THE MARITIME STRATEGY: CAN THE NAVY LEARN FROM THE PAST FOR AN EFFECTIVE MARITIME STRATEGY FOR THE FUTURE? A STUDY OF THE NAVY'S 1980S STRATEGY DEVELOPMENT

This thesis addresses how the Navy implemented and institutionalized The Maritime Strategy in the 1980s. This issue encompasses several more specific questions, namely: how did naval strategists convince the public that naval power could be relevant in a European land power battle against the Soviet Union? Who were the leaders who made the strategy stick? How was the articulated strategy able to last through multiple Chiefs of Naval Operations? And how does a service innovate and communicate a new strategy? Today, with the growing threat of China in the Western Pacific, this thesis argues that the Navy can relook at institutional processes it executed well in the 1980s and reestablish them. The thesis concludes with implications and recommendations on how the Navy can rejuvenate its strategy-making apparatus to better align the service for a twenty-first century naval buildup.Outstanding ThesisLieutenant, United States NavyApproved for public release. Distribution is unlimited

Feasibility and initial efficacy of project-based treatment for people with ABI

Background: Communication impairments are common and pervasive for people a long time following acquired brain injury (ABI). These impairments have a significant impact on a person's quality of life (QOL) post‐injury. Project‐based treatment is a treatment approach that could have an impact on communication skills and QOL for people with ABI a long‐term post‐injury. This treatment is embedded in a context of meaningful activities chosen by people with ABI, whereby, as a group, they work collaboratively to achieve a tangible end product. Aims: To evaluate the feasibility and initial efficacy of project‐based treatment on improving the communication skills and QOL for people with ABI. Methods & Procedures: An exploratory controlled trial with alternate allocation of groups, and follow‐up at 6–8 weeks, was completed. Twenty‐one people with chronic ABI were recruited in groups of two to three from community settings, allocated to either a TREATMENT (n = 11) or WAITLIST group (n = 10). Participants attended a 20‐h group‐based treatment over 6 weeks where they worked towards achieving a project that helped others. To determine feasibility, four criteria were used: demand, implementation, practicality and acceptability. A range of communication and QOL outcomes was used to determine a fifth feasibility criterion, initial efficacy. Some of these criteria were additionally used to evaluate the feasibility of the outcomes. Outcomes & Results: All participants received the treatment as allocated with high attendance and no dropouts. The treatment was feasible to deliver as intended and was highly acceptable to participants. Medium and large effect sizes were found from pre‐ to post‐treatment, and from pre‐treatment to follow‐up for measures of conversation, perceived communicative ability and QOL. Conclusions & Implications: Project‐based treatment is feasible with indications of initial efficacy for both communication skills and QOL. The treatment provides a promising new approach for improving communication skills and QOL in people with chronic acquired brain injuries in the community setting

Global Perspective of the Risks of Falsified and Counterfeit Medicines: A Critical Review of the Literature

Background The increasing prevalence of falsified and counterfeit medicines globally poses risks to international travellers. This narrative literature review examines the global challenge of falsified and counterfeit medicines, with a specific focus on risks for travellers. The aim is to provide a comprehensive understanding of this multidimensional issue, exploring potential solutions for effective intervention. Methods A comprehensive search of databases, including PubMed, MEDLINE, and Scopus, as well as relevant reports from international organisations, was undertaken. There was a focus on extracting information pertaining to the prevalence, types, and geographical patterns of falsified and counterfeit medicines encountered by international travellers. Synthesising this information helped to identify overarching trends and patterns. This narrative review utilised a thematic analysis approach to synthesise the findings. Results The findings revealed a diverse range of counterfeit drug categories, spanning from antibiotics to lifestyle medications, posing unique risks to travellers navigating the global pharmaceutical landscape. The review emphasises the geographical distribution of these drugs, with varying consequences for both high- and low-income nations. The inadequate formulations and inconsistent drug release arising from these practices pose severe threats to public health, especially for individuals travelling abroad. The review also highlights the significance of international collaboration in addressing this global challenge, as pharmaceutical supply chains seamlessly cross borders, necessitating a collaborative approach for effective regulation and enforcement. Conclusions This review underscores the need for targeted research, collaborative interventions, and technological innovations to address the complexities associated with falsified and counterfeit medicines, ensuring the safety and well-being of international travellers

Semantic-based policy engineering for autonomic systems

This paper presents some important directions in the use of ontology-based semantics in achieving the vision of Autonomic Communications. We examine the requirements of Autonomic Communication with a focus on the demanding needs of ubiquitous computing environments, with an emphasis on the requirements shared with Autonomic Computing. We observe that ontologies provide a strong mechanism for addressing the heterogeneity in user task requirements, managed resources, services and context. We then present two complimentary approaches that exploit ontology-based knowledge in support of autonomic communications: service-oriented models for policy engineering and dynamic semantic queries using content-based networks. The paper concludes with a discussion of the major research challenges such approaches raise

Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: A randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine

Background: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods: This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion: Exercise medicine may positively alter tumour biology through numerous mechanical and nonmechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration: anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016

A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversificatio

Liesegang patterns: Effect of dissociation of the invading electrolyte

The effect of dissociation of the invading electrolyte on the formation of Liesegang bands is investigated. We find, using organic compounds with known dissociation constants, that the spacing coefficient, 1+p, that characterizes the position of the n-th band as x_n ~ (1+p)^n, decreases with increasing dissociation constant, K_d. Theoretical arguments are developed to explain these experimental findings and to calculate explicitly the K_d dependence of 1+p.Comment: RevTex, 8 pages, 3 eps figure

Translational control of the SigR-directed oxidative stress response in streptomyces via IF3-mediated repression of a noncanonical GTC start codon

The major oxidative stress response in Streptomyces is controlled by the sigma factor SigR and its cognate antisigma factor RsrA, and SigR activity is tightly controlled through multiple mechanisms at both the transcriptional and posttranslational levels. Here we show that sigR has a highly unusual GTC start codon and that this leads to another level of SigR regulation, in which SigR translation is repressed by translation initiation factor 3 (IF3). Changing the GTC to a canonical start codon causes SigR to be overproduced relative to RsrA, resulting in unregulated and constitutive expression of the SigR regulon. Similarly, introducing IF3* mutations that impair its ability to repress SigR translation has the same effect. Thus, the noncanonical GTC sigR start codon and its repression by IF3 are critical for the correct and proper functioning of the oxidative stress regulatory system. sigR and rsrA are cotranscribed and translationally coupled, and it had therefore been assumed that SigR and RsrA are produced in stoichiometric amounts. Here we show that RsrA can be transcribed and translated independently of SigR, present evidence that RsrA is normally produced in excess of SigR, and describe the factors that determine SigR-RsrA stoichiometry.IMPORTANCE In all sigma factor-antisigma factor regulatory switches, the relative abundance of the two proteins is critical to the proper functioning of the system. Many sigma-antisigma operons are cotranscribed and translationally coupled, leading to a generic assumption that the sigma and antisigma factors are produced in a fixed 1:1 ratio. In the case of sigR-rsrA, we show instead that the antisigma factor is produced in excess over the sigma factor, providing a buffer to prevent spurious release of sigma activity. This excess arises in part because sigR has an extremely rare noncanonical GTC start codon, and as a result, SigR translation initiation is repressed by IF3. This finding highlights the potential significance of noncanonical start codons, very few of which have been characterized experimentally. It also emphasizes the limitations of predicting start codons using bioinformatic approaches, which rely heavily on the assumption that ATG, GTG, and TTG are the only permissible start codons