geologic history of this regional karst system, we examined the stratigraphic record preserved in the fill of a large doline near the largest spring in the region. Samples of fill from natural exposures and drill core were analyzed using thermoluminescence (TL) and 10Be cosmogenic techniques, and the physical/chemical characteristics of the fill material were determined by visual inspection, X-ray analyses, and grain-size measurements. Drill-hole data indicate that the allochthonous doline fill is 36.3 m thick and rests on at least 15.6 m of cave breakdown and sediment. The doline fill is divisible into 7 zones. Analysis of 10Be concentrations suggest that the entire doline fill was derived from local residuum during the middle (Illinoian) to late Pleistocene (Wisconsinan). X-ray diffraction analyses of clays throughout the doline fill indicate that they consist of nearly equal amounts of kaolinite and illite, consistent with terrestrial weathering.

Pemphigus foliaceus in a patient with gastrointestinal stromal tumor treated with adjuvant imatinib mesylate

Pemphigus is an autoimmune bullous disease with a number of described associations, including medications, which have been grouped into three structural categories - thiol drugs, phenol drugs, and drugs with neither functional group [1]. Discontinuation of the offending medication is considered a mainstay of therapy. We report a patient in whom the onset of pemphigus foliaceus was associated with initiation of imatinib mesylate adjuvant therapy in a patient with resected gastrointestinal stromal tumor (GIST). Imatinib was continued because of the survival benefit to the patient with a resected, high risk GIST. Treatment with rituximab resulted in near resolution of his blistering rash and follow up enzyme-linked immunosorbent assay (ELISA) demonstrated reference range immunoreactivity for both desmoglein 1 and desmoglein 3. After dose increase of imatinib therapy owing to tumor growth, the patient subsequently again developed a similar eruption. Re-biopsy and ELISA were consistent with recurrence of pemphigus. In conclusion, although the patient's pemphigus was cleared with a single cycle of rituximab infusions while continuing imatinib therapy, the disease returned after imatinib dose was increased a year later, suggesting a dose-response relationship

Shotgun metagenomics reveals differences in antibiotic resistance genes among bacterial communities in Western Balkans glacial lakes sediments

Long-term overuse of antibiotics has driven the propagation and spreading of antibiotic resistance genes (ARGs) such as efflux pumps in the environment, which can be transferred to clinically relevant pathogens. This study explored the abundance and diversity of ARGs and mobile genetic elements within bacterial communities from sediments of three Western Balkans glacial lakes: Plav Lake (high impact of human population), Black Lake (medium impact of human population) and Donje Bare Lake (remote lake, minimal impact of human population) via shotgun metagenomics. Assembled metagenomic sequences revealed that Resistance-Nodulation-Division (RND) efflux pumps genes were most abundant in metagenome from the Plav Lake. The Integron Finder bioinformatics tool detected 38clusters ofattCsiteslackingintegron-integrases (CALIN) elements: 20 from Plav Lake, four from Black Lake and 14 from Donje Bare Lake. A complete integron sequence was recovered only from the assembled metagenome from Plav Lake. Plasmid contents within the metagenomes were similar, with proportions of contigs being plasmid-related: 1.73% for Plav Lake, 1.59% for Black Lake and 1.64% for Donje Bare Lake. The investigation showed that RNDs and mobile genetic elements content correlated with human population impact