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While pillaging the brood of other ant colonies, Eciton army ants accumulate prey in piles, or caches, along their foraging trails. Widely documented, these structures have historically been considered as by-products of heavy traffic or aborted relocations of the ants' temporary nest, or bivouac. However, we recently observed that caches of the hook-jawed army ant, Eciton hamatum, appeared independently from heavy traffic or bivouac relocations. In addition, the flow of prey through caches varied based on the quantity of prey items workers transported. As this suggested a potential adaptive function, we developed agent-based simulations to compare raids of caching and non-caching virtual army ants. We found that caches increased the amount of prey that relatively low numbers of raiders were able to retrieve. However, this advantage became less conspicuous-and generally disappeared-as the number of raiders increased. Based on these results, we hypothesize that caches maximize the amount of prey that limited amounts of raiders can retrieve, especially as prey colonies coordinately evacuate their brood. In principle, caches also allow workers to safely collect multiple prey items and efficiently transport them to the bivouac. Further field observations are needed to test this and other hypotheses emerging from our study.
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Formigas , Animais , HumanosRESUMO
High costs for installing, maintaining, and updating a standard picture archiving and communication system (PACS) can be prohibitive for small/medium-sized veterinary facilities. The aims of this prospective, exploratory study were to describe the design, implementation, and author experiences for 1 year's use of a low-cost PACS based on network-attached storage. The system described here was easily installed and resiliently stored redundant copies of data. It excellently balanced data recovery, system speed, security, and available memory for storage. A virtual private network also allowed off-site data review. This system can also be used for future off-site backup of data in the cloud.
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Sistemas de Informação em Radiologia , Animais , Estudos ProspectivosRESUMO
The rheumatoid arthritis impact of disease (RAID) score was developed as a patient-derived composite response index for the evaluation of the disease impact on cases with rheumatoid arthritis (RA). The aim of this study was to evaluate the psychometric properties and performance of RAID score in the real-life settings. Cases with RA from our multi-center, nationwide registry called Biologic and targeted Synthetic antirheumatic drugs Registry RA (BioStaR RA) were included in this cross-sectional observational study. Demographic data, disease duration, pain, patient's global assessment (PGA) and physician's global assessment (PhyGA) were recorded. DAS28-ESR, DAS28-CRP, the simplified disease activity index (SDAI) and the clinical disease activity index (CDAI) were assessed as disease activity evaluations. The health assessment questionnaire-disability index (HAQ-DI) and RAID were completed by all the participants. The construct validity was tested by the analysis of correlations between RAID score and scores of PGA, disease activity indexes and HAQ-DI. We also evaluated the discriminatory ability of RAID to distinguish patients with different levels of disease activity and disability and the cut-off values were calculated by ROC analysis. 585 cases with RA were included in this investigation. The RAID score was significantly positively correlated with PGA, all disease activity indexes and HAQ-DI (p < 0.001). The discriminatory ability of RAID score in different disease activity and disability groups was also demonstrated (p < 0.001). To estimate DAS28-ESR (remission/low + moderate + high), RAID score cut-off points were 2.88 (sensitivity 73%, specificity 62%), 3.23 (sensitivity 75%, specificity 60%) and 3.79 (sensitivity 74%, specificity 58%), respectively. Our study indicated that RAID was a reliable tool in daily clinical practice by presenting its correlations with disease activity and disability assessments and by showing its discriminatory ability in these parameters in the real-life experiences.
