A multi-INT semantic reasoning framework for intelligence analysis support

Lockheed Martin Corp. has funded research to generate a framework and methodology for developing semantic reasoning applications to support the discipline oflntelligence Analysis. This chapter outlines that framework, discusses how it may be used to advance the information sharing and integrated analytic needs of the Intelligence Community, and suggests a system I software architecture for such applications

Building the case for insulin-like growth factor receptor-I involvement in thyroid-associated ophthalmopathy

The pathogenesis of orbital Graves' disease (GD), a process known as thyroid-associated ophthalmopathy (TAO), remains incompletely understood. The thyrotropin receptor (TSHR) represents the central autoantigen involved in GD and has been proposed as the thyroid antigen shared with the orbit that could explain the infiltration of immune cells into tissues surrounding the eye. Another cell surface protein, insulin-like growth factor-I receptor (IGF-IR), has recently been proposed as a second antigen that participates in TAO by virtue of its interactions with anti-IGF-IR antibodies generated in GD, its apparent physical and functional complex formation with TSHR, and its necessary involvement in TSHR post-receptor signaling. The proposal that IGF-IR is involved in TAO has provoked substantial debate. Furthermore, several studies from different laboratory groups, each using different experimental models, have yielded conflicting results. In this article, we attempt to summarize the biological characteristics of IGF-IR and TSHR. We also review the evidence supporting and refuting the postulate that IGF-IR is a self-antigen in GD and that it plays a potentially important role in TAO. The putative involvement of IGF-IR in disease pathogenesis carries substantial clinical implications. Specifically, blocking this receptor with monoclonal antibodies can dramatically attenuate the induction by TSH and pathogenic antibodies generated in GD of proinflammatory genes in cultured orbital fibroblasts and fibrocytes. These cell types appear critical to the development of TAO. These observations have led to the conduct of a now-completed multicenter therapeutic trial of a fully human monoclonal anti-IGF-IR blocking antibody in moderate to severe, active TAO

Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy

Complex immunological mechanisms underlie the pathogenesis of thyroid-associated ophthalmopathy (TAO). Historical models of Graves’ diseas

The need for additional care in patients with classical galactosaemia

Purpose: Classical galactosaemia is an inborn error of galactose metabolism which may lead to impairments in body functions and accordingly, need for additional care. The primary aim of this study was to establish the type and intensity of this additional care. Materials and methods: Patients with classical galactosaemia aged >/=2 years were evaluated with the Capacity Profile, a standardised method to classify additional care needs according to type and intensity. Based on a semi-structured interview, current impairments in five domains of body functions were determined. The intensity of additional care was assessed (from 0, usual care, to 5, total dependence). Results: Forty-four patients with classical galactosaemia, 18 males and 26 females (median age 15 years, range 2-49 years), were included. There was a wide spectrum of impairments in mental functions. Motor function impairments were present in four patients, and mild speech impairments in eight patients. Additional care for sensory functions was uncommon. All patients needed a diet, which care is scored in the physical health domain. Conclusions: Apart from the diet all patients need, classical galactosaemia leads to the need for additional care mainly in the domains of mental functions and speech and voice functions. Implications for rehabilitation The Capacity Profile is a useful tool to demonstrate additional care needs in classical galactosaemia. In classical galactosaemia additional care is mostly indicated by mental impairments and speech and voice functions. One-fifth of patients have impairment of speech and voice functions at time of the study, and half of all patients had received speech therapy in childhood. Over 70% of patients need additional care/help due to impairment of mental functions, ranging from coaching due to social vulnerability to full day care

A Scalable Middleware Solution for Advanced Wide Area Web Services

To alleviate scalability problems in the Web, many researchers concentrate on how to incorporate advanced caching and replication techniques. Many solutions incorporate object-based techniques. In particular, Web resources are considered as distributed objects offering a well-defined interface. We argue that most proposals ignore two important aspects. First, there is little discussion on what kind of coherence should be provided. Proposing specific caching or replication solutions makes sense only if we know what coherence model they should implement. Second, most proposals treat all Web resources alike. Such a one-size-fits-all approach will never work in a wide-area system. We propose a solution in which Web resources are encapsulated in physically distributed shared objects. Each object should encapsulate not only state and operations, but also the policy by which its state is distributed, cached, replicated, migrated, etc

