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Introduction: Previous studies have demonstrated early-career James Cook University (JCU) medical graduates are more likely to practise in regional, rural and remote areas than other Australian medical practitioners. This study investigates whether these non-metropolitan practice location outcomes continue into mid-career, and identifies the key underlying demographic, selection process, curriculum and postgraduate training factors associated with JCU graduates choosing to currently practise in regional, rural and remote areas of Australia. Methods: This study used the JCU medical school's graduate tracking database to identify 2019 Australian practice location data for 931 JCU medical graduates across postgraduate years (PGY) 5-14. This data was sourced primarily from the Australian Health Practitioner Regulation Agency, and then categorised into Modified Monash Model (MMM) rurality classifications using the Department of Health's DoctorConnect website. For these mid-career (PGY5-14) cohorts, multinominal logistic regression was undertaken to identify specific demographic, selection process, undergraduate training and postgraduate career variables found to be associated with a 2019 practice location in a regional city (MMM2), large to small rural town (MMM3-5) or remote community (MMM6-7). Additional multinominal logistic regression analysis was then used to determine the key independent predictors of mid-career JCU medical graduates working in regional cities (MMM2), rural towns (MMM3-5) and remote communities (MMM6-7) in 2019. Results: Around one-third of mid-career (PGY5-14) JCU medical graduates were working in regional cities during 2019, mostly in North Queensland, with a further 14% in rural towns and 3% in remote communities. These first 10 cohorts were undertaking careers in general practice (n=300, 33%), as subspecialists (n=217, 24%), rural generalists (n=96, 11%), generalist specialists (n=87, 10%) or hospital non-specialists (n=200, 22%). Key statistically significant, independent predictors of JCU MBBS graduates practising in MMM3-5 and MMM6-7 locations in 2019 were, respectively, being awarded a rurally bonded Australian Government undergraduate Medical Rural Bonded Scholarship (MRBS) (p=0.004, prevalence odds ratio (POR)=3.5; p=0.017, POR=7.3); graduation from the JCU postgraduate general practice training program, JCU General Practice Training (p=0.001, POR=3.9; p

Targeted delivery of therapeutic and imaging agents in the vascular compartment represents a significant hurdle in using nanomedicine for treating hemorrhage, thrombosis, and atherosclerosis. While several types of nanoparticles have been developed to meet this goal, their utility is limited by poor circulation, limited margination, and minimal targeting. Platelets have an innate ability to marginate to the vascular wall and specifically interact with vascular injury sites. These platelet functions are mediated by their shape, flexibility, and complex surface interactions. Inspired by this, we report the design and evaluation of nanoparticles that exhibit platelet-like functions including vascular injury site-directed margination, site-specific adhesion, and amplification of injury site-specific aggregation. Our nanoparticles mimic four key attributes of platelets, (i) discoidal morphology, (ii) mechanical flexibility, (iii) biophysically and biochemically mediated aggregation, and (iv) heteromultivalent presentation of ligands that mediate adhesion to both von Willebrand Factor and collagen, as well as specific clustering to activated platelets. Platelet-like nanoparticles (PLNs) exhibit enhanced surface-binding compared to spherical and rigid discoidal counterparts and site-selective adhesive and platelet-aggregatory properties under physiological flow conditions in vitro. In vivo studies in a mouse model demonstrated that PLNs accumulate at the wound site and induce ∼65% reduction in bleeding time, effectively mimicking and improving the hemostatic functions of natural platelets. We show that both the biochemical and biophysical design parameters of PLNs are essential in mimicking platelets and their hemostatic functions. PLNs offer a nanoscale technology that integrates platelet-mimetic biophysical and biochemical properties for potential applications in injectable synthetic hemostats and vascularly targeted payload delivery.

Targeted and efficient gene delivery systems hold tremendous potential for the improvement of cancer therapy by enabling appropriate modification of biological processes. Herein, we report the design and synthesis of a novel cationic di-block copolypeptide, incorporating homoarginine (HAG) and shikimoyl (LSA) functionalities (HDA-b-PHAGm-b-PLSAn), tailored for enhanced gene transfection specifically in cancer cells. The di-block copolypeptide was synthesized via sequential N-carboxyanhydride (NCA) ring-opening polymerization (ROP) techniques and its physicochemical properties were characterized, including molecular weight, dispersity, secondary conformation, size, morphology, and surface charge. In contrast to the cationic poly- L -homoarginine, we observed a significantly reduced cytotoxic effect of this di-block copolypeptide due to the inclusion of the shikimoyl glyco-polypeptide block, which also added selectivity in internalizing particular cells. This di-block copolypeptide was internalized via mannose-receptor-mediated endocytosis, which was investigated by competitive receptor blocking with mannan. We evaluated the transfection efficiency of the copolypeptide in HEK 293T (noncancerous cells), MDA-MB-231 (breast cancer cells), and RAW 264.7 (dendritic cells) and compared it with commonly employed transfection agents (Lipofectamine). Our findings demonstrate that the homoarginine and shikimoyl-functionalized cationic di-block copolypeptide exhibits potent gene transfection capabilities with minimal cytotoxic effects, particularly in cancer cells, while it is ineffective for normal cells, indicative of its potential as a promising platform for cancer cell-specific gene delivery systems. To evaluate this, we delivered an artificially designed miRNA-plasmid against Hsp90 (amiR-Hsp90) which upon successful transfection depleted the Hsp90 (a chaperone protein responsible for tumour growth) level specifically in cancerous cells and enforced apoptosis. This innovative approach offers a new avenue for the development of targeted therapeutics with an improved efficacy and safety profile in cancer treatment. [ABSTRACT FROM AUTHOR]

