Interventions to control nosocomial infections : study designs and statistical issues

There is a wide range of potential study designs for intervention studies to decrease nosocomial infections in hospitals. The analysis is complex due to competing events, clustering, multiple timescales and time-dependent period and intervention variables. This review considers the popular pre-post quasi-experimental design and compares it with randomized designs. Randomization can be done in several ways: randomization of the cluster [intensive care unit (ICU) or hospital] in a parallel design; randomization of the sequence in a cross-over design; and randomization of the time of intervention in a stepped-wedge design. We introduce each design in the context of nosocomial infections and discuss the designs with respect to the following key points: bias, control for nonintervention factors, and generalizability. Statistical issues are discussed. A pre-post-intervention design is often the only choice that will be informative for a retrospective analysis of an outbreak setting. It can be seen as a pilot study with further, more rigorous designs needed to establish causality. To yield internally valid results, randomization is needed. Generally, the first choice in terms of the internal validity should be a parallel cluster randomized trial. However, generalizability might be stronger in a stepped-wedge design because a wider range of ICU clinicians may be convinced to participate, especially if there are pilot studies with promising results. For analysis, the use of extended competing risk models is recommended.

Non-market use and non-use values for preserving ecosystem services over time : a choice experiment application to coral reef ecosystems in New Caledonia

Non-use values (i.e. economic values assigned by individuals to ecosystem goods and services unrelated to current or future uses) provide one of the most compelling incentives for the preservation of ecosystems and biodiversity. Assessing the non-use values of non-users is relatively straightforward using stated preference methods, but the standard approaches for estimating non-use values of users (stated decomposition) have substantial shortcomings which undermine the robustness of their results. In this paper, we propose a pragmatic interpretation of non-use values to derive estimates that capture their main dimensions, based on the identification of a willingness to pay for ecosystem protection beyond one's expected life. We empirically test our approach using a choice experiment conducted on coral reef ecosystem protection in two coastal areas in New Caledonia with different institutional, cultural, environmental and socio-economic contexts. We compute individual willingness to pay estimates, and derive individual non-use value estimates using our interpretation. We find that, a minima, estimates of non-use values may comprise between 25 and 40% of the mean willingness to pay for ecosystem preservation, less than has been found in most studies.

Exit polls, turnout, and bandwagon voting: Evidence from a natural experiment

We exploit a voting reform in France to estimate the causal effect of exit poll information on turnout and bandwagon voting. Before the change in legislation, individuals in some French overseas territories voted after the election result had already been made public via exit poll information from mainland France. We estimate that knowing the exit poll information decreases voter turnout by about 11 percentage points. Our study is the first clean empirical design outside of the laboratory to demonstrate the effect of such knowledge on voter turnout. Furthermore, we find that exit poll information significantly increases bandwagon voting; that is, voters who choose to turn out are more likely to vote for the expected winner.

Control of rabbits in arid Australia: destroying the drought refuge

Rabbits continued to infest Bulloo Downs in southwest Queensland even after rabbit haemorrhagic disease virus (RHDV) had effectively reduced rabbit populations to very low levels in most other arid parts of Australia. Control efforts for over 100 years have all appeared unable to stop rabbits causing damage to cattle production and native plants and animals in the area. In 2001 an experiment established to measure the benefit of rabbit control to biodiversity and cattle production showed warren ripping to cause an immediate reduction in rabbit activity. Three months after ripping there were still 98% fewer rabbits in ripped plots despite these plots being exposed to invasion from surrounding populations. The cost of ripping was high because of the high density of warrens and is prohibitive for a full-scale programme. Nevertheless, ripping warrens just in the rabbit’s drought refuge (2002 -2004) appears to have effectively controlled rabbits over the entire property. Following one good season rabbits still have not recovered where the drought refuge was effectively ripped. Destroying warrens in the areas where rabbits survived droughts achieved a reduction in rabbits of over 99% ompared to a similar area near Coongie Lakes in South Australia. Low rabbit numbers allowed cattle to continue to be run on the property even though the area experienced seven consecutive years with below average rainfall. It still remains to be seen whether rabbits can recover from this low population-base during a run of good seasons. If rabbit numbers remain suppressed after a run of good seasons then rabbit control by destruction of drought refuge could be repeated at Coongie Lakes and other drought refuge areas in the arid zone. Identification and treatment of areas similar to Bulloo Downs where rabbits survive drought may relieve a very large area of arid Australia from the damage caused by rabbits.

Stem injection: a control technique often overlooked for exotic woody weeds

In the rangelands of northern Australia, basal bark, cut stump, hand applied residual herbicides and foliar spraying have traditionally been the main herbicide techniques for control of individual exotic woody weeds growing within scattered to medium density infestations. In this paper we report on the preliminary results of stem injection as an alternate technique for the control of yellow oleander ( Cascabela thevetia (L.) Lippold), a woody weed that is difficult to kill. A randomised complete block experiment comprising 12 herbicide treatments (including a control) and three replicates was undertaken. Two rates of triclopyr + picloram, hexazinone, glyphosate, 2,4- D + picloram and metsufuron methyl and one rate of imazapyr were tested. At 15 months after application, triclopyr + picloram, glyphosate, 2,4-D + picloram and imazapyr all recorded high mortality (>90%) for at least one application rate. These results suggest that stem injection warrants further investigation as a control technique for other exotic woody weeds growing in rangelands.

