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Using a Partnership-Based Approach to Strengthen Acute Care Systems in the Pacific and Timor-Leste
No full textEmergency and critical care services are essential to universal health coverage. World Health Assembly (WHA) Resolution 76.2, adopted in 2023, outlined the importance of integrated emergency, critical and operative care systems in strengthening primary healthcare capabilities. Recent research has determined that system strengthening and partnership-based approaches to healthcare capacity development have the potential to achieve greater equity and sustainability. The Regional Emergency and Critical Care Systems Strengthening Initiative (RECSI) is an Australian Government funded programme under the Partnerships for a Healthy Region (PHR) initiative. It aims to enhance acute care capacity and healthcare system resilience across the Pacific and Timor Leste. RECSI is led by a consortium of acute care organisations and provides a vehicle for progressing WHA 76.2. The programme focuses on four thematic areas: workforce capacity and training, systems and processes, data and research, and leadership and governance. As part of RECSI's inception, a structured programme logic was developed, which describes programme activities and outputs, and how they contribute to defined intermediate and end-of-programme outcomes. RECSI's monitoring, evaluation and learning (MEL) plan, which supplements the programme logic, incorporates sustainability indicators that are focused on monitoring the impact of mechanisms designed to enable ongoing benefits from programme outcomes. Utilising a partner-led and context-specific programme design, RECSI represents a rigorous approach to acute care system strengthening. This strategy aims to build genuine partnerships to leverage skills, knowledge and opportunity across the Pacific and Timor-Leste
Enviromimetics: From exercise mimetics to cognitomimetics in the quest for enhanced brain health and cognition
No full textEnviromimetics were first proposed over two decades ago, as novel therapeutics to mimic or enhance the beneficial effects of environmental stimulation. In the intervening period, subclasses of enviromimetics have been proposed, most notably exercise mimetics. Epimimetics constitute an additional subclass of enviromimetics, which act via epigenetic mechanisms. In this article, the concept of enviromimetics is updated, including its subclasses, and explored in the context of the development of novel therapeutic approaches to a wide range of human disorders, with a specific focus on neurological diseases and psychiatric disorders. Furthermore, a new concept is introduced, that of 'cognitomimetics', which specifically mimic or enhance the therapeutic effects of cognitive stimulation. One focus of discussion is the beneficial molecular and cellular mechanisms induced by environmental exposures and lifestyle factors, including increased physical activity and cognitive stimulation. Exercise mimetics represent the largest, and most experimentally tractable, subclass of enviromimetics, due to the biologically pervasive and readily quantifiable therapeutic impacts of physical activity, both within the nervous system, and throughout the body. These mechanisms provide new insights into molecular targets for these novel therapeutic approaches. It is hoped that this will lead to new ways to prevent, ameliorate and eventually cure a wide range of human illnesses, particularly brain disorders, which collectively constitute the largest, and most rapidly growing, global burden of disease
The Australian Economy in 2024–2025: Living and Housing Affordability
No full textABSTRACT
The economy grew at a well below‐trend pace in 2023/2024. Inflation fell, and the unemployment rate edged higher, but these changes were not sufficient to convince the Reserve Bank of Australia to start cutting the cash rate. In 2024, the federal Budget included cost‐of‐living financial support, as well as measures to support housing affordability, but living standards continued to slip as real GDP per capita fell. Overall, the Misery Index for Australia remains high and ongoing uncertainty about the United States and Chinese economies are downside risks to the outlook for 2024/2025
A novel mechanism of sperm midpiece epididymal maturation and the role of CCDC112 in sperm midpiece formation and establishing an optimal flagella waveform
