Host risk factors for rifamycin-resistant clostridium difficile infection: A case control study

Objective. To evaluate the host risk factors associated with rifamycin-resistant Clostridium difficile (C. diff) infection in hospitalized patients compared to rifamycin-susceptible C.diff infection.^ Background. C. diff is the most common definable cause of nosocomial diarrhea affecting elderly hospitalized patients taking antibiotics for prolonged durations. The epidemiology of Clostridium difficile associated disease is now changing with the reports of a new hypervirulent strain causing hospital outbreaks. This new strain is associated with increased disease severity and mortality. The conventional therapy for C. diff includes metronidazole and vancomycin but high recurrence rates and treatment failures are now becoming a major concern. Rifamycin antibiotics are being developed as a new therapeutic option to treat C. diff infection after their efficacy was established in a few in vivo and in vitro studies. There are some recent studies that report an association between the hypervirulent strain and emerging rifamycin resistance. These findings assess the need for clinical studies to better understand the efficacy of rifamycin drugs against C. diff.^ Methods. This is a hospital-based, matched case-control study using de-identified data drawn from two prospective cohort studies involving C. diff patients at St Luke's Hospital. The C. diff isolates from these patients are screened for rifamycin resistance using agar dilution methods for minimum inhibitory concentrations (MIC) as part of Dr Zhi-Dong Jiang's study. Twenty-four rifamycin-rifamycin resistant C. diff cases were identified and matched with one rifamycin susceptible C. diff control on the basis of ± 10 years of age and hospitalization 30 days before or after the case. De-identified data for the 48 subjects was obtained from Dr Kevin Garey's clinical study at St Luke's Hospital enrolling C. diff patients. It was reviewed to gather information about host risk factors, outcome variables and relevant clinical characteristic.^ Results. Medical diagnosis at the time of admission (p = 0.0281) and history of chemotherapy (p = 0.022) were identified as a significant risk factor while hospital stay ranging from 1 week to 1 month and artificial feeding were identified as an important outcome variable (p = 0.072 and p = 0.081 respectively). Horn's Index assessing the severity of underlying illness and duration of antibiotics for cases and controls showed no significant difference.^ Conclusion. The study was a small project designed to identify host risk factors and understand the clinical implications of rifamycin-resistance. The study was underpowered and a larger sample size is needed to validate the results.^

Apply response adaptive randomization to group sequential with early stopping

Group sequential methods and response adaptive randomization (RAR) procedures have been applied in clinical trials due to economical and ethical considerations. Group sequential methods are able to reduce the average sample size by inducing early stopping, but patients are equally allocated with half of chance to inferior arm. RAR procedures incline to allocate more patients to better arm; however it requires more sample size to obtain a certain power. This study intended to combine these two procedures. We applied the Bayesian decision theory approach to define our group sequential stopping rules and evaluated the operating characteristics under RAR setting. The results showed that Bayesian decision theory method was able to preserve the type I error rate as well as achieve a favorable power; further by comparing with the error spending function method, we concluded that Bayesian decision theory approach was more effective on reducing average sample size.^

The role of p53 in skin cancer induction by UV radiation and as a potential tumor antigen in UV-induced murine skin tumors

