Radiotherapy Ergonomic Patient Positioning System

External beam radiotherapy is a powerful tool to combat cancer, but requires precise positioning of patients. The standard practice involves patients lying on treatment tables within immobilization equipment. These systems have limited clearance between treatment sources and the patient that can be uncomfortable or claustrophobic for patients. Patients may move when uncomfortable, leading to improper dose delivery, possibly causing painful side effects or further cancers. We present an alternative, open configuration patient positioning solution for more ergonomic setup options with competitive positioning capabilities compared to conventional systems. Our ergonomic positioning system consists of a seat for patients on a scissor lift for vertical positioning, a gantry system for horizontal positioning, all assembled onto a rotating base for treatment of tumors from any angle. Motion up to ±25 cm in 3D was achieved by controlling stepper motors with a Raspberry Pi computer. Computer-aided design was performed to complete finite element analysis on all load-bearing structures to ensure a maximum load of 200 lbs. The design developed allows new treatment configurations with static radiation sources while the positioning system moves at a distance, which allows greater flexibility in patient positioning. Replacing conventional treatment tables enables patients to be seated during treatment, which could improve patient comfort for more comfortable immobilization and more effective radiotherapy.https://scholarscompass.vcu.edu/capstone/1215/thumbnail.jp

Backup in gene regulatory networks explains differences between binding and knockout results

The complementarity of gene expression and protein–DNA interaction data led to several successful models of biological systems. However, recent studies in multiple species raise doubts about the relationship between these two datasets. These studies show that the overwhelming majority of genes bound by a particular transcription factor (TF) are not affected when that factor is knocked out. Here, we show that this surprising result can be partially explained by considering the broader cellular context in which TFs operate. Factors whose functions are not backed up by redundant paralogs show a fourfold increase in the agreement between their bound targets and the expression levels of those targets. In addition, we show that incorporating protein interaction networks provides physical explanations for knockout effects. New double knockout experiments support our conclusions. Our results highlight the robustness provided by redundant TFs and indicate that in the context of diverse cellular systems, binding is still largely functional

Business Consulting – Inversiones Hegresi S.A.C.

