Motion-insensitive determination of B1+ amplitudes based on the bloch-siegert shift in single voxels of moving organs including the human heart.

PURPOSE To reliably determine the amplitude of the transmit radiofrequency ( B1+) field in moving organs like the liver and heart, where most current techniques are usually not feasible. METHODS B1+ field measurement based on the Bloch-Siegert shift induced by a pair of Fermi pulses in a double-triggered modified Point RESolved Spectroscopy (PRESS) sequence with motion-compensated crusher gradients has been developed. Performance of the sequence was tested in moving phantoms and in muscle, liver, and heart of six healthy volunteers each, using different arrangements of transmit/receive coils. RESULTS B1+ determination in a moving phantom was almost independent of type and amplitude of the motion and agreed well with theory. In vivo, repeated measurements led to very small coefficients of variance (CV) if the amplitude of the Fermi pulse was chosen above an appropriate level (CV in muscle 0.6%, liver 1.6%, heart 2.3% with moderate amplitude of the Fermi pulses and 1.2% with stronger Fermi pulses). CONCLUSION The proposed sequence shows a very robust determination of B1+ in a single voxel even under challenging conditions (transmission with a surface coil or measurements in the heart without breath-hold). Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Antibiotic Susceptibility and Sequence Type Distribution of Ureaplasma Species Isolated from Genital Samples in Switzerland.

Antibiotic resistance in Ureaplasma urealyticum/Ureaplasma parvum and Mycoplasma hominis is an issue of increasing importance. However, data regarding the susceptibility and, more importantly, the clonality of these organisms are limited. We analyzed 140 genital samples obtained in Bern, Switzerland, in 2014. Identification and antimicrobial susceptibility tests were performed by using the Mycoplasma IST 2 kit and sequencing of 16S rRNA genes. MICs for ciprofloxacin and azithromycin were obtained in broth microdilution assays. Clonality was analyzed with PCR-based subtyping and multilocus sequence typing (MLST), whereas quinolone resistance and macrolide resistance were studied by sequencing gyrA, gyrB, parC, and parE genes, as well as 23S rRNA genes and genes encoding L4/L22 ribosomal proteins. A total of 103 samples were confirmed as positive for U. urealyticum/U. parvum, whereas 21 were positive for both U. urealyticum/U. parvum and M. hominis. According to the IST 2 kit, the rates of nonsusceptibility were highest for ciprofloxacin (19.4%) and ofloxacin (9.7%), whereas low rates were observed for clarithromycin (4.9%), erythromycin (1.9%), and azithromycin (1%). However, inconsistent results between microdilution and IST 2 kit assays were recorded. Various sequence types (STs) observed previously in China (ST1, ST2, ST4, ST9, ST22, and ST47), as well as eight novel lineages, were detected. Only some quinolone-resistant isolates had amino acid substitutions in ParC (Ser83Leu in U. parvum of serovar 6) and ParE (Val417Thr in U. parvum of serovar 1 and the novel Thr417Val substitution in U. urealyticum). Isolates with mutations in 23S rRNA or substitutions in L4/L22 were not detected. This is the first study analyzing the susceptibility of U. urealyticum/U. parvum isolates in Switzerland and the clonality outside China. Resistance rates were low compared to those in other countries. We hypothesize that some hyperepidemic STs spread worldwide via sexual intercourse. Large combined microbiological and clinical studies should address this important issue.

A first chironomid-based summer temperature reconstruction (13–5 ka BP) around 49°N in inland Europe compared with local lake development

