Using a TRAPS upstream transmission detector to verify multileaf collimator positions during dynamic radiotherapy delivery.

With the advancement of high-precision radiotherapy and the increasing use of higher intensity beams, the risk to the patient increases should the radiotherapy machine malfunction. Hence more accurate treatment verification is required. In this paper we provide a solution for real-time monitoring of X-ray beams from radiotherapy linear accelerators using monolithic active pixel sensors. We show that leaf errors can be detected with high precision in static fields and IMRT step and shoot, and accurate leaf tracking is possible in Volumetric Modulated Arc Therapy. The prototype MAPS detector meets the criteria of 1% attenuation acceptable for clinical use.

Host Range and Population Survey of Spodoptera frugiperda Rhabdovirus.

The Sf9 and Sf21 cell lines derived from ovarian tissues of the wide-host-range phytophagous lepidopteran Spodoptera frugiperda are widely used for research and commercial-scale production of recombinant proteins. These cell lines are chronically infected with a rhabdovirus (Sf-RV) that does not cause any overt cytopathic effects. We demonstrate that wild populations of S. frugiperda in the eastern United States and Caribbean are infected with genetically diverse strains of Sf-RV and that this virus is also capable of infecting cells of Spodoptera exigua, Heliothis subflexa, and Bombyx mori Feeding studies demonstrated the ability of S. frugiperda larvae to deposit Sf-RV onto human-consumed vegetables during feeding. Although no evidence for replication in two species of plant cells was detected, subcellular localization studies demonstrated that the Sf-RV nucleocapsid was targeted to plasmodesmata, while two forms of the accessory protein were differentiated on the basis of their ability to localize to nuclei. Collectively, the results from this study suggest that environmental exposure of humans to Sf-RV is likely to be commonplace and frequent, but its inability to replicate in plant or human cells suggests that there is no substantial risk to human health.IMPORTANCE Insect-derived cell lines are widely used commercially for the production of vaccines and protein-based pharmaceuticals. After decades of safe and beneficial use, it was a surprise to the biotechnology industry to discover an endemic rhabdovirus in Sf9 cells. This discovery was made possible only by the substantial advancements in DNA sequencing technologies. Given the public health concerns associated with many rhabdovirus species, several initiatives were undertaken to establish that Spodoptera frugiperda rhabdovirus (Sf-RV) does not pose a threat to humans. Such actions include the generation of cell lines that have been cleared of Sf-RV. Given that Sf9 is derived from a moth whose larvae feed on human-edible foods, we explored the prevalence of Sf-RV in its wild and lab-grown populations, as well as its ability to be deposited on food items during feeding. Collectively, our data suggest that there is no overt risk from exposure to Sf-RV.

Personalized risk prediction of postoperative cognitive impairment - rationale for the EU-funded BioCog project.

Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions - particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost-benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.

Subliminal and supraliminal processing of reward-related stimuli in anorexia nervosa.

BACKGROUND: Previous studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC). METHODS: fMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group × stimulation condition × stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis. RESULTS: AN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity. CONCLUSION: Increased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN.

Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach.

The symptoms of malaria are brought about by blood-stage parasites, which are established when merozoites invade human erythrocytes. Our understanding of the molecular events that underpin erythrocyte invasion remains hampered by the short-period of time that merozoites are invasive. To address this challenge, a Plasmodium falciparum gamma-irradiated long-lived merozoite (LLM) line was developed and investigated. Purified LLMs invaded erythrocytes by an increase of 10-300 fold compared to wild-type (WT) merozoites. Using an integrated omics approach, we investigated the basis for the phenotypic difference. Only a few single nucleotide polymorphisms within the P. falciparum genome were identified and only marginal differences were observed in the merozoite transcriptomes. By contrast, using label-free quantitative mass-spectrometry, a significant change in protein abundance was noted, of which 200 were proteins of unknown function. We determined the relative molar abundance of over 1100 proteins in LLMs and further characterized the major merozoite surface protein complex. A unique processed MSP1 intermediate was identified in LLM but not observed in WT suggesting that delayed processing may be important for the observed phenotype. This integrated approach has demonstrated the significant role of the merozoite proteome during erythrocyte invasion, while identifying numerous unknown proteins likely to be involved in invasion.

Mobile pump deep vein thrombosis prophylaxis: just say no to drugs.

AIMS: The purpose of this article was to review the current literature pertaining to the use of mobile compression devices (MCDs) for venous thromboembolism (VTE) following total joint arthroplasty (TJA), and to discuss the results of data from our institution. PATIENTS AND METHODS: Previous studies have illustrated higher rates of post-operative wound complications, re-operation and re-admission with the use of more aggressive anticoagulation regimens, such as warfarin and factor Xa inhibitors. This highlights the importance of the safety, as well as efficacy, of the chemoprophylactic regimen. RESULTS: Studies have shown a symptomatic VTE rate of 0.92% with use of MCDs for prophylaxis, which is comparable with rates seen with more aggressive anticoagulation protocols. A prior prospective study found that use of a pre-operative risk stratification protocol based on personal history of deep vein thrombosis, family history of VTE, active cancer, or a hypercoaguable state allowed for the avoidance of aggressive prophylactic anticoagulation in over 70% of patients while maintaining a low incidence of symptomatic VTE. CONCLUSION: Further investigation is needed into the role of aspirin in VTE prophylaxis as well as the efficacy of MCDs as stand-alone prophylactic treatment. Cite this article: Bone Joint J 2017;99-B(1 Supple A):8-13.