Inversiones Hegresi S.A.C. es una empresa de comercio mayorista que pertenece a un grupo de otras tres empresas familiares. Inició sus operaciones en el 2021, con el propósito de ofrecer una atención de calidad a través de la venta al por mayor de productos de uso doméstico, alimentos y confitería en las provincias del Santa, Casma y Huarmey; brindado desarrollo y oportunidad a todos sus colaboradores y clientes. La consultoría consistió en identificar los principales problemas que tiene la compañía y que no le permiten contar, desde el 2022, con una rentabilidad positiva; para ello, se realizaron entrevistas con todos los puestos claves y mandos medios de la empresa, y reuniones de trabajo con las áreas proveedoras de información. Una vez identificados los problemas, se procedió a analizar las principales causas raíz, para luego proponer las alternativas de solución que permitan a Hegresi lograr superar su escenario actual. Dentro del análisis y desarrollo, se han utilizado metodologías como las cinco fuerzas de Porter, PESTEL, FODA y AMOFHIT; también, la metodología del diagrama de Ishikawa y finalmente una matriz de complejidad vs beneficio; siendo el resultado, que el problema principal de la empresa es: La deficiente gestión en el manejo de almacenes e inventarios, limitada gestión administrativa y comercial, e inadecuada estructura organizacional. De esta manera y con la finalidad de mejorar la actual rentabilidad de la compañía, se propone que se debe realizar una planificación estratégica enfocada en tres frentes: a) La estructura Organizacional, redefiniendo su misión y visión, además, de contratar y retener un personal más idóneo; b) Los planes y políticas comerciales, orientados a productos y canales de ventas; y mejoras en la gestión administrativa, en cuanto a lineamientos, políticas y presupuestos sostenibles en el corto, mediano y largo plazo; y por último, c) un sistema informático integrado, que soporte y brinde información confiable para tomar mejores decisiones. Así mismo, para la presente propuesta se deberá contar con una inversión de S/96,000.00 y para evidenciar la viabilidad y rentabilidad de ella se tiene un valor actual neto (VAN) de S/ 737,864.24 y una tasa interna de retorno (TIR) de 75.92% que es superior al costo del capital de 10.22%, la inversión será recuperada en un periodo de 1.99 años.Inversiones Hegresi S.A.C. is a wholesale trading company that belongs to a group of three other family businesses. The company started operations in 2021, with the purpose of offering quality customer service through the wholesale of household products, food and confectionery products in the provinces of Santa, Casma and Huarmey, providing improvement and opportunity to all its associates and clients. The consultancy consisted of identifying the main problems that the company has and didn’t allow the company with a positive profitability since 2022; for this, interviews were conducted with all the key positions and middle managers of the company, and work meetings with the suppliers. Once the problems were identified, proceeded to analyze the main root causes, and then propose the alternative solutions that allow Hegresi to overcome the current scenario. Within the analysis and development, methodologies such as Porter's five forces, PESTEL, FODA and AMOFHIT have been used. Also, the methodology of the Ishikawa's diagram and finally a complex matrix vs benefit; being the result, that the main problem of the company is: Poor management in the management of warehouses and inventories, very limited administration and commercial management skills, and lacking of structural organization. In this way and in order to improve the current profitability of the company, it is proposed that strategic planning should be carried out focused on three fronts: a) The organizational structure, redefining its mission and vision, in addition to recruiting and retaining more qualified employees; b) Commercial plans and policies, oriented to products and sales channels; and improvements in administrative management, in terms of guidelines, policies and budgets. sustainable in the short, medium and long term; and finally, c) an integrated computer system, which supports and provides reliable information to make better decisions. Likewise, for this proposal, an investment of S/96,000.00 must be available and to demonstrate its viability and profitability, there is a net present value (NPV) of S/737,864.24 and an internal rate of return (IRR) of 75.92% that is higher than the cost of capital of 10.22%, the investment will be recovered in a period of 1.99 years

Central pain modulatory mechanisms of attentional analgesia are preserved in fibromyalgia

Fibromyalgia is a prevalent pain condition that is associated with cognitive impairments including in attention, memory, and executive processing. It has been proposed that fibromyalgia may be caused by altered central pain processing characterised by a loss of endogenous pain modulation. We tested whether attentional analgesia, where cognitive engagement diminishes pain percept, was attenuated in patients with fibromyalgia (n = 20) compared with matched healthy controls (n = 20). An individually calibrated, attentional analgesia paradigm with a 2 × 2 factorial design was used with brain and brainstem-focussed functional magnetic resonance imaging. Patients with fibromyalgia had both lower heat pain thresholds and speeds in a visual attention task. When this was taken into account for both attentional task and thermal stimulation, both groups exhibited an equivalent degree of attentional analgesia. Functional magnetic resonance imaging analysis showed similar patterns of activation in the main effects of pain and attention in the brain and brainstem (with the sole exceptions of increased activation in the control group in the frontopolar cortex and the ipsilateral locus coeruleus). The attentional analgesic effect correlated with activity in the periaqueductal gray and rostral ventromedial medulla. These findings indicate that patients with fibromyalgia can engage the descending pain modulatory system if the attentional task and noxious stimulus intensity are appropriately titrated

Simultaneous brain, brainstem and spinal cord pharmacological-fMRI reveals involvement of an endogenous opioid network in attentional analgesia