Temperature reconstructions for the end of the Pleistocene and the first half of the Holocene based on biotic proxies are rare for inland Europe around 49°N. We analysed a 7 m long sequence of lake deposits in the Vihorlat Mts in eastern Slovakia (820 m a.s.l.). Chironomid head capsules were used to reconstruct mean July temperature (TJuly), other proxies (diatoms, green algae, pollen, geochemistry) were used to reconstruct local environmental changes that might have affected the climate reconstruction, such as epilimnetic total phosphorus concentrations (TP), lake level changes and development of surrounding vegetation. During the Younger Dryas (YD), temperature fluctuated between 7 and 11 °C, with distinct, decadal to centennial scale variations, that agree with other palaeoclimate records in Europe such as δ18O content in stalagmites or Greenland ice cores. The results indicate that the site was somewhat colder than expected from the general south-to-north YD temperature gradient within Europe, possibly because of north-facing exposition. The warmer phases of the YD were characterised by low water level or even complete desiccation of the lake (12,200-12,400 cal yr BP). At the Late-Glacial/Holocene transition TJuly steeply increased from from 11 to 15.5 °C (11,700-11,400 cal yr BP) - the highest TJuly for entire sequence. This rapid climate change was reflected by all proxies as a compositional change and increasing species diversity. The open woodlands of Pinus, Betula, Larix and Picea were replaced by broad-leaved temperate forests dominated by Betula, later by Ulmus and finally by Corylus (ca 9700 cal yr BP). At the same time, input of eroded coarse-grained material into the lake decreased and organic matter (LOI) and biogenic silica increased. The Early-Holocene climate was rather stable till 8700 cal yr BP, with temporary decrease in TJuly around 11,200 cal yr BP. The lake was productive with a well-developed littoral, as indicated by both diatoms and chironomids. A distinct decline of TJuly to 10 °C between 8700 and 8000 cal yr BP was associated with decreasing chironomid diversity and increasing climate moistening indicated by pollen. Tychoplanktonic and phosphorus-demanding diatoms increased which might be explained by hydrological and land-cover changes. Later, a gradual warming started after 7000 cal yr BP and representation of macrophytes, periphytic diatoms and littoral chironomids increased. Our results suggest that the Holocene thermal maximum was taking place unusually early in the Holocene at our study site, but its timing might be affected by topography and mesoclimate. We further demonstrated that temperature changes had coincided with variations in local hydrology

The sequence comparison index: A novel method for comparing proteins and proteomes

Historically morphological features were used as the primary means to classify organisms. However, the age of molecular genetics has allowed us to approach this field from the perspective of the organism's genetic code. Early work used highly conserved sequences, such as ribosomal RNA. The increasing number of complete genomes in the public data repositories provides the opportunity to look not only at a single gene, but at organisms' entire parts list. ^ Here the Sequence Comparison Index (SCI) and the Organism Comparison Index (OCI), algorithms and methods to compare proteins and proteomes, are presented. The complete proteomes of 104 sequenced organisms were compared. Over 280 million full Smith-Waterman alignments were performed on sequence pairs which had a reasonable expectation of being related. From these alignments a whole proteome phylogenetic tree was constructed. This method was also used to compare the small subunit (SSU) rRNA from each organism and a tree constructed from these results. The SSU rRNA tree by the SCI/OCI method looks very much like accepted SSU rRNA trees from sources such as the Ribosomal Database Project, thus validating the method. The SCI/OCI proteome tree showed a number of small but significant differences when compared to the SSU rRNA tree and proteome trees constructed by other methods. Horizontal gene transfer does not appear to affect the SCI/OCI trees until the transferred genes make up a large portion of the proteome. ^ As part of this work, the Database of Related Local Alignments (DaRLA) was created and contains over 81 million rows of sequence alignment information. DaRLA, while primarily used to build the whole proteome trees, can also be applied shared gene content analysis, gene order analysis, and creating individual protein trees. ^ Finally, the standard BLAST method for analyzing shared gene content was compared to the SCI method using 4 spirochetes. The SCI system performed flawlessly, finding all proteins from one organism against itself and finding all the ribosomal proteins between organisms. The BLAST system missed some proteins from its respective organism and failed to detect small ribosomal proteins between organisms. ^

Correlation between dental care utilization and oral cavity cancer in a large sample of community-based United States residents

Cancer of the oral cavity and pharynx remains one of the ten leading causes of cancer death in the United States (US). Besides smoking and alcohol consumption, there are no well established risk factors. While poor dental care had been implicated, it is unknown if the lack of dental care, implying poor dental hygiene predisposes to oral cavity cancer. This study aimed to assess the relationship between dental care utilization during the past twelve months and the prevalence of oral cavity cancer. A cross-sectional design of the National Health Interview Survey of adult, non-institutionalized US residents (n=30,475) was used to assess the association between dental care utilization and self reported diagnosis of oral cavity cancer. Chi square statistic was used to examine the crude association between the predictor variable, dental care utilization and other covariates, while unconditional logistic regression was used to assess the relationship between oral cavity cancer and dental care utilization. There were statistically significant differences between those who utilized dental care during the past twelve months and those who did not with respect to education, income, age, marital status, and gender (p < 0.05), but not health insurance coverage (p = 0.53). Also, those who utilized dental care relative to those who did not were 65% less likely to present with oral cavity cancer, prevalence odds ratio (POR), 0.35, 95% Confidence Interval (CI), 0.12–0.98. Further, higher income advanced age, people of African heritage, and unmarried status were statistically significantly associated with oral cavity cancer, (p < 0.05), but health insurance coverage, alcohol use and smoking were not, p > 0.05. However, after simultaneously controlling for the relevant covariates, the association between dental care and oral cavity cancer did not attenuate nor persist. Thus, compared with those who did not use dental care, those who did wee 62% less likely to present with oral cavity cancer adjusted POR, 0.38, 95% CI, 0.13-1.10. Among US adults residing in community settings, use of dental care during the past twelve months did not significantly reduce the predisposition to oral cavity cancer. However, due to the nature of the data used in this study, which restricts temporal sequence, a large sample prospective study that may identify modifiable factors associated with oral cancer development namely poor dental care, is needed. ^