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Artrite Reumatoide/fisiopatologia , Avaliação da Deficiência , Qualidade de Vida , Índice de Gravidade de Doença , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Sistema de Registros , Inquéritos e QuestionáriosRESUMO
Homo sapiens orphan G protein-coupling receptor PEIG-1 was first cloned and characterized by applying differential display to T84 colonic carcinoma cells incubated in the presence of phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (GenBank AF506289.1). Later, Lotan's laboratory found the same gene product in response to retinoic acid analogues, naming it with the symbol RAIG1. Now the official HGNC symbol is GPRC5A. Here, we report the extension of its original cDNA fragment towards the 5' and 3' end. In addition, we show that TPA (100 ng/ml, 162 nM) strongly stimulated GPRC5A mRNA in T84 colonic carcinoma cells, with maximal expression at 4 h and 100 ng/ml (162 nM). Western blots showed several bands between 35 and 50 kDa, responding to TPA stimulation. Confocal microscopy confirmed its TPA upregulation and the location in the plasma membrane. The PKC inhibitor Gö 6983 (10 µM), and the Ca2+ chelator BAPTA-AM (150 µM), strongly inhibited its TPA induced upregulation. The PKA inhibitor H-89 (10 µM), and the MEK1/2 inhibitor U0126 (10 µM), also produced a significant reduction in the TPA response (~50%). The SGK1 inhibitor GSK650394 stimulated GPRC5A basal levels at low doses and inhibit its TPA-induced expression at concentrations ≥10 µM. The IL-1ß autocrine loop and downstream signalling did not affect its expression. In conclusion, RAIG1/RAI3/GPRC5A corresponds to the originally reported PEIG-1/TIG1; the inhibition observed in the presence of Gö 6983, BAPTA and U0126, suggests that its TPA-induced upregulation is mediated through a PKC/Ca2+ âMEK1/2 signalling axis. PKA and SGK1 kinases are also involved in its TPA-induced upregulation.
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Proteína Quinase C/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Sequência de Aminoácidos , Butadienos/farmacologia , Linhagem Celular Tumoral , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Humanos , Indóis/farmacologia , Isoquinolinas/farmacologia , Maleimidas/farmacologia , Nitrilas/farmacologia , Conformação Proteica em alfa-Hélice , Estrutura Terciária de Proteína , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Regulação para Cima/efeitos dos fármacosRESUMO
NAND flash memory-based storage devices are vulnerable to errors induced by NAND flash memory cells. Error-correction codes (ECCs) are integrated into the flash memory controller to correct errors in flash memory. However, since ECCs show inherent limits in checking the excessive increase in errors, a complementary method should be considered for the reliability of flash storage devices. In this paper, we propose a scheme based on lossless data compression that enhances the error recovery ability of flash storage devices, which applies to improve recovery capability both of inside and outside the page. Within a page, ECC encoding is realized on compressed data by the adaptive ECC module, which results in a reduced code rate. From the perspective of outside the page, the compressed data are not placed at the beginning of the page, but rather is placed at a specific location within the page, which makes it possible to skip certain pages during the recovery phase. As a result, the proposed scheme improves the uncorrectable bit error rate (UBER) of the legacy system.
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Objectives: This study aims to cross-culturally adapt the Rating Anxiety in Dementia (RAID) scale into Arabic language, evaluate its psychometric properties in a sample of Lebanese patients with dementia and determine the optimal cutoff for the identification of anxiety.Methods: A cross-sectional study was carried out with a sample of 136 patients with dementia aged 55 years and above. RAID-A was administered to a formal caregiver of the patient as well as a battery of psychological tools namely Hamilton anxiety scale (HAM-A) and Neuropsychiatric Inventory anxiety subscale (NPI-A). The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) was used to establish a clinical diagnosis of generalized anxiety disorder (GAD).Results: RAID-A scale demonstrated high internal consistency (Cronbach's a = 0.82) and test-retest reliability (Intraclass coefficient = 0.99). Significant correlations were found between RAID-A total score and both NPI-A (r = 0.43) and HAM-A (r = 0.88) suggesting good concurrent validity. Results from the receiver operating curve analysis identified a score of 11 as the optimal cutoff for the diagnosis of GAD with a sensitivity of 91% and a specificity of 82%.Conclusions: The Arabic version of the RAID scale exhibits good psychometric properties.Clinical Implications: RAID is a valid tool to measure anxiety in Arabic elder patients suffering from dementia.
