Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis.

BACKGROUND: Biologic pathways and metabolic mechanisms underpinning early systemic disease in cystic fibrosis (CF) are poorly understood. The Baby Observational and Nutrition Study (BONUS) was a prospective multi-center study of infants with CF with a primary aim to examine the current state of nutrition in the first year of life. Its secondary aim was to prospectively explore concurrent nutritional, metabolic, respiratory, infectious, and inflammatory characteristics associated with early CF anthropometric measurements. We report here metabolomics differences within the urine of these infants as compared to infants without CF. METHODS: Urine metabolomics was performed for 85 infants with predefined clinical phenotypes at approximately one year of age enrolled in BONUS via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Samples were stratified by disease status (non-CF controls (n = 22); CF (n = 63, All-CF)) and CF clinical phenotype: respiratory hospitalization (CF Resp, n = 22), low length (CF LL, n = 23), and low weight (CF LW, n = 15). RESULTS: Global urine metabolomics profiles in CF were heterogeneous, however there were distinct metabolic differences between the CF and non-CF groups. Top pathways altered in CF included tRNA charging and methionine degradation. ADCYAP1 and huntingtin were identified as predicted unique regulators of altered metabolic pathways in CF compared to non-CF. Infants with CF displayed alterations in metabolites associated with bile acid homeostasis, pentose sugars, and vitamins. CONCLUSIONS: Predicted metabolic pathways and regulators were identified in CF infants compared to non-CF, but metabolic profiles were unable to discriminate between CF phenotypes. Targeted metabolomics provides an opportunity for further understanding of early CF disease. TRIAL REGISTRATION: United States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).

Metabolic characterization of serum from mice challenged with Orientia tsutsugamushi-infected mites.

Scrub typhus is an acute zoonosis caused by the obligate intracellular Gram-negative bacterium Orientia tsutsugamushi. To better understand the host response elicited by natural infection by chigger feeding, ICR mice were infected by Leptotrombidium chiangraiensis (Lc1) chiggers, and the metabolic profiles of their serum were examined over several time points after initiation of feeding. ICR mice were infected by either naive Lc1 chiggers (i.e. not infected by O. tsutsugamushi, NLc1) or O. tsutsugamushi-infected Lc1 chiggers (OLc1). Serum was collected from both groups of mice at 6 hours and 10 days after initiation of feeding. Metabolites were extracted from the serum and analysed by ultra performance liquid chromatography-tandem mass spectrometry. The resulting ion/chromatographic features were matched to a library of chemical standards for identification and quantification. Biochemicals that differed significantly between the experimental groups were identified using Welch's two-sample t tests; p ≤ 0.05 was considered statistically significant. A number of biochemicals linked to immune function were found to be significantly altered between mice infected by the NLc1 and OLc1 chiggers, including itaconate, kynurenine and histamine. Several metabolites linked to energy production were also found to be altered in the animals. In addition lipid and carbohydrate metabolism, bile acid and phospholipid homeostasis, and nucleotide metabolism were also found to be different in these two groups of mice. Markers of stress and food intake were also significantly altered. Global untargeted metabolomic characterization revealed significant differences in the biochemical profiles of mice infected by the NLc1 versus OLc1 chiggers. These findings provide an important platform for further investigation of the host responses associated with chigger-borne O. tsutsugamushi infections.

Identifying environmental correlates of intraspecific genetic variation.

Genetic variation is critical to the persistence of populations and their capacity to adapt to environmental change. The distribution of genetic variation across a species' range can reveal critical information that is not necessarily represented in species occurrence or abundance patterns. We identified environmental factors associated with the amount of intraspecific, individual-based genetic variation across the range of a widespread freshwater fish species, the Murray cod Maccullochella peelii. We used two different approaches to statistically quantify the relative importance of predictor variables, allowing for nonlinear relationships: a random forest model and a Bayesian approach. The latter also accounted for population history. Both approaches identified associations between homozygosity by locus and both disturbance to the natural flow regime and mean annual flow. Homozygosity by locus was negatively associated with disturbance to the natural flow regime, suggesting that river reaches with more disturbed flow regimes may support larger, more genetically diverse populations. Our findings are consistent with the hypothesis that artificially induced perennial flows in regulated channels may provide greater and more consistent habitat and reduce the frequency of population bottlenecks that can occur frequently under the highly variable and unpredictable natural flow regime of the system. Although extensive river regulation across eastern Australia has not had an overall positive effect on Murray cod numbers over the past century, regulation may not represent the primary threat to Murray cod survival. Instead, pressures other than flow regulation may be more critical to the persistence of Murray cod (for example, reduced frequency of large floods, overfishing and chemical pollution).

Cultural implications of late Holocene climate change in the Cuenca Oriental, Mexico.

