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The current applications and future directions of terlipressin
No full textTerlipressin is a vasopressin analog with potent splanchnic vasoconstrictor properties. It has an established role in managing portal hypertensive bleeding and hepatorenal syndrome-acute kidney injury, with a growing body of evidence demonstrating improved safety and efficacy with continuous infusion-based administration compared to bolus dosing. We discuss previously reported adverse effects of terlipressin and evidence-based strategies to maximize the safety of administration. We also review the literature surrounding emerging indications for terlipressin in decompensated cirrhosis, particularly in the management of refractory ascites. Furthermore, we present data on novel ambulatory programs utilizing long-term continuous terlipressin infusion as bridging therapy for liver transplant candidates with recurrent hepatorenal syndrome-acute kidney injury, diuretic-refractory ascites, or hydrothorax
Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial
No full textEncorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403-4.253; 99.8% CI: 1.019-5.855; one-sided P = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318-0.691; repeated CI: 0.166-1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421
Interacting and Dynamical Properties of Su-Schrieffer-Heeger like Systems
No full text© 2025 Anirban GhoshTopological phases constitute an important aspect of modern condensed matter physics, and the Su-Schrieffer-Heeger (SSH) model is one of the most simple ways to construct such a system. As a result, it remains one of the most heavily applied/studied systems across classical and quantum settings. Two important aspects of this model are that it is essentially a single particle and hosts robust edge states in certain regions of parameter space, but it does not in other regions. These attributes have intrigued interest in a couple of directions, and among these, one is the effect of interactions on the topology of the system. Another such direction is the dynamics of the topological edge state in response to that of the quantum quench. In this thesis, we present our work in these two directions. Starting from the core concepts, we examine the non-equilibrium dynamics of an extended SSH model under quantum quenches across topological phases, unveiling the role of path of winding number transitions in shaping information transport. We then introduce complex impurities into the SSH system, demonstrating the emergence of asymmetric post-quench transport, where reflection asymmetry undergoes polarity switching with increasing quench extent. Finally, we investigate how interactions modify the topological edge states of a bosonic SSH system, employing an interacting continuum Dirac equation approach and a novel algorithm to extract boundary states in the presence of interactions. This then motivates an investigation of topological edge states in a 1D interacting ultra cold Bose gas in a periodic potential using the Gross-Pitaevskii equation, employing the algorithm. Overall, these studies provide insight into the fate of the edge states with respect to quenching and interactions
Consumer insights from a feasibility study on remote and extended use of a novel non-invasive wearable fetal electrocardiogram monitor
No full textThe COVID-19 pandemic accelerated the adoption of telehealth and remote monitoring in obstetric care. This study assessed pregnant patients' perceptions before and after using a novel non-invasive fetal electrocardiogram (NI-FECG) device. The trial is prospectively registered on the Australia New Zealand Clinical Trials Registry (ANZCTRN12621001260819; submitted June 9th, 2021; approved September 17th, 2021). Seventy participants from 36 weeks' gestation completed pre- and post-use surveys. Interest in continuous and home fetal monitoring was high (79% and 90%, respectively). Post-use, 89% reported satisfaction; over 90% comfortable wearing and removing the sensor. Extended use was acceptable to 76%, and only 3% reported high skin irritation. Sentiment analysis highlighted themes of reassurance, convenience, and reduced anxiety. Some suggested smaller, wireless design. Analysis by natural language processing and clustering provided deeper insights. Findings support strong interest in at-home fetal monitoring; further refinement and education are needed to enhance acceptability. Future research should assess long-term effects on anxiety and clinical outcomes
Landscapes—a lens for assessing sustainability
