A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

Comparative 3D analyses and palaeoecology of giant early amphibians (Temnospondyli: Stereospondyli)

Macroevolutionary, palaeoecological and biomechanical analyses in deep time offer the possibility to decipher the structural constraints, ecomorphological patterns and evolutionary history of extinct groups. Here, 3D comparative biomechanical analyses of the extinct giant early amphibian group of stereospondyls together with living lissamphibians and crocodiles, shows that: i) stereospondyls had peculiar palaeoecological niches with proper bites and stress patterns very different than those of giant salamanders and crocodiles; ii) their extinction may be correlated with the appearance of neosuchians, which display morphofunctional innovations. Stereospondyls weathered the end-Permian mass extinction, re-radiated, acquired gigantic sizes and dominated (semi) aquatic ecosystems during the Triassic. Because these ecosystems are today occupied by crocodilians, and stereospondyls are extinct amphibians, their palaeobiology is a matter of an intensive debate: stereospondyls were a priori compared with putative living analogous such as giant salamanders and/or crocodilians and our new results try to close this debate.Peer ReviewedPostprint (published version

A critical evaluation of the fish early-life stage toxicity test for engineered nanomaterials: experimental modifications and recommendations

There are concerns that regulatory toxicity tests are not fit for purpose for engineered nanomaterials (ENMs) or need modifications. The aim of the current study was to evaluate the OECD 210 fish, early-life stage toxicity test for use with TiO2 ENMs, Ag ENMs, and MWCNT. Both TiO2 ENMS (≤160 mg l(-1)) and MWCNT (≤10 mg l(-1)) showed limited acute toxicity, whilst Ag ENMs were acutely toxic to zebrafish, though less so than AgNO3 (6-day LC50 values of 58.6 and 5.0 µg l(-1), respectively). Evidence of delayed hatching, decreased body length and increased muscle width in the tail was seen in fish exposed to Ag ENMs. Oedema (swollen yolk sacs) was also seen in fish from both Ag treatments with, for example, mean yolk sac volumes of 17, 35 and 39 µm(3) for the control, 100 µg l(-1) Ag ENMs and 5 µg l(-1) AgNO3 treatments, respectively. Among the problems with the standard test guidelines was the inability to maintain the test solutions within ±20 % of nominal concentrations. Pronounced settling of the ENMs in some beakers also made it clear the fish were not being exposed to nominal concentrations. To overcome this, the exposure apparatus was modified with the addition of an exposure chamber that ensured mixing without damaging the delicate embryos/larvae. This allowed more homogeneous ENM exposures, signified by improved measured concentrations in the beakers (up to 85.7 and 88.1 % of the nominal concentrations from 10 mg l(-1) TiO2 and 50 µg l(-1) Ag ENM exposures, respectively) and reduced variance between measurements compared to the original method. The recommendations include: that the test is conducted using exposure chambers, the use of quantitative measurements for assessing hatching and morphometrics, and where there is increased sensitivity of larvae over embryos to conduct a shorter, larvae-only toxicity test with the ENMs

Citizen science: a new approach to advance ecology, education, and conservation

Citizen science has a long history in the ecological sciences and has made substantial contributions to science, education, and society. Developments in information technology during the last few decades have created new opportunities for citizen science to engage ever larger audiences of volunteers to help address some of ecology’s most pressing issues, such as global environmental change. Using online tools, volunteers can find projects that match their interests and learn the skills and protocols required to develop questions, collect data, submit data, and help process and analyze data online. Citizen science has become increasingly important for its ability to engage large numbers of volunteers to generate observations at scales or resolutions unattainable by individual researchers. As a coupled natural and human approach, citizen science can also help researchers access local knowledge and implement conservation projects that might be impossible otherwise. In Japan, however, the value of citizen science to science and society is still underappreciated. Here we present case studies of citizen science in Japan, the United States, and the United Kingdom, and describe how citizen science is used to tackle key questions in ecology and conservation, including spatial and macro-ecology, management of threatened and invasive species, and monitoring of biodiversity. We also discuss the importance of data quality, volunteer recruitment, program evaluation, and the integration of science and human systems in citizen science projects. Finally, we outline some of the primary challenges facing citizen science and its future.Dr. Janis L. Dickinson was the keynote speaker at the international symposium at the 61th annual meeting of the Ecological Society of Japan. We appreciate the Ministry of Education, Culture, Sports, Science and Technology in Japan for providing grant to Hiromi Kobori (25282044). Tatsuya Amano is financially supported by the European Commission’s Marie Curie International Incoming Fellowship Programme (PIIF-GA-2011- 303221). The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agencies or the Department of the Interior or the US Government.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s11284-015-1314-

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Current trends in the surgical management of Dupuytren’s disease in Europe: an analysis of patient charts