Carcinoma of the skin is the most common type of human cancer in the United States. Ultraviolet radiation (UVR) present in the sunlight is thought to be the major carcinogen responsible for induction of skin cancer. In UV-associated skin carcinogenesis, mutations in p53 are not only present with very high frequency, but occur early in the course of tumor development. In addition, UV-induced skin tumors in mice exhibit unique immunological characteristics. They are highly antigenic and express both individually-specific tumor transplantation antigens recognized by effector T cells and the UV-associated common antigen recognized by UV-induced suppressor T cells. ^ To examine the hypothesis that p53 plays a critical role in preventing skin cancer induction by UVR, mice constitutively lacking one or two functional p53 alleles were compared to wild-type mice for their susceptibility to UV carcinogenesis. Both p53 +/– and –/– mice showed greater susceptibility to skin cancer induction than wild-type mice, and –/– mice were the most susceptible, Accelerated tumor development in the p53 +/– mice was not associated with loss of the remaining wild-type allele of p53 , but in many cases was associated with UV-induced mutations in p53. Our studies clearly demonstrate the essential role of p53 in protection against UV carcinogenesis, particularly in the eye and epidermis. ^ The role of p53 in the antigenicity of UV-induced murine skin tumors was also addressed. Primary UV-induced tumors from p53 –/–, +/– and +/+ mice were transplanted into both normal and immunosuppressed mice, and rates of tumor rejection were compared. Tumors from mice with only one or no functional p53 alleles were less antigenic than those from mice with two functional p53 alleles. Moreover, tumors with no functional p53 also failed to grow well in chronically UV-irradiated mice. These results indicate that p53 contributes to the strong antigenicity of UV-induced murine skin tumors, and suggest that it may play a critical role in expression of the UV-associated common antigen recognized by suppressor T cells. ^ In this study we also monitored the effect of UVR on the development of lymphoid malignancies in p53 deficient mice. The incidence of lymphoid malignancies in UV-irradiated p53 +/– mice was drastically enhanced compared to that in unirradiated counterparts. The immune responses of the mice were identical and were suppressed to the same extent by UV irradiation regardless of the p53 genotype. These data provide the first experimental evidence that exposure to UVR can contribute to the development of lymphoid neoplasms in genetically susceptible hosts. ^

