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High Concentrations of Non-Esterified Fatty Acids During Bovine In Vitro Fertilisation Are Detrimental for Spermatozoa Quality and Pre-Implantation Embryo Development
Get PDFHigh non-esterified fatty acids (NEFAs) during negative energy balance in dairy cattle can impair reproduction. While their effects on oocyte maturation and preimplantation embryo development are known, their impact during fertilisation is largely unexplored. This study examined the effects of high NEFA exposure exclusively during in vitro fertilisation (IVF). Bovine oocytes were matured in vitro and fertilised under physiological or high NEFA concentrations. High NEFA concentrations decreased fertilisation, cleavage, and blastocyst rates. Reactive oxygen species production in zygotes was not affected, but blastocysts derived from the High-NEFA group had fewer cells. Spermatozoa exposed to high NEFA concentrations exhibited increased plasma membrane and acrosome damage, higher DNA fragmentation, and reduced mitochondrial membrane potential. The expression of H3K27me3, a repressive histone mark normally erased from fertilisation to embryonic genome activation, was higher in 2-cell than in 4-cell embryos on day 2 after IVF, but only in the High-NEFA group. This delayed H3K27me3 loss, along with increased DNA damage, could partially explain the reduced blastocyst formation observed. In conclusion, high NEFA concentrations can impair pre-implantation embryo development during zygote formation, potentially via effects on both the oocyte and spermatozoon. The latter warrants further investigation using an intracytoplasmic sperm injection model
The Economics, Politics and Law of Infrastructure Financing in Sub-Saharan Africa: A Critical Tertium Comparationis CTC
No full textSometime around 2012, an investigative news outlet published a special report regarding its findings about the number of abandoned projects in Nigeria. In its preliminary findings it was discovered that about 12000 projects were abandoned due to reason largely ascribed to lack of political will and largely, corruption. Fast forward to 2021, a report by the Nigerian Institute of Quantity Surveyors put the figure of abandoned projects to a staggering 56000, the sum of which valued at N12 trillion (that is 10 billion to Kenya’s Lamu Coal Power Plant. From the 12Km Moonlight rail worth 50 billion) in Rivers State Nigeria to Zambia’s Mongu proposed 20000-capacity stadium, the list of abandoned project continues surging in sub-Saharan Africa (SSA) region. While different factors have been identified as the reasons for project abandonment cum infrastructure gap in SSA, one word has always been used to sum it all, and that is, the risk factor (economic, political and legal), which of course has invariably been pinned down as the cause of financing deficit, refinancing issue, repayment conundrum cum infrastructural gap in Saharan Africa (SSA). In view of this, this research took a novel approach to addressing the menace of project abandonment, finance deficit, refinancing cum infrastructural gap in SSA by deconstructing this malaise within the prisms of the trio, economics, politics and law. Drawing from preliminary research that I carried out, over a short period of time, I tactically deployed four distinct economics theories to philosophise A3S as a four-wheel factor which were identified as pivotal towards formulating a model that can be used to tackle, head-on, the menace of financing deficit, infrastructure gap and financing sustainability in SSA. The A3S pillars are: affordability, accessibility, accountability and sustainability, codenamed (A3S) in this research. The A3S was considered as an overarching benchmark to reviewing the existing literature about infrastructure financing in SSA, I subsequently philosophised a feasible formula in economics that can be adopted as a principal formula that can be used for tackling the question of financing deficit and infrastructure dearth. Through synthetic but an in-depth literature review, it was discovered that a negligible or terse attention is given to the concepts of affordability, accessibility, accountability and sustainability when intellectually and practically confronting the malaise of infrastructure financing and delivery in SSA. According to the World Bank on data relating to Public-Private Partnership, SSA consists of 48 countries, therefore, I considered this reasonably too big to cover, hence the adoption of sampling, that is focusing on 3 of the most vibrant economies in each of the western, eastern and southern regions of Africa. Through a unique mixed-method and methodology, this thesis identifies and proves that the sampled countries cannot afford the repayment of the rising loans that are contracted all in the guise of financing infrastructure. Also, that Africa’s infrastructure gap requires huge financial investments and access to such funds in not realistically feasible to generate through local financial institutions. That the tenet of accountability is bastardised and it’s too susceptible to manipulation in favour of the political elite in the sampled states in SSA. Lastly, it is construed that for the financing deficit and infrastructural gap to be bridged, the parameters identified as fiscal gauge of affordability must be economically construed, the procedure for measuring accessibility must be institutionalised, and the mandate of validating adherence to accountability must revert to the citizenry (principal) on whose behalf the government (agent) negotiate for financing. It is in the light of this proposition that I philosophised a general but feasibly financing and sustainability model or economics formula that is feasible as a measure to the affordability, accessibility, accountability and sustainability gauges that can be used to measure financing strength of a borrowing country for sustainability in financing and development
