Characteristics of Precession Electron Diffraction Intensities from Dynamical Simulations

Precession Electron Diffraction (PED) offers a number of advantages for crystal structure analysis and solving unknown structures using electron diffraction. The current article uses many-beam simulations of PED intensities, in combination with model structures, to arrive at a better understanding of how PED differs from standard unprecessed electron diffraction. It is shown that precession reduces the chaotic oscillatory behavior of electron diffraction intensities as a function of thickness. An additional characteristic of PED which is revealed by simulations is reduced sensitivity to structure factor phases. This is shown to be a general feature of dynami-cal intensities collected under conditions in which patterns with multiple incident beam orienta-tions are averaged together. A new and significantly faster method is demonstrated for dynami-cal calculations of PED intensities, based on using information contained in off-central columns of the scattering matrix.Comment: 20 pages, 7 Figure

Does use of touch screen computer technology improve classroom engagement in children?

Many studies have shown that the use of technology in the classroom may influence pupil engagement. Despite the recent widespread use of tablet technology, however, very little research has been carried out into their use in a primary school setting. We investigated the use of tablet computers, specifically Apple’s ‘iPad’, in an upper primary school setting with regard to children’s engagement. Cognitive, emotional and general engagement was higher in lessons based on iPads than those which were not. There was no difference in behavioral engagement. Of particular significance was the increase in engagement seen in boys, which resulted in their engagement levels increasing to levels comparable to those seen in girls. These findings suggest that tablet technology has potential as a tool in the classroom setting

Therapeutic antibodies: current state and future trends--is a paradigm change coming soon?

Antibody-based therapeutics currently enjoy unprecedented success, growth in research and revenues, and recognition of their potential. It appears that the promise of the "magic bullet" has largely been realized. There are currently 22 monoclonal antibodies (mAbs) approved by the United States Food and Drug Administration (FDA) for clinical use and hundreds are in clinical trials for treatment of various diseases including cancers, immune disorders, and infections. The revenues from the top five therapeutic antibodies (Rituxan, Remicade, Herceptin, Humira, and Avastin) nearly doubled from $6.4 billion in 2004 to$11.7 billion in 2006. During the last several years major pharmaceutical companies raced to acquire antibody companies, with a recent example of MedImmune being purchased for $15.6 billion by AstraZeneca. These therapeutic and business successes reflect the major advances in antibody engineering which have resulted in the generation of safe, specific, high-affinity, and non-immunogenic antibodies during the last three decades. Currently, second and third generations of antibodies are under development, mostly to improve already existing antibody specificities. However, although the refinement of already known methodologies is certainly of great importance for potential clinical use, there are no conceptually new developments in the last decade comparable, for example, to the development of antibody libraries, phage display, domain antibodies (dAbs), and antibody humanization to name a few. A fundamental question is then whether there will be another change in the paradigm of research as happened 1-2 decades ago or the current trend of gradual improvement of already developed methodologies and therapeutic antibodies will continue. Although any prediction could prove incorrect, it appears that conceptually new methodologies are needed to overcome the fundamental problems of drug (antibody) resistance due to genetic or/and epigenetic alterations in cancer and chronic infections, as well as problems related to access to targets and complexity of biological systems. If new methodologies are not developed, it is likely that gradual saturation will occur in the pipeline of conceptually new antibody therapeutics. In this scenario we will witness an increase in combination of targets and antibodies, and further attempts to personalize targeted treatments by using appropriate biomarkers as well as to develop novel scaffolds with properties that are superior to those of the antibodies now in clinical use

SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons.

The mechanism for the earliest response of central neurons to hypoxia-an increase in voltage-gated sodium current (INa)-has been unknown. Here, we show that hypoxia activates the Small Ubiquitin-like Modifier (SUMO) pathway in rat cerebellar granule neurons (CGN) and that SUMOylation of NaV1.2 channels increases INa. The time-course for SUMOylation of single NaV1.2 channels at the cell surface and changes in INa coincide, and both are prevented by mutation of NaV1.2-Lys38 or application of a deSUMOylating enzyme. Within 40 s, hypoxia-induced linkage of SUMO1 to the channels is complete, shifting the voltage-dependence of channel activation so that depolarizing steps evoke larger sodium currents. Given the recognized role of INa in hypoxic brain damage, the SUMO pathway and NaV1.2 are identified as potential targets for neuroprotective interventions

Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia

Objectives To assess the cost effectiveness of strategies to screen for and treat familial hypercholesterolaemia. Design Cost effectiveness analysis. A care pathway for each patient was delineated and the associated probabilities, benefits, and costs were calculated. Participants Simulated population aged 16­54 years in England and Wales. Interventions Identification and treatment of patients with familial hypercholesterolaemia by universal screening, opportunistic screening in primary care, screening of people admitted to hospital with premature myocardial infarction, or tracing family members of affected patients. Main outcome measure Cost effectiveness calculated as cost per life year gained (extension of life expectancy resulting from intervention) including estimated costs of screening and treatment. Results Tracing of family members was the most cost effective strategy (£3097 (&5066, $4479) per life year gained) as 2.6 individuals need to be screened to identify one case at a cost of £133 per case detected. If the genetic mutation was known within the family then the cost per life year gained (£4914) was only slightly increased by genetic confirmation of the diagnosis. Universal population screening was least cost effective (£13 029 per life year gained) as 1365 individuals need to be screened at a cost of £9754 per case detected. For each strategy it was more cost effective to screen younger people and women. Targeted strategies were more expensive per person screened, but the cost per case detected was lower. Population screening of 16 year olds only was as cost effective as family tracing (£2777 with a clinical confirmation). Conclusions Screening family members of people with familial hypercholesterolaemia is the most cost effective option for detecting cases across the whole population