Explore the vast range of titles available.

The aim of this study was to determine the critical care and associated hospital costs for 2009 influenza A/H1N1 patients admitted to intensive care units (ICU) in Australia and New Zealand during the southern hemisphere winter. All 762 patients admitted to ICUs in Australian and New Zealand between 1 June and 31 August 2009 with confirmed 2009 H1N1 influenza A were included. Costs were assigned based on ICU and hospital length-of-stay, using data from a single Australian ICU which estimated the daily cost of an ICU bed, along with published costs for a ward bed. Additional costs were assigned for allied health, overheads and extracorporeal membrane oxygenation services. The median (interquartile range) ICU and total hospital costs per patient were AU $35,942 ($ 10,269 to$82,152) and AU$ 51,294 ( $22,849 to $ 110,340) respectively, while the mean (standard deviation) ICU and total hospital costs per patient were AU $63,298 ($ 78,722) and AU $85,395 ($ 147,457), respectively. A multivariate analysis found death was significantly associated with a reduction in the log of total costs, while the use of mechanical ventilation and ICU admission with viral pneumonitis/acute respiratory distress syndrome or secondary bacterial pneumonia were significantly associated with an increase in the log of total costs. The cost of 2009 H1N1 patients in ICU was significantly higher than the previously published costs for an average ICU admission, and the total cost of treating 2009 H1N1 patients in ICU admitted during winter 2009 was more than $65,000,000.

The ability to pattern surfaces on a microscopic length scale is of importance for technological applications such as the fabrication of microelectronic circuits and digital storage media. Devices fabricated entirely from polymers are now available, opening up the possibility of adapting polymer processing technologies to fabricate cheap, large-area devices using non-lithographic techniques 1 , 2 —for example, by exploiting dewetting 3 and phase separation 4 , 5 , 6 in thin films. But the final pattern adopted by the polymer film using such approaches requires a template printed onto the substrate by optical lithography, microcontact printing 4 , 5 or vapour deposition 3 . Here we describe a simple process for patterning surfaces that does not require a template. Our method involves the spinodal dewetting of a polymer surface by a thin polymer film, in which a liquid film breaks up owing to the amplification of thermal fluctuations in film thickness induced by dispersion forces 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 . A preferred orientation is imposed on the dewetting process simply by rubbing the substrate, and this gives rise to patterns of remarkably well-aligned polymer lines. The width of these lines is well-defined, and is controlled by the magnitude of the dispersion forces at the interface, which in turn can be varied by varying the thickness of the polymer substrate. We expect that further work will make it possible to optimize the degree of order in the final morphology.

Using observation, eye tracking, and clinical simulation with embedded errors, we studied the impact of bar-code verification on error identification and recovery during medication administration. Data supported that bar-code verification may reduce but does not eliminate patient identification (ID) and medication errors during clinical simulation of medication administration.

Bacteriophages represent a group of viruses that specifically infect and replicate in bacteria and could potentially be used to reduce recovery of Salmonella from poultry carcasses. Bacteriophages were isolated from municipal wastewater in the presence of Salmonella enteritidis phage type 13A (SE). In the first 2 experiments, commercially processed broiler carcass rinse water was pooled and divided. The addition of 10(10) pfu/mL of a single bacteriophage (PHL 4) with selected concentrations of SE reduced (P < 0.05) frequency of SE recovered as compared with the control rinse water sample. In experiments 3 and 4, broiler carcasses were intentionally inoculated with SE, sprayed with selected concentrations of PHL 4, and rinsed for SE enrichment and isolation. Application of 5.5 mL of 10(8) or 10(10) pfu/mL of PHL 4 reduced (P < 0.05) the frequency of SE recovery as compared with controls. In experiments 5 and 6, commercially processed turkeys were rinsed with water containing 72 wild-type bacteriophages isolated against SE, which were amplified in SE, or the Salmonella isolated antemortem from drag swabs from the flock selected for in-plant treatment, or a combination of bacteriophages amplified by each bacterial host. All bacteriophage treatments reduced (P < 0.05) frequency of Salmonella recovery as compared with controls. Sufficient concentrations of an appropriate bacteriophage, or a bacteriophage mixture, can significantly reduce recoverable Salmonella from carcass rinses.

Mechanisms that regulate the growth of eyelashes have remained obscure. We ascertained two families from Pakistan who presented with familial trichomegaly, or extreme eyelash growth. Using a combination of whole exome sequencing and homozygosity mapping, we identified distinct pathogenic mutations within fibroblast growth factor 5 (FGF5) that underlie the disorder. Subsequent sequencing of this gene in several additional trichomegaly families identified an additional mutation in FGF5 . We further demonstrated that hair fibers from forearms of these patients were significantly longer than hairs from control individuals, with an increased proportion in the growth phase, anagen. Using hair follicle organ cultures, we show that FGF5 induces regression of the human hair follicle. We have identified FGF5 as a crucial regulator of hair growth in humans for the first time, to our knowledge, and uncovered a therapeutic target to selectively regulate eyelash growth.