Proceedings of the Twenty-Sixth Annual Biochemical Engineering Symposium

This volume contains the Proceedings of the Twenty-Sixth Annual Biochemical Engineering Symposium held at Kansas State University on September 21, 1996. The program included 10 oral presentations and 14 posters. Some of the papers describe the progress of ongoing projects, and others contain the results of completed projects. Only brief summaries are given of some of the papers; many of the papers will be published in full elsewhere. A listing of those who attended is given below. ContentsForeign Protein Production from SV40 Early Promoter in Continuous Cultures of Recombinant CHO Cells - Gautam Banik, Paul Todd, and Dhinakar Kampala Enhanced Cell Recruitment Due to Cell-Cell Interactions - Brad Farlow and Matthias Nollert The Recirculation of Hybridoma Suspension Cultures: Effects on Cell Death, Metabolism and Mab Productivity - Peng Jin and Carole A. Heath The Importance of Enzyme Inactivation and Self-Recovery in Cometabolic Biodegradation of Chlorinated Solvents - Xi-Hui Zhang, Shanka Banerji, and Rakesh Bajpai Phytoremediation of VOC contaminated Groundwater using Poplar Trees - Melissa Miller, Jason Dana, L.C. Davis, Murlidharan Narayanan, and L.E. Erickson Biological Treatment of Off-Gases from Aluminum Can Production: Experimental Results and Mathematical Modeling - Adeyma Y. Arroyo, Julio Zimbron, and Kenneth F. Reardon Inertial Migration Based Separation of Chlorella Microalgae in Branched Tubes - N.M. Poflee, A.L. Rakow, D.S. Dandy, M.L. Chappell, and M.N. Pons Contribution of Electrochemical Charge to Protein Partitioning in Aqueous Two-Phase Systems - Weiyu Fan and Charles C. Glatz Biodegradation of Some Commercial Surfactants Used in Bioremediation - Jun Gu, G.W. Preckshot, S.K. Banerji, and Rakesh Bajpai Modeling the Role of Biomass in Heavy Metal Transport Ln Vadose Zone - K.V. Nedunuri, L.E. Erickson, and R.S. Govindaraju Multivariable Statistical Methods for Monitoring Process Quality: Application to Bioinsecticide Production by 73 89 Bacillus Thuringiensis - c. Puente and M.N. Karim The Use of Polymeric Flocculants in Bacterial Lysate Streams - H. Graham, A.S. Cibulskas and E.H. Dunlop Effect of Water Content on transport of Trichloroethylene in a Chamber with Alfalfa Plants - Muralidharan Narayanan, Jiang Hu, Lawrence C. Davis, and Larry E. Erickson Detection of Specific Microorganisms using the Arbitrary Primed PCR in the Bacterial Community of Vegetated Soil - X. Wu and L.C. Davis Flux Enhancement Using Backpulsing - V.T. Kuberkar and R.H. Davis Chromatographic Purification of Oligonucleotides: Comparison with Electrophoresis - Stephen P. Cape, Ching-Yuan Lee, Kevin Petrini, Sean Foree, Micheal G. Sportiello and Paul Todd Determining Singular Arc Control Policies for Bioreactor Systems Using a Modified Iterative Dynamic Programming Algorithm - Arun Tholudur and W. Fred Ramirez Pressure Effect on Subtilisins Measured via FTIR, EPR and Activity Assays, and Its Impact on Crystallizations - J.N. Webb, R.Y. Waghmare, M.G. Bindewald, T.W. Randolph, J.F. Carpenter, C.E. Glatz Intercellular Calcium Changes in Endothelial Cells Exposed to Flow - Laura Worthen and Matthias Nollert Application of Liquid-Liquid Extraction in Propionic Acid Fermentation - Zhong Gu, Bonita A. Glatz, and Charles E. Glatz Purification of Recombinant T4 Lysozyme from E. Coli: Ion-Exchange Chromatography - Weiyu Fan, Matt L. Thatcher, and Charles E. Glatz Recovery and Purification of Recombinant Beta-Glucuronidase from Transgenic Corn - Ann R. Kusnadi, Roque Evangelista, Zivko L. Nikolov, and John Howard Effects of Auxins and cytokinins on Formation of Catharanthus Roseus G. Don Multiple Shoots - Ying-Jin Yuan, Yu-Min Yang, Tsung-Ting Hu, and Jiang Hu Fate and Effect of Trichloroethylene as Nonaqueous Phase Liquid in Chambers with Alfalfa - Qizhi Zhang, Brent Goplen, Sara Vanderhoof, Lawrence c. Davis, and Larry E. Erickson Oxygen Transport and Mixing Considerations for Microcarrier Culture of Mammalian Cells in an Airlift Reactor - Sridhar Sunderam, Frederick R. Souder, and Marylee Southard Effects of Cyclic Shear Stress on Mammalian Cells under Laminar Flow Conditions: Apparatus and Methods - M.L. Rigney, M.H. Liew, and M.Z. Southard

(Table 2) Mineralogy, stable isotopes, and mineral percentages of the carbonate fraction of samples from the South China Sea

Chemoherm carbonates, as well as numerous other types of methane seep carbonates, were discovered in 2004 along the passive margin of the northern South China Sea. Lithologically, the carbonates are micritic containing peloids, clasts and clam fragments. Some are highly brecciated with aragonite layers of varying thicknesses lining fractures and voids. Dissolution and replacement is common. Mineralogically, the carbonates are dominated by high magnesium calcites (HMC) and aragonite. Some HMCs with MgCO3 contents of between 30-38 mol%-extreme-HMC, occur in association with minor amounts of dolomite. All of the carbonates are strongly depleted in d13C, with a range from -35.7 to -57.5 per mil PDB and enriched in d18O (+ 4.0 to + 5.3 per mil PDB). Abundant microbial rods and filaments were recognized within the carbonate matrix as well as aragonite cements, likely fossils of chemosynthetic microbes involved in carbonate formation. The microbial structures are intimately associated with mineral grains. Some carbonate mineral grains resemble microbes. The isotope characteristics, the fabrics, the microbial structure, and the mineralogies are diagnostic of carbonates derived from anaerobic oxidation of methane mediated by microbes. From the succession of HMCs, extreme-HMC, and dolomite in layered tubular carbonates, combined with the presence of microbial structure and diagenetic fabric, we suggest that extreme-HMC may eventually transform into dolomites. Our results add to the worldwide record of seep carbonates and establish for the first time the exact locations and seafloor morphology where such carbonates formed in the South China Sea. Characteristics of the complex fabric demonstrate how seep carbonates may be used as archives recording multiple fluid regimes, dissolution, and early transformation events.