Introduction: Dupuytren's disease (DD) causes progressive digital flexion contracture and is more common in men of European descent. Methods: Orthopaedic and plastic surgeons in 12 European countries (the Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, The Netherlands, Poland, Spain, Sweden and the UK) with >3 and <30 years experience reviewed the medical charts of five consecutive patients they had treated surgically for DD in 2008. Descriptive statistics are reported. Results: In total, 3,357 patient charts were reviewed. Mean (standard deviation) patient age was 61.9 (10.2) years; 81% were men. At the time of the procedure, 11% of patients were at Tubiana stage Ia (0-20° total flexion); 30%, stage Ib (21-45°); 34%, stage II (46-90°); 17%, stage III (91-135°); and 5%, stage IV (&135°). Percutaneous needle fasciotomy was performed in 10%, fasciotomy in 13%, fasciectomy in 69% and dermofasciectomy (DF) in 6% of patients. After surgery, fingers improved a mean of 1.9 Tubiana stages, and 54% of patients had no nodules or contracture. The rate of reported complications during the procedure was 4% overall (11% in patients undergoing DF). The most common postoperative complications reported were haematoma (8%), wound healing complications (6%) and pain (6%). No postoperative complications were reported in 77% of patients. Conclusions: In this European study of more than 3,000 patients with DD, most patients were diagnosed at Tubiana stage I or II, the majority received fasciectomy and more than half had no nodules or contracture remaining after surgery

Arthritis of the base of the thumb

The purpose of this article is to outline the pathophysiology and epidemiology of arthritis of the base of the thumb. The usual presentation and diagnosis will be discussed along with the current conservative treatment options. Surgical treatment options are determined by the stage of the arthritis as well as the demands of the patient. The current standard surgical treatment options will be reviewed along with their results in the literature

Accumulation of Endogenous LITAF in Aggresomes

LITAF is a 161 amino acid cellular protein which includes a proline rich N-terminus and a conserved C-terminal domain known as the simple-like domain. Mutations in LITAF have been identified in Charcot-Marie tooth disease, a disease characterized by protein aggregates. Cells transfected with cellular LITAF reveal that LITAF is localized to late endosomes/lysosomes. Here we investigated the intracellular localization of endogenous LITAF. We demonstrated that endogenous LITAF accumulates at a discrete cytoplasmic site in BGMK cells that we identify as the aggresome. To determine the domain within LITAF that is responsible for the localization of LITAF to aggresomes, we created a construct that contained the C-terminal simple-like domain of LITAF and found that this construct also localizes to aggresomes. These data suggest the simple-like domain is responsible for targeting endogenous LITAF to the aggresome

Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples

<p>Abstract</p> <p>Background</p> <p>Dependences on addictive substances are substantially-heritable complex disorders whose molecular genetic bases have been partially elucidated by studies that have largely focused on research volunteers, including those recruited in Baltimore. Maryland. Subjects recruited from the Baltimore site of the Epidemiological Catchment Area (ECA) study provide a potentially-useful comparison group for possible confounding features that might arise from selecting research volunteer samples of substance dependent and control individuals. We now report novel SNP (single nucleotide polymorphism) genome wide association (GWA) results for vulnerability to substance dependence in ECA participants, who were initially ascertained as members of a probability sample from Baltimore, and compare the results to those from ethnically-matched Baltimore research volunteers.</p> <p>Results</p> <p>We identify substantial overlap between the home address zip codes reported by members of these two samples. We find overlapping clusters of SNPs whose allele frequencies differ with nominal significance between substance dependent <it>vs </it>control individuals in both samples. These overlapping clusters of nominally-positive SNPs identify 172 genes in ways that are never found by chance in Monte Carlo simulation studies. Comparison with data from human expressed sequence tags suggests that these genes are expressed in brain, especially in hippocampus and amygdala, to extents that are greater than chance.</p> <p>Conclusion</p> <p>The convergent results from these probability sample and research volunteer sample datasets support prior genome wide association results. They fail to support the idea that large portions of the molecular genetic results for vulnerability to substance dependence derive from factors that are limited to research volunteers.</p

Left ventricular volume: an optimal parameter to detect systolic dysfunction on prospectively triggered 64-multidetector row computed tomography: another step towards reducing radiation exposure

In this study, we define the correlation between LV volumes (both LV end-diastolic volume [LVEDV] and LV end-systolic volume [LVESV]) and ejection fraction (EF) on 64 slice multi-detector computed tomography (MDCT). We also determine the accuracy of all the LV volume (LVV) parameters to detect LV systolic dysfunction (LVSD) and investigate the feasibility of using LVV as a surrogate of LVSD on prospectively gated imaging to prevent the radiation exposure of retrospective imaging. 568 patients undergoing 64-detector MDCT were divided into 2 groups: Group 1—subjects without any heart disease and LVEF ≥ 50%; and Group 2—patients with coronary artery disease and LVEF < 50% (defined as LVSD). The LVV (LV cavity only) and Total LV volume (cavity + LV mass) at end-systole and end-diastole (LVESV, Total LVESV, LVEDV and Total LVEDV) were measured. The upper limit values (mean + 2 SD) of all LVV parameters in Group 1 were used as the reference criterion to diagnose LVSD in Group 2. An exponential correlation was found between LVEF and all the LVV parameters. The specificity to detect LVSD in Group 2 was >90% and the sensitivity was 88.9, 83.3, 61.3 and 74.9% by using LVESV, Total LVESV, LVEDV and Total LVEDV, respectively. Systolic and diastolic LV volumes had a high correlation with LVEF and a high accuracy to detect LVSD. Thus, on prospectively triggered imaging, ventricular volumes can predict patients with reduced LVEF, and appropriate referrals can be made