Foliar herbicide control of sticky florestina (Florestina tripteris DC.)

Sticky florestina (Florestina tripteris DC.) is an annual exotic weed that has become naturalised near the townships of Tambo and Barcaldine in central western Queensland, Australia. Three experiments conducted near Barcaldine identified foliar herbicides effective in killing sticky florestina plants and in providing residual activity to reduce recruitment from the soil seed bank. An initial chemical screening experiment evaluated the efficacy of 28 herbicide treatments. The most promising herbicides were then further evaluated in two response-rate experiments. Overall, 2,4-D/picloram, aminopyralid/fluroxypyr, clopyralid, metsulfuron-methyl and triclopyr/picloram proved to be the most effective selective herbicides. Two of these, metsulfuron-methyl at 18 g active ingredient (a.i) ha–1 and 2,4-D + picloram at 900 g a.i. ha–1 + 225 g a.i. ha–1 have now been included in a minor use permit (PER11920) with the Australian Pesticides and Veterinary Medicines Authority (APVMA) for the control of sticky florestina in pasture, stock route, roadside and non-crop situations using both spot and boom-spray applications (APVMA 2010). The permit also allows the use of 2,4-D amine for the control of seedlings only.

Field and laboratory evaluation of fungicides for the control of Phytophthora fruit rot of papaya in far north Queensland, Australia

Results from the first of two artificially inoculated field experiments showed foliar applications of copper hydroxide (Blue Shield Copper) at 600 g a.i./100 L−1 (0% infected fruit), copper hydroxide + metalaxyl-M (Ridomil Gold Plus.) at 877.5 g a.i./100 L−1 (0.27%), metiram + pyraclostrobin (Aero) at 720 g a.i./100 L−1 (0.51%), chlorothalonil (Bravo WeatherStik) at 994 g a.i./100 L−1 (0.63%) and cuprous oxide (Nordox 750 WG) at 990 g a.i./100 L−1 (0.8%) of water significantly reduced the percentage of infected fruit compared to potassium phosphonate (Agri-Fos 600) at 1200 g a.i./100 L−1 (8.22%), dimethomorph (Acrobat) at 108 g a.i./100 L−1 (11.18%) and the untreated control (16%). Results from the second experiment showed fruit sprayed with copper hydroxide (Champ Dry Prill) at 300 (2.0% infected fruit), 375 (0.4%) and 450 g a.i./100 L−1 (0.6%) and metiram + pyraclostrobin (Aero) at 360 (2.8%), 480 (0.6%) and 600 g a.i./100 L−1 of water (1.0%) significantly reduced the percentage of infected fruit compared to the untreated control (19.4%). Foliar sprays of copper hydroxide at 375 g a.i./100 L−1 in rotation with chlorothalonil at 994 g a.i./100 L−1 every two weeks is now recommended to growers for controlling Phytophthora fruit rot of papaya.

Evaluation of chlorothalonil and paraffinic oil alone and in combinations with registered fungicides for the control of yellow Sigatoka (Mycosphaerella musicola) of bananas in Northern Queensland, Australia

The efficacy of chlorothalonil and paraffinic oil alone and in combinations with the registered fungicides propiconazole, tebuconazole, difenoconazole, epoxiconazole and pyrimethanil was evaluated in a field experiment over two cropping cycles in 2013 and 2014 in Northern Queensland, Australia, for control of yellow Sigatoka (caused by Mycosphaerella musicola) of banana. The predominantly applied by the banana industry treatment mancozeb with paraffinic oil was included for comparison. The results from the two cropping cycles suggested that all chemicals used with paraffinic oil were as effective or more effective than when applied with chlorothalonil, and chlorothalonil alone. Difenoconazole and epoxiconazole with paraffinic oil followed by propiconazole with paraffinic oil were the most effective treatments. Pyrimethanil and tebuconazole plus chlorothalonil were the least effective treatments. None of the chemical treatments was phytotoxic or reduced yield.

Dual-trap optical tweezers with real-time force clamp control

Single molecule force clamp experiments are widely used to investigate how enzymes, molecular motors, and other molecular mechanisms work. We developed a dual-trap optical tweezers instrument with real-time (200 kHz update rate) force clamp control that can exert 0–100 pN forces on trapped beads. A model for force clamp experiments in the dumbbell-geometry is presented. We observe good agreement between predicted and observed power spectra of bead position and force fluctuations. The model can be used to predict and optimize the dynamics of real-time force clamp optical tweezers instruments. The results from a proof-of-principle experiment in which lambda exonuclease converts a double-stranded DNA tether, held at constant tension, into its single-stranded form, show that the developed instrument is suitable for experiments in single molecule biology.