Competitive banks aggressively invest in information and communication technologies (ICT) to enhance their market share and reduce Customer Acquisition Costs (CAC). This study examines the impact of cumulative stock of ICT investment on (a) deposit and loan market share and (b) CAC of banks operating in India. The analysis uses a longitudinal dataset of 84 domestic and 70 foreign banks from 2000 to 2020, employing a two-step system Generalized Method of Moment (GMM). It is found that ICT investment adversely affects the market share of domestic banks, indicating a need for these banks to strategically invest more in CAC. Conversely, foreign banks are able to increase their market share through ICT investment and reduced CAC, thereby demonstrating greater efficiency in utilizing ICT. The study underscores the strategic importance of cumulative stock of ICT investment for banks. Nonetheless, it is emphasized that ICT investment must be complemented with innovative marketing strategies to enhance customer experience, reduce CAC, and increase market share. Overall, while foreign banks are able to leverage ICT to boost efficiency, domestic banks must leverage ICT to implement targeted marketing strategies and strive to enhance their customer service. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs) have proven to be a wonderful material for water remediation, but their stability has been a long-standing challenge. Herein, to address this problem, a novel 'giant' COF containing thiol group (SH-COF) was synthesized and infused into a sequential interpenetrating polymeric matrix through the formation of exchangeable imine bonds in situ. This COF-tagged IPN membrane, besides enhancing its stability, served as a versatile platform for membrane engineering, particularly for efficient interaction with heavy metals such as mercury. Moreover, the in situ formation of dynamic bonds endowed the membrane with recyclability, a focal point of current membrane research, which is not amenable using the conventional routes of introducing COFs on thin-film composite membranes. The structure of the synthesized SH-COF was characterized using DFT simulations to gain insights from a fundamental perspective. The SH-COF inclusion within the membrane structure not only reduced the pore size but also facilitated the incorporation of significant numbers of charge-carrying centers. These engineered membranes exhibited high and sustained water flux for 3 weeks, along with enhanced separation capabilities for dyes (>99%), antibiotics (>97%), and monovalent salts (>98%). Thiol groups facilitated effective mercury removal (up to 97%), while the hydrophilic surface maintained antifouling properties and tolerance to chlorine. Importantly, these membranes are non-cytotoxic and re-processable, making them promising candidates for advancing sustainable water treatment technologies. This research has the potential to address the adverse effects of microplastic pollution resulting from inadequate membrane disposal practices. Furthermore, it presents a timely solution for the development of environmentally friendly and sustainable membranes. [ABSTRACT FROM AUTHOR]

Magnetometer measurements are one of the critical components necessary for improving our understanding of the intricate physical processes coupling mass, momentum, and energy within near-Earth space and throughout our solar system. However, these measurements are often contaminated by stray magnetic fields from the spacecraft hosting the magnetic-field sensors, and the data often require the application of interference mitigation algorithms prior to scientific use. Rigorous numerical validation of these techniques can be challenging when the techniques are applied to in situ spaceflight data as a ground truth for the local magnetic field is often unavailable. This paper introduces and details the generation of an open-source dataset designed to facilitate the assessment of interference mitigation techniques for magnetic-field data collected during spaceflight missions. The dataset contains over 100 h of magnetic-field data, comprising mixtures of near-direct-current (near-DC) trends, physically synthesized interference, and pseudo-geophysical phenomena. These constituent source signals have been independently captured by four synchronized magnetometers sampling at a high cadence and combined into 30 min intervals of data representing events and interference seen in historic missions. The physical locations of the four magnetometers relative to the interference sources enable researchers to test their interference mitigation algorithms with various magnetometer suite configurations, and the dataset also provides a ground truth for the underlying interference signals, enabling the rigorous quantification of the results of past, present, and future interference mitigation efforts. [ABSTRACT FROM AUTHOR]