Pain perception is decreased by shifting attentional focus away from a threatening event. This attentional analgesia engages parallel descending control pathways from anterior cingulate (ACC) to locus coeruleus, and ACC to periaqueductal grey (PAG) - rostral ventromedial medulla (RVM), indicating possible roles for noradrenergic or opioidergic neuromodulators. To determine which pathway modulates nociceptive activity in humans we used simultaneous whole brain-spinal cord pharmacological-fMRI (N=39) across three sessions. Noxious thermal forearm stimulation generated somatotopic-activation of dorsal horn (DH) whose activity correlated with pain report and mirrored attentional pain modulation. Activity in an adjacent cluster reported the interaction between task and noxious stimulus. Effective connectivity analysis revealed that ACC interacts with PAG and RVM to modulate spinal cord activity. Blocking endogenous opioids with Naltrexone impairs attentional analgesia and disrupts RVM-spinal and ACC-PAG connectivity. Noradrenergic augmentation with Reboxetine did not alter attentional analgesia. Cognitive pain modulation involves opioidergic ACC-PAG-RVM descending control which suppresses spinal nociceptive activity

Parallel cortical-brainstem pathways to attentional analgesia

Pain demands attention, yet pain can be reduced by focusing attention elsewhere. The neural processes involved in this robust psychophysical phenomenon, attentional analgesia, are still being defined. Our previous fMRI study linked activity in the brainstem triad of locus coeruleus (LC), rostral ventromedial medulla (RVM) and periaqueductal grey (PAG) with attentional analgesia. Here we identify and model the functional interactions between these regions and the cortex in healthy human subjects (n = 57), who received painful thermal stimuli whilst simultaneously performing a visual attention task. RVM activity encoded pain intensity while contralateral LC activity correlated with attentional analgesia. Psycho-Physiological Interaction analysis and Dynamic Causal Modelling identified two parallel paths between forebrain and brainstem. These connections are modulated by attentional demand: a bidirectional anterior cingulate cortex (ACC) – right-LC loop, and a top-down influence of task on ACC-PAG-RVM. By recruiting discrete brainstem circuits, the ACC is able to modulate nociceptive input to reduce pain in situations of conflicting attentional demand

Longitudinal cytokine profiling identifies GRO-α and EGF as potential biomarkers of disease progression in Essential Thrombocythemia

Myeloproliferative neoplasms (MPNs) are characterized by deregulation of mature blood cell production and increased risk of myelofibrosis (MF) and leukemic transformation. Numerous driver mutations have been identified but substantial disease heterogeneity remains unexplained, implying the involvement of additional as yet unidentified factors. The inflammatory microenvironment has recently attracted attention as a crucial factor in MPN biology, in particular whether inflammatory cytokines and chemokines contribute to disease establishment or progression. Here we present a large-scale study of serum cytokine profiles in more than 400 MPN patients and identify an essential thrombocythemia (ET)-specific inflammatory cytokine signature consisting of Eotaxin, GRO-α, and EGF. Levels of 2 of these markers (GRO-α and EGF) in ET patients were associated with disease transformation in initial sample collection (GRO-α) or longitudinal sampling (EGF). In ET patients with extensive genomic profiling data (n = 183) cytokine levels added significant prognostic value for predicting transformation from ET to MF. Furthermore, CD56+CD14+ pro-inflammatory monocytes were identified as a novel source of increased GRO-α levels. These data implicate the immune cell microenvironment as a significant player in ET disease evolution and illustrate the utility of cytokines as potential biomarkers for reaching beyond genomic classification for disease stratification and monitoring.The serum cytokine studies were supported by a research grant from the Rosetrees Trust. NFØ was supported by grants from the Danish Lundbeck Foundation and Danish Cancer Society, J.G. was supported by fellowships from Bloodwise and the Kay Kendall Leukaemia Fund; and M.S.S. is the recipient of a Biotechnology and Biological Sciences Research Council Industrial Collaborative Awards in Science and Engineering PhD Studentship. Work in the R.C.S. laboratory was supported by grants from the Stiftung Blutspendezentrum SRK beider Basel, the Swiss National Science Foundation (31003A-147016/1 and 31003A_166613), and the Swiss Cancer League (KLS-2950-02-2012 and KFS-3655-02-2015). A.K. was supported by the Else Kröner-Fresenius Foundation. Work in the A.R.G. laboratory is supported by the Wellcome Trust, Bloodwise, Cancer Research UK, the Kay Kendall Leukaemia Fund, and the Leukemia and Lymphoma Society of America. Work in the D.G.K. laboratory is supported by a Bloodwise Bennett Fellowship (15008), a European Hematology Association Non-Clinical Advanced Research Fellowship, and an ERC Starting Grant (ERC-2016-STG–715371). D.G.K. and A.R.G. are supported by a core support grant from the Wellcome Trust and Medical Research Council to the Wellcome MRC Cambridge Stem Cell Institute, the National Institute for Health Research Cambridge Biomedical Research Centre, and the CRUK Cambridge Cancer Centre