No full textBACKGROUND: The mitochondrial sheath is a defining feature of mammalian sperm with proposed functions in structural support and energy production for flagella movement. Recently, coiled coil domain containing (CCDC) protein 112 (CCDC112) was suggested to play a role in the regulation of ciliogenesis. CCDC112 is a poorly characterised protein and there is virtually no knowledge of its in vivo function. METHODS: Here, we define CCDC112 as crucial for male fertility using a Ccdc112 loss-of-function mouse line. To characterize and analyze male fertility, and to identify a novel process of epididymal midpiece maturation, we utilized a range of assays including fertility testing, scanning electron microscopy, high-resolution sperm motility and power output analysis, in vitro fertilization, intracytoplasmic sperm injection, mitochondria stress test assays and glycolytic flux assays. Localization of CCDC112 in cilia was assessed via the transfection of IMCD-3 cells with a CCDC112-eGFP vector and subsequent immunofluorescent staining. RESULTS: Results reveal CCDC112 as a requirement for male fertility in the mouse with an essential role in mitochondrial sheath formation. Our data reveal the critical role of CCDC112 in mitochondrial morphogenesis during midpiece formation, with the lack of CCDC112 leading to significantly reduced respiration capacity, irregular flagellar waveforms, diminished progressive motility and ultimately male sterility. In the absence of CCDC112, sperm are unable to traverse the female reproductive tract to the site of fertilization and in vitro have a poor capacity to penetrate the zonae pellucidae of oocytes or fuse with the oocyte. We further unveil a previously unrecognized process of epididymal mitochondrial sheath maturation. We show the sperm midpiece is structurally immature upon exiting the testis and maturation continues during transit from the caput to the cauda epididymis. Finally, we identify CCDC112 as a component of the distal appendages of the mother centriole in IMCD-3 cells suggestive of a facilitative role for CCDC112 in protein entry into the ciliary compartment within germ cells. CONCLUSION: Collectively, we establish CCDC112 as a key regulator of sperm midpiece assembly and function while further expanding our understanding on functional sperm production, energy generation and flagella kinematics
Knowledge, attitudes, and practices toward depression among people living with depression in Vietnam: the cultural dynamics in the era of globalization
No full textBackground: Despite the high burden of depression in Vietnam, little is known about the knowledge, attitudes, beliefs, and practices among Vietnamese people with depression in contemporary society. The study aims to explore in depth knowledge, attitudes, and practices related to depression among those with depressive symptoms of depression in contemporary Vietnamese society. Methods: This is a qualitative study with 40 adults, 18–64 years old, with symptoms of depression. In-depth interviews were conducted to explore knowledge (symptoms, causes, treatment), attitudes, and practices to seek support or care for depression. Results: Participants demonstrated relatively adequate literacy regarding depression symptoms and treatment. Most people with depression know about psychotherapy and pharmacological treatment. Stigma related to depression seems lesser compared to that in the past. People with depression receive support from family and friends. A significant knowledge-practice gap was found, concealment of illness is common, access to care is limited, medicines are frequently discontinued, and praying and offering to altars to treat mental illness still exist. Based on analysis guided by the ‘glocalization theory’ we offer an explanatory account of the current state off knowledge, attitudes, and practices toward depression amongst people living with depression in Vietnam. This analysis recognizes the co-existence of global and local influences. People are creating and adapting their “glocal” views, attitudes, and norms around depression as well as mental illness. This explanatory model recognizes the co-existence of global and local influences, the influence of “glocal” dynamics to rationales the knowledge, attitudes and practices of people related to depression, therefore, it helps better explain and sharpen the responses to depression in Vietnam. Conclusions: Societal changes have influenced the knowledge, attitudes, and behaviors towards depression in Vietnam in positive ways; however, historical, cultural challenges continue, while new challenges are emerging. Our findings point to the need for renewed, continued efforts to improve mental health related awareness, while simultaneously improving the availability, accessibility, and responsiveness of mental health services. These efforts should take into account both global and local influences on how people in Vietnam think and act regarding mental health issues. Trial registration: Clinicaltrials.gov, NCT06456775. Registered June 13, 2024 – Retrospectively registered, https://clinicaltrials.gov/study/NCT06456775?cond=depression%26intr=Tele-SSM%26rank=1
