Brantleyasmussen4592
BACKGROUND Clinical trials are expensive and often require funding from the pharmaceutical industry (PI). We aimed to compare studies funded by the PI with studies funded by other sources in terms of costs, reported results and strength of evidence. METHODS We searched PubMed for clinical trial reports on metastatic NSCLC published between 2012 and 2017. We divided all studies into two groups studies funded by the PI or by other sources. The primary endpoint was to compare the evidence strength of each group. MSC2530818 Secondary endpoints were to compare the number of patients included, the number and costs of innovative drugs studied, whether there was preferential reporting of positive results in the experimental arm and the risk of bias. RESULTS We found 3,004 studies and, of these, analyzed 477 studies (275 sponsored by the PI and 202 funded by other sources). 85,328 patients overall were included (64,434 in studies sponsored by the PI and 20,894 in studies with other funding sources; p less then 0.001). The studies funded by the PI had stronger evidence (p less then 0.001), evaluated more innovative therapies (72% versus 36%; p less then 0.001) and resulted in a higher proportion of open access manuscripts (63% versus 47%; p less then 0.001). There was no significant difference regarding the reporting of experimental arm superiority between the two groups or the risk of bias. CONCLUSIONS Compared with other sources of funding, studies funded by the PI in the lung cancer field collected stronger evidence, assessed more expensive and innovative therapies and seem to equally emphasize positive and negative results. Recent evidence suggests that the human brain automatically constructs a rich model of other people's attention, beyond registering low-level cues such as someone else's gaze direction. This model is not a physically accurate representation of attention, but instead appears to contain simplifying and physically incoherent features. For example, without explicitly realizing it, people treat the attentive gaze of others as though it exerts a gentle force pushing on objects. Here we specify another aspect of that implicit model of attention. People treat the attentive gaze of an agent as though it were traveling through space, with an implied motion encoded literally enough that it causes a perceptual motion adaptation effect. This implicit model of other people's attention may facilitate the process of keeping track of who is attending to what, which is essential for reading and predicting the minds and behavior of social agents. This implicit model of attention may also have shaped culturally widespread ideas about mind and spirit. PURPOSE To investigate the utility of diffusion-weighted arterial spin labeling (DW-ASL) for detecting the progression of brain white matter lesions. MATERIALS AND METHODS A total of 492 regions of interest (ROIs) in 41 patients were prospectively analyzed. DW-ASL was performed using the diffusion gradient prepulse of five b-values (0, 25, 60, 102, and 189) before the ASL readout. We calculated the water exchange rate (Kw) with post-processing using the ASL signal information for each b-value. The cerebral blood flow (CBF) was also calculated using b0 images. Using the signal information in FLAIR (fluid-attenuated inversion recovery) images, we classified the severity of white matter lesions into three grades non-lesion, moderate, and severe. In addition, the normal Kw level was measured from DW-ASL data of 60 ROIs in five control subjects. The degree of variance of the Kw values (Kw-var) was calculated by squaring the value of the difference between each Kw value and the normal Kw level. All patient's ROIs were divided into non-progressive and progressive white matter lesions by comparing the present FLAIR images with those obtained 2 years before this acquisition. RESULTS Compared to the non-progressive group, the progressive group had significantly lower CBF, significantly higher severity grades in FLAIR, and significantly greater Kw-var values. In a receiver operator characteristic curve analysis, a high area under the curve (AUC) of 0.89 was obtained with the use of Kw-var. In contrast, the AUCs of 0.59 for CBF and 0.72 for severity grades in FLAIR were obtained. CONCLUSIONS The DW-ASL technique can be useful to detect the progression of brain white matter lesions. This technique will become a clinical tool for patients with various degrees of white matter lesions. Recombinant expression and purification of proteins is key for biochemical and biophysical investigations. Although this has become a routine and standard procedure for many proteins, intrinsically disordered ones and those with low complexity sequences pose difficulties. Proteins containing low complexity regions (LCRs) are increasingly becoming significant for their roles in both norm and pathology. Here, we report cloning, expression and purification of N-terminal LCR of RanBP9 protein (Nt-RanBP9). RanBP9 is a scaffolding protein present in both cytoplasm and nucleus that is implicated in many cellular processes. Nt-RanBP9 is poorly understood region of the protein perhaps due to sequence with low complexity. Indeed, conventional methods presented difficulties in Nt-RanBP9 cloning due to its high GC content resulting in insignificant protein expression. These led us to use a different approach of cloning by expressing the protein as a fusion construct containing mCherry or mEGFP using in vivo DNA recombination methods. Our results indicate that expression of mEGFP-tagged Nt-RanBP9 followed by thrombin cleavage of the tag was the most effective method to obtain the protein with >90% purity and good yields. We report and discuss the challenges and optimal methods to obtain the N-terminal region of RanBP9, a protein with functional implications in multiple biological processes and neurodegenerative diseases. OBJECTIVE To determine baseline knowledge of emergency medicine (EM) residents at 2 different residency training programs and assess if a 4-week orthopedic surgery rotation would improve musculoskeletal (MSK) knowledge as assessed by the basic competency exam (BCE). This study also sought to compare variations of the BCE to determine how emergency physicians would perform on the full 25-question assessment vs a modified 18-question test. DESIGN Residents from 2 different EM residency training programs were given the BCE to determine baseline MSK knowledge prior to their orthopedic surgery rotations. A postrotation BCE was given to the residents from both EM training programs upon completion of their orthopedic surgery rotation. Both prerotation and postrotation tests were reviewed and scored independently by a panel of experts and later assessed by 2 independent reviewers. SETTING San Antonio Military Medical Center, SA Tx Level I Trauma, Tertiary Care Center University of Texas Health, SA, Tx, Level 1 Trauma, Tertiary Care Center.