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Ansiedade/psicologia , Demência/psicologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria/métodos , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Comparação Transcultural , Estudos Transversais , Demência/complicações , Demência/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Idioma , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Questionário de Saúde do Paciente , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , TraduçãoRESUMO
OBJECTIVES: Our aim was to conduct a national audit assessing the impact and experience of early management of inflammatory arthritis by English and Welsh rheumatology units. The audit enables rheumatology services to measure for the first time their performance, patient outcomes and experience, benchmarked to regional and national comparators. METHODS: All individuals >16 years of age presenting to English and Welsh rheumatology services with suspected new-onset inflammatory arthritis were included in the audit. Clinician- and patient-derived outcome and patient-reported experience measures were collected. RESULTS: Data are presented for the 6354 patients recruited from 1 February 2014 to 31 January 2015. Ninety-seven per cent of English and Welsh trusts participated. At the first specialist assessment, the 28-joint DAS (DAS28) was calculated for 2659 (91%) RA patients [mean DAS28 was 5.0 and mean Rheumatoid Arthritis Impact of Disease (RAID) score was 5.6]. After 3 months of specialist care, the mean DAS28 was 3.5 and slightly >60% achieved a meaningful DAS28 reduction. The average RAID score and reduction in RAID score were 3.6 and 2.4, respectively. Of the working patients ages 16-65 years providing data, 7, 5, 16 and 37% reported that they were unable to work, needed frequent time off work, occasionally and rarely needed time off work due to their arthritis, respectively; only 42% reported being asked about their work. Seventy-eight per cent of RA patients providing data agreed with the statement 'Overall in the last 3 months I have had a good experience of care for my arthritis'; <2% disagreed. CONCLUSION: This audit demonstrates that most RA patients have severe disease at the time of presentation to rheumatology services and that a significant number continue to have high disease activity after 3 months of specialist care. There is a clear need for the National Health Service to develop better systems for capturing, coding and integrating information from outpatient clinics, including measures of patient experience and outcome and measures of ability to work.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Atividades Cotidianas , Adaptação Psicológica , Adolescente , Adulto , Idoso , Artrite/diagnóstico , Artrite/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Auditoria Clínica , Inglaterra , Fadiga , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Medição da Dor , Sono , Inquéritos e Questionários , Resultado do Tratamento , País de Gales , Adulto JovemRESUMO
Multi-OMICS approaches aim on the integration of quantitative data obtained for different biological molecules in order to understand their interrelation and the functioning of larger systems. This paper deals with several data integration and data processing issues that frequently occur within this context. To this end, the data processing workflow within the PROFILE project is presented, a multi-OMICS project that aims on identification of novel biomarkers and the development of new therapeutic targets for seven important liver diseases. Furthermore, a software called CrossPlatformCommander is sketched, which facilitates several steps of the proposed workflow in a semi-automatic manner. Application of the software is presented for the detection of novel biomarkers, their ranking and annotation with existing knowledge using the example of corresponding Transcriptomics and Proteomics data sets obtained from patients suffering from hepatocellular carcinoma. Additionally, a linear regression analysis of Transcriptomics vs. Proteomics data is presented and its performance assessed. It was shown, that for capturing profound relations between Transcriptomics and Proteomics data, a simple linear regression analysis is not sufficient and implementation and evaluation of alternative statistical approaches are needed. Additionally, the integration of multivariate variable selection and classification approaches is intended for further development of the software. Although this paper focuses only on the combination of data obtained from quantitative Proteomics and Transcriptomics experiments, several approaches and data integration steps are also applicable for other OMICS technologies. Keeping specific restrictions in mind the suggested workflow (or at least parts of it) may be used as a template for similar projects that make use of different high throughput techniques. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan.
