The PI3K/Akt Pathway in Tumors of Endocrine Tissues

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a key driver in carcinogenesis. Defects in this pathway in human cancer syndromes such as Cowden’s disease and Multiple Endocrine Neoplasia result in tumors of endocrine tissues, highlighting its importance in these cancer types. This review explores the growing evidence from multiple animal and in vitro models and from analysis of human tumors for the involvement of this pathway in the following: thyroid carcinoma subtypes, parathyroid carcinoma, pituitary tumors, adrenocortical carcinoma, phaeochromocytoma, neuroblastoma, and gastroenteropancreatic neuroendocrine tumors. While data are not always consistent, immunohistochemistry performed on human tumor tissue has been used alongside other techniques to demonstrate Akt overactivation. We review active Akt as a potential prognostic marker and the PI3K pathway as a therapeutic target in endocrine neoplasia

Content and Methods of Teaching Literacy: The Effect of One-on-One Tutoring in Preservice Clinical Education in Two Low-Performing, Diverse School Settings on the Effectiveness of Preservice Teachers’ Reading Instruction

This is a study of preservice teachers’ ability to teach reading to struggling, diverse students, after participating in a school-embedded course incorporating a one-on-one tutorial directly supervised by reading experts. Changes in reading performance as well as plans to analyze changes in the preservice teachers will be discussed

Body Inversion Effects With Photographic Images of Body Postures: Is It About Faces?

As with faces, participants are better at discriminating upright bodies than inverted bodies. This inversion effect is reliable for whole figures, namely, bodies with heads, but it is less reliable for headless bodies. This suggests that removal of the head disrupts typical processing of human figures, and raises questions about the role of faces in efficient body discrimination. In most studies, faces are occluded, but the aim here was to exclude faces in a more ecologically valid way by presenting photographic images of human figures from behind (about-facing), as well as measuring gaze to different parts of the figures. Participants determined whether pairs of sequentially presented body postures were the same or different for whole and headless figures. Presenting about-facing figures (heads seen from behind) and forward-facing figures with faces enabled a comparison of the effect of the presence or absence of faces. Replicating previous findings, there were inversion effects for forward-facing whole figures, but less reliable effects for headless images. There were also inversion effects for about-facing whole figures, but not about-facing headless figures. Accuracy was higher in the forward- compared to the about-facing conditions, but proportional dwell time was greater to bodies in about-facing images. Likewise, despite better discrimination of forward-facing upright compared to inverted whole figures, participants focused more on the heads and less on the bodies in upright compared to inverted images. However, there was no clear relationship between performance and dwell time proportions to heads. Body inversion effects (BIEs) were found with about-facing whole figures and headless forward-facing figures, despite the absence of faces. With inverted whole figures, there was a significant relationship between performance and greater looking at bodies, and less at heads suggesting that in more difficult conditions a focus on bodies is associated with better discrimination. Overall, the findings suggest that the visual system has greater sensitivity to bodies in their most experienced form, which is typically upright and with a head. Otherwise, the more a face is implied by the context, as in whole figures or forward- rather than about-facing headless bodies, the better the performance as holistic/configural processing is likely stronger

Space Qualified 200-Watt Q-Band Linearized Traveling-Wave Tube Amplifier

L3 Technologies Electron Devices Division, (L3 EDD) and L3 Technologies Narda Microwave West (L3 NMW), are completing space-flight qualification for a 200-watt Q-band linearized channelized traveling-wave tube amplifier (LCTWTA) capable of over 5 GHz instantaneous bandwidth in a conduction-cooled package. This paper will discuss the LCTWTA performance, manufacturing and flight qualification test results

Capability in the digital: institutional media management and its dis/contents

This paper explores how social media spaces are occupied, utilized and negotiated by the British Military in relation to the Ministry of Defence’s concerns and conceptualizations of risk. It draws on data from the DUN Project to investigate the content and form of social media about defence through the lens of ‘capability’, a term that captures and describes the meaning behind multiple representations of the military institution. But ‘capability’ is also a term that we hijack and extend here, not only in relation to the dominant presence of ‘capability’ as a representational trope and the extent to which it is revealing of a particular management of social media spaces, but also in relation to what our research reveals for the wider digital media landscape and ‘capable’ digital methods. What emerges from our analysis is the existence of powerful, successful and critically long-standing media and reputation management strategies occurring within the techno-economic online structures where the exercising of ‘control’ over the individual – as opposed to the technology – is highly effective. These findings raise critical questions regarding the extent to which ‘control’ and management of social media – both within and beyond the defence sector – may be determined as much by cultural, social, institutional and political influence and infrastructure as the technological economies. At a key moment in social media analysis, then, when attention is turning to the affordances, criticisms and possibilities of data, our research is a pertinent reminder that we should not forget the active management of content that is being similarly, if not equally, effective