A 50% higher prevalence of life-shortening chronic conditions among cancer patients with low socioeconomic status

Background: Comorbidity and socioeconomic status (SES) may be related among cancer patients. Method : Population-based cancer registry study among 72 153 patients diagnosed during 1997-2006. Results : Low SES patients had 50% higher risk of serious comorbidity than those with high SES. Prevalence was increased for each cancer site. Low SES cancer patients had significantly higher risk of also having cardiovascular disease, chronic obstructive pulmonary diseases, diabetes mellitus, cerebrovascular disease, tuberculosis, dementia, and gastrointestinal disease. One-year survival was significantly worse in lowest vs highest SES, partly explained by comorbidity. Conclusion : This illustrates the enormous heterogeneity of cancer patients and stresses the need for optimal treatment of cancer patients with a variety of concomitant chronic conditions

Development of a novel user-friendly platform to couple light regime characterization with particle tracking - cells' light history determination during phototrophic cultivations

Depending on the light regime inside the photobioreactor (PBR) and the flow pattern verified, cells experience different histories with respect to the light regimes they are exposed to, wavelengths of light absorbed and period of time spent under each specific condition. The high heterogeneity of the radiation field inside the PBR due to absorption and scattering of radiation by microalgae/cyanobacteria cells - and the fluctuating cells' light history (CLH), greatly influence photosynthetic conversion and ultimately biomass productivity. This work presents a relatively low-cost, simple, experimental technique which combines light regime and flow pattern characterization, to determine the CLH inside PBRs. A fibre optic spectrometer and probes were employed for quantitative and qualitative light characterization/mapping inside the PBR in this study a split cylinder airlift photobioreactor (SCAPBR) was used while the flow pattern was determined by means of two perpendicular digital cameras which were used to follow fluorescent alginate particles. Temporal and spatial aspects of light patterns were obtained using a MATLAB algorithm that enables automatic merging and synchronization of the data obtained by those two approaches. This provided information about the average time during which cells are subjected to each light regime and how they alternate between them, thus characterizing their CLH.This research work was supported by the grant SFRH/BPD/98694/2013 (Bruno Fernandes) and SFRH/BD/52335/2013 (Pedro Geada) from Fundação para a Ciência e a Tecnologia (Portugal). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684), Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and FCT Strategic Project of UID/BIO/04469/2013 and UID/Multi/04423/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Movement disorders and nonmotor neuropsychological symptoms in children and adults with classical galactosemia

Although movement disorders (MDs) are known complications, the exact frequency and severity remains uncertain in patients with classical galactosemia, especially in children. We determined the frequency, classification and severity of MDs in a cohort of pediatric and adult galactosemia patients, and assessed the association with nonmotor neuropsychological symptoms and daily functioning. Patients from seven centers in the United Kingdom and the Netherlands with a confirmed galactosemia diagnosis were invited to participate. A videotaped neurological examination was performed and an expert panel scored the presence, classification and severity of MDs. Disease characteristics, nonmotor neuropsychological symptoms, and daily functioning were evaluated with structured interviews and validated questionnaires (Achenbach, Vineland, Health Assessment Questionnaire, SIP68). We recruited 37 patients; 19 adults (mean age 32.6 years) and 18 children (mean age 10.7 years). Subjective self-reports revealed motor symptoms in 19/37 (51.4%), similar to the objective (video) assessment, with MDs in 18/37 patients (48.6%). The objective severity scores were moderate to severe in one third (6/37). Dystonia was the overall major feature, with additional tremor in adults, and myoclonus in children. Behavioral or psychiatric problems were present in 47.2%, mostly internalizing problems, and associated with MDs. Daily functioning was significantly impaired in the majority of patients. Only one patient received symptomatic treatment for MDs. We show that MDs and nonmotor neuropsychological symptoms are frequent in both children and adults with classical galactosemia

Evaluating the Number of Stages in Development of Squamous Cell and Adenocarcinomas across Cancer Sites Using Human Population-Based Cancer Modeling

BACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages) were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype being more strongly associated with ACs/SCCs histotype than with organ/site