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Proteômica , Transcriptoma , Fluxo de Trabalho , Biomarcadores/metabolismo , Cromatografia Líquida , Espectrometria de MassasRESUMO
Proteomics methods, especially high-throughput mass spectrometry analysis have been continually developed and improved over the years. The analysis of complex biological samples produces large volumes of raw data. Data storage and recovery management pose substantial challenges to biomedical or proteomic facilities regarding backup and archiving concepts as well as hardware requirements. In this article we describe differences between the terms backup and archive with regard to manual and automatic approaches. We also introduce different storage concepts and technologies from transportable media to professional solutions such as redundant array of independent disks (RAID) systems, network attached storages (NAS) and storage area network (SAN). Moreover, we present a software solution, which we developed for the purpose of long-term preservation of large mass spectrometry raw data files on an object storage device (OSD) archiving system. Finally, advantages, disadvantages, and experiences from routine operations of the presented concepts and technologies are evaluated and discussed. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan.
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Aminoácidos/química , Proteômica , Espectrometria de MassasRESUMO
RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery. Thus far, only eight cases have been reported in the literature. Here, we report four families with three novel and one previously described pathogenic variant in RELA. These four families included 23 affected individuals for which genetic testing was available in 16. Almost half of these patients had been previously diagnosed with more common rheumatologic entities (such as Behcet's Disease; BD) prior to the discovery of their pathogenic RELA variants. The most common clinical features were orogenital ulcers, rash, joint inflammation, and fever. The least common were conjunctivitis and recurrent infections. Clinical variability was remarkable even among familial cases, and incomplete penetrance was observed. Patients in our series were treated with a variety of medications, and benefit was observed with glucocorticoids, colchicine, and TNF inhibitors. Altogether, our work adds to the current literature and doubles the number of reported cases with RELA-Associated Inflammatory Disease (RAID). It reaffirms the central importance of the NF-κB pathway in immunity and inflammation, as well as the important regulatory role of RELA in mucosal homeostasis. RELA associated inflammatory disease should be considered in all patients with BD, particularly those with early onset and/or with a strong family history.
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Síndrome de Behçet , NF-kappa B , Humanos , NF-kappa B/metabolismo , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/genética , Testes Genéticos , Inflamação/genética , Transdução de Sinais/genética , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismoRESUMO
For forensic examiners, investigating the RAID systems of servers has been challenging, as the examiners must reconstruct multiple high-capacity disks to identify digital evidence. Software-based RAID systems' use has been released for personal use, so examiners should consider RAID systems even when they investigate personal computers. Although there is a high probability that the software-based RAID will become a target of crime, there has been little research into digital forensic methodology for software-based RAID, as exemplified by Storage Space. In this paper, we introduce details about the structure of Storage Space found through reverse engineering. Storage Space was analyzed by applying the digital forensic process of NIST. We explain how to reconstruct a virtual disk configured using Storage Space and develop an automated tool to do so. To evaluate our study and the tool developed, we created an experimental scenario and describe in detail the forensic procedure and technical methods for the analysis of Storage Space. Our research can be used as the basis of forensic investigations for Storage Space.
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Medicina Legal , Software , CrimeRESUMO
The purpose of this article is to discuss the hypocrisy of American ethics. This hypocrisy allows certain members of our society to breach their ethical duties and responsibilities without concern for the collective or regard for the oaths they pledge. This hypocrisy wields great power that continues to support the systemic discrimination that will be the downfall of this Country. By analyzing the January 6, 2021, raid on the Capital, we will examine how government officials and American citizens disregarded their oaths and committed unethical acts to overthrow the government. They used the American flag, that they pledge their lives in the name of Democracy, as a tool to incite violence and insurrection. Analysis of this incident clearly reflects that this selective application of ethical responsibility allows some government officials and members of society to commit violent acts against the government officials, institutions, and its citizenry, without the same criminal reprisal other Americans endure.
