Multicenter data acquisition made easy

<p>Abstract</p> <p>Background</p> <p>The process for data collection in multicenter trials may be troublesome and expensive. We report our experience with the spreadsheet function in Googledocs for this purpose.</p> <p>Methods</p> <p>In Googledocs the data manager creates a form similar to the paper case record form, which will function as a decentral data entry module. When the forms are submitted, they are presented in a spreadsheet in Googledocs, which can be exported to different standard spreadsheet formats.</p> <p>Results</p> <p>For a multicenter randomized clinical trial with five different participating hospitals we created a decentral data entry module using the spreadsheet function in Googledocs. The study comprised 332 patients (clinicaltrials.gov identifier: NCT00815698) with five visits per patient. One person at each study site entered data from the original paper based case report forms which were kept at the study sites as originals. We did not experience any technical problems using the system.</p> <p>Conclusions</p> <p>The system allowed for decentral data entry, and it was easy to use, safe, and free of charge. The spreadsheet function in Googledocs may potentially replace current expensive solutions for data acquisition in multicenter trials.</p> <p>Trial registration</p> <p>clinicaltrials.gov NCT00815698</p

Non-randomised patients in a cholecystectomy trial: characteristics, procedures, and outcomes

BACKGROUND: Laparoscopic cholecystectomy is now considered the first option for gallbladder surgery. However, 20% to 30% of cholecystectomies are completed as open operations often on elderly and fragile patients. The external validity of randomised trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy has not been studied. The aim of this study is to analyse characteristics, procedures, and outcomes for all patients who underwent cholecystectomy without being included in such a trial. METHODS: Characteristics (age, sex, co-morbidity, and ASA-score), operation time, hospital stay, and mortality were compared for patients who underwent cholecystectomy outside and within a randomised controlled trial comparing mini-laparotomy and laparoscopic cholecystectomy. RESULTS: During the inclusion period 1719 patients underwent cholecystectomy. 726 patients were randomised and 724 of them completed the trial; 993 patients underwent cholecystectomy outside the trial. The non-randomised patients were older – and had more complications from gallstone disease, higher co-morbidity, and higher ASA – score when compared with trial patients. They were also more likely to undergo acute surgery and they had a longer postoperative hospital stay, with a median 3 versus 2 days (p < 0.001 for all comparisons). Standardised mortality ratio within 90 days of operation was 3.42 (mean) (95% CI 2.17 to 5.13) for non-randomised patients and 1.61 (mean) (95%CI 0.02 to 3.46) for trial patients. For non-randomised patients, operation time did not differ significantly between mini-laparotomy and open cholecystectomy in multivariate analysis. However, the operation for laparoscopic cholecystectomy lasted 20 minutes longer than open cholecystectomy. Hospital stay was significantly shorter for both mini-laparotomy and laparoscopic cholecystectomy compared to open cholecystectomy. CONCLUSION: Non-randomised patients were older and more sick than trial patients. The assignment of healthier patients to trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy limits the external validity of conclusions reached in such trials

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

&lt;p&gt;Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.&lt;/p&gt; &lt;p&gt;Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.&lt;/p&gt

Early lens aging is accelerated in subjects with a high risk of ischemic heart disease: an epidemiologic study

BACKGROUND: Ischemic heart disease (IHD) is one of the most important causes of mortality and morbidity in the Western world. There is a relationship between aging of the lens of the human eye and cardiovascular disease. The present study was conducted to examine if the risk of ischemic heart disease could be estimated by fluorophotometric assessment of lens aging. METHODS: A total of 421 subjects were included. Risk of IHD was estimated from non-ocular data using the Precard (® )software. Lens aging was quantified by lens fluorometry. RESULTS: The risk of IHD was strongly related to lens fluorophore accumulation (p = 0.001). The relationship between IHD and lens aging was attributable to tobacco smoking and dysglycemia. CONCLUSION: The risk of ischemic heart disease related to smoking and diabetes mellitus can be estimated using the aging of the lens of the eye as a biomarker for generalized tissue-damage

Knee-clicks and visual traits indicate fighting ability in eland antelopes: multiple messages and back-up signals

Abstract Background Given the costs of signalling, why do males often advertise their fighting ability to rivals using several signals rather than just one? Multiple signalling theories have developed largely in studies of sexual signals, and less is known about their applicability to intra-sexual communication. We here investigate the evolutionary basis for the intricate agonistic signalling system in eland antelopes, paying particular attention to the evolutionary phenomenon of loud knee-clicking. Results A principal components analysis separated seven male traits into three groups. The dominant frequency of the knee-clicking sound honestly indicated body size, a main determinant of fighting ability. In contrast, the dewlap size increased with estimated age rather than body size, suggesting that, by magnifying the silhouette of older bulls disproportionately, the dewlap acts as an indicator of age-related traits such as fighting experience. Facemask darkness, frontal hairbrush size and body greyness aligned with a third underlying variable, presumed to be androgen-related aggression. A longitudinal study provided independent support of these findings. Conclusion The results show that the multiple agonistic signals in eland reflect three separate components of fighting ability: (1) body size, (2) age and (3) presumably androgen-related aggression, which is reflected in three backup signals. The study highlights how complex agonistic signalling systems can evolve through the simultaneous action of several selective forces, each of which favours multiple signals. Specifically, loud knee-clicking is discovered to be an honest signal of body size, providing an exceptional example of the potential for non-vocal acoustic communication in mammals.</p

