An approach for developing a preliminary cost estimating methodology for USCG vessels

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Ocean Engineering, 1987.Bibliography: v. 2, leaves 287-291.by Mark James Gray.M.S

Special Issue "Cancer Biomarker Research and Personalized Medicine 2.0”

In 2022, there was an estimated incidence of 20 million cancer cases and 9.7 million deaths from cancer worldwide. By the year 2050, the rates of cancer incidence and death are projected to increase to 35.3 and 18.5 million, respectively [1]. It is thought that cancer mortality rates will surpass cardiovascular disease mortality rates in the near future [2]. While improvements have been made in the diagnosis and treatment of various cancer types, it is evident from these statistics that further breakthrough advancements are necessary to decrease the significant social and economic impact this disease has on the population</p

Profiling ambivalence in the context of nonsuicidal self-injury

Background: We aimed to identify profiles of ambivalence among individuals with a history of non-suicidal self-injury (NSSI) and tested whether profiles differed across various theoretically informed constructs: NSSI-related characteristics, cognitive (outcome expectancies, self-efficacy to resist NSSI), emotional (psychological distress, difficulties in emotion regulation), personality, and incentives to engage/not engage in NSSI. Methods: Individuals with a lifetime history of NSSI (n = 224) reported the extent to which they wanted to and did not want to engage in NSSI and completed well-validated measures of the constructs of interest. Results: Latent profile analysis indicated four ambivalence profiles (avoid: n = 39; moderately ambivalent: n = 85; highly ambivalent: n = 30; approach: n = 70). The profiles differed across a number of NSSI-related characteristics, cognitive, emotional, and incentive-related variables. Differences between the ambivalence profiles and the avoid/approach profiles varied across constructs. For example, the ambivalence and approach profiles were similar for NSSI-related outcome expectancies, but the ambivalence and avoidance profiles were similar for self-efficacy to resist NSSI. Conclusion: Findings highlight variation between the desire to engage or not engage in NSSI that are consistent with the notion of ambivalence. Understanding these differences may allow for a more person-centered approach in treatment for NSSI

Synthesis and evaluation of halogenated nitrophenoxazinones as nitroreductase substrates for the detection of pathogenic bacteria

The synthesis and microbiological evaluation of 7-, 8- and 9-nitro-1,2,4-trihalogenophenoxazin-3-one substrates with potential in the detection of nitroreductase-expressing pathogenic microorganisms are described. The 7- and 9-nitrotrihalogenophenoxazinone substrates were reduced by most Gram negative microorganisms and were inhibitory to the growth of certain Gram positive bacteria; however, the majority of Gram positive strains that were not inhibited by these agents, along with the two yeast strains evaluated, did not reduce the substrates. These observations suggest there are differences in the active site structures and substrate requirements of the nitroreductase enzymes from different strains; such differences may be exploited in the future for differentiation between pathogenic microorganisms. The absence of reduction of the 8-nitrotrihalogenophenoxazinone substrates is rationalized according to their electronic properties and correlates well with previous findings

Tissue- and Liquid-Based Biomarkers in Prostate Cancer Precision Medicine

Worldwide, prostate cancer (PC) is the second-most-frequently diagnosed male cancer and the fifth-most-common cause of all cancer-related deaths. Suspicion of PC in a patient is largely based upon clinical signs and the use of prostate-specific antigen (PSA) levels. Although PSA levels have been criticised for a lack of specificity, leading to PC over-diagnosis, it is still the most commonly used biomarker in PC management. Unfortunately, PC is extremely heterogeneous, and it can be difficult to stratify patients whose tumours are unlikely to progress from those that are aggressive and require treatment intensification. Although PC-specific biomarker research has previously focused on disease diagnosis, there is an unmet clinical need for novel prognostic, predictive and treatment response biomarkers that can be used to provide a precision medicine approach to PC management. In particular, the identification of biomarkers at the time of screening/diagnosis that can provide an indication of disease aggressiveness is perhaps the greatest current unmet clinical need in PC management. Largely through advances in genomic and proteomic techniques, exciting pre-clinical and clinical research is continuing to identify potential tissue, blood and urine-based PC-specific biomarkers that may in the future supplement or replace current standard practices. In this review, we describe how PC-specific biomarker research is progressing, including the evolution of PSA-based tests and those novel assays that have gained clinical approval. We also describe alternative diagnostic biomarkers to PSA, in addition to biomarkers that can predict PC aggressiveness and biomarkers that can predict response to certain therapies. We believe that novel biomarker research has the potential to make significant improvements to the clinical management of this disease in the near future

The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer

IL6-like cytokines are a family of regulators with a complex, pleiotropic role in both the healthy organism, where they regulate immunity and homeostasis, and in different diseases, including cancer. Here we summarise how these cytokines exert their effect through the shared signal transducer IL6ST (gp130) and we review the extensive evidence on the role that different members of this family play in breast cancer. Additionally, we discuss how the different cytokines, their related receptors and downstream effectors, as well as specific polymorphisms in these molecules, can serve as predictive or prognostic biomarkers with the potential for clinical application in breast cancer. Lastly, we also discuss how our increasing understanding of this complex signalling axis presents promising opportunities for the development or repurposing of therapeutic strategies against cancer and, specifically, breast neoplasms

The signal transducer IL6ST (gp130) as a predictive and 2 prognostic biomarker in breast cancer

Novel biomarkers are needed to continue to improve breast cancer clinical management and outcome. IL6-like cytokines, whose pleiotropic functions include roles in many hallmarks of malignancy, rely on the signal transducer IL6ST (gp130) for all their signalling. To date, 10 separate independent studies based on the analysis of clinical breast cancer samples have identified IL6ST as a predictor. Consistent findings suggest that IL6ST is a positive prognostic factor and is associated with ER status. Interestingly, these studies include 4 multigene signatures (EndoPredict, EER4, IRSN-23 and 42GC) that incorporate IL6ST to predict risk of recurrence or outcome from endocrine or chemotherapy. Here we review the existing evidence on the promising predictive and prognostic value of IL6ST. We also discuss how this potential could be further translated into clinical practice beyond the EndoPredict tool, which is already available in the clinic. The most promising route to further exploit IL6ST’s promising predicting power will likely be through additional hybrid multifactor signatures that allow for more robust stratification of ER+ breast tumours into discrete groups with distinct outcomes, thus enabling greater refinement of the treatment-selection process

The Impact of Tumour pH on Cancer Progression; Strategies for Clinical Intervention

Dysregulation of cellular pH is frequent in solid tumours and provides potential opportunities for therapeutic intervention. The acidic microenvironment within a tumour can promote migration, invasion and metastasis of cancer cells through a variety of mechanisms. Pathways associated with the control of intracellular pH that are under consideration for intervention include carbonic anhydrase IX, the monocarboxylate transporters (MCT, MCT1 and MCT4), the vacuolar-type H(+)-ATPase proton pump, and the sodium-hydrogen exchanger 1. This review will describe progress in the development of inhibitors to these targets