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OBJECTIVE: This study aimed to analyze the clinical value of applying RAID quality improvement model in closed-loop management of central retinal artery occlusion (CRAO) nursing. METHODS: Twelve ophthalmic nurses were trained. Soon afterwards, their related knowledge, operation and scene simulation test scores before and after training were examined and compared. Before and after training, 20 CRAO patients who admitted to the second ward of ophthalmology (Ophthalmology Section 2) of our hospital were included into control group and research group. The former applied routine management, while the latter employed RAID quality improvement model. RESULTS: Before intervention, the ESCA scores and the time window of first-aid of the two groups had no significant difference (all P>0.05). While after intervention, the scores of the research group were dramatically improved; the self-care skills, health knowledge, self-responsibility and self-awareness were obviously higher than those of the control group (all P<0.05); the time window of first-aid in the research group was remarkably shorter than that before intervention, dramatically higher than that in the control group (32.34±8.14 vs. 49.46±8.13; P<0.05). After nursing, the overall satisfaction of patients in the research group (95.00%) was higher than that in the control group (70.00%; P<0.05). Meanwhile, compared with those before training, the examination scores of related knowledge and skills of ophthalmic nurses after training were obviously improved (all P<0.05). The incidence of complications in the research group was 5.00%, while that in the control group was 30.00%. The indexes in the research group were lower than those in the control group, with statistically remarkable differences (P<0.05). CONCLUSION: RAID quality improvement model is effective in closed-loop management of CRAO nursing, which can effectively improve the quality of nursing for specific diseases and control related indicators. Hence, it's worthy to be promoted.
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Network-attached storage (NAS) is a system that uses a redundant array of disks (RAID) to create virtual disks comprising multiple disks and provide network services such as FTP, SSH, and WebDAV. Using these services, the NAS's virtual disks store data about individuals or groups, making them a critical analysis target for digital forensics. Well-known storage manufacturers like Seagate, Synology, and NETGEAR use Linux-based software RAID, and they usually support Berkeley RAID (e.g., RAID 0, 1, 5, 6, and 10) as well as self-developed hybrid RAID. Those manufacturers have published data on the introduction and features of hybrid RAID, but there is not enough information to reassemble RAID from a digital forensic perspective. Besides, digital forensic tools (such as EnCase, FTK, X-ways, and RAID Reconstructor) do not support automatic RAID reassembly for hybrid RAID, so research on hybrid RAID reassembly methods is necessary. This paper analyzes the disk array composed of hybrid RAID and explains the layout of disk array, partition layout in hybrid RAID, and hybrid RAID configuration strategy. Furthermore, it suggests parameters that are required for RAID reassembly and then propose a hybrid RAID reassembly procedure using them. Finally, we propose a proof-of-concept tool (Hybrid RAID Reconstructor) that identifies hybrid RAID from disk array and parse RAID parameters.
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OBJECTIVE: The aim was to assess how the patient-reported outcome RA impact of disease (RAID) relates to DAS28 categories in routine care, its utility in identifying patients in DAS28 remission (RDAS) or low disease activity (LDAS) and the burden of unmet patient-reported needs in those achieving RDAS/LDAS. METHODS: DAS28 and RAID scores were collected from patients with established RA attending for routine review. The relationship between RAID and DAS28 was assessed with univariate pairwise correlation and mixed-effects linear regression analyses. RAID <2 was defined as a patient-acceptable state. RESULTS: One hundred and ninety-eight patients were assessed, with 220 observations, using DAS28-CRP categories: 47.5% RDAS, 14.1% LDAS, 31.8% moderate DAS (MDAS) and 6.6% high DAS (HDAS). Both patient visual analog scale score and tender joint count exhibited a high statistical association with RAID using linear regression (P < 0.0001). The mean RAID score per DAS28-CRP category was RDAS 1.84, LDAS 4.78, MDAS 5.60 and HDAS 7.68, with a statistically significant increase in RAID per unit increase in DAS-CRP or DAS28-ESR on linear regression (P < 0.001). Of 66 patients with RAID <2, 64 (97%) were in RDAS and 65 (98.5%) in RDAS/LDAS. Of 134 patients in RDAS/LDAS, RAID was ≥2 in 69 (51.5%), with fatigue and sleep being the worst-scoring domains. CONCLUSION: RAID functions well as a patient-reported outcome in routine care. Patients with RAID <2 have a high likelihood of being in RDAS/LDAS and, if pre-screened, could avoid a clinic visit. Analysis of RAID domains provides individualized targets for holistic care in RA management, with fatigue and sleep problems dominating unmet needs in those in RDAS/LDAS.
