Simulation of cellular irradiation with the CENBG microbeam line using GEANT4

Light-ion microbeams provide a unique opportunity to irradiate biological samples at the cellular level and to investigate radiobiological effects at low doses of high LET ionising radiation. Since 1998 a single-ion irradiation facility has been developed on the focused horizontal microbeam line of the CENBG 3.5 MV Van de Graaff accelerator. This setup delivers in air single protons and alpha particles of a few MeV onto cultured cells, with a spatial resolution of a few microns, allowing subcellular targeting. In this paper, we present results from the use of the GEANT4 toolkit to simulate cellular irradiation with the CENBG microbeam line, from the entrance to the microprobe up to the cellular medium.Comment: 6 pages, 8 figures, presented at the 2003 IEEE-NSS conference, Portland, OR, USA, October 20-24, 200

Modelling transmission and control of Mycobacterium avium subspecies paratuberculosis within Irish dairy herds with compact spring calving

Paratuberculosis is a chronic bacterial infection of the intestine in cattle caused by Mycobacterium avium subspecies paratuberculosis (Map). To better understand Map transmission in Irish dairy herds, we adapted the French stochastic individual-based epidemiological simulation model to account for seasonal herd demographics. We investigated the probability of Map persistence over time, the within-herd prevalence over time, and the relative importance of transmission pathways, and assessed the relative effectiveness of test-and-cull control strategies. We investigated the impact on model outputs of calf separation from cows (calves grazed on pasture adjacent to cows vs. were completely separated from cows) and test-and-cull. Test-and-cull scenarios consisted of highly test-positive cows culled within 13 or 4 weeks after detection, and calf born to highly test-positive cows kept vs removed. We simulated a typical Irish dairy herd with on average 82 lactating cows, 112 animals in total. Each scenario was iterated 1000 times to adjust variation caused by stochasticity. Map was introduced in the fully naive herd through the purchase of a moderately infectious primiparous cow. Infection was considered to persist when at least one infected animal remained in the herd or when Map was present in the environment. The probability of Map persistence 15 years after introduction ranged between 32.2-42.7 % when calves and cows had contact on pasture, and between 18.9-29.4 % when calves and cows were separated on pasture. The most effective control strategy was to cull highly test-positive cows within four weeks of detection (absolute 10 % lower persistence compared to scenarios without control). Removing the offspring of highly test-positive dams did not affect either Map persistence or within-herd prevalence of Map. Mean prevalence 15 years after Map introduction was highest (63.5 %) when calves and cows had contact on pasture. Mean prevalence was 15 % lower (absolute decrease) when cows were culled within 13 weeks of a high test-positive result, and 28 % lower when culled within 4 weeks. Around calving, the infection rate was high, with calves being infected in utero or via the general indoor environment (most important transmission routes). For the remainder of the year, the incidence rate was relatively low with most calves being infected on pasture when in contact with cows. Testing and culling was an effective control strategy when it was used prior to the calving period to minimize the number of highly infectious cows present when calves were born

Bacteriophage and H. pylori: an underestimated phenomena

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Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth. In a previous study conducted in non-diabetic subjects, we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci (ACF). ACF have been considered as a useful surrogate biomarker of CRC, although the biological significance of these lesions remains controversial. We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients.</p> <p>Methods/Design</p> <p>This study is a multi-center, double-blind, placebo-controlled, randomized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy. All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study. Eligible patients will then be allocated randomly into either one of two groups: the metformin group and the placebo group. Patients in the metformin group shall receive oral metformin at 250 mg per day, and those in the placebo group shall receive an oral placebo tablet. At the end of 1 year of administration of metformin/placebo, colonoscopy will be performed to evaluate the polyp formation.</p> <p>Discussion</p> <p>This is the first study proposed to explore the effect of metformin against colorectal polyp formation. Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation. Patients with type 2 diabetes taking under treatment with metformin have been reported to be at a lower risk of cancer development than those not taking under treatment with metformin. We showed in a previous study that metformin suppressed the formation of human colorectal ACF. We therefore decided to conduct a study to determine whether metformin might suppress the formation of human colorectal polyps.</p> <p>Trial registration</p> <p>This trial has been registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry as <a href="http://www.clinicaltrials.gov/ct2/show/UMIN000006254">UMIN000006254</a></p

Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2)

BACKGROUND: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition. METHODS: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate &lt;2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099. FINDINGS: After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p&lt;0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [&lt;1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [&lt;1%]; 3·7 [1·03-13·2; p=0·04). INTERPRETATION: In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition. FUNDING: La Roche-sur-Yon Departmental Hospital and French Ministry of Health

Roadless and Low-Traffic Areas as Conservation Targets in Europe

With increasing road encroachment, habitat fragmentation by transport infrastructures has been a serious threat for European biodiversity. Areas with no roads or little traffic (“roadless and low-traffic areas”) represent relatively undisturbed natural habitats and functioning ecosystems. They provide many benefits for biodiversity and human societies (e.g., landscape connectivity, barrier against pests and invasions, ecosystem services). Roadless and low-traffic areas, with a lower level of anthropogenic disturbances, are of special relevance in Europe because of their rarity and, in the context of climate change, because of their contribution to higher resilience and buffering capacity within landscape ecosystems. An analysis of European legal instruments illustrates that, although most laws aimed at protecting targets which are inherent to fragmentation, like connectivity, ecosystem processes or integrity, roadless areas are widely neglected as a legal target. A case study in Germany underlines this finding. Although the Natura 2000 network covers a significant proportion of the country (16%), Natura 2000 sites are highly fragmented and most low-traffic areas (75%) lie unprotected outside this network. This proportion is even higher for the old Federal States (western Germany), where only 20% of the low-traffic areas are protected. We propose that the few remaining roadless and low-traffic areas in Europe should be an important focus of conservation efforts; they should be urgently inventoried, included more explicitly in the law and accounted for in transport and urban planning. Considering them as complementary conservation targets would represent a concrete step towards the strengthening and adaptation of the Natura 2000 network to climate change