Integrating sequence information in microarray data analysis by free energy modeling

Microarray technology is a high-throughput method for genotyping and gene expression profiling. Limited sensitivity and specificity are one of the essential problems for this technology. Most of existing methods of microarray data analysis have an apparent limitation for they merely deal with the numerical part of microarray data and have made little use of gene sequence information. Because it's the gene sequences that precisely define the physical objects being measured by a microarray, it is natural to make the gene sequences an essential part of the data analysis. This dissertation focused on the development of free energy models to integrate sequence information in microarray data analysis. The models were used to characterize the mechanism of hybridization on microarrays and enhance sensitivity and specificity of microarray measurements. ^ Cross-hybridization is a major obstacle factor for the sensitivity and specificity of microarray measurements. In this dissertation, we evaluated the scope of cross-hybridization problem on short-oligo microarrays. The results showed that cross hybridization on arrays is mostly caused by oligo fragments with a run of 10 to 16 nucleotides complementary to the probes. Furthermore, a free-energy based model was proposed to quantify the amount of cross-hybridization signal on each probe. This model treats cross-hybridization as an integral effect of the interactions between a probe and various off-target oligo fragments. Using public spike-in datasets, the model showed high accuracy in predicting the cross-hybridization signals on those probes whose intended targets are absent in the sample. ^ Several prospective models were proposed to improve Positional Dependent Nearest-Neighbor (PDNN) model for better quantification of gene expression and cross-hybridization. ^ The problem addressed in this dissertation is fundamental to the microarray technology. We expect that this study will help us to understand the detailed mechanism that determines sensitivity and specificity on the microarrays. Consequently, this research will have a wide impact on how microarrays are designed and how the data are interpreted. ^

Recommendations for dementia caregiver stress interventions based on Intervention Mapping guidelines

Stress can affect a person's psychological and physical health and cause a variety of conditions including depression, immune system changes, and hypertension (Alzheimer's Association, 2010; Aschbacher et al., 2009; Fredman et al., 2010; Long et al., 2004; Mills et al., 2009; von Känel et al., 2008). The severity and consequences of these conditions can vary based on the duration, amount, and sources of stress experienced by the individual (Black & Hyer, 2010; Coen et al., 1997; Conde-Sala et al., 2010; Pinquart & Sörensen, 2007). Caregivers of people with dementia have an elevated risk for stress and its related health problems because they experience more negative interactions with, and provide more emotional support for, their care recipients than other caregivers. ^ This paper uses a systematic program planning process of Intervention Mapping to organize evidence from literature, qualitative research and theory to develop recommendations for a theory- and evidence-based intervention to improve outcomes for caregivers of people with dementia. A needs assessment was conducted to identify specific dementia caregiver stress influences and a logic model of dementia caregiver stress was developed using the PRECEDE Model. Necessary behavior and environmental outcomes are identified for dementia caregiver stress reduction and performance objectives for each were combined with selected determinants to produce change objectives. Planning matrices were then designed to inform effective theory-based methods and practical applications for recommended intervention delivery. Recommendations for program components, their scope and sequence, the completed program materials, and the program protocols are delineated along with ways to insure that the program is adopted and implemented after it is shown to be effective.^

MOLECULAR AND GENOMIC BASED INSIGHTS INTO THE EVOLUTION OF ENTEROCOCCUS FAECIUM FROM COMMENSAL TO HOSPITAL-ADAPTED PATHOGEN