Area-level socioeconomic inequalities in activities of daily living disability-free life expectancy in England: a modelling study
Get PDFBackground: More evidence of socioeconomic inequalities in disability-free life expectancy (DFLE) is needed to help develop approaches to narrow the gap between the most and least socioeconomically deprived people. Activities of daily living (ADL) disability represents the most severe and expensive disablement stage. Using combined longitudinal data, we aimed to quantify area-level socioeconomic inequalities in ADL-DFLE and the total person-years lived with ADL disability, in older men and women in England.Methods: In this modelling study, we harmonised data on ADL disability, area deprivation, age, and self-reported gender for individuals aged 50 years or older from three longitudinal studies in England: the English Longitudinal Study of Ageing (n=11 337), the Cognitive Function and Ageing Study II (n=7469), and the Newcastle 85+ Study (n=847). We used multistate modelling, and calculated the remaining life expectancy with and without ADL disability by gender and area-level socioeconomic status (80% of Index of Multiple Deprivation). From these data and Office for National Statistics population figures for the year 2024, we estimated the extra person-years lived with ADL disability by those aged 65 years from the most socioeconomically deprived areas. Findings: Those living in the least deprived areas had a reduced risk of ADL disability compared with those in the most deprived areas (hazard ratio [HR] 0·61 [95% CI 0·55–0·69]; p<0·0001), as did those in the middle area-level socioeconomic group (HR 0·76 [0·69–0·84]; p<0·0001). Increasing area-level socioeconomic disadvantage was associated with reduced life expectancy and more time spent with ADL disability, particularly for women. Living in the most disadvantaged areas was associated with people having ADL disability 11·0 years earlier for men and 12·0 years earlier for women, compared with living in the least deprived areas. An extra 59 000 person-years for men and 88 000 person-years for women were lived with ADL disability by those in the most deprived areas, at the population level, compared with the least deprived areas. Interpretation: Targeted policies to address underlying socioeconomic inequalities in health are likely to be the long-term definitive solution. Funding: National Institute for Health and Care Research Policy Research Unit in Healthy Ageing
Support for hospital doctors' workplace well-being in England: The Care under Pressure 3 realist evaluation
Get PDFIntroduction: The vital role of medical workforce well-being for improving patient experience and population health while assuring safety and reducing costs is recognised internationally. Yet the persistence of poor well-being outcomes suggests that current support initiatives are suboptimal. The aim of this research study was to work with, and learn from, diverse hospital settings to understand how to optimise strategies to improve doctors' well-being and reduce negative impacts on the workforce and patient care. Methods: Realist evaluation consistent with the Realist And Meta-narrative Evidence Synthesis: Evolving Standards (RAMESES) II quality standards. Realist interviews (n=124) with doctors, well-being intervention implementers/practitioners and leaders in eight hospital settings (England) were analysed using realist logic. Results: There were four key findings, underpinned by 21 context-mechanism-outcome configurations: (1) solutions needed to align with problems, to support doctor well-being and avoid harm to doctors; (2) doctors needed to be involved in creating solutions to their well-being problems; (3) doctors often did not know what support was available to help them with well-being problems and (4) there were physical and psychological barriers to accessing well-being support. Discussion and conclusion: Doctors are mandated to 'first, do no harm' to their patients, and the same consideration should be extended to doctors themselves. Since doctors can be harmed by poorly designed or implemented well-being interventions, new approaches need careful planning and evaluation. Our research identified many ineffective or harmful interventions that could be stopped. The findings are likely transferable to other settings and countries, given the realist approach leading to principles and causal explanations