Diatom biostratigraphy and sea ice concentration reconstruction from core DA06-139G, Vaigat Strait in Disko Bugt, West Greenland

A diatom-based sea-ice concentration (SIC) transfer function is developed using 72 surface samples from west of Greenland and around Iceland, and through comparison with the associated modern SIC. Canonical correspondence analysis on surface sediment diatoms and monthly average of SIC reveals that April SIC is the most important environmental factor controlling the distribution of diatoms in the area, and permits the development of a diatom-based SIC transfer function. The consistency between reconstructed SIC based on diatoms from West Greenland and the instrumental and documentary data during the last ~75 years demonstrates that the diatom-based SIC reconstruction is reliable for studying the palaeoceanography off West Greenland. Relatively warm conditions with strong influence of the Irminger Current (IC) are indicated for the early part of the record (~5000-3860 cal. yr BP), corresponding in time to the latest part of the Holocene Thermal Maximum. The April SIC oscillated around the mean value between 3860 and 1510 cal. yr BP and was above mean afterwards, particularly during the time interval 1510-1120 cal. yr BP and after 650 cal. yr BP, indicating more extensive sea-ice cover in Disko Bugt. A high degree of consistency between the reconstructed April SIC and changes in the diatom species suggests that the sea-ice condition in Disko Bugt is strongly influenced by variations in the relative strength of two components of the West Greenland Current, i.e. the cold East Greenland Current and the relatively warm IC.

Radiocarbon ages and diatom abundance in cores GA306-BC4 and GA306-GC4 obtained during Galathea 3 cruise, West Greenland

Diatom assemblages from Holsteinsborg Dyb on the West Greenland shelf were analysed with high temporal resolution for the last 1200 years. A high degree of consistency between changes in frequency of selected diatom species and instrumental data from the same area during the last 70 years confirms the reliability of diatoms (particularly sea-ice species and warm-water species) for the study of palaeoceanographic changes in this area. A general cooling trend with some fluctuations is marked by an increase in sea-ice species throughout the last 1200 years. A relatively warm period with increased influence of Atlantic water masses of the Irminger Current (IC) is found at AD 750-1330, although with some oceanographic variability after AD 1000. A pronounced oceanographic shift occurred at AD 1330, corresponding in time to the transition from the so-called 'Medieval Warm Period' (MWP) to the 'Little Ice Age' (LIA). The LIA cold episode is characterized by three intervals with particularly cold sea-surface conditions at AD 1330-1350, AD 1400-1575 and AD 1660-1710 as a result of variable influence of Polar waters in the area. During the last 70 years, two relatively warm periods and one cold period (the early 1960s to mid-1990s) are indicated by changes in the diatom components. Our study demonstrates that sedimentary records on the West Greenland shelf provide valuable palaeoenvironment data that confirm a linkage between local and large-scale North Atlantic oceanographic and atmospheric oscillations.

Nannofossil and stable isotope record across the Paleocene/Eocene Thermal Maximum in ODP Hole 183-1135A