The basis for the recent transition of Enterococcus faecium from a primarily commensal organism to one of the leading causes of hospital-acquired infections in the United States is not yet understood. To address this, the first part of my project assessed isolates from early outbreaks in the USA and South America using sequence analysis, colony hybridizations, and minimal inhibitory concentrations (MICs) which showed clinical isolates possess virulence and antibiotic resistance determinants that are less abundant or lacking in community isolates. I also revealed that the level of ampicillin resistance increased over time in clinical strains. By sequencing the pbp5 gene, I demonstrated an ~5% difference in the pbp5 gene between strains with MICs <4ug/ml and those with MICs >4µg/ml, but no specific sequence changes correlated with increases in MICs within the latter group. A 3-10% nucleotide difference was also seen in three other genes analyzed, which suggested the existence of two distinct subpopulations of E. faecium. This led to the second part of my project analyzing concatenated core gene sequences, SNPs, the 16S rRNA, and phylogenetics of 21 E. faecium genomes confirming two distinct clades; a community-associated (CA) clade and hospital-associated (HA) clade. Molecular clock calculations indicate that these two clades likely diverged ~ 300,000 to > 1 million years ago, long before the modern antibiotic era. Genomic analysis also showed that, in addition to core genomic differences, HA E. faecium harbor specific accessory genetic elements that may confer selection advantages over CA E. faecium. The third part of my project discovered 6 E. faecium genes with the newly identified “WxL” domain. My analyses, using RT-PCR, western blots, patient sera, whole-cell ELISA, and immunogold electron microscopy, indicated that E. faecium WxL genes exist in operons, encode bacterial cell surface localized proteins, that WxL proteins are antigenic in humans, and are more exposed on the surface of clinical isolates versus community isolates (even though they are ubiquitous in both clades). ELISAs and BIAcore analyses also showed that proteins encoded by these operons bind several different host extracellular matrix proteins, as well as to each other, suggesting a novel cell-surface complex. In summary, my studies provide new insights into the evolution of E. faecium by showing that there are two distantly related clades; one being more successful in the hospital setting. My studies also identified operons encoding WxL proteins whose characteristics could also contribute to colonization and virulence within this species.

Depths and ages of seismic sequence boundaries in ODP Leg 166 holes

High-resolution, multichannel seismic data collected across the Great Bahama Bank margin and the adjacent Straits of Florida indicate that the deposition of Neogene-Quaternary strata in this transect are controlled by two sedimentation mechanisms: (1) west-dipping layers of the platform margin, which are a product of sea-level-controlled, platform-derived downslope sedimentation; and (2) east- or north-dipping drift deposits in the basinal areas, which are deposited by ocean currents. These two sediment systems are active simultaneously and interfinger at the toe-of-slope. The prograding system consists of sigmoidal clinoforms that advanced the margin some 25 km into the Straits of Florida. The foresets of the clinoforms are approximately 600 m high with variable slope angles that steepen significantly in the Pleistocene section. The seismic facies of the prograding clinoforms on the slope is characterized by dominant, partly chaotic, cut-and-fill geometries caused by submarine canyons that are oriented downslope. In the basin axis, seismic geometries and facies document deposition from and by currents. Most impressive is an 800-m-thick drift deposit at the confluence of the Santaren Channel and the Straits of Florida. This "Santaren Drift" is slightly asymmetric, thinning to the north. The drift displays a highly coherent seismic facies characterized by a continuous succession of reflections, indicating very regular sedimentation. Leg 166 of the Ocean Drilling Program (ODP) drilled a transect of five deep holes between 2 and 30 km from the modern platform margin and retrieved the sediments from both the slope and basin systems. The Neogene slope sediments consist of peri-platform oozes intercalated with turbidites, whereas the basinal drift deposits consist of more homogeneous, fine-grained carbonates that were deposited without major hiatuses by the Florida Current starting at approximately 12.4 Ma. Sea-level fluctuations, which controlled the carbonate production on Great Bahama Bank by repeated exposure of the platform top, controlled lithologic alternations and hiatuses in sedimentation across the transect. Both sedimentary systems are contained in 17 seismic sequences that were identified in the Neogene-Quaternary section. Seismic sequence boundaries were identified based on geometric unconformities beneath the Great Bahama Bank. All the sequence boundaries could be traced across the entire transect into the Straits of Florida. Biostratigraphic age determinations of seismic reflections indicate that the seismic reflections of sequence boundaries have chronostratigraphic significance across both depositional environments.