Seed Longevity of Melaleuca quinquenervia: A Burial Experiment in South Florida

Burial and removal techniques with seed bags were used to examine the viability and longevity of Melaleuca quinquenervia seeds at four field sites representing different soil types and hydrological conditions in South Florida. Seed viability was determined over different burial durations in the soil through a combination of germination tests and 2,3,5-triphenyl- tetrazolium chloride (TTC) treatments. Control seeds kept dry at 25 C in the laboratory maintained same viability of ca. 15% over the 3-year study. In the field, seed viability decreased with increased burial duration.(PDF has 4 pages.)

Biotic vs. Abiotic Control of Decomposition: A Comparison of the Effects of Simulated Extinctions and Changes in Temperature

The loss of species is known to have significant effects on ecosystem functioning, but only recently has it been recognized that species loss might rival the effects of other forms of environmental change on ecosystem processes. There is a need for experimental studies that explicitly manipulate species richness and environmental factors concurrently to determine their relative impacts on key ecosystem processes such as plant litter decomposition. It is crucial to understand what factors affect the rate of plant litter decomposition and the relative magnitude of such effects because the rate at which plant litter is lost and transformed to other forms of organic and inorganic carbon determines the capacity for carbon storage in ecosystems and the rate at which greenhouse gasses such as carbon dioxide are outgassed. Here we compared how an increase in water temperature of 5 degrees C and loss of detritivorous invertebrate and plant litter species affect decomposition rates in a laboratory experiment simulating stream conditions. Like some prior studies, we found that species identity, rather than species richness per se, is a key driver of decomposition, but additionally we showed that the loss of particular species can equal or exceed temperature change in its impact on decomposition. Our results indicate that the loss of particular species can be as important a driver of decomposition as substantial temperature change, but also that predicting the relative consequences of species loss and other forms of environmental change on decomposition requires knowledge of assemblages and their constituent species' ecology and ecophysiology.

Active phase control and frequency chirp effects on supercontinuum generation in high birefringence photonic crystal fiber

An acoustic-optics programmable dispersive filter (AOPDF) was first employed to actively control the linearly polarized femtosecond pump pulse frequency chirp for supercontinuum (SC) generation in a high birefringence photonic crystal fiber (PCF). By accurately controlling the second order phase distortion and polarization direction of incident pulses, the output SC spectrum can be tuned to various spectral energy distributions and bandwidths. The pump pulse energy and bandwidth are preserved in our experiment. It is found that SC with broader bandwidth can be generated with positive chirped pump pulses except when the chirp value is larger than the optimal value, and the same optimal value exists for the pump pulses polarized along the two principal axes. With optimal positive chirp, more than 78% of the pump energy can be transferred to below 750 nm. Otherwise, negative chirp will weaken the blue-shift broadening and the SC bandwidth. (C) 2007 Elsevier B.V. All rights reserved.

Characterization of the neural mechanisms supporting the implementation of cognitive control in human decision making

Humans are particularly adept at modifying their behavior in accordance with changing environmental demands. Through various mechanisms of cognitive control, individuals are able to tailor actions to fit complex short- and long-term goals. The research described in this thesis uses functional magnetic resonance imaging to characterize the neural correlates of cognitive control at two levels of complexity: response inhibition and self-control in intertemporal choice. First, we examined changes in neural response associated with increased experience and skill in response inhibition; successful response inhibition was associated with decreased neural response over time in the right ventrolateral prefrontal cortex, a region widely implicated in cognitive control, providing evidence for increased neural efficiency with learned automaticity. We also examined a more abstract form of cognitive control using intertemporal choice. In two experiments, we identified putative neural substrates for individual differences in temporal discounting, or the tendency to prefer immediate to delayed rewards. Using dynamic causal models, we characterized the neural circuit between ventromedial prefrontal cortex, an area involved in valuation, and dorsolateral prefrontal cortex, a region implicated in self-control in intertemporal and dietary choice, and found that connectivity from dorsolateral prefrontal cortex to ventromedial prefrontal cortex increases at the time of choice, particularly when delayed rewards are chosen. Moreover, estimates of the strength of connectivity predicted out-of-sample individual rates of temporal discounting, suggesting a neurocomputational mechanism for variation in the ability to delay gratification. Next, we interrogated the hypothesis that individual differences in temporal discounting are in part explained by the ability to imagine future reward outcomes. Using a novel paradigm, we imaged neural response during the imagining of primary rewards, and identified negative correlations between activity in regions associated the processing of both real and imagined rewards (lateral orbitofrontal cortex and ventromedial prefrontal cortex, respectively) and the individual temporal discounting parameters estimated in the previous experiment. These data suggest that individuals who are better able to represent reward outcomes neurally are less susceptible to temporal discounting. Together, these findings provide further insight into role of the prefrontal cortex in implementing cognitive control, and propose neurobiological substrates for individual variation.