Carbon stock growth in a forest stand: the power of age

BACKGROUND: Understanding the relationship between the age of a forest stand and its biomass is essential for managing the forest component of the global carbon cycle. Since biomass increases with stand age, postponing harvesting to the age of biological maturity may result in the formation of a large carbon sink. This article quantifies the carbon sequestration capacity of forests by suggesting a default rule to link carbon stock and stand age. RESULTS: The age dependence of forest biomass is shown to be a power-law monomial where the power of age is theoretically estimated to be 4/5. This theoretical estimate is close to the known empirical estimate; therefore, it provides a scientific basis for a quick and transparent assessment of the benefits of postponing the harvest, suggesting that the annual magnitude of the sink induced by delayed harvest lies in the range of 1–2% of the baseline carbon stock. CONCLUSION: The results of this study imply that forest age could be used as an easily understood and scientifically sound measure of the progress in complying with national targets on the protection and enhancement of forest carbon sinks

Age- and Sex-Specific Mortality Patterns in an Emerging Wildlife Epidemic: The Phocine Distemper in European Harbour Seals

Analyses of the dynamics of diseases in wild populations typically assume all individuals to be identical. However, profound effects on the long-term impact on the host population can be expected if the disease has age and sex dependent dynamics. The Phocine Distemper Virus (PDV) caused two mass mortalities in European harbour seals in 1988 and in 2002. We show the mortality patterns were highly age specific on both occasions, where young of the year and adult (>4 yrs) animals suffered extremely high mortality, and sub-adult seals (1–3 yrs) of both sexes experienced low mortality. Consequently, genetic differences cannot have played a main role explaining why some seals survived and some did not in the study region, since parents had higher mortality levels than their progeny. Furthermore, there was a conspicuous absence of animals older than 14 years among the victims in 2002, which strongly indicates that the survivors from the previous disease outbreak in 1988 had acquired and maintained immunity to PDV. These specific mortality patterns imply that contact rates and susceptibility to the disease are strongly age and sex dependent variables, underlining the need for structured epidemic models for wildlife diseases. Detailed data can thus provide crucial information about a number of vital parameters such as functional herd immunity. One of many future challenges in understanding the epidemiology of the PDV and other wildlife diseases is to reveal how immune system responses differ among animals in different stages during their life cycle. The influence of such underlying mechanisms may also explain the limited evidence for abrupt disease thresholds in wild populations

Accurate masses and radii of normal stars: modern results and applications

This paper presents and discusses a critical compilation of accurate, fundamental determinations of stellar masses and radii. We have identified 95 detached binary systems containing 190 stars (94 eclipsing systems, and alpha Centauri) that satisfy our criterion that the mass and radius of both stars be known to 3% or better. To these we add interstellar reddening, effective temperature, metal abundance, rotational velocity and apsidal motion determinations when available, and we compute a number of other physical parameters, notably luminosity and distance. We discuss the use of this information for testing models of stellar evolution. The amount and quality of the data also allow us to analyse the tidal evolution of the systems in considerable depth, testing prescriptions of rotational synchronisation and orbital circularisation in greater detail than possible before. The new data also enable us to derive empirical calibrations of M and R for single (post-) main-sequence stars above 0.6 M(Sun). Simple, polynomial functions of T(eff), log g and [Fe/H] yield M and R with errors of 6% and 3%, respectively. Excellent agreement is found with independent determinations for host stars of transiting extrasolar planets, and good agreement with determinations of M and R from stellar models as constrained by trigonometric parallaxes and spectroscopic values of T(eff) and [Fe/H]. Finally, we list a set of 23 interferometric binaries with masses known to better than 3%, but without fundamental radius determinations (except alpha Aur). We discuss the prospects for improving these and other stellar parameters in the near future.Comment: 56 pages including figures and tables. To appear in The Astronomy and Astrophysics Review. Ascii versions of the tables will appear in the online version of the articl

Macroevolutionary diversification of glands for chemical communication in squamate reptiles

Chemical communication plays a central role in social, sexual and ecological interactions among animals. However, the macroevolutionary diversification of traits responsible for chemical signaling remains fundamentally unknown. Most research investigating evolutionary diversification of glands responsible for the production of chemical signals has focused on arthropods, while its study among vertebrates remains neglected. Using a global-scale dataset covering > 80% (7,904 species) of the living diversity of lizards and snakes (squamates), we investigate rates, trajectories and phylogenetic patterns of diversification of their follicular glands for chemical communication. We observed these glands in 13.66% of species, that their expression has varying phylogenetic signal among lineages, and that the crown squamate ancestor lacked follicular glands, which therefore originated and diversified subsequently during their evolutionary history. Additionally, our findings challenge the longstanding view that within squamates the Iguania are visually oriented while Scleroglossa are chemically-oriented, given that Iguania doubles Scleroglossa in the frequency of glands. Our phylogenetic analyses identified stabilizing selection as the best model describing follicular gland diversification, and revealed high rates of disparity. We provide the first global-scale analysis investigating the diversification of one of the main forms of communication among reptiles, presenting a macroevolutionary angle to questions traditionally explored at microevolutionary scale