The prospective evaluation of the TB strain typing service in England: a mixed methods study.

BACKGROUND: In response to rising TB notification rates in England, universal strain typing was introduced in 2010. We evaluated the acceptability, effectiveness and cost-effectiveness of the TB strain typing service (TB-STS). METHODS: We conducted a mixed-methods evaluation using routine laboratory, clinic and public health data. We estimated the effect of the TB-STS on detection of false positive Mycobacterium tuberculosis diagnoses (2010-2012); contact tracing yield (number of infections or active disease per pulmonary TB case); and diagnostic delay. We developed a deterministic age-structured compartmental model to explore the effectiveness of the TB-STS, which informed a cost-effectiveness analysis. RESULTS: Semi-structured interviews explored user experience. Strain typing identified 17 additional false positive diagnoses. The TB-STS had no significant effect on contact tracing yield or diagnostic delay. Mathematical modelling suggested increasing the proportion of infections detected would have little value in reducing TB incidence in the white UK-born population. However, in the non-white UK-born and non-UK-born populations, over 20 years, if detection of latent infection increases from 3% to 13% per year, then TB incidence would decrease by 11%; reducing diagnostic delay by one week could lead to 25% reduction in incidence. The current TB-STS was not predicted to be cost-effective over 20 years (£95 628/quality-adjusted life-years). Interviews found people had mixed experiences, but identified broader benefits, of the TB-STS. CONCLUSIONS: To reduce costs, improve efficiency and increase effectiveness, we recommend changes to the TB-STS, including discontinuing routine cluster investigations and focusing on reducing diagnostic delay across the TB programme. This evaluation of a complex intervention informs the future of strain typing in the era of rapidly advancing technologies.

Evaluating stakeholder's perspective on referred out genetic testing in Canada: a discrete choice experiment.

The expanding number and increasing utility of clinical genetic tests is creating a growing burden on the Canadian healthcare system. Administrators are faced with the challenge of determining which genetic tests should be publicly funded. A discrete choice experiment (DCE) was utilized to assess the importance stakeholders place on five attributes of a genetic test. One hundred ninety individuals completed the DCE questions. Analysis of the data revealed that medical benefit of a test had the greatest impact on a respondent's decision to select a test for funding. The detection rate of the test ranked second in importance followed by severity of the condition, aim of the test, and cost. With limited resources available for referred out molecular genetic testing within a public healthcare setting such as Canada's, funding guidelines are critical. Our findings provide further evidence for the value of a decision-making framework and the relative importance of specific test attributes within such a framework.

An assessment of Canadian systems for triaging referred out genetic testing.

The field of genetics is evolving rapidly, significantly expanding the number of clinically useful genetic tests. The cost of genetic testing has created an increasing burden on public health care budgets. In Canada, funding bodies have responded by developing independent systems. Key individuals in each province and territory participated in a semi-structured interview regarding the process in their jurisdiction to approve funding for referred out genetic testing and their decision-making criteria. Two themes were identified: the importance of clinical utility in decision-making and the utilization of genetic specialists as gate keepers. Allocation of a specific budget appears to be associated with some fiscal responsibility. Collaboration between provincial and territorial bodies may lead to a more unified approach across Canada.

Formation of phase space holes and clumps.

It is shown that the formation of phase space holes and clumps in kinetically driven, dissipative systems is not restricted to the near threshold regime, as previously reported and widely believed. Specifically, we observe hole-clump generation from the edges of an unmodulated phase space plateau, created via excitation, phase mixing and subsequent dissipative decay of a linearly unstable bulk plasma mode in the electrostatic bump-on-tail model. This has now allowed us to elucidate the underlying physics of the hole-clump formation process for the first time. Holes and clumps develop from negative energy waves that arise due to the sharp gradients at the interface between the plateau and the nearly unperturbed, ambient distribution and destabilize in the presence of dissipation in the bulk plasma. We confirm this picture by demonstrating that the formation of such nonlinear structures in general does not rely on a "seed" wave, only on the ability of the system to generate a plateau. In addition, we observe repetitive cycles of plateau generation and erosion, the latter due to hole-clump formation and detachment, which appear to be insensitive to initial conditions and can persist for a long time. We present an intuitive discussion of why this continual regeneration occurs.