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We assessed energy compensation, appetite, and reward value of foods during a 14-day military expedition in Greenland realized by 12 male French soldiers, during which energy compensation was optimized by providing them with easy-to-eat palatable foods in excess. Although daily energy expenditure (estimated by accelerometry) stayed relatively constant throughout the expedition (15 ± 9 MJ·day-1), energy intake (EI; estimated by self-reported diaries) was 17% higher during the D8-D14 period compared with the D1-D7 period, leading to a neutral energy balance (EB). Body fat mass (BFM) significantly decreased (-1.0 ± 0.7 kg, p < 0.001) but not body mass (BM). Neither hunger scores (assessed by visual analog scales) nor components of the reward value of food (explicit liking (EL) and food preference) were significantly altered. However, changes in EL at D10 were positively correlated with changes in BM (r = 0.600, p < 0.05) and BFM (r = 0.680, p < 0.05) and changes in hunger in the EI of the relevant period (r = 0.743, p < 0.01 for D1-D7, r = 0.652, p < 0.05 for D8-14). This study shows that the negative EB and BM loss can be attenuated by an appropriate food supply and that subjective components of eating behaviour, such as hunger and EL, may be useful to predict the magnitude of energy compensation. Novelty Energy intake increases during of a 14-day expedition in the cold. Energy compensation was likely facilitated by providing participants with easy-to-eat palatable and familiar foods. Hunger scores and EL for energy-dense foods were associated with high EIs and low BM changes.
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Temperatura Baixa , Metabolismo Energético , Comportamento Alimentar , Adulto , Apetite , Ingestão de Energia , Expedições , Preferências Alimentares , Groenlândia , Humanos , Fome , Masculino , Pessoa de Meia-Idade , MilitaresRESUMO
A typical colony of Neotropical army ants (subfamily Ecitoninae) regularly raids a large area around their bivouac by forming a narrow directional column that can reach up to one hundred meters in length. The raid is finished and then relaunched 12-17 times, each time toward different orientation. After completing all bouts the colony relocates to a new area. A hypothetical alternative to this foraging mode is raiding radially and symmetrically by expanding the search front in every direction like a circular bubble. Using an existing agent-based modeling software that simulates army ants' behavior, we compared the two possible modes of foraging in different food distributions. Regardless of the food patch abundance, the radial raiding was superior to the directional raiding when food patches had low quality, and the directional raiding was favorable when the patches were rich. In terms of energy efficiency, the radial raiding was the better strategy in a wide range of conditions. In contrast, the directional raiding tended to yield more food per coverage area. Based on our model, we suggest that the directional raiding by army ants is an adaptation to the habitats with abundance of high-quality food patches. This conclusion fits well with the ecology of army ants.
