The use of segmented regression in analysing interrupted time series studies : an example in pre-hospital ambulance care

Peer reviewedPublisher PD

Determination of phototropism by UV-B radiation

UV-B phototropism in etiolated Arabidopsis seedlings has only been shown recently and needs further exploration. Here we elaborate on how to generate a customized setup with a unilateral UV-B light source, the required plant materials, different growth substrates, and a framework for data analysis

Regions identity between the genome of vertebrates and non-retroviral families of insect viruses

<p>Abstract</p> <p>Background</p> <p>The scope of our understanding of the evolutionary history between viruses and animals is limited. The fact that the recent availability of many complete insect virus genomes and vertebrate genomes as well as the ability to screen these sequences makes it possible to gain a new perspective insight into the evolutionary interaction between insect viruses and vertebrates. This study is to determine the possibility of existence of sequence identity between the genomes of insect viruses and vertebrates, attempt to explain this phenomenon in term of genetic mobile element, and try to investigate the evolutionary relationship between these short regions of identity among these species.</p> <p>Results</p> <p>Some of studied insect viruses contain variable numbers of short regions of sequence identity to the genomes of vertebrate with nucleotide sequence length from 28 bp to 124 bp. They are found to locate in multiple sites of the vertebrate genomes. The ontology of animal genes with identical regions involves in several processes including chromatin remodeling, regulation of apoptosis, signaling pathway, nerve system development and some enzyme-like catalysis. Phylogenetic analysis reveals that at least some short regions of sequence identity in the genomes of vertebrate are derived the ancestral of insect viruses.</p> <p>Conclusion</p> <p>Short regions of sequence identity were found in the vertebrates and insect viruses. These sequences played an important role not only in the long-term evolution of vertebrates, but also in promotion of insect virus. This typical win-win strategy may come from natural selection.</p

Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework

Background: The Theoretical Domains Framework (TDF) was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without xrays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine xrays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays. Methods: Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF. Results: Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences); beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied (social/professional role & identity); the influence of formal training, colleagues, and patients also appeared to be important factors (social influences); conflicting comments regarding levels of confidence and comfort in managing patients without x-rays (belief about capabilities); and guideline awareness and agreements (knowledge). Conclusions: Chiropractors’ use of diagnostic imaging appears to be influenced by a number of factors. Five key domains may be important considering the presence of conflicting beliefs, evidence of strong beliefs likely to impact the behavior of interest, and high frequency of beliefs. The results will inform the development of a theorybased survey to help identify potential targets for behavioral-change strategies

Variation in styles of rifting in the Gulf of California

Author Posting. © Nature Publishing Group, 2007. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 448 (2007): 466-469, doi:10.1038/nature06035.The rifting of continental lithosphere is a fundamental solid-earth process that leads to the formation of rifted continental margins and ocean basins. Understanding of this process comes from observations of the geometry of rifted margins and the magmatism resulting from rifting, which inform us about the strength of the lithosphere, the state of the underlying mantle, and the transition from rifting to seafloor spreading. Here we describe results from the PESCADOR seismic experiment in the southern Gulf of California and present the first crustal-scale images across conjugate margins of multiple segments within a single rift that has reached the stage of oceanic spreading. A surprisingly large variation in rifting style and magmatism is observed between these segments, from wide rifting with minor syn-rift magmatism to narrow rifting in magmatically robust segments. These differences encompass much of the variation observed across nearly all other non-end-member continental margins. The characteristics of magmatic endmember margins are typically explained in terms of mantle temperature. Our explanations for the variation in the Gulf of California, in contrast, invoke mantle depletion to account for wide, magma-poor rifting and mantle fertility and possibly the influence of sediments to account for robust rift and post-rift magmatism in the Gulf of California. These factors may vary laterally over small distances in regions that have transitioned from convergence to extension, as is the case for the Gulf of California and many other rifts.This work was funded by a grant from the U.S. NSF-MARGINS program

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

8-Cl-cAMP antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor

The growth factor-activated mitogenic pathways are often disregulated in tumour cells and, therefore, they can provide specific molecular targets for novel anti-tumour approaches. 8-Chloro-cAMP (8-Cl-cAMP), a synthetic cAMP analogue, is a novel anti-tumour agent that has recently undergone clinical evaluation. We investigated the effects of 8-CI-cAMP on the epidermal growth factor (EGF)/EGF receptor (EGF-R) signalling in human epidermoid cancer KB cells, which are responsive to the mitogenic stimulus of EGF. We found that the growth-promoting activity of EGF was completely abolished when EGF treatment was performed in combination with 8-CI-cAMP. The inhibition of the EGF-induced proliferation by 8-CI-cAMP was paralleled by the blockade of the EGF-stimulated activation of mitogen-activated protein kinases (MAPK), ERK-1 and ERK-2. Conversely, we found an increase of EGF-R expression and EGF-R tyrosine phosphorylation when KB cells were growth inhibited by 8-Cl-cAMP. Moreover, the activity of Raf-1 and MEK-1 protein kinases, the activators upstream MAPK in the phosphorylation cascade induced by EGF, was not modified in 8-Cl-cAMP-treated cells. We concluded that the impairment of KB cell response to EGF, induced by 8-Cl-cAMP, resides in the specific inhibition of MAPK/ERKs activity while the function of the upstream elements in the EGF-R signalling is preserved. © 1999 Cancer Research Campaig

The reference frame for encoding and retention of motion depends on stimulus set size

YesThe goal of this study was to investigate the reference frames used in perceptual encoding and storage of visual motion information. In our experiments, observers viewed multiple moving objects and reported the direction of motion of a randomly selected item. Using a vector-decomposition technique, we computed performance during smooth pursuit with respect to a spatiotopic (nonretinotopic) and to a retinotopic component and compared them with performance during fixation, which served as the baseline. For the stimulus encoding stage, which precedes memory, we found that the reference frame depends on the stimulus set size. For a single moving target, the spatiotopic reference frame had the most significant contribution with some additional contribution from the retinotopic reference frame. When the number of items increased (Set Sizes 3 to 7), the spatiotopic reference frame was able to account for the performance. Finally, when the number of items became larger than 7, the distinction between reference frames vanished. We interpret this finding as a switch to a more abstract nonmetric encoding of motion direction. We found that the retinotopic reference frame was not used in memory. Taken together with other studies, our results suggest that, whereas a retinotopic reference frame may be employed for controlling eye movements, perception and memory use primarily nonretinotopic reference frames. Furthermore, the use of nonretinotopic reference frames appears to be capacity limited. In the case of complex stimuli, the visual system may use perceptual grouping in order to simplify the complexity of stimuli or resort to a nonmetric abstract coding of motion information

Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer.

We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial

Murine and Bovine γδ T Cells Enhance Innate Immunity against Brucella abortus Infections

γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ−/− mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα−/−, and GMCSF−/− mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ−/− mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections