An experimental evaluation of the solute transport volume in biodegraded municipal solid waste

International audienceA large undisturbed sample (3.5 m3) of 22-year-old, biodegraded solid waste set up to estimate the volume fraction participating in the transport of solutes through the waste material. Altogether, five tracer tests were performed under ponding and sprinkling conditions, and under steady-state and transient conditions. The experimental break through curves (BTCs), which indicated a non-equilibrium transport of the solute by early peaks and long right-hand tails, were used to parameterize log-normal solute travel time probability density functions. The expected solute travel times (i.e. the median solute travel times) were assessed and the corresponding fraction of the experimental volumes active in the transport of solutes was estimated. The solute transport volume fractions defined by the median solute travel times were estimated to vary between 5 and 10% of the total experimental volume. Further, the magnitudes of the solute transport volume fractions defined by the modal (peak) solute travel times were estimated to vary between 1 and 2% of the total experimental volume. In addition, possible boundary effects in terms of rapid flow along the wall of the experimental column were investigated

Enhancing the immunogenicity of tumour lysate-loaded dendritic cell vaccines by conjugation to virus-like particles

BACKGROUND: Tumour cell lysates are an excellent source of many defined and undefined tumour antigens and have been used clinically in immunotherapeutic regimes but with limited success. METHODS: We conjugated Mel888 melanoma lysates to rabbit haemorrhagic disease virus virus-like particles (VLP), which can act as vehicles to deliver multiple tumour epitopes to dendritic cells (DC) to effectively activate antitumour responses. RESULTS: Virus-like particles did not stimulate the phenotypic maturation of DC although, the conjugation of lysates to VLP (VLP-lysate) did overcome lysate-induced suppression of DC activation. Lysate-conjugated VLP enhanced delivery of antigenic proteins to DC, while the co-delivery of VLP-lysates with OK432 resulted in cross-priming of naïve T cells, with expansion of a MART1(+) population of CD8(+) T cells and generation of a specific cytotoxic response against Mel888 tumour cell targets. The responses generated with VLP-lysate and OK432 were superior to those stimulated by unconjugated lysate with OK432. CONCLUSION: Collectively, these results show that the combination of VLP-lysate with OK432 delivered to DC overcomes the suppressive effects of lysates, and enables priming of naïve T cells with superior ability to specifically kill their target tumour cells

Risk-based prioritization of pharmaceuticals in the natural environment in Iraq

Numerous studies have demonstrated the occurrence of pharmaceuticals in the natural environment, raising concerns about their impact on non-target organisms or human health. One region where little is known about the exposure and effects of pharmaceuticals in the environment is Iraq. Due to the high number of pharmaceuticals used by the public health sector in Iraq (hospitals and care centres) and distributed over the counter, there is a need for a systematic approach for identifying substances that should be monitored in the environment in Iraq and assessed in terms of environmental risk. In this study, a risk-based prioritization approach was applied to 99 of the most dispensed pharmaceuticals in three Iraqi cities, Baghdad, Mosul and Basrah. Initially, information on the amounts of pharmaceuticals used in Iraq was obtained. The top used medicines were found to be paracetamol, amoxicillin and metformin with total annual consumption exceeding 1000 tonnes per year. Predicted environmental concentrations (PECs) and predicted no-effect concentrations (PNECs), derived from ecotoxicological end-points and effects related to the therapeutic mode of action, were then used to rank the pharmaceuticals in terms of risks to different environmental compartments. Active pharmaceutical ingredients used as antibiotics, antidepressants and analgesics were identified as the highest priority in surface water, sediment and the terrestrial environment. Antibiotics were also prioritized according to their susceptibility to kill or inhibit the growth of bacteria or to accelerate the evolution and dissemination of antibiotic-resistant genes in water. Future work will focus on understanding the occurrence, fate and effects of some of highly prioritized substances in the environment

Older women with non-ST-elevation acute coronary syndrome undergoing invasive or conservative management: an individual patient data meta-analysis

\ua9 The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.Aims. Women and older patients are underrepresented in randomized controlled trials (RCTs) investigating treatment strategies following acute coronary syndrome. This study aims to evaluate the benefit of invasive vs. conservative strategy of older women with non-ST-elevation acute coronary syndrome (NSTEACS). Methods and results. This analysis from an individual patient data meta-analysis included six RCTs comparing an invasive management with a conservative management in older NSTEACS patients. The primary endpoint was the composite of all-cause mortality or myocardial infarction (MI). Secondary endpoints included all-cause mortality, cardiovascular death, MI, urgent revascularization, and stroke. Follow-up time was censored at 1 year. In total, 717 women [median age 84.0 (interquartile range 81.0–87.0) years] were included. The primary endpoint occurred in 21.0% in the invasive strategy vs. 27.8% in the conservative strategy [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.52–1.13, P = 0.160 using random effect] at 1-year follow-up. The invasive management was associated with reduced risk of MI (HR 0.49, 95% CI 0.32–0.73, P < 0.001) and urgent revascularization (HR 0.44, 95% CI 0.20–0.98, P = 0.045). No significant differences were identified in the risk of all-cause mortality, cardiovascular death, and stroke. Among males, there was no significant association between the treatment strategy and primary or secondary endpoints. Conclusion. An invasive strategy compared with a conservative strategy did not reduce the composite outcome of all-cause mortality or MI in older NSTEACS women at 1-year follow-up. An invasive strategy reduced the individual risk of MI and urgent revascularization. Our results support the beneficial role of the invasive strategy in older NSTEACS women