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OBJECTIVES: To assess the validity of the rheumatoid arthritis impact of disease (RAID) for measuring disease activity of rheumatoid arthritis (RA) and to determine cut-off values for defining the disease activity states. METHODS: A total of 622 RA patients from an European database have been included. Cross-validation was based on assessment of convergent and discriminant validity. Optimal cut-offs were determined against external criteria by calculating the respective 25th and 75th percentiles mean values of RAID. External criteria included definitions for remission (REM), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA), cut-offs of the 28-joint disease activity score-C-reactive protein (DAS28-CRP) score. RESULTS: The RAID showed a moderate degree of correlation with respect to DAS28-CRP (rho=0.417; P<0.0001). The receiver operating characteristic (ROC) curves to discriminate the ability of RAID to distinguish patients with active and non-active disease was very good with an area under the curve (AUC) of 0.847 (95% confidence interval [CI]: 0.816 to 0.878; P<0.0001). Based on the distributions of RAID in the different disease activity groups, we propose the following cut-off values for REM: RAID ≤3; for LDA: RAID >3 and ≤4; for MDA: RAID >4 and ≤6; for HDA: RAID >6. Mean RAID differed significantly between patients classified as REM, LDA, MDA or HDA (P=0.001). CONCLUSIONS: The cut-offs revealed good measurement characteristics in cross-validation analysis, had great discriminatory performance in distinguishing patients with different levels of disease activity and are suited for widespread use in everyday practice application and research.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Reumatologistas/estatística & dados numéricos , Perfil de Impacto da Doença , Adulto , Idoso , Área Sob a Curva , Proteína C-Reativa/análise , Estudos Transversais , Bases de Dados Factuais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Índice de Gravidade de DoençaRESUMO
Rheumatic Autoimmune Inflammatory Diseases such as Sjögren's and lupus lack modern treatments. Less than 5% of drugs approved by the FDA from 2014 to mid-2016 had a RAID indication. Many RAID standard-of-care drugs were repurposed based on serendipitous observations, similarity-of-disease categorization, and/or off-target effects. Recently, drug repurposing has become more intentional, relying on an evolving awareness of molecular underpinnings, as well as a better understanding of drug-target interactions by computational modeling. Understanding mechanisms of disease pathogenesis can be synergistic in identifying new drug candidates and target pathways using unbiased Big-Data repositioning approaches as genomics, PheWAS (disease mechanism-of-action), GWAS and/or epigenetic-profiling.
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Doenças Autoimunes/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Doenças Reumáticas/tratamento farmacológico , Inteligência Artificial , Doenças Autoimunes/genética , Simulação por Computador , Quimioterapia Assistida por Computador , Humanos , Modelos Moleculares , Doenças Reumáticas/genéticaRESUMO
OBJECTIVE: To collect data on vitamin D (25(OH)D) serum levels in a large number of rheumatoid arthritis (RA) patients from different European countries, to investigate their relation with disease activity, disability, quality of life, and possibly to construct a new Patient Reported Outcome (PRO) questionnaire in order to self-estimate if they are at risk for vitamin D insufficiency/deficiency-related clinical implications (D-PRO). METHODS: This was a European League Against Rheumatism (EULAR) supported cross-sectional study (project No CLI064) which involved 625 RA patients (mean age 55±11years, mean disease duration 11±9years), 276 age and sex matched healthy subjects, and rheumatologists working in academic institutions or hospital centres, as well as PARE organizations (patient representatives) from 13 European countries. Serum samples for 25(OH)D level measurement were collected during winter time and analyzed in a central laboratory using chemiluminescence immunoassay (DiaSorin). Patient past medical history was recorded. RA patients were provided with three questionnaires: the Rheumatoid Arthritis Impact Diseases score (RAID), the Health Assessment Questionnaire (HAQ), and the new D-PRO questionnaire at the time of 25(OH)D serum sampling. D-PRO questionnaire consisted of three domains, Symptom Risk Score (SRS), Habitus Risk Score (HRS) and Global Risk Score (SRS+HRS=GRS), constructed with items possibly related to vitamin D deficiency. D-PRO was correlated with both clinical and PRO scores. DAS28-CRP was also evaluated. Statistical analysis was performed by non parametric tests. RESULTS: Mean serum concentration of 25(OH)D in RA patients (17.62±9.76ng/ml) was found significantly lower if compared to the levels obtained in matched controls (18.95±9.45ng/ml) (p=0.01), with statistically significant differences among several European countries. Negative correlations were found between 25(OH)D serum levels and DAS28-CRP (p<0.001), RAID (p=0.05) and HAQ (p=0.04) scores in the RA patients group. Negative correlations were also found in the cohort of enrolled RA patients between 25(OH)D serum concentrations and SRS (p=0.04), HRS (p=0.02) and GRS (p=0.02) domains of the D-PRO questionnaire. CONCLUSIONS: This first multicentre European survey add new evidences that vitamin D insufficiency/deficiency is frequent in RA patients with statistically significant differences among several countries. Vitamin D serum concentrations seem to correlate negatively and significantly with the D-PRO Global Risk Score, clinimetric indexes for quality of life, disease activity and disability in present cohort of RA European patients.