Obesity in total hip arthroplasty: does it make a difference?

AIMS: The purpose of our study is to summarise the current scientific findings regarding the impact of obesity on total hip arthroplasty (THA); specifically the influence of obesity on the timing of THA, incidence of complications, and effect on clinical and functional outcomes. MATERIALS AND METHODS: We performed a systematic review that was compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify prospective studies from the PubMed/Medline, Embase, and Cochrane Library databases that evaluated primary THA in obese (body mass index (BMI) ≥ 30 kg/m2) patients. RESULTS: There were 17 articles included in the review, which encompassed 13 722 THA patients. Analysis of the included studies showed that, when compared with non-obese patients, obesity was associated with younger age at time of primary THA, and an increased incidence of complications (up to four-fold). Results were mixed on the influence of obesity on the outcomes of primary THA, with three studies showing a detrimental effect on outcomes of a BMI ≥ 30 kg/m2, while eight studies showed no effect. CONCLUSION: Obesity is associated with significantly younger age at time of primary THA and obese patients are likely to experience a higher rate of peri-operative complications. More investigation is needed into the effect of obesity on clinical outcomes, as the current literature is mixed. Cite this article: Bone Joint J 2017;99-B(1 Supple A):31-6.

Characterising the developmental profile of human embryonic stem cell-derived medium spiny neuron progenitors and assessing mature neuron function using a CRISPR-generated human DARPP-32WT/eGFP-AMP reporter line.

In the developing ventral telencephalon, cells of the lateral ganglionic eminence (LGE) give rise to all medium spiny neurons (MSNs). This development occurs in response to a highly orchestrated series of morphogenetic stimuli that pattern the resultant neurons as they develop. Striatal MSNs are characterised by expression of dopamine receptors, dopamine-and cyclic AMP-regulated phosphoprotein (DARPP32) and the neurotransmitter GABA. In this study, we demonstrate that fine tuning Wnt and hedgehog (SHH) signaling early in human embryonic stem cell differentiation can induce a subpallial progenitor molecular profile. Stimulation of TGFß signaling pathway by activin-A further supports patterning of progenitors to striatal precursors which adopt an LGE-specific gene signature. Moreover, we report that these MSNs also express markers associated with mature neuron function (cannabinoid, adenosine and dopamine receptors). To facilitate live-cell identification we generated a human embryonic stem cell line using CRISPR-mediated gene editing at the DARPP32 locus (DARPP32WT/eGFP-AMP-LacZ). The addition of dopamine to MSNs either increased, decreased or had no effect on intracellular calcium, indicating the presence of multiple dopamine receptor subtypes. In summary, we demonstrate greater control over early fate decisions using activin-A, Wnt and SHH to direct differentiation into MSNs. We also generate a DARPP32 reporter line that enables deeper pharmacological profiling and interrogation of complex receptor interactions in human MSNs.

Petascale supercomputing to accelerate the design of high-temperature alloys.

Recent progress in high-performance computing and data informatics has opened up numerous opportunities to aid the design of advanced materials. Herein, we demonstrate a computational workflow that includes rapid population of high-fidelity materials datasets via petascale computing and subsequent analyses with modern data science techniques. We use a first-principles approach based on density functional theory to derive the segregation energies of 34 microalloying elements at the coherent and semi-coherent interfaces between the aluminium matrix and the θ'-Al2Cu precipitate, which requires several hundred supercell calculations. We also perform extensive correlation analyses to identify materials descriptors that affect the segregation behaviour of solutes at the interfaces. Finally, we show an example of leveraging machine learning techniques to predict segregation energies without performing computationally expensive physics-based simulations. The approach demonstrated in the present work can be applied to any high-temperature alloy system for which key materials data can be obtained using high-performance computing.

Preparation of Underrepresented Males for Scientific Careers: A Study of the Dr. John H. Hopps Jr. Defense Research Scholars Program at Morehouse College.

Equal representation within higher education science, technology, engineering, and mathematics (STEM) fields and the STEM workforce in the United States across demographically diverse populations is a long-standing challenge. This study uses two-to-one nearest-neighbor matched-comparison group design to examine academic achievement, pursuit of graduate science degree, and classification of graduate institution attended by students participating in the Hopps Scholars Program (Hopps) at Morehouse College. Hopps is a highly structured enrichment program aimed at increasing participation of black males in STEM fields. Morehouse institutional records, Hopps Program records, and National Student Clearinghouse data were used to examine differences between Hopps and non-Hopps STEM graduates of Morehouse. Two-way sample t tests and chi-square tests revealed significant differences in academic achievement, likelihood of STEM degree pursuit, and the classification of graduate institutions attended by Hopps versus non-Hopps students. Hopps Scholars were significantly more likely than non-Hopps STEM graduates both to pursue STEM doctoral degrees and to attend doctoral-granting institutions with higher research activity. The Hopps Program's approach to training black male students for scientific careers is a model of success for other programs committed to increasing the number of black males pursuing advanced degrees in STEM.