Redefining co-design for social-ecological research and practice: A systematic literature review
No full textCollaborative processes such as co-design are increasingly crucial in generating social-ecological research and practice. Fostering change within complex adaptive systems requires collaboratively working with real-world actors or stakeholders to resolve complicated issues. Co-design is a distinct and fundamental component of the co-paradigm, a collective term for co-design, co-production, and co-creation. However, scientific literature currently provides limited definitions of the key concepts within the co-paradigm, leading to misinterpretations or inconsistent usage. Improving the clarity of these definitions is essential because it permits scientific progress and better implementation of processes and engagement in practice. To address this gap, the following paper presents research which critically examines the practice of co-design through a systematic literature review. Using a systematic approach, this study identifies fifty-two papers with empirical methodologies, which are thematically analysed to understand the purpose and process of the co-design approach within social-ecological research and practice. The paper identifies effective co-design methods and discusses the implications of their utilisation within social-ecological study and practice. The review also identifies and examines definitions of co-design and the challenges of implementing a co-design approach, highlighting potential solutions. The paper concludes by proposing an integrative definition of co-design to further understand and enhance the process's implementation within social-ecological systems. The definition proposed in this paper can serve as a roadmap for researchers and practitioners aiming to use co-design as part of sustainable transformation efforts in social-ecological systems
Ten steps to improve outcomes of in-facility neonatal resuscitation
No full textBACKGROUND: Up to 10 % of all newborns require assistance to breathe at birth. Although neonatal resuscitation guidelines and educational platforms exist, best practices to implement high-quality neonatal resuscitation care have not been defined. AIM: To establish a Neonatal Global Resuscitation Alliance and develop ten steps to improve outcomes of in-facility neonatal resuscitation across global settings. METHODS: Three-stage iterative consensus-based process: (1) invited input from the neonatal resuscitation community to identify pertinent measures, (2) convened a face-to-face meeting of 28 global neonatal resuscitation content experts to refine consensus steps, (3) presented draft steps and related content to stakeholders; solicited public comment and revised ten steps based on feedback. RESULTS: The consensus-based ten steps include: Implement effective education systems; Ensure team and equipment readiness; Identify high-risk pregnancies and prevent perinatal risks; Respond to every birth; Perform guideline based resuscitation; Deliver guideline based post-resuscitation care; Collect data throughout resuscitation care; Improve quality of resuscitation; Support parent and family well-being; Cultivate a culture of excellence. For each of these steps, key concepts and suggested approaches to put the steps into practice are identified. CONCLUSION: These ten steps to improve outcomes of in-facility neonatal resuscitation represent a clear framework for healthcare professionals, institutions, and policymakers to evaluate and strengthen their readiness, training, and response to newborns who need resuscitation at birth. This consensus-based guidance can be used to optimize in-facility neonatal resuscitation and improve outcomes for newborns worldwide
A CDK11-dependent RNA polymerase II pause-checkpoint precedes CDK9-mediated transition to transcriptional elongation
