Dynamic biospeckle analysis, a new tool for the fast screening of plant nematicide selectivity

Background: Plant feeding, free-living nematodes cause extensive damage to plant roots by direct feeding and, in the case of some trichodorid and longidorid species, through the transmission of viruses. Developing more environmentally friendly, target-specific nematicides is currently impeded by slow and laborious methods of toxicity testing. Here, we developed a bioactivity assay based on the dynamics of light 'speckle' generated by living cells and we demonstrate its application by assessing chemicals' toxicity to different nematode trophic groups.Results: Free-living nematode populations extracted from soil were exposed to methanol and phenyl isothiocyanate (PEITC). Biospeckle analysis revealed differing behavioural responses as a function of nematode feeding groups. Trichodorus nematodes were less sensitive than were bacterial feeding nematodes or non-trichodorid plant feeding nematodes. Following 24 h of exposure to PEITC, bioactivity significantly decreased for plant and bacterial feeders but not for Trichodorus nematodes. Decreases in movement for plant and bacterial feeders in the presence of PEITC also led to measurable changes to the morphology of biospeckle patterns.Conclusions: Biospeckle analysis can be used to accelerate the screening of nematode bioactivity, thereby providing a fast way of testing the specificity of potential nematicidal compounds. With nematodes' distinctive movement and activity levels being visible in the biospeckle pattern, the technique has potential to screen the behavioural responses of diverse trophic nematode communities. The method discriminates both behavioural responses, morphological traits and activity levels and hence could be used to assess the specificity of nematicidal compounds.</p

Understanding the limits to generalizability of experimental evolutionary models.

Post print version of article deposited in accordance with SHERPA RoMEO guidelines. The final definitive version is available online at: http://www.nature.com/nature/journal/v455/n7210/abs/nature07152.htmlGiven the difficulty of testing evolutionary and ecological theory in situ, in vitro model systems are attractive alternatives; however, can we appraise whether an experimental result is particular to the in vitro model, and, if so, characterize the systems likely to behave differently and understand why? Here we examine these issues using the relationship between phenotypic diversity and resource input in the T7-Escherichia coli co-evolving system as a case history. We establish a mathematical model of this interaction, framed as one instance of a super-class of host-parasite co-evolutionary models, and show that it captures experimental results. By tuning this model, we then ask how diversity as a function of resource input could behave for alternative co-evolving partners (for example, E. coli with lambda bacteriophages). In contrast to populations lacking bacteriophages, variation in diversity with differences in resources is always found for co-evolving populations, supporting the geographic mosaic theory of co-evolution. The form of this variation is not, however, universal. Details of infectivity are pivotal: in T7-E. coli with a modified gene-for-gene interaction, diversity is low at high resource input, whereas, for matching-allele interactions, maximal diversity is found at high resource input. A combination of in vitro systems and appropriately configured mathematical models is an effective means to isolate results particular to the in vitro system, to characterize systems likely to behave differently and to understand the biology underpinning those alternatives

Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration

BACKGROUND: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: OBJECTIVES: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. DESIGN: A proof of concept double-masked randomized controlled study. PARTICIPANTS: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile. INTERVENTION: Simvastatin 40 mg/day or placebo, allocated 1:1. MAIN OUTCOME MEASURES: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. CONCLUSION/SIGNIFICANCE: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065

Serological profile of foot-and-mouth disease in wildlife populations of West and Central Africa with special reference to Syncerus caffer subspecies

The role which West and Central African wildlife populations might play in the transmission dynamics of FMD is not known nor have studies been performed in order to assess the distribution and prevalence of FMD in wild animal species inhabiting those specific regions of Africa. This study reports the FMD serological profile extracted from samples (n = 696) collected from wildlife of West and Central Africa between 1999 and 2003. An overall prevalence of FMDV NSP reactive sera of 31.0% (216/696) was estimated, where a significant difference in seropositivity (p = 0.000) was reported for buffalo (64.8%) as opposed to other wild animal species tested (17.8%). Different levels of exposure to the FMDV resulted for each of the buffalo subspecies sampled (p = 0.031): 68.4%, 50.0% and 0% for Nile Buffalo, West African Buffalo and African Forest Buffalo, respectively. The characterisation of the FMDV serotypes tested for buffalo found presence of antibodies against all the six FMDV serotypes tested, although high estimates for type O and SAT 3 were reported for Central Africa. Different patterns of reaction to the six FMDV serotypes tested were recorded, from sera only positive for a single serotype to multiple reactivities. The results confirmed that FMDV circulates in wild ruminants populating both West and Central Africa rangelands and in particular in buffalo, also suggesting that multiple FMDV serotypes might be involved with type O, SAT 2 and SAT 1 being dominant. Differences in serotype and spill-over risk between wildlife and livestock likely reflect regional geography, historical circulation and differing trade and livestock systems

A novel outbred mouse model of 2009 pandemic influenza and bacterial co-infection severity

Influenza viruses pose a significant health risk and annually impose a great cost to patients and the health care system. The molecular determinants of influenza severity, often exacerbated by secondary bacterial infection, are largely unclear. We generated a novel outbred mouse model of influenza virus, Staphylococcus aureus, and coinfection utilizing influenza A/CA/07/2009 virus and S. aureus (USA300). Outbred mice displayed a wide range of pathologic phenotypes following influenza virus or co-infection ranging broadly in severity. Influenza viral burden positively correlated with weight loss although lung histopathology did not. Inflammatory cytokines including IL-6, TNF-α, G-CSF, and CXCL10 positively correlated with both weight loss and viral burden. In S. aureus infection, IL-1β, G-CSF, TNF-α, and IL-6 positively correlated with weight loss and bacterial burden. In co-infection, IL-1β production correlated with decreased weight loss suggesting a protective role. The data demonstrate an approach to identify biomarkers of severe disease and to understand pathogenic mechanisms in pneumonia. © 2013 McHugh et al

Two approaches to the study of the origin of life.