(Table 1) Age model for ODP Site 175-1077 based on oxygen isotopes of Globigerinoides ruber pink

Palynological records from the Congo fan reveal environmental change in equatorial Africa occurring 1.05 Ma ago, 100 k.y. before the mid-Pleistocene climatic shift at 0.9 Ma. Prior to 1.05 Ma, a glacial-interglacial rhythm is not obvious in the African vegetation variation. Afterwards, Podocarpus spread in the mountains of central Africa mainly during glacials and Congo River discharge decreased. The sequence of vegetation variation associated with the mid-Pleistocene glacials and interglacials differed from that observed during the late Pleistocene. Between 0.9 and 0.6 Ma, interglacials were characterized by warm dry conditions and glacials were characterized by cool humid conditions, while during the past 0.2 Ma glacials were cold and dry and interglacials warm and humid. Our data indicate that before the Northern Hemisphere ice caps dramatically increased in size (0.9-0.6 Ma), low-latitude climate forcing and response in the tropics played an important role in the initiation of 100 k.y. ice-age cycles. During the mid to late Pleistocene, however, the climate conditions in the tropics were increasingly influenced by the glacial-interglacial variations of continental ice sheets.

Stable isotope, seismic sequence boundaries and bioevents in ODP Hole 166-1006A

During ODP Leg 166, the recovery of cores from a transect of drill sites across the Bahamas margin from marginal to deep basin environments was an essential requirement for the study of the response of the sedimentary systems to sea-level changes. A detailed biostratigraphy based on planktonic foraminifera was performed on ODP Hole 1006A for an accurate stratigraphic control. The investigated late middle Miocene-early Pliocene sequence spans the interval from about 12.5 Ma (Biozone N12) to approximately 4.5 Ma (Biozone N19). Several bioevents calibrated with the time scale of Berggren et al. (1995a,b) were identified. The ODP Site 1006 benthic oxygen isotope stratigraphy can be correlated to the corresponding deep-water benthic oxygen isotope curve from ODP Site 846 in the Eastern Equatorial Pacific (Shackleton et al., 1995. Proc. ODP Sci. Res. 138, 337-356), which was orbitally tuned for the entire Pliocene into the latest Miocene at 6.0 Ma. The approximate stratigraphic match of the isotopic signals from both records between 4.5 and 6.0 Ma implies that the paleoceanographic signal from the Bahamas is not simply a record of regional variations but, indeed, represents glacio-eustatic fluctuations. The ODP Site 1006 oxygen and carbon isotope record, based on benthic and planktonic foraminifera, was used to define paleoceanographic changes on the margin, which could be tied to lithostratigraphic events on the Bahamas carbonate platform using seismic sequence stratigraphy. The oxygen isotope values show a general cooling trend from the middle to late Miocene, which was interrupted by a significant trend towards warmer sea-surface temperatures (SST) and associated sea-level rise with decreased ice volume during the latest Miocene. This trend reached a maximum coincident with the Miocene/Pliocene boundary. An abrupt cooling in the early Pliocene then followed the warming which continued into the earliest Pliocene. The late Miocene paleoceanographic evolution along the Bahamas margin can be observed in the ODP Site 1006 delta13C values, which support other evidence for the beginning of the closure of the Panama gateway at 8 Ma followed by a reduced intermediate water supply of water from the Pacific into the Caribbean at about 5 Ma. A general correlation of lower sedimentation rates with the major seismic sequence boundaries (SSBs) was observed. Additionally, the SSBs are associated with transitions towards more positive oxygen isotope excursions. This observed correspondence implies that the presence of a SSB, representing a density impedance contrast in the sedimentary sequence, may reflect changes in the character of the deposited sediment during highstands versus those during lowstands. However, not all of the recorded oxygen isotope excursions correspond to SSBs. The absence of a SSB in association with an oxygen isotope excursion indicates that not all oxygen isotope sea-level events impact the carbonate margin to the same extent, or maybe even represent equivalent sea-level fluctuations. Thus, it can be tentatively concluded that SSBs produced on carbonate margins do record sea-level fluctuations but not every sea-level fluctuation is represented by a SSB in the sequence stratigraphic record.

A region based approach to background modeling in a wavelet multi-resolution framework

In the field of detection and monitoring of dynamic objects in quasi-static scenes, background subtraction techniques where background is modeled at pixel-level, although showing very significant limitations, are extensively used. In this work we propose a novel approach to background modeling that operates at region-level in a wavelet based multi-resolution framework. Based on a segmentation of the background, characterization is made for each region independently as a mixture of K Gaussian modes, considering the model of the approximation and detail coefficients at the different wavelet decomposition levels. Background region characterization is updated along time, and the detection of elements of interest is carried out computing the distance between background region models and those of each incoming image in the sequence. The inclusion of the context in the modeling scheme through each region characterization makes the model robust, being able to support not only gradual illumination and long-term changes, but also sudden illumination changes and the presence of strong shadows in the scene