Campylobacteriosis outbreak associated with consumption of undercooked chicken liver pâté in the East of England, September 2011: identification of a dose-response risk.

A foodborne outbreak with 49 cases (22 culture positive for Campylobacter sp.) following a wedding party in the East of England was investigated. A retrospective cohort study identified an association between consumption of chicken liver pâté and infection with Campylobacter jejuni/coli. There was a statistically significant association between dose (amount of chicken liver pâté eaten) and the risk of disease ['tasted': odds ratio (OR) 1·5, 95% confidence interval (CI) 0·04-∞; 'partly eaten': OR 8·4, 95% CI 1·4-87·5; 'most or all eaten': OR 36·1, 95% CI 3·3-2119). The local authority found evidence that the preparation of chicken livers breached Food Standards Agency's guidelines. This epidemiological investigation established a clear dose-response relationship between consumption of chicken liver pâté and the risk of infection with Campylobacter. The continuing need to raise public awareness of the risk to human health posed by undercooked chicken liver is evident.

A centralized approach to out-of-province genetic testing leads to cost savings: the Alberta experience.

The Genetic Resource Center (GRC) is a centralized process for requesting genetic testing that is not available within the province (Alberta, Canada). In order to assess potential cost savings associated with this process, all applications received by the GRC in 2010 were reviewed, and cost savings were recorded for statistical analysis. Seven areas of cost savings were identified: (i) negotiated pricing, (ii) laboratory selection, (iii) testing setup in-province, (iv) duplicate testing, (v) inappropriate testing, (vi) sequential testing and (vii) testing offered within the province.The total test cost of the 615 applications submitted in 2010 without the GRC process would have been $766,783 (Canadian dollars). A total cost savings of $112,201 was achieved through the GRC, which represents 15% of the total cost of requested testing ($112,201/$766,783). This is the first study to examine areas of cost savings for genetic testing sent out-of-province. The greatest cost savings resulted from the areas of laboratory selection and negotiated pricing. A centralized process to manage out-of-province genetic test requests results in consistency in testing and significant cost savings.

Genetic factors affecting food-plant specialization of an oligophagous seed predator.

Several ecological and genetic factors affect the diet specialization of insect herbivores. The evolution of specialization may be constrained by lack of genetic variation in herbivore performance on different food-plant species. By traditional view, trade-offs, that is, negative genetic correlations between the performance of the herbivores on different food-plant species favour the evolution of specialization. To investigate whether there is genetic variation or trade-offs in herbivore performance between different food plants that may influence specialization of the oligophagous seed-eating herbivore, Lygaeus equestris (Heteroptera), we conducted a feeding trial in laboratory using four food-plant species. Although L. equestris is specialized on Vincetoxicum hirundinaria (Apocynaceae) to some degree, it occasionally feeds on alternative food-plant species. We did not find significant negative genetic correlations between mortality, developmental time and adult biomass of L. equestris on the different food-plant species. We found genetic variation in mortality and developmental time of L. equestris on some of the food plants, but not in adult biomass. Our results suggest that trade-offs do not affect adaptation and specialization of L. equestris to current and novel food-plant species, but the lack of genetic variation may restrict food-plant utilization. As food-plant specialization of herbivores may have wide-ranging effects, for instance, on coevolving plant-herbivore interactions and speciation, it is essential to thoroughly understand the factors behind the specialization process. Our findings provide valuable information about the role of genetic factors in food-plant specialization of this oligophagous herbivore.

A human metapneumovirus outbreak at a community hospital in England, July to September 2010.

We describe an outbreak of human metapneumovirus (hMPV) which occurred in July-September 2010 at a community hospital in the East of England. Based on the medical and nursing records, cases were retrospectively defined as suspected if they had had an influenza-like illness (ILI), and probable if they had had an ILI and an epidemiological link to a laboratory-confirmed case. Of a total of 17 symptomatic inpatients, five were classified as probable cases, five were laboratory confirmed and seven were suspected. The attack rate was 29.4% for confirmed and probable cases combined. The median age of symptomatic inpatients was 85 years-old (range 68-96) and the majority (16/17) of symptomatic inpatients had an underlying medical condition. Control measures introduced appeared to restrict further exposure of susceptible patients to infection although modelling suggested that up to four of 10 confirmed and probable cases (40%) could have been prevented through more timely diagnosis and recognition of an outbreak. These findings suggest that there should be increased awareness of hMPV infection within healthcare settings, particularly when the population at risk has a high prevalence of underlying co-morbidities.