Strategy to Enhance Influenza Surveillance Worldwide1

Sentinel surveillance for severe acute respiratory infection and influenza-like illness is effective in resource-limited settings

Longitudinal Cytokine Profiling Identifies GRO-α and EGF as Potential Biomarkers of Disease Progression in Essential Thrombocythemia.

Myeloproliferative neoplasms (MPNs) are characterized by deregulation of mature blood cell production and increased risk of myelofibrosis (MF) and leukemic transformation. Numerous driver mutations have been identified but substantial disease heterogeneity remains unexplained, implying the involvement of additional as yet unidentified factors. The inflammatory microenvironment has recently attracted attention as a crucial factor in MPN biology, in particular whether inflammatory cytokines and chemokines contribute to disease establishment or progression. Here we present a large-scale study of serum cytokine profiles in more than 400 MPN patients and identify an essential thrombocythemia (ET)-specific inflammatory cytokine signature consisting of Eotaxin, GRO-α, and EGF. Levels of 2 of these markers (GRO-α and EGF) in ET patients were associated with disease transformation in initial sample collection (GRO-α) or longitudinal sampling (EGF). In ET patients with extensive genomic profiling data (n = 183) cytokine levels added significant prognostic value for predicting transformation from ET to MF. Furthermore, CD56+CD14+ pro-inflammatory monocytes were identified as a novel source of increased GRO-α levels. These data implicate the immune cell microenvironment as a significant player in ET disease evolution and illustrate the utility of cytokines as potential biomarkers for reaching beyond genomic classification for disease stratification and monitoring.The serum cytokine studies were supported by a research grant from the Rosetrees Trust. NFØ was supported by grants from the Danish Lundbeck Foundation and Danish Cancer Society, J.G. was supported by fellowships from Bloodwise and the Kay Kendall Leukaemia Fund; and M.S.S. is the recipient of a Biotechnology and Biological Sciences Research Council Industrial Collaborative Awards in Science and Engineering PhD Studentship. Work in the R.C.S. laboratory was supported by grants from the Stiftung Blutspendezentrum SRK beider Basel, the Swiss National Science Foundation (31003A-147016/1 and 31003A_166613), and the Swiss Cancer League (KLS-2950-02-2012 and KFS-3655-02-2015). A.K. was supported by the Else Kröner-Fresenius Foundation. Work in the A.R.G. laboratory is supported by the Wellcome Trust, Bloodwise, Cancer Research UK, the Kay Kendall Leukaemia Fund, and the Leukemia and Lymphoma Society of America. Work in the D.G.K. laboratory is supported by a Bloodwise Bennett Fellowship (15008), a European Hematology Association Non-Clinical Advanced Research Fellowship, and an ERC Starting Grant (ERC-2016-STG–715371). D.G.K. and A.R.G. are supported by a core support grant from the Wellcome Trust and Medical Research Council to the Wellcome MRC Cambridge Stem Cell Institute, the National Institute for Health Research Cambridge Biomedical Research Centre, and the CRUK Cambridge Cancer Centre

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course

Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical car