Effects of fleas on nest success of Arctic barnacle geese:experimentally testing the mechanism

Parasites have detrimental effects on their hosts' fitness. Therefore, behavioural adaptations have evolved to avoid parasites or, when an individual is already in contact with a parasite, prevent or minimize infections. Such anti-parasite behaviours can be very effective, but can also be costly for the host. Specifically, ectoparasites can elicit strong host anti-parasite behaviours and interactions between fleas (Siphonaptera) and their hosts are one of the best studied. In altricial bird species, nest fleas can negatively affect both parent and offspring fitness components. However, knowledge on the effects of fleas on precocial bird species is scarce. Research on geese in the Canadian Arctic indicated that fleas have a negative impact on reproductive success. One possible hypothesis is that fleas may affect female incubation behaviour. Breeding females with many fleas in their nest may increase the frequency and/or duration of incubation breaks and could even totally desert their nest. The aim of our study was to 1) determine if a similar negative relationship existed between flea abundance and reproductive success in our study colony of Arctic breeding barnacle geese Branta leucopsis and 2) experimentally quantify if such effects could be explained by a negative effect of nest fleas on female behaviour. We compared host anti-parasite and incubation behaviour between experimentally flea-reduced and control nests using wildlife cameras and temperature loggers. We found that flea abundance was negatively associated with hatching success. We found little experimental support, however, for changes in behaviour of the breeding female as a possible mechanism to explain this effect

The effects of vaccination and immunity on bacterial infection dynamics in vivo.

Salmonella enterica infections are a significant global health issue, and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body.This work was supported by the Biotechnology and Biological Sciences Research Council [grant number BB/I002189/1].This is the published manuscript. It was originally published by PLOS One here: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004359

Does Reduced IGF-1R Signaling in Igf1r+/− Mice Alter Aging?

Mutations in insulin/IGF-1 signaling pathway have been shown to lead to increased longevity in various invertebrate models. Therefore, the effect of the haplo- insufficiency of the IGF-1 receptor (Igf1r+/−) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and end-of-life pathology were measured under optimal husbandry conditions using large sample sizes. Igf1r+/− mice exhibited reductions in IGF-1 receptor levels and the activation of Akt by IGF-1, with no compensatory increases in serum IGF-1 or tissue IGF-1 mRNA levels, indicating that the Igf1r+/− mice show reduced IGF-1 signaling. Aged male, but not female Igf1r+/− mice were glucose intolerant, and both genders developed insulin resistance as they aged. Female, but not male Igf1r+/− mice survived longer than wild type mice after lethal paraquat and diquat exposure, and female Igf1r+/− mice also exhibited less diquat-induced liver damage. However, no significant difference between the lifespans of the male Igf1r+/− and wild type mice was observed; and the mean lifespan of the Igf1r+/− females was increased only slightly (less than 5%) compared to wild type mice. A comprehensive pathological analysis showed no significant difference in end-of-life pathological lesions between the Igf1r+/− and wild type mice. These data show that the Igf1r+/− mouse is not a model of increased longevity and delayed aging as predicted by invertebrate models with mutations in the insulin/IGF-1 signaling pathway

Molecular detection of Coxiella burnetii infection in small mammals from Moshi Rural and Urban Districts, northern Tanzania

Coxiella burnetii is an obligate intracellular bacterium that causes Q fever, a zoonotic disease of public health importance. In northern Tanzania, Q fever is a known cause of human febrile illness, but little is known about its distribution in animal hosts. We used a quantitative real‐time PCR (qPCR) targeting the insertion element IS1111 to determine the presence and prevalence of C. burnetii infections in small mammals trapped in 12 villages around Moshi Rural and Moshi Urban Districts, northern Tanzania. A total of 382 trapped small mammals of seven species were included in the study; Rattus rattus (n = 317), Mus musculus (n = 44), Mastomys natalensis (n = 8), Acomys wilson (n = 6), Mus minutoides (n = 3), Paraxerus flavovottis (n = 3) and Atelerix albiventris (n = 1). Overall, 12 (3.1%) of 382 (95% CI: 1.6–5.4) small mammal spleens were positive for C. burnetii DNA. Coxiella burnetii DNA was detected in five of seven of the small mammal species trapped; R. rattus (n = 7), M. musculus (n = 1), A. wilson (n = 2), P. flavovottis (n = 1) and A. albiventris (n = 1). Eleven (91.7%) of twelve (95% CI: 61.5–99.8) C. burnetii DNA positive small mammals were trapped within Moshi Urban District. These findings demonstrate that small mammals in Moshi, northern Tanzania are hosts of C. burnetii and may act as a source of C. burnetii infection to humans and other animals. This detection of C. burnetii infections in small mammals should motivate further studies into the contribution of small mammals to the transmission of C. burnetii to humans and animals in this region

A novel multiplex real-time PCR for the identification of mycobacteria associated with zoonotic tuberculosis.

Tuberculosis (TB) is the leading cause of death worldwide from a single infectious agent. An ability to detect the Mycobacterium tuberculosis complex (MTC) in clinical material while simultaneously differentiating its members is considered important. This allows for the gathering of epidemiological information pertaining to the prevalence, transmission and geographical distribution of the MTC, including those MTC members associated with zoonotic TB infection in humans. Also differentiating between members of the MTC provides the clinician with inherent MTC specific drug susceptibility profiles to guide appropriate chemotherapy

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

The Central Limit Theorem

The applets in this section of Statistical Java allow you to see how the Central Limit Theorem works. The main page gives the characteristics of five non-normal distributions (Bernoulli, Poisson, Exponential, U-shaped, and Uniform). Users then select one of the distributions and change the sample size to see how the distribution of the sample mean approaches normality. Users can also change the number of samples. To select between the different applets you can click on Statistical Theory, the Central Limit Theorem and then the Main Page. At the bottom of this page you can make your applet selection

Confidence Intervals

The applets in this section of Statistical Java allow you to see how levels of confidence are achieved through repeated sampling. The confidence intervals are related to the probability of successes in a Binomial experiment. The main page gives the equation for finding confidence intervals and describes the parameters (p, n, alpha). Each applet allows you to change a different parameter and simulate sampling to demonstrate the long run proportion of intervals that contain the true probability of success. The applets are available from a pull-down menu at the bottom of the page

Exponential Probabilities

The applet, created by Virginia Tech's Department of Statistics, allows you see how probabilities are determined from the exponential distribution. The user determines the mean of the distribution and the limits of probability. Three different probability expressions are available. Click "Calculate" to see the pdf and the cdf. The probability is highlighted in green on the pdf. This is a nice reference tool for anyone studying statistics