Streptococcus pyogenes cluster in a care home in England April to June 2010.

Two fatal cases of Streptococcus pyogenes emm st22.6 bacteraemia occurred in a care home in England during April and June 2010, initiating a cluster investigation. The first case had left the home 13 days before the second case took up residence. We sought further cases and carriers. We swabbed throat and chronic skin lesions from residents and staff and examined these specimens for the presence of S. pyogenes. 61 specimens were taken from 18 of 19 residents and 39 of 39 staff. All results from swabbing were culture negative. We observed infection control practices and the environment at the care home for deficiencies. Issues were identified relating to the correct use of personal protective equipment, hand hygiene, clinical waste and laundry. Infection control practices were improved and training given. Infection control practices and the environment at a care home should be examined as part of the investigation of a S. pyogenes cluster. Screening for carriage of S. pyogenes should be done before antibiotic chemoprophylaxis is issued to care home residents and staff.

Genetic variation in herbivore resistance and tolerance: the role of plant life-history stage and type of damage.

Information of the patterns of genetic variation in plant resistance and tolerance against herbivores and genetic trade-offs between these two defence strategies is central for our understanding of the evolution of plant defence. We found genetic variation in resistance to two specialist herbivores and in tolerance to artificial damage but not to a specialist leaf herbivore in a long-lived perennial herb. Seedlings tended to have genetic variation in tolerance to artificial damage. Genetic variation in tolerance of adult plants to artificial damage was not consistent in time. Our results suggest that the level of genetic variation in tolerance and resistance depends on plant life-history stage, type of damage and timing of estimating the tolerance relative to the occurrence of the damage, which might reflect the pattern of selection imposed by herbivory. Furthermore, we found no trade-offs between resistance and tolerance, which suggests that the two defence strategies can evolve independently.

The quantum event of oceanic crustal accretion: impacts of diking at mid-ocean ridges.

Seafloor diking-eruptive events represent the irreducible, quantum events of upper oceanic crustal accretion. They record events by which a large portion of the oceanic crust has formed through geological history. Since 1993, the U.S. Navy's real-time Sound Surveillance System has allowed location of ongoing acoustic signatures of dike emplacement and basalt eruptions at ridge crests in the northeast Pacific. These diking-eruptive events trigger a sequence of related, rapidly evolving physical, chemical, and biological processes. Magmatic volatiles released during these events may provide nutrients for communities of subsea-floor microorganisms, some of which thrive in high-temperature anaerobic environments. Many of the organisms identified from these systems are Archaea. If microorganisms can thrive in the water-saturated pores and cracks within deep, volcanically active portions of our planet, other hydrothermally active planets may harbor similar life forms.

Biogeography and ecological setting of Indian Ocean hydrothermal vents.

Within the endemic invertebrate faunas of hydrothermal vents, five biogeographic provinces are recognized. Invertebrates at two Indian Ocean vent fields (Kairei and Edmond) belong to a sixth province, despite ecological settings and invertebrate-bacterial symbioses similar to those of both western Pacific and Atlantic vents. Most organisms found at these Indian Ocean vent fields have evolutionary affinities with western Pacific vent faunas, but a shrimp that ecologically dominates Indian Ocean vents closely resembles its Mid-Atlantic counterpart. These findings contribute to a global assessment of the biogeography of chemosynthetic faunas and indicate that the Indian Ocean vent community follows asymmetric assembly rules biased toward Pacific evolutionary alliances.

Patterns of invasive ctenophore Mnemiopsis leidyi distribution and variability in different recipient environments of the Eurasian seas: A review.