Holloway Prison: Representations and realities in the history of a women's prison, 1902 to 1955
Get PDFThis article explores the media and cultural representations of HMP Holloway, London, England between 1902 and 1955 and contrasts this with the realities of the day-to-day female population and experience in the institution. Drawing on extensive historical analysis, the research examines how representations of the prison, and the women held within it, both titillated the public and reinforced existing or prevailing popular stereotypes about women's criminality and imprisonment in the first half of the twentieth century. These representations contributed to a distinctive and ferocious reputation, that cemented Holloway's notoriety in the popular imagination notwithstanding the contrasting realities of the institution
The Animal-AI Environment: A virtual laboratory for comparative cognition and artificial intelligence research
Get PDFThe Animal-AI Environment is a unique game-based research platform designed to facilitate collaboration between the artificial intelligence and comparative cognition research communities. In this paper, we present the latest version of the Animal-AI Environment, outlining several major features that make the game more engaging for humans and more complex for AI systems. These features include interactive buttons, reward dispensers, and player notifications, as well as an overhaul of the environment’s graphics and processing for significant improvements in agent training time and quality of the human player experience. We provide detailed guidance on how to build computational and behavioural experiments with the Animal-AI Environment. We present results from a series of agents, including the state-of-the-art deep reinforcement learning agent Dreamer-v3, on newly designed tests and the Animal-AI testbed of 900 tasks inspired by research in the field of comparative cognition. The Animal-AI Environment offers a new approach for modelling cognition in humans and non-human animals, and for building biologically inspired artificial intelligence
Identification of the Interacting Domains Between Tissue Factor and β1-Integrin and the Signalling Properties of the Two Fibronectin-like Domains of Tissue Factor
Get PDFBackground: Interactions between tissue factor (TF) and β1-integrin induce cell signals, but the molecular mechanisms are not completely understood. The extracellular domain of TF and EGF4-βTD domains of β1-integrin were hypothesised to be the most likely domains involved in the interaction. Additionally, the interaction may induce a conformational change in β1-integrin, which results in changes in signalling. Methods: Peptide constructs corresponding to the upper (residues 1–110; UED), lower (residues 106–219; LED) or combined extracellular domain (residues 1–219; TED) of TF were produced, as well as peptides corresponding to EGF4-βTD or EGF4 domains of β1-integrin. These constructs were expressed in TF-rich MDA-MB-231 cells and TF-deficient primary endothelial cells. The association of the peptides with endogenous-TF or β1-integrin was assessed by a proximity ligation assay and co-immunoprecipitation. Additionally, the influence of the constructs on β1-integrin conformation and the outcome on ERK1/2 activation, cyclin D expression and cell proliferation was analysed. Results: In MDA-MB-231 cells, all TF-constructs were associated with β1-integrin whilst LED was co-immunopurified with β1-integrin. EGF4-βTD was associated with and co-immunopurified with endogenous TF. Additionally, the expression of UED or EGF4-βTD reduced ERK phosphorylation and cyclin D expression and suppressed proliferation. In endothelial cells, the expression of UED, and to a lesser extent, LED, reduced the proportion of β1-integrin in the active conformation and induced ERK1/2 phosphorylation but did not induce cyclin D expression or proliferation. Conclusions: Collectively, these data indicate the extracellular domains of TF function together, with the lower domain forming a robust interaction with the βTD of β1-integrin and the upper domain inducing cell signalling by regulating β1-integrin conformation
BREATHLEssness in INDIA (BREATHE-INDIA): realist review to develop explanatory programme theory about breathlessness self-management in India
Get PDFBreathlessness is highly prevalent in low and middle-income countries (LMICs). Low-cost, non-drug, breathlessness self-management interventions are effective in high-income countries. However, health beliefs influence acceptability and have not been explored in LMIC settings. Review with stakeholder engagement to co-develop explanatory programme theories for whom, if, and how breathlessness self-management might work in community settings in India. Iterative and systematic searches identified peer-reviewed articles, policy and media, and expert-identified sources. Data were extracted in terms of contribution to theory (high, medium, low), and theories developed with stakeholder groups (doctors, nurses and allied professionals, people with lived experiences, lay health workers) and an International Steering Group (RAMESES guidelines (PROSPERO42022375768)). One hundred and four data sources and 11 stakeholder workshops