No full textCONTEXT: There are urgent calls to transition society to more sustainable trajectories, at scales ranging from local to global. Landscape sustainability (LS), or the capacity for landscapes to provide equitable access to ecosystem services essential for human wellbeing for both current and future generations, provides an operational approach to monitor these transitions. However, the complexity of landscapes complicates how and what to consider when assessing LS. OBJECTIVES: To identify important features of landscapes that remain challenging to consider in LS assessments and provide guidance to strengthen future assessments. METHODS: We conducted two workshops to identify the complex features of landscapes that remain under-considered in LS assessments, and developed guidelines on how to better incorporate these features. RESULTS: We identify open and connected boundaries and diversity of values as landscape features that must be better considered in LS assessments or risk exacerbating offstage sustainability burdens and power inequalities. We provide guidelines to avoid these pitfalls which emphasize assessing ecosystem service interactions across interconnected landscapes and incorporating local actors' diverse values. CONCLUSIONS: Our guidelines provide a stepping stone for researchers and practitioners to better incorporate landscape complexities into LS assessments to inform landscape-level decisions and actions
Management of Osteoporosis in Parkinson's Disease: A Systematic Review of Clinical Practice Guidelines
No full textBACKGROUND: Parkinson's disease (PD) is the fastest-growing neurological disorder globally. Defining features include tremor, muscular rigidity, bradykinesia, and postural instability, which in combination with nonmotor symptoms such as cognitive impairment and orthostatic hypotension increase the risk of falls. Along with low bone mineral density, fracture risk is high in PD. OBJECTIVES: The aims were to identify and appraise clinical practice guidelines, consensus statements, and treatment algorithms containing recommendations for bone health in people with PD (PwP). METHODS: We systematically searched 4 electroninc databases (MEDLINE, Embase, Emcare, and Web of Science) (n = 78), in addition to the websites of organizations, societies, and professional bodies focused on PD or osteoporosis (n = 28), up to April 22, 2024. RESULTS: After duplicate removal, screening, and full-text review, 6 records were included. Included records were appraised using the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. All records recognized bone health as a concern in PD, yet recommendations for fracture-risk screening were inconsistent. Two of six records grouped PD under the broad category of neurological diseases. The acceptability and tolerance of anti-osteoporosis medications in PwP was discussed only in 1 record, which incorporated national osteoporosis guidelines into a PD-specific treatment algorithm. CONCLUSIONS: This review highlights that despite the documented high fracture rates of PwP, health professionals do not always have adequate resources to support them when considering how to manage osteoporosis. Osteoporosis screening and management needs to be incorporated into PD treatment guidelines, and equally providing specific recommendations for PwP related to bone health in national osteoporosis guidelines should be a priority given the high burden of fracture in the patient population
Actions and negotiations: art and the aesthetics of risk
No full text© 2025 Mark Erwin FriedlanderThis research begins with a question: to what extent, and in what kinds of ways, does the negotiation of risk—including associated bureaucratic procedures—shape the production, reception and interpretation of artworks? Like many aspects of artistic production, risk is continuous with the world beyond the work. Here, the entangled roles of human and non-humans are pivotal, from the central figure of the artist to numerous other entities engaged in risk management of an artwork. From curators, technicians, and engineers to digital technologies, and fabrication standards, bureaucratic and practical procedures are an often overlooked and underestimated source of meaning making. Throughout the research the definition of risk moves across many points of encounter - from real bodily risk to cultural risk, and to the systems that negotiate risk - and yet it remains at all times firmly tied to the aesthetic realm. This is the space where artworks are conceived, fabricated, and finally brought into encounters with those who apprehend them - but it is also the looping back through research - where a prolonged fascination with risk in art making has generated its own aesthetic outcomes.
Developed through both personal and professional experience, this research outlines a series of typologies designed to clarify how risk management operates within actual artistic practice. The first typology examines risk as material, focusing on Chris Burden’s work, where hazard functions as both a conceptual device and a productive tension deliberately embedded in the artwork. The second considers the approaches of artists Simone Forti and Robert Morris, exploring how their divergent choreographic methodologies produce varying degrees of risk—despite shared formal structures. The third typology analyses Christoph Buchel’s practice, where socio-political risk is intentionally provoked to generate public tension. This approach highlights how institutional and societal systems attempt to manage such provocation.