Harmful invader ctenophore Mnemiopsis leidyi's expansions in the Eurasian Seas, its spatio-temporal population dynamics depending on environmental conditions in recipient habitats have been synthesized. M. leidyi found suitable temperature, salinity and productivity conditions in the temperate and subtropical environments of the semi-enclosed seas, in the coastal areas of open basins and in closed water bodies, where it created autonomous populations. M. leidyi changes its phenology depending on seasonal temperature regime in different environments. We assessed ranges of sea surface temperature, sea surface salinity and sea surface chlorophyll values, sufficient for M. leidyi general occurrence and reproduction based on comprehensive long-term datasets, contributed by co-authors. This assessment revealed that there are at least two eco-types (Southern and Northern) in the recipient seas of Eurasia with features specific for their donor areas. The range of thresholds for M. leidyi establishment, occurrence and life cycle in both eco-types depends on variability of environmental parameters in their native habitats.

Linkages between mineralogy, fluid chemistry, and microbial communities within hydrothermal chimneys from the Endeavour Segment, Juan de Fuca Ridge.

Rock and fluid samples were collected from three hydrothermal chimneys at the Endeavour Segment, Juan de Fuca Ridge to evaluate linkages among mineralogy, fluid chemistry, and microbial community composition within the chimneys. Mössbauer, midinfrared thermal emission, and visible-near infrared spectroscopies were utilized for the first time to characterize vent mineralogy, in addition to thin-section petrography, X-ray diffraction, and elemental analyses. A 282°C venting chimney from the Bastille edifice was composed primarily of sulfide minerals such as chalcopyrite, marcasite, and sphalerite. In contrast, samples from a 300°C venting chimney from the Dante edifice and a 321°C venting chimney from the Hot Harold edifice contained a high abundance of the sulfate mineral anhydrite. Geochemical modeling of mixed vent fluids suggested the oxic-anoxic transition zone was above 100°C at all three vents, and that the thermodynamic energy available for autotrophic microbial redox reactions favored aerobic sulfide and methane oxidation. As predicted, microbes within the Dante and Hot Harold chimneys were most closely related to mesophilic and thermophilic aerobes of the Betaproteobacteria and Gammaproteobacteria and sulfide-oxidizing autotrophic Epsilonproteobacteria. However, most of the microbes within the Bastille chimney were most closely related to mesophilic and thermophilic anaerobes of the Deltaproteobacteria, especially sulfate reducers, and anaerobic hyperthermophilic archaea. The predominance of anaerobes in the Bastille chimney indicated that other environmental factors promote anoxic conditions. Possibilities include the maturity or fluid flow characteristics of the chimney, abiotic Fe2+ and S2- oxidation in the vent fluids, or O2 depletion by aerobic respiration on the chimney outer wall.

Antiasthmatic effects of a leukotriene biosynthesis inhibitor (MK-0591) in allergic dogs.

Peptidoleukotrienes may be important mediators of human bronchial asthma. Accordingly, the effects of a selective leukotriene (LT) biosynthesis inhibitor (MK-0591) were assessed in allergic dogs characterized by acute bronchoconstriction and subsequent airway hyperresponsiveness induced by inhaled ragweed allergen. Peak acute increases in airway resistance (Rrs) induced by ragweed were associated with increased bronchoalveolar lavage histamine concentration, and neither parameter was inhibited by MK-0591 (8 micrograms.kg-1.min-1 i.v.). However, the duration of the bronchoconstriction was significantly decreased by MK-0591, with a reduction in the area under the curve of 40% (P < 0.05). Associated with the acute bronchoconstriction in placebo-treated animals was a fivefold increase in urinary LTE4 excretion (as seen with allergic asthmatic patients), which was reduced to < 10% of basal values by MK-0591. Similarly, whole blood LTB4 biosynthesis was abolished in the MK-0591-treated animals. Bronchial hyperresponsiveness preallergen (measured as the percent concentration of acetylecholine required to increase Rrs by 5 cmH2O.l-1.s) tended to improve with MK-0591 (0.41 +/- 0.15 vs. 0.23 +/- 0.05%). Five hours after allergen inhalation, the percent concentration declined substantially in the placebo group (0.07 +/- 0.02%; P < 0.01), revealing an increased airway responsiveness that was significantly blunted by MK-0591 (0.26 +/- 0.07%; P < 0.001). These data suggest that selective inhibition of LT biosynthesis by novel compounds such as MK-0591 may modify the airway changes associated with bronchial hyperresponsiveness, as well as offer symptomatic relief in asthma.

Development of chronic airway hyperresponsiveness in ragweed-sensitized dogs.