The Paleocene/Eocene Thermal Maximum (PETM, ca. 55 Ma) is an abrupt, profound perturbation of climate and the carbon cycle associated with a massive injection of isotopically light carbon into the ocean-atmosphere system. As such, it provides an analogue for understanding the interplay between phytoplankton and climate under modern anthropogenic global-warming conditions. However, the accompanying enhanced dissolution poses uncertainty on the reconstruction of the affected ecology and productivity. We present a high-resolution record of bulk isotopes and nannofossil absolute abundance from Ocean Drilling Program (ODP) Site 1135 on the Kerguelen Plateau, Southern Indian Ocean to quantitatively constrain for the first time the influence of dissolution on paleoecological reconstruction. Our bulk-carbonate isotope record closely resembles that of the classic PETM site at ODP Site 690 on the opposite side of the Antarctic continent, and its correlation with those from ODP Sites 690, 1262 and 1263 records allows recognition of 14 precessional cycles upsection from the onset of the carbon isotopic excursion (CIE). This, together with a full range of common Discoasteraraneus and an abundance crossover between Fasciculithus and Zygrhablithusbijugatus, indicates the presence of the PETM at Site 1135, a poorly known record with calcareous fossils throughout the interval. The strong correlation between the absolute abundances of Chiasmolithus and coccolith assemblages reveals a dominant paleoecological signal in the poorly preserved fossil assemblages, while the influence of dissolution is only strong during the CIE. This suggests that r-selected taxa can preserve faithful ecological information even in the severely-altered assemblages studied here, and therefore provide a strong case for the application of nannofossils to paleoecological studies in better-preserved PETM sections. The inferred nannoplankton productivity drops abruptly at the CIE onset, but rapidly increases after the CIE peak, both of which may be driven by nutrient availability related to ocean stratification and vertical mixing due to changed sea-surface temperatures.

Late Miocene palaeoflora and palaeoclimate of Lincang (China)

The Miocene Lincang leaf assemblage is used in this paper as proxy data to reconstruct the palaeoclimate of southwestern Yunnan (SW China) and the evolution of monsoon intensity. Three quantitative methods were chosen for this reconstruction, i.e. Leaf Margin Analysis (LMA), Climate Leaf Analysis Multivariate Program (CLAMP), and the Coexistence Approach (CA). These methods, however, yield inconsistent results, particularly for the precipitation, as also shown in European and other East Asian Cenozoic floras. The wide range of the reconstructed climatic parameters includes the Mean Annual Temperature (MAT) of 18.5-24.7 °C and the Mean Annual Precipitation (MAP) of 1213-3711 mm. Compared with the modern Lincang climate (MAT, 17.3 °C; MAP, 1178.7 mm), the Miocene climate is slightly warmer, wetter and has a higher temperature seasonality. A detailed comparison on the palaeoclimatic variables with the coeval Late Miocene Xiaolongtan flora from the eastern part of Yunnan allows us to investigate the development and interactions of both South Asian and East Asian monsoons during the Late Miocene in southwest China, now under strong influence of these monsoon systems. Our results suggest that the monsoon climate has already been established in southwest Yunnan during the Late Miocene. Furthermore, our results support that both Southeast Asian and East Asian monsoons co-occurred in Yunnan during the Late Miocene.

Nannofossil biostratigraphy of ODP Hole 206-1256B sediments

Site 1256 of Ocean Drilling Program Leg 206 to the Guatemala Basin on the eastern flank of the East Pacific Rise yielded a near-complete, middle Miocene-Quaternary carbonate-rich section that provides an opportunity to study low-latitude biostratigraphic and paleoceanographic events. The sedimentary sequence in Hole 1256B has been zoned using calcareous nannofossils according to the biostratigraphic schemes by Martini of 1971 (modified by Martini and Müller in 1986) and Okada and Bukry of 1980. The nannofossil assemblage is characteristic of the low latitudes, with abundant Gephyrocapsa, Discoaster, and Sphenolithus, and is in general moderately to well preserved, depending on nannofossil abundance and the presence of diatoms. Age estimates for the first occurrence and last occurrence of Reticulofenestra rotaria were derived from biostratigraphy and magnetostratigraphy independently and assigned to 7.18 and 6.32 Ma, respectively. Linear sedimentation rates, calculated using 28 nannofossil datums and age estimates, are high in the middle Miocene, decrease from the late Miocene to the Pliocene, then increase upsection. The abrupt drop in carbonate mass accumulation rates during the early late Miocene is referred to as the "carbonate crash." This pattern reflects (1) the long-trend decrease of productivity as the site moves away from the upwelling system at the equatorial divergence as well as (2) fluctuation in the chemistry of the bottom waters associated with production of the North Atlantic Bottom Water and ventilation via the Panama Gateway. A basement age of 14.5 Ma was obtained by extrapolating the 39.1-m/m.y. rate in the middle Miocene to the basement at 250.7 meters below seafloor, and is consistent with the ~15-Ma age of the oceanic crust estimated from marine magnetic anomalies. Reworked nannofossils and lithologic changes were used to unravel postdepositional history, and three episodes were recognized, one of which in the latest Miocene can be widely correlated.