An affordance perspective of team collaboration and enforced working from home during COVID-19

COVID-19 has caused unprecedented challenges to our lives. Many governments have forced people to stay at home, leading to a radical shift from on-site to virtual collaboration for many knowledge workers. Existing remote working literature does not provide a thorough explanation of government-enforced working from home situations. Using an affordance lens, this study explores the sudden and enforced issues that COVID-19 has presented, and the technological means knowledge workers use to achieve their team collaboration goals. We interviewed 29 knowledge workers about their experiences of being required to work from home and introduced the term “enforced work from home”. This paper contributes to the affordance theory by providing an understanding of the substitution of affordances for team collaboration during COVID-19. The shifting of affordances results in positive and negative effects on team collaboration as various affordances of technology were perceived and actualised to sustain “business as usual”

River research and applications across borders

Rivers flow across national borders, unfettered by political distinctions, and the ecological health of rivers is closely linked to their degree of connectivity. River research today is more global than it has ever been, but we show that river research, engineering, and management still operate within homegrown local paradigms. As a basis for this discussion, we studied the citation networks surrounding the most widely cited papers in our field, assessing the degree to which researchers have collaborated across geographical boundaries and fully drawn from the international literature. Despite gains over time, our field remains surprisingly and pervasively provincial. The likely explanation for provincial bias is that researchers are generally more familiar and comfortable with their own research methods, sites, and agendas. However, local focus has tangible consequences. For example, contrasting paradigms and differing approaches to river restoration and to flood-risk management show that opportunities are lost when we fail to learn from the successes and failures of other regions. As Sharp and Leshner (2014; p. 579) have argued, "the search for solutions needs to draw upon the talents and innovative ideas of scientists, engineers, and societal leaders worldwide to overcome traditional and nationalistic paradigms that have so far been inadequate to meeting these challenges.

The Lid Domain of Caenorhabditis elegans Hsc70 Influences ATP Turnover, Cofactor Binding and Protein Folding Activity

Hsc70 is a conserved ATP-dependent molecular chaperone, which utilizes the energy of ATP hydrolysis to alter the folding state of its client proteins. In contrast to the Hsc70 systems of bacteria, yeast and humans, the Hsc70 system of C. elegans (CeHsc70) has not been studied to date

Lithium side effects and toxicity: prevalence and management strategies

Despite its virtually universal acceptance as the gold standard in treating bipolar disorder, prescription rates for lithium have been decreasing recently. Although this observation is multifactorial, one obvious potential contributor is the side effect and toxicity burden associated with lithium. Additionally, side effect concerns assuredly play some role in lithium nonadherence. This paper summarizes the knowledge base on side effects and toxicity and suggests optimal management of these problems. Thirst and excessive urination, nausea and diarrhea and tremor are rather common side effects that are typically no more than annoying even though they are rather prevalent. A simple set of management strategies that involve the timing of the lithium dose, minimizing lithium levels within the therapeutic range and, in some situations, the prescription of side effect antidotes will minimize the side effect burden for patients. In contrast, weight gain and cognitive impairment from lithium tend to be more distressing to patients, more difficult to manage and more likely to be associated with lithium nonadherence. Lithium has adverse effects on the kidneys, thyroid gland and parathyroid glands, necessitating monitoring of these organ functions through periodic blood tests. In most cases, lithium-associated renal effects are relatively mild. A small but measurable percentage of lithium-treated patients will show progressive renal impairment. Infrequently, lithium will need to be discontinued because of the progressive renal insufficiency. Lithium-induced hypothyroidism is relatively common but easily diagnosed and treated. Hyperparathyroidism from lithium is a relatively more recently recognized phenomenon

A case of mistaken identity: HSPs are no DAMPs but DAMPERs

Until recently, the immune system was seen solely as a defense system with its primary task being the elimination of unwanted microbial invaders. Currently, however, the functional significance of the immune system has obtained a much wider perspective, to include among others the maintenance and restoration of homeostasis following tissue damage. In this latter aspect, there is a growing interest in the identification of molecules involved, such as the so-called danger or damage-associated molecular patterns (DAMPs), also called alarmins. Since heat shock proteins are archetypical molecules produced under stressful conditions, such as tissue damage or inflammation, they are frequently mentioned as prime examples of DAMPs (Bianchi, J Leukoc Biol 81:1–5, 2007; Kono and Rock, Nat Rev Immunol 8:279–289, 2008; Martin-Murphy et al., Toxicol Lett 192:387–394, 2010). See for instance also a recent review (Chen and Nunez, Science 298:1395–1401, 2010). Contrary to this description, we recently presented some of the arguments against a role of heat shock protein as DAMPs (Broere et al., Nat Rev Immunol 11:565-c1, 2011). With this perspective and reflection article, we hope to elaborate on this debate and provide additional thoughts to further ignite this discussion on this critical and evolving issue