There is currently no consensus on the importance of climate change in Mesoamerican prehistory. Some invoke drought as a causal factor in major cultural transitions, including the abandonment of many sites at 900 CE, while others conclude that cultural factors were more important. This lack of agreement reflects the fact that the history of climate change in many regions of Mesoamerica is poorly understood. We present paleolimnological evidence suggesting that climate change was important in the abandonment of Cantona between 900 CE and 1050 CE. At its peak, Cantona was one of the largest cities in pre-Columbian Mesoamerica, with a population of 90,000 inhabitants. The site is located in the Cuenca Oriental, a semiarid basin east of Mexico City. We developed a subcentennial reconstruction of regional climate from a nearby maar lake, Aljojuca. The modern climatology of the region suggests that sediments record changes in summer monsoonal precipitation. Elemental geochemistry (X-ray fluorescence) and δ(18)O from authigenic calcite indicate a centennial-scale arid interval between 500 CE and 1150 CE, overlaid on a long-term drying trend. Comparison of this record to Cantona's chronology suggests that both the city's peak population and its abandonment occurred during this arid period. The human response to climate change most likely resulted from the interplay of environmental and political factors. During earlier periods of Cantona's history, increasing aridity and political unrest may have actually increased the city's importance. However, by 1050 CE, this extended arid period, possibly combined with regional political change, contributed to the city's abandonment.

Use of a microsatellite-based pedigree in estimation of heritabilities for economic traits in Australian blue mussel, Mytilus galloprovincialis.

This study aimed to estimate the heritabilities of three economically important traits (total weight, shell shape and meat yield) in Australian blue mussels. The estimates were derived using a pedigree reconstructed from a suite of both published and newly developed microsatellite markers. A total of 135 microsatellite loci were tested, of which 10 loci produced consistent PCR amplification and reliable results across all samples (74 full-sibling families including 74 pairs of parents and 2536 offspring). Lack of polymorphism at the non-repetitive region of the adhesive protein gene confirmed that the broodstock were derived from a single species. A total of 1538 progenies (62.5%) could be assigned to single parent pairs, and the remainder were assigned to two families or more, so were discarded from further analysis. Heritabilities for total weight, shell shape and meat yield were low (0.051 ± 0.027, 0.085 ± 0.038 and 0.049 ± 0.028, respectively) but reflected large environmental variation rather than limited genetic variation, suggesting a family-based breeding programme could improve these traits. The genetic correlation between weight and meat yield, expressed as percentage of total mussel which was not shell, was negative, while the genetic correlation between meat yield and shell shape was weakly positive.

Variable stocking effect and endemic population genetic structure in Murray cod Maccullochella peelii.

Microsatellite markers were utilized to examine the genetic structure of Murray cod Maccullochella peelii throughout its distribution in the Murray--Darling Basin (MDB) of eastern Australia, and to assess the genetic effects of over three decades of stocking hatchery-reared fingerlings. Bayesian analysis using the programme Structure indicated that the species is largely genetically panmictic throughout much of its extensive range, most probably due to the high level of connectivity between catchments. Three catchments with terminal wetlands (the Lachlan, Macquarie and Gwydir), however, contained genetically distinct populations. No stocking effects were detected in the catchments that were genetically panmictic (either because of low genetic power or lack of effects), but the genetically differentiated Gwydir and Macquarie catchment populations were clearly affected by stocking. Conversely, there was no genetic evidence for survival and reproduction of stocked fish in the Lachlan catchment. Therefore, stocking of M. peelii throughout the MDB has resulted in a range of genetic effects ranging from minimal detectable effect, to substantial change in wild population genetic structure.

Factorial aerobic scope is independent of temperature and primarily modulated by heart rate in exercising Murray cod (Maccullochella peelii peelii).

Several previous reports, often from studies utilising heavily instrumented animals, have indicated that for teleosts, the increase in cardiac output (Vb) during exercise is mainly the result of an increase in cardiac stroke volume (V(S)) rather than in heart rate (fH). More recently, this contention has been questioned following studies on animals carrying less instrumentation, though the debate continues. In an attempt to shed more light on the situation, we examined the heart rates and oxygen consumption rates (Mo2; normalised to a mass of 1 kg, given as Mo2kg) of six Murray cod (Maccullochella peelii peelii; mean mass+/-SE = 1.81+/-0.14 kg) equipped with implanted fH and body temperature data loggers. Data were determined during exposure to varying temperatures and swimming speeds to encompass the majority of the biological scope of this species. An increase in body temperature (Tb) from 14 degrees C to 29 degrees C resulted in linear increases in Mo2kg (26.67-41.78 micromol min(-1) kg(-1)) and fH (22.3-60.8 beats min(-1)) during routine exercise but a decrease in the oxygen pulse (the amount of oxygen extracted per heartbeat; 1.28-0.74 micromol beat(-1) kg(-1)). During maximum exercise, the factorial increase in Mo2kg was calculated to be 3.7 at all temperatures and was the result of temperature-independent 2.2- and 1.7-fold increases in fH and oxygen pulse, respectively. The constant factorial increases in fH and oxygen pulse suggest that the cardiovascular variables of the Murray cod have temperature-independent maximum gains that contribute to maximal oxygen transport during exercise. At the expense of a larger factorial aerobic scope at an optimal temperature, as has been reported for species of salmon and trout, it is possible that the Murray cod has evolved a lower, but temperature-independent, factorial aerobic scope as an adaptation to the largely fluctuating and unpredictable thermal climate of southeastern Australia.