Paleocene-Eocene calcareous nannofossils of onshore wells from the Coastal Plain of New Jersey and Maryland, USA

Paleogene calcareous nannofossils from split spoon cores recovered from five wells along the Coastal Plain of New Jersey and Maryland have been analyzed in order to provide onshore information complementary to that derived from the offshore DSDP Site 605 (upper continental rise off New Jersey). Hiatuses are more numerous and of greater extent in the onshore sections, but the major ones correlate well with those noted in the offshore section. At one site at least (Leggett Well), sedimentation may well have been continuous across the Cretaceous/Tertiary boundary, as it is believed to have been at DSDP Site 605. These various correlations are discussed elsewhere in a companion paper (Olsson and Wise, this volume). Important differences in nannofossil assemblages are noted between the onshore (shelf paleoenvironment) and offshore (slope-rise paleoenvironment) sections. Lithostromation simplex, not present offshore, is consistently present onshore and seems to be confined to the Eocene shelf sediments of this region. The same relationship holds for the zonal marker, Rhabdosphaera gladius Locker. The Rhomboaster-Tribrachiatus plexus is more diverse and better preserved in the onshore sections, where the lowermost Eocene Zone CP9 is well represented. Differential preservation is postulated to account for two morphotypes of Tribrachiatus bramlettei (Brönnimann and Stradner). Type A is represented at DSDP Site 605 by individuals with short, stubby arms, but these forms are not present in the equivalent onshore sections. There they are replaced by the Type B morphotypes, which exhibit a similar basic construction but possess much longer, more delicate arms.

Global LAI uncertainty and relative uncertainty datasets derived from a Triple Collocation Error Model (TCEM)

Uncertainty information for global leaf area index (LAI) products is important for global modeling studies but usually difficult to systematically obtain at a global scale. Here, we present a new method that cross-validates existing global LAI products and produces consistent uncertainty information. The method is based on a triple collocation error model (TCEM) that assumes errors among LAI products are not correlated. Global monthly absolute and relative uncertainties, in 0.05° spatial resolutions, were generated for MODIS, CYCLOPES, and GLOBCARBON LAI products, with reasonable agreement in terms of spatial patterns and biome types. CYCLOPES shows the lowest absolute and relative uncertainties, followed by GLOBCARBON and MODIS. Grasses, crops, shrubs, and savannas usually have lower uncertainties than forests in association with the relatively larger forest LAI. With their densely vegetated canopies, tropical regions exhibit the highest absolute uncertainties but the lowest relative uncertainties, the latter of which tend to increase with higher latitudes. The estimated uncertainties of CYCLOPES generally meet the quality requirements (± 0.5) proposed by the Global Climate Observing System (GCOS), whereas for MODIS and GLOBCARBON only non-forest biome types have met the requirement. Nevertheless, none of the products seems to be within a relative uncertainty requirements of 20%. Further independent validation and comparative studies are expected to provide a fair assessment of uncertainties derived from TCEM. Overall, the proposed TCEM is straightforward and could be automated for the systematic processing of real time remote sensing observations to provide theoretical uncertainty information for a wider range of land products.