No full textControlled gene expression is achieved through the intricate regulation of RNA polymerase II (Pol II) progression through transcription-cycle checkpoints. While the contribution of CDK9 for Pol II pause-release is well established, the requirement for other cyclin-dependent kinases (CDKs) has not been fully elucidated. In this study, we propose a critical role for CDK11 in the Pol II pausing-to-elongation transition at a checkpoint that precedes and is independent from CDK9. Selective CDK11 inhibition or degradation results in acute ablation of RNA synthesis near the beginning of transcriptional units and genome-wide stalling of Pol II at transcription start site (TSS)-proximal regions. High-resolution chromatin immunoprecipitation and precision nuclear run-on assays reveal spatial differences between CDK11- and CDK9-dependent Pol II pause sites, with CDK11 regulating Pol II upstream of the CDK9 checkpoint within the pausing zone. Cancer cells exhibit profound reliance on CDK11, with CDK11 inhibition reducing tumor burden in in vivo models of blood cancer, demonstrating the importance of CDK11-dependent Pol II regulation for aggressive hematological malignancies
Enhanced Influenza Vaccines Extend A(H3N2) Antibody Reactivity in Older Adults but Prior Vaccination Effects Persist
No full textBACKGROUND: Influenza vaccine effectiveness can be reduced in older adults and among repeatedly vaccinated groups. Results from year 1 of "PIVOT," a randomized trial among adults aged ≥65 years in Hong Kong, showed that adjuvanted (Adj), high-dose (HD), and recombinant hemagglutinin (rHA) vaccines induced greater antibody responses against vaccine viruses than standard-dose (SD) influenza vaccine. Here, we examine the breadth of A(H3N2)-reactive antibodies induced during the first 2 study years (2017/2018, 2018/2019), and compare participants who received influenza vaccination annually, or not at all, for 5 years preceding enrollment. METHODS: 14-20 PIVOT participants per vaccine and prior vaccination group (0/5 or 5/5 prior years) who provided sera on days 0, 30, and 182 in year 1 and days 0 and 30 in year 2 were assessed. Hemagglutination inhibition (HAI) antibody titers were measured against 30 viruses spanning 1968 to 2018. RESULTS: In year 1, rHA and Adj but not HD vaccines induced titers ≥40 and titer rises ≥4-fold (seroconversion) against significantly more strains than SD vaccine among participants vaccinated 0/5 prior years. Only rHA and Adj vaccines induced titers ≥40 against post-vaccine strains. Antibody responses were poor among participants vaccinated 5/5 compared with 0/5 prior years and only rHA increased the breadth of seroconversion compared with the SD vaccine in this group. Antibody responses were weaker across groups in year 2. CONCLUSIONS: The results suggest that Adj and particularly rHA vaccines may improve the breadth of protection against A(H3N2) viruses but may not overcome attenuating effects of repeated vaccination in older adults. CLINICAL TRIALS REGISTRATION: NCT03330132
Improving the accuracy of remotely sensed TSS and turbidity using quality enhanced water reflectance by a statistical resampling technique
No full textSatellite-based optical Remote Sensing (RS) presents a unique opportunity for monitoring the water quality of complex riverine systems stretching over large regions. However, due to the weak reflectance and resulting low signal-to-noise ratio of water bodies, interference of clouds and cloud shadows significantly impacts the accuracy of remotely sensed water quality parameters. This study presents a scalable, innovative cloud and cloud-shadow masking using the Gaussian Mixture Model (GMM) combined with a spatially aggregated reflectance sampling approach that can robustly monitor the Total Suspended Solids (TSS) and turbidity over selected sections of the study site, the Hooghly River in West Bengal, India. The statistical resampling approach based on GMM was applied to Sentinel-2 (S2) imagery to produce input to Machine Learning (ML) algorithms to retrieve the TSS and turbidity for target river sections. The resampled reflectance data was spatially aggregated over the selected regions of interest to further improve the input quality. Out of 80 cloud-contaminated images, we were able to use 70 images with 40%–50% clouds/cloud shadows for TSS and turbidity retrievals after applying the GMM-based masking and spatial aggregation. The resampled spectral data and in-situ TSS and turbidity measurements were used to train four ML models: Partial Least Squares Regression (PLSR), Random Forest Regression (RFR), Extreme Gradient Boosting (XGBoost), and Support Vector Regression (SVR). Our approach improved the estimation accuracy of the TSS by 33% and turbidity by 28% compared to the input processed using the built-in Sentinel-2 cloud and cloud shadow masks. This work emphasizes the importance of careful satellite image preparation for cloud and cloud-shadow screening and the utility of spatially aggregated reflectance samples over homogeneous regions of interest to enable robust water quality assessment under variable atmospheric conditions