A notational analysis of elite tennis strategy.

A notational analysis of singles events at all four Grand Slam tournaments between 1997 and 1999 was conducted to determine the influence of the sex of the player and court surface on elite tennis strategy. Rallies of 7.1 +/- 2.0 s in women's singles were significantly longer than those in men's singles (5.2 +/- 1.8 s; P < 0.001). Rallies of 6.3 +/- 1.8 s at the Australian Open, 7.7 +/- 1.7 s at the French Open, 4.3 +/- 1.6 s at Wimbledon and 5.8 +/- 1.9 s at the US Open were recorded. Rallies were significantly longer at the French Open than at any other tournament (P< 0.05) and significantly shorter at Wimbledon than at any other tournament (P< 0.05). In women's singles, 52.8 +/- 12.4% of points were baseline rallies, significantly more than in men's singles (28.6 +/- 19%; P < 0.001). The proportion of baseline rallies played at the French Open (51.9 +/- 14.2% of points) was significantly greater than at the Australian Open (46.6 +/- 12.5%), Wimbledon (19.7 +/- 19.4%) and the US Open (35.4 +/- 19.5%; P < 0.05). The results show that both the sex of the player and surface of the court have a significant influence on the nature of singles tennis at Grand Slam tournaments.

Measuring services: a district nursing dependency tool.

The government has highlighted the importance of reducing inequalities in health and providing an equal and high quality service to all patients. The district nursing service in Wolverhampton monitors the provision of services across the town to ensure high quality care for all patients.

Client satisfaction data and quality improvement planning in managed mental health care organizations.

Quality improvement (QI) planning is enhanced when TQM administrators ensure appropriate analysis of client satisfaction (CS) survey data. A cost-effective QI strategy is to shift "moderately satisfied" into "maximally satisfied" clients. Use of a categorical variable derived from CS data and development of a predictive model with Chi Square Automatic Interaction Detection (CHAID) produces recommendations for quality improvement.

Strontium isotopic composition of mid-cretaceous seawater.

The (87)Sr/(86)Sr ratio in fish teeth separated from mid-Cretaceous marl and black shale from the northeastern Apennines and Venetian Alps (Italy) define three periods of low (87)Sr/(86)Sr ratio at 121 to 124 million years ago (Ma), 110 to 115 Ma, and 89 to 91 Ma. The (87)Sr/(86)Sr excursions correspond to oceanic anoxic events represented by the Livello Selli, Livello 113, Livello Urbino, and Livello Bonarelli black shale marker beds and probably reflect an increase in the low-(87)Sr/(86)Sr hydrothermal strontium flux associated with the emplacement of the Ontong-Java and Kerguelen plateaus (120 to 110 Ma) and the Caribbean Plateau (89 to 91 Ma). The modeled flux is consistent with the volumes and eruption rates of the oceanic plateaus but is far smaller than expected from the proposed Cretaceous crustal production rates of 50 to 100 percent greater than modern.

Innovations in quality.

To strengthen their operations many hospitals have embraced total quality management (TQM) strategies used by companies throughout the world. California Hospitals examines how some of these hospitals have used TQM to improve clinical outcomes, cut costs, boost staff morale and increase patient satisfaction.

Strontium isotopic composition of estuarine sediments as paleosalinity-paleoclimate indicator.

The strontium isotopic composition of biogenic precipitates that occur in estuarine sediments can be used as proxy indicator of paleosalinity and for assessing precipitation and river discharge rates over thousands of years. In the San Francisco Bay estuary, river water with low (87)Sr/(86)Sr ratio (average, 0.7065) and low Sr concentration (0.13 parts per million) mixes with seawater with a higher (87)Sr/(86)Sr ratio (0.7092) and Sr concentration (7.9 parts per million). The predicted mixing relation between salinity and Sr isotopic composition is confirmed by measurements of modern estuarine surface waters. A paleosalinity record obtained from foraminifera for the ancestral San Francisco Bay during oxygen isotope substage 5e of the last interglacial reflects a global rise and fall of sea level, and short time-scale variations related to fluctuations in discharge rates of the Sacramento and San Joaquin rivers.

The therapeutic use of tape-recorded repetitions of flooding stimuli.

This clinical report describes an enhancement of imaginal flooding therapy developed in clinical practice with outpatient phobics. During the session, anxiety-producing fantasies are solicited, and the verbalizations immediately preceding peaks in emotional arousal are captured on a three-minute repeating "endless loop" cassette tape. Patients' repeated exposure to the recording, in the office and as homework, enhances the efficiency and economy of imaginal flooding.