Background: Missing outcome data from randomized trials lead to greater uncertainty and possible bias in estimating the effect of an experimental treatment. An intention-to-treat analysis should take account of all randomized participants even if they have missing observations. Purpose: To review and develop imputation methods for missing outcome data in meta-analysis of clinical trials with binary outcomes. Methods: We review some common strategies, such as simple imputation of positive or negative outcomes, and develop a general approach involving `informative missingness odds ratios' (IMORs). We describe several choices for weighting studies in the meta-analysis, and illustrate methods using a meta-analysis of trials of haloperidol for schizophrenia. Results: IMORs describe the relationship between the unknown risk among missing participants and the known risk among observed participants. They are allowed to differ between treatment groups and across trials. Application of IMORs and other methods to the haloperidol trials reveals the overall conclusion to be robust to different assumptions about the missing data. Limitations: The methods are based on summary data from each trial (number of observed positive outcomes, number of observed negative outcomes and number of missing outcomes) for each intervention group. This limits the options for analysis, and greater flexibility would be available with individual participant data. Conclusions: We propose that available reasons for missingness be used to determine appropriate IMORs. We also recommend a strategy for undertaking sensitivity analyses, in which the IMORs are varied over plausible ranges. Clinical Trials 2008; 5: 225—239. http://ctj.sagepub.com

Glucocorticoids might prevent bronchopulmonary dysplasia in extremely preterm infants but have adverse neurodevelopmental effects. In this trial involving preterm infants, there was little difference in survival without bronchopulmonary dysplasia or in the occurrence of neurodevelopmental impairment with hydrocortisone as compared with placebo.

An oncogenic mutation (G49A:E17K) in the AKT1 gene has been described recently in human breast, colon, and ovarian cancers. The low frequency of this mutation and perhaps other selective pressures have prevented the isolation of human cancer cell lines that harbor this mutation thereby limiting functional analysis. Here, we create a physiologic in vitro model to study the effects of this mutation by using somatic cell gene targeting using the nontumorigenic human breast epithelial cell line, MCF10A. Surprisingly, knock in of E17K into the AKT1 gene had minimal phenotypic consequences and importantly, did not recapitulate the biochemical and growth characteristics seen with somatic cell knock in of PIK3CA hotspot mutations. These results suggest that mutations in critical genes within the PI3-kinase (PI3K) pathway are not functionally equivalent, and that other cooperative genetic events may be necessary to achieve oncogenic PI3K pathway activation in cancers that contain the AKT1 E17K mutation.

Animals can be important in nutrient cycling in particular ecosystems, but few studies have examined how this importance varies along environmental gradients. In this study we quantified the nutrient cycling role of an abundant detritivorous fish species, the gizzard shad (Dorosoma cepedianum), in reservoir ecosystems along a gradient of ecosystem productivity. Gizzard shad feed mostly on sediment detritus and excrete sediment-derived nutrients into the water column, thereby mediating a cross-habitat translocation of nutrients to phytoplankton. We quantified nitrogen and phosphorus cycling (excretion) rates of gizzard shad, as well as nutrient demand by phytoplankton, in seven lakes over a four-year period (16 lake-years). The lakes span a gradient of watershed land use (the relative amounts of land used for agriculture vs. forest) and productivity. As the watersheds of these lakes became increasingly dominated by agricultural land, primary production rates, lake trophic state indicators (total phosphorus and chlorophyll concentrations), and nutrient flux through gizzard shad populations all increased. Nutrient cycling by gizzard shad supported a substantial proportion of primary production in these ecosystems, and this proportion increased as watershed agriculture (and ecosystem productivity) increased. In the four productive lakes with agricultural watersheds (>78% agricultural land), gizzard shad supported on average 51% of phytoplankton primary production (range 27-67%). In contrast, in the three relatively unproductive lakes in forested or mixed-land-use watersheds (>47% forest, <52% agricultural land), gizzard shad supported 18% of primary production (range 14-23%). Thus, along a gradient of forested to agricultural landscapes, both watershed nutrient inputs and nutrient translocation by gizzard shad increase, but our data indicate that the importance of nutrient translocation by gizzard shad increases more rapidly. Our results therefore support the hypothesis that watersheds and gizzard shad jointly regulate primary production in reservoir ecosystems.

Rationale Selective 5-HT 2C receptor agonists, such as lorcaserin, are being developed for the treatment of obesity. Studies suggest that they may also have therapeutic potential for addictive behaviours including nicotine dependence, although few drugs of this class have been evaluated. Objectives The primary aim was to evaluate the highly selective 5-HT 2C agonist, CP-809101, against food-motivated (operant FR5 and progressive ratio schedules, palatability-induced feeding) and nicotine-motivated (intravenous self-administration, drug discrimination) behaviours in rats and to compare with equivalent findings for the structurally distinct 5-HT 2C receptor agonists lorcaserin and Ro 60–0175. The secondary aims were to evaluate the side effect profiles of lorcaserin and CP-809101 and to determine the plasma levels of lorcaserin at a dose (1 mg/kg) that reduces both food and nicotine reinforcement for comparison to plasma concentrations reported in human trials. Results CP-809101 (0.3–3 mg/kg SC) reduced responding for both nicotine and food and blocked the discriminative stimulus properties of nicotine in a similar manner to lorcaserin and Ro 60–0175. Behaviours such as hypolocomotion, chewing and ptosis became evident following both CP-809101 and lorcaserin administration at higher doses. Plasma levels of lorcaserin were of similar range to those reported in obesity trials. Conclusions These studies support the utility of 5-HT 2C agonists as a therapeutic approach to treat nicotine dependence. Plasma exposure levels after acute lorcaserin treatment suggest that equivalent dosages could be used to evaluate these drugs in obesity and smoking cessation trials. Finally, there may be differences in the side effect profiles between lorcaserin and CP-809101, raising the possibility for tolerability differences amongst 5-HT 2C agonists.