Using the lens of the typologies, the creative component of this dissertation considers three significant artworks from a large number produced over the course of the research. The first of these, Boiling kettle (after Risk Assessment), (2025), foregrounds risk as material in relation to the Burden typology. Following this, a performance at Fiona and Sidney Myer Gallery, BendAid, (2025), synthesises the philosophies and practice of Forti and Morris from the second typology to consider the bodily proximity of risk and pedagogical levers of control that can assume the risk management role. Finally, two works produced in Japan contrast my response to the situated nature of risk with Buchel’s activation of confusion – with both of us negotiating the complexity of specific cultural contexts
DNA replication stress underpins the vulnerability to oxidative phosphorylation inhibition in colorectal cancer
No full textMitochondrial oxidative phosphorylation (OXPHOS) is a therapeutic vulnerability in glycolysis-deficient cancers. Here we show that inhibiting OXPHOS similarly suppresses the proliferation and tumorigenicity of glycolytically competent colorectal cancer (CRC) cells in vitro and in patient-derived CRC xenografts. While the increased glycolytic activity rapidly replenished the ATP pool, it did not restore the reduced production of aspartate upon OXPHOS inhibition. This shortage in aspartate, in turn, caused nucleotide deficiencies, leading to S phase cell cycle arrest, replication fork stalling, and enrichment of the p53 pathway, manifestations of replication stress. The addition of purine nucleobases adenine and guanine along with the pyrimidine nucleoside uridine restored replication fork progression and cell proliferation, whereas the supplementation of exogenous aspartate recovered the nucleotide pool, demonstrating a causal role of the aspartate shortage in OXPHOS inhibition-induced nucleotide deficiencies and consequently replication stress and reductions in proliferation. Moreover, we demonstrate that glutamic-oxaloacetic transaminase 1 (GOT1) is critical for maintaining the minimum aspartate pool when OXPHOS is inhibited, as knockdown of GOT1 further reduced aspartate levels and rendered CRC cells more sensitive to OXPHOS inhibition both in vitro and in vivo. These results propose GOT1 targeting as a potential avenue to sensitize cancer cells to OXPHOS inhibitors, thus lowering the necessary doses to efficiently inhibit cancer growth while alleviating their adverse effects
A Qualitative Study of Aboriginal Peoples’ Health Care Experiences With Chronic Obstructive Pulmonary Disease
No full textAboriginal Australians experience a high prevalence of chronic obstructive pulmonary disease (COPD), with high rates of potentially preventable hospitalisations. However, little is known about Aboriginal peoples' experiences of living with COPD and how they navigate health care systems. This study used thematic analysis and Aboriginal methodology to explore Aboriginal peoples' lived experiences of COPD, their health care journey from receiving a diagnosis of COPD to the clinical management, and the impact of COPD on their daily lives. We conducted in-depth semi-structured interviews over a 6-month period with 18 Aboriginal adults diagnosed with COPD from four Aboriginal Community Controlled Health Services (ACCHS) in New South Wales, Australia. Reflexive thematic analysis was employed to ensure rigour. The findings revealed deeply personal and reflective stories shaped by historical, social, and cultural realities of Aboriginal peoples living with COPD. Four themes were identified characterising their experiences. Based on the findings, the following guidance is provided on future COPD care for Aboriginal peoples: Better alignment of existing COPD management with Aboriginal peoples' cultural contexts and perspectives to improve access to culturally safe care; Increased funding for ACCHS to enhance COPD management, such as early detection through case finding and access to ACCHS-led pulmonary rehabilitation; Engaging family members in COPD management and providing culturally centred COPD education that facilitates discussions and builds health literacy and self-management skills; Implementing health promotion initiatives to increase awareness and counteract fear and shame to improve early COPD detection
Neoadjuvant Pembrolizumab Enables Successful Downstaging and Resection of Borderline Resectable MSI-H/dMMR Pancreatic Ductal Adenocarcinoma: A Case Report and Literature Review
No full textBACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis. While immunotherapy has shown limited efficacy in most PDAC cases due to an immunosuppressive tumour microenvironment, tumours with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) status exhibit increased responsiveness to immune checkpoint inhibitors. CASE PRESENTATION: We report the case of a 45-year-old woman with Lynch syndrome who was diagnosed with MSI-H/dMMR PDAC during routine surveillance. Given the borderline resectable nature of her tumour and previous chemotherapy-related neurotoxicity, she was treated with neoadjuvant pembrolizumab instead of conventional chemotherapy. Following four cycles of pembrolizumab, imaging revealed a marked metabolic response, allowing for successful R0 pancreatoduodenectomy. Postoperative histology confirmed a significant reduction in tumour size, and immunohistochemical analysis demonstrated increased CD8 + T cell infiltration, supporting an enhanced anti-tumour immune response. The patient continues adjuvant pembrolizumab therapy without complications. CONCLUSION: This case highlights the potential role of neoadjuvant pembrolizumab in MSI-H/dMMR PDAC, demonstrating successful tumour downstaging and facilitating surgical resection. Our findings support further investigation into the integration of immunotherapy as a neoadjuvant strategy for select PDAC patients