Vitamin intake is associated with improved visuospatial and verbal semantic memory in middle-aged individuals

Objectives: Factors maintaining cognitive health are still largely unknown. In particular, the cognitive benefits associated with vitamin intake and vitamin supplementation are disputed. We investigated self-reported vitamin intake and serum vitamin levels with performance in cognitive factors sensitive to dementia progression in two large middle-aged general population cohorts. Methods: Survey data was used to assess regular vitamin intake in 4400 NCDS 1958 and 1177 TwinsUK cohort members, and serum homocysteine and B vitamin levels were measured in 675 individuals from the TwinsUK study. Principal component analysis was applied to cognitive test performance from both cohorts resulting in two dementia-sensitive cognitive factors reflecting visuospatial associative memory and verbal semantic memory. Results: In both cohorts, individuals who reported regular intake of vitamins, particularly B vitamins, showed significantly better performance in visuospatial associative memory and verbal semantic memory (p < 0.001). A significant association was also found between homocysteine levels, vitamin serum concentration and visuospatial associative memory performance which indicated that individuals with high B vitamin and homocysteine levels showed better visuospatial associative memory performance than individuals with low vitamin B levels (p < 0.05). Discussion: The findings demonstrate that early dementia-sensitive cognitive changes can be identified in middle-aged asymptomatic individuals and that regular vitamin intake is associated with improved cognitive performance. These findings reinforce the potential cognitive benefits of regular vitamin intake, which should be considered as an economically viable therapeutic strategy for maintaining cognitive health

Vitamin D with Calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials

Introduction: Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium. Subjects and Methods: Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies. Results: The IPD analysis yielded data on 70,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62–77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88–0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84–0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88–0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91–1.06). Conclusion: Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone

The importance of RT-qPCR primer design for the detection of siRNA-mediated mRNA silencing

<p>Abstract</p> <p>Background</p> <p>The use of RNAi to analyse gene function <it>in vitro </it>is now widely applied in biological research. However, several difficulties are associated with its use <it>in vivo</it>, mainly relating to inefficient delivery and non-specific effects of short RNA duplexes in animal models. The latter can lead to false positive results when real-time RT-qPCR alone is used to measure target mRNA knockdown.</p> <p>Findings</p> <p>We observed that detection of an apparent siRNA-mediated knockdown <it>in vivo </it>was dependent on the primers used for real-time RT-qPCR measurement of the target mRNA. Two siRNAs specific for <it>RRM1 </it>with equivalent activity <it>in vitro </it>were administered to A549 xenografts via intratumoural injection. In each case, apparent knockdown of <it>RRM1 </it>mRNA was observed only when the primer pair used in RT-qPCR flanked the siRNA cleavage site. This false-positive result was found to result from co-purified siRNA interfering with both reverse transcription and qPCR.</p> <p>Conclusions</p> <p>Our data suggest that using primers flanking the siRNA-mediated cleavage site in RT-qPCR-based measurements of mRNA knockdown <it>in vivo </it>can lead to false positive results. This is particularly relevant where high concentrations of siRNA are introduced, particularly via intratumoural injection, as the siRNA may be co-purified with the RNA and interfere with downstream enzymatic steps. Based on these results, using primers flanking the siRNA target site should be avoided when measuring knockdown of target mRNA by real-time RT-qPCR.</p

Acceptability, benefits, and challenges of video consulting: a qualitative study in primary care

Background People increasingly communicate online, using visual communication mediums such as Skype and FaceTime. Growing demands on primary care services mean that new ways of providing patient care are being considered. Video consultation (VC) over the internet is one such mode. Aim To explore patients’ and clinicians’ experiences of VC. Design and setting Semi-structured interviews in UK primary care. Method Primary care clinicians were provided with VC equipment. They invited patients requiring a follow-up consultation to an online VC using the Attend Anywhere web-based platform. Participating patients required a smartphone, tablet, or video-enabled computer. Following VCs, semi-structured interviews were conducted with patients (n = 21) and primary care clinicians (n = 13), followed by a thematic analysis. Results Participants reported positive experiences of VC, and stated that VC was particularly helpful for them as working people and people with mobility or mental health problems. VCs were considered superior to telephone consultations in providing visual cues and reassurance, building rapport, and improving communication. Technical problems, however, were common. Clinicians felt, for routine use, VCs must be more reliable and seamlessly integrated with appointment systems, which would require upgrading of current NHS IT systems. Conclusion The visual component of VCs offers distinct advantages over telephone consultations. When integrated with current systems VCs can provide a time-saving alternative to face-to-face consultations when formal physical examination is not required, especially for people who work. Demand for VC services in primary care is likely to rise, but improved technical infrastructure is required to allow VC to become routine. However, for complex or sensitive problems face-to-face consultations remain preferable