This paper compares two approaches that attempt to explain the origin of life, or biogenesis. The more established approach is one based on chemical principles, whereas a new, yet not widely known approach begins from a physical perspective. According to the first approach, life would have begun with - often organic - compounds. After having developed to a certain level of complexity and mutual dependence within a non-compartmentalised organic soup, they would have assembled into a functioning cell. In contrast, the second, physical type of approach has life developing within tiny compartments from the beginning. It emphasises the importance of redox reactions between inorganic elements and compounds found on two sides of a compartmental boundary. Without this boundary, ¿life¿ would not have begun, nor have been maintained; this boundary - and the complex cell membrane that evolved from it - forms the essence of life

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Survey of patient satisfaction with the Breastfeeding Education and Support Services of The Royal Women's Hospital, Melbourne

<p>Abstract</p> <p>Background</p> <p>The Breastfeeding Education and Support Services (BESS) is a unit of The Royal Women's Hospital in Melbourne, Australia, staffed by International Board Certified Lactation Consultants (IBCLCs), providing day/short-stay and an outpatient clinic for mothers and infants with breastfeeding problems. It is important to measure women's experience of visiting the service as part of quality assurance. The aim of this project was to conduct an anonymous postal survey of clients' satisfaction with BESS.</p> <p>Methods</p> <p>An anonymous survey was posted on 16 November 2005 and again on 31 January 2006, to all women who had attended BESS in September 2005.</p> <p>Results</p> <p>The response rate was 60.5% (78/129). Eighty percent (62/78) of respondents attended day-stay, 33% (26/78) attended short-stay and 15% (12/78) attended the outpatient clinic. The percentage of women who responded "strongly agree" to the statement "Overall, I am satisfied with the services" was 49% (35/72) and 50% (6/12) for those who went to day/short-stay and the outpatient clinic respectively. Overall, 56% of all respondents responded that the quality of BESS was "better than expected". The most common breastfeeding problem reported was difficulty attaching the baby to the breast, followed by nipple damage, low milk supply and painful feeding.</p> <p>Conclusion</p> <p>BESS seems to have provided a satisfactory service to most clients. Most respondents were clearly satisfied with the support given by the IBCLCs and have also responded that the staff were professional and knowledgeable in their field of work.</p

The Lactobacillus flora in vagina and rectum of fertile and postmenopausal healthy Swedish women

<p>Abstract</p> <p>Background</p> <p><it>Lactobacillus </it>species are the most often found inhabitants of vaginal ecosystem of fertile women. In postmenopausal women with low oestrogen levels, <it>Lactobacillus </it>flora is diminishing or absent. However, no studies have been performed to investigate the correlation between oestrogen levels and the lactobacilli in the gut. The aim of the present study was to investigate the relation in healthy women between vaginal and rectal microbial flora as well as possible variations with hormone levels.</p> <p>Methods</p> <p>Vaginal and rectal smears were taken from 20 healthy fertile women, average 40 years (range 28-49 years), in two different phases of the menstrual cycle, and from 20 postmenopausal women, average 60 years (range 52-85 years). Serum sex hormone levels were analyzed. Bacteria from the smears isolated on Rogosa Agar were grouped by Randomly Amplified Polymorphic DNA and identified by multiplex PCR and partial 16S rRNA gene sequencing.</p> <p>Results</p> <p><it>Lactobacillus crispatus </it>was more often found in the vaginal flora of fertile women than in that of postmenopausal (p = 0.036). Fifteen of 20 fertile women had lactobacilli in their rectal smears compared to 10 postmenopausal women (p = 0.071). There was no correlation between the number of bacteria in vagina and rectum, or between the number of bacteria and hormonal levels. Neither could any association between the presence of rectal lactobacilli and hormonal levels be found.</p> <p>Conclusion</p> <p><it>Lactobacillus crispatus </it>was more prevalent in the vaginal flora of fertile women, whereas the <it>Lactobacillus </it>flora of rectum did not correlate to the vaginal flora nor to hormonal levels.</p

Motives for corporate cash holdings:the CEO optimism effect

We examine the chief executive officer (CEO) optimism effect on managerial motives for cash holdings and find that optimistic and non-optimistic managers have significantly dissimilar purposes for holding more cash. This is consistent with both theory and evidence that optimistic managers are reluctant to use external funds. Optimistic managers hoard cash for growth opportunities, use relatively more cash for capital expenditure and acquisitions, and save more cash in adverse conditions. By contrast, they hold fewer inventories and receivables and their precautionary demand for cash holdings is less than that of non-optimistic managers. In addition, we consider debt conservatism in our model and find no evidence that optimistic managers’ cash hoarding is related to their preference to use debt conservatively. We also document that optimistic managers hold more cash in bad times than non-optimistic managers do. Our work highlights the crucial role that CEO characteristics play in shaping corporate cash holding policy