produced 8 initial programme theories and 3 consolidated programme theories. (1) Context: breathlessness is common due to illness, environment, and lifestyle. Cultural beliefs shape misunderstandings about breathlessness; hereditary, part of aging, linked to asthma. It is stigmatised and poorly understood as a treatable issue. People often use rest, incense, or tea, while avoiding physical activity due to fear of worsening breathlessness. Trusted voices, such as healthcare workers and community members, can help address misconceptions with clear, simple messages. (2) Breathlessness intervention applicability: nonpharmacological interventions can work across different contexts when they address unhelpful beliefs and behaviours. Introducing concepts like “too much rest leads to deconditioning” aligns with cultural norms while promoting beneficial behavioural changes, such as gradual physical activity. Acknowledging breathlessness as a medical issue is key to improving patient and family well-being. (3) Implementation: community-based healthcare workers are trusted but need simple, low-cost resources/skills integrated into existing training. Education should focus on managing acute episodes and daily breathlessness, reducing fear, and encouraging behavioural change. Evidence-based tools are vital to gain support from policymakers and expand implementation. Breathlessness management in India must integrate symptom management alongside public health and disease treatment strategies. Self-management interventions can be implemented in an LMIC setting. However, our novel methods indicate that understanding the context for implementation is essential so that unhelpful health beliefs can be addressed at the point of intervention delivery
A Performance Modeling Study for Zero Fossil CO2 Stack Operation and Solvent Thermal Reclaiming in Post-Combustion Capture Industrial Applications
Get PDFPost-combustion capture (PCC) of CO2 is widely recognized as the most mature technology to mitigate CO2 emissions from existing fossil fuel-based power plants and industrial sources, and successful deployment will predominantly rely on the ability of the PCC plant to consistently achieve high capture fractions. To this end, the performance modeling study presented herein is the first attempt to identify engineering options for long-term, cost-effective windows for zero fossil CO2 stack emission PCC operation, when 100% of the added fuel CO2 (100% of the fossil CO2) is captured, in key industrial applications including combined cycle gas turbine (CCGT) power plants, steel, cement, energy from waste (EfW), and oil refining (fluidized catalytic crackers). Furthermore, low-cost designs for effective solvent recovery through thermal reclaiming with effective energy recovery are analyzed for the first time for nonproprietary, open-art aqueous MEA solvent at 35% w/w (unloaded). At 100% capture of the added fuel CO2, low lean loadings (between 0.1 and 0.12 molCO2/molMEA) enhance mass transfer in the absorber, while a raised desorber pressure of 2.4 bar limits excessive energy consumption. In fact, for an absorber packing height of 20 m (2 × 10 m beds), the optimum specific reboiler duty (SRD) to capture 100% of the added fuel CO2 (zero fossil CO2 stack operation) was found to lie between 3.62 and 3.96 GJ/tCO2, while for a 3 × 8 m bed absorber, i.e., 24 m, the SRD drops to 3.46–3.75 GJ/tCO2, both cases well within the range of reported energy penalty for 90–95% capture, which has significantly higher residual CO2 emissions. Furthermore, we analyzed two strategies of continuously operating a thermal reclaimer, i.e., single-stage and two-stage reclaiming systems (the first operates at stripper pressure while the second one at atmospheric) with effective energy integration and consideration of both volatile and nonvolatile components. Two-stage reclaiming can substantially reduce water addition compared to single-stage reclaiming from 100 to 400% of the reclaimer solvent flow to 0–50%. Yet, there exists a trade-off, namely, the greater the MEA recovery, the greater the uptake of volatile thermal degradation products. For example, in the case of single-stage reclaiming operation, for ∼90% MEA recovery, approximately 35% of the HEEDA is recycled to the PCC, and when MEA recovery increases to ∼95%, the associated HEEDA return reaches ∼52%. Effective integration of thermal reclaiming with the desorber results in a small additional electricity output penalty, i.e., ranging from 0.3 to 1.13% relative to the output with capture but with no reclaiming. However, it should be noted that a solvent management technique is essential to an amine-based PCC as accumulation of degradation products will affect capture efficiency and associated energy costs and eventually will be a showstopper. Overall, the study suggests that industrial applications fitted with PCC can achieve deep decarbonization in a cost-efficient manner with effective solvent degradation remedial strategies and contrary to the consensus that high capture fractions are associated with excessive energy penalties. Hence, the results can provide meaningful information for engineering deployment and policy decision making