We studied dogs neonatally sensitized to ragweed and their littermate controls at 4, 6, 8, 10, 12, and 15 mo of age. Acute allergic airway response to inhalation of ragweed in the sensitized dogs was marked (greater than 12-fold increase from base line) and reproducible at all times. Nonallergic airway responsiveness, measured as the concentration of acetylcholine required to increase airway resistance by 5 cmH2O.l-1.s (PC5), increased in sensitized and decreased in nonsensitized dogs from 4 to 15 mo of age (P less than 0.01). Before antigen, at 12 and 15 mo, sensitized dogs were significantly (P less than 0.05) more responsive to acetylcholine than controls. Six hours after antigen, sensitized dogs were 11-fold more responsive (P less than 0.005) than controls at those times. More eosinophils and mast cells and fewer macrophages (P less than 0.05) were present in bronchoalveolar lavage (BAL) from 12- and 15-mo-old sensitized dogs than their controls. BAL fluid histamine was higher (P less than 0.05) in sensitized than control dogs. Regression analysis revealed r = -0.75 (P = 0.003) between BAL mast cells and PC5 in sensitized dogs and R2 = 0.89 for PC5 and BAL mast cells, macrophages, and eosinophils. Neonatally sensitized dogs represent an excellent animal model in which to study the pathophysiology of asthma.

Large particle number limit in rain.

The way we conceptualize rain is fundamental in many branches of science since it provides the basis not only for rain modeling notably in meteorology and hydrology, but also for interpreting rain data (from gauges and radars). In order to empirically address this question, we use stereophotographic data to measure the positions and volumes of raindrops from approximately 10 m(3) regions containing 5000-15,000 of these drops. By determining the drop statistics in spheres of increasing size, we conduct a basic continuum mechanics thought experiment. We show that-presumably due to turbulence-there is no microscale-macroscale separation. We find that the large particle number (N) limit in rain is not a homogeneous continuum, but rather it is nonclassical, strongly inhomogeneous, and approaching a multifractal discontinuum.

Portable X-ray fluorescence instruments for the analysis of lead in paints.

In a study in the laboratories of the Chicago Board of Health, the results from determination of lead in paint films by X-ray fluorescence were compared with results from determination by atomic absorption. Portable instruments of three suppliers were used for X-ray fluorescence measurements. An improved version of one of these instruments was also tested. The results of X-ray fluorescence readings on painted card stock panels with one of these instruments compared satisfactorily with the results as determined by the atomic absorption method at levels below 10 mg of lead per square centimeter. Readings on multiple layers of these panels were additive and independent of the order of these panels. All four instruments were tested in the laboratory on painted surfaces from the walls of condemned buildings. The most recent version of each instrument gave a correlation coefficient of 0.96 or better for the linear regression of lead values in milligrams per square centimeter by atomic absorption against instrument readings. It was calculated that a reading of 3.2 or greater on any of the instruments would indicate with greater than 95 percent confidence that 1 mg or more of lead per square centimeter would be found when a sample of the paint was analyzed by atomic absorption. When the readings of one of the instruments showed lead to be absent, that result would inidcate with better than 95 percent confidence that less than 1 mg of lead per square centimeter would be found by the atomic absorption method. Portable X-ray fluorescence instruments can be used in situ to determine whether the walls of a building give readings for lead above the range of 0 to 3.2. Walls with readings above this range can be considered to have 1 mg or more of lead per square centimeter and would not be in conformance with the code of the City of Chicago. Samples would need to be taken for analysis in the laboratory by atomic absorption only from those walls with readings within the range of 0 to 3.2.

Composite materials for x-ray protection.

We have developed and tested a radiation protection material that provides similar attenuation for diagnostic x-ray spectra to that of conventional Pb apron materials with approximately 30% reduced weight. By combining a number of elements with different K absorption energies, such as Ba, W, and Pb, energy attenuation for given spectra can be optimized with respect to total cross-sectional mass loading. Alternatively, garments with much higher protective factors at equivalent weight to conventional garments could be produced. The reduction in the amount of Pb used also reduces problems associated with the toxicity of the material during manufacture and disposal. Back strain can be reduced for personnel performing special radiological procedures that require wearing protective garments for long periods of time.