Sporopollenin exines as a novel drug delivery system

Microcapsules are fast becoming the most successful delivery systems for the oral delivery of drugs and food additives. Since many drugs are proteins and are destroyed in acidic conditions, microcapsules offer protection against the harsh environment of the gastrointestinal (GI) tract. Although the use of microcapsules achieves controlled release of the inner material, many synthetically designed microcapsules lack consistency in their size and morphology.The outer coat (exine) of plant pollen grains and spores is composed of the material sporopollenin. Sporopollenin exines (25µm diameter) were extracted from Lycopodium clavatum and were investigated as a novel drug delivery system that was inexpensive, non-toxic, from a renewable source, and exhibited a large internal cavity for loading of hydrophobic and hydrophilic substances. They showed many advantages over conventional microcapsules, including their constant chemical structure and size within a species, and their ability to offer UV and air-oxidation protection.Previous studies have shown that particles such as pollen, spores and starch migrate into the bloodstream following ingestion by a process termed 'Persorption'. Such findings intrigued many researchers but the phenomenon has not been unanimously accepted. This research is a body of evidence giving unequivocal confirmation that spores of Lycopodium clavatum and their emptied exines were absorbed into the bloodstream of man to the same extent following oral ingestion, with a maximum of 10% (± 2%) of the dose recovered just 15-30 minutes after ingestion. These findings resolve the debate between researchers in support of persorption and those against, whom doubted the transport of particles of micron size into the bloodstream, but did not disprove such a phenomenon. An extensive study was undertaken to investigate the effect of factors such as gender, age, quantity and the method of ingestion on the rate and extent of exine absorption into the bloodstream. In a preliminary in vivo experiment the successful delivery of fish oil into the bloodstream via sporopollenin exines was illustrated.A major breakthrough has formed the foundations of this research. Although sporopollenin exhibits incredible stability to organIc and inorganic solvents, in contrast, this research has shown that exines degrade very rapidly in blood plasma both in vitro and in vivo. In vitro experiments were conducted in an attempt to characterise the specific mechanism responsible for exine degradation. Progression of work has provided much evidence that the conversion of plasminogen to the enzyme plasmin is either partially or wholly responsible for the characteristic degradation of sporopollenin in the blood.Further investigations showed that it was possible to load a sufficient quantity of substances into sporopollenin exines, such as human growth hormone (hGH) , Enfurvitide (an antiretroviral agent used in the treatment of AIDS) and Cyclosporine (an antifungal agent). Their successful release from exines into different media in vitro and in vivo (carried out in Beagle dogs) was shown.These in vivo experiments highlighted the need for extra protection of the drug from the GI tract and additional coatings were applied to sporopollenin exines, including a soluble form of sporopollenin. Exines with coatings were assessed to ensure they were still able to degrade in blood and release the encapsulated substance.Current results are highly indicative that sporopollenin could become a practicable oral delivery system for molecules that are otherwise problematic to administer, such as protein drugs that degrade rapidly in acidic conditions

On the specifics of modelling of rotary forging processes

Rotary forging process, in spite of its various advantages, has still not reached industrial production scale owing to its complex nature. With the advent of sophisticated finite-element modelling capabilities, it is now possible to make rotary forging more predictable and optimise it for industrial production standards. However, modelling by nature involves a series of assumptions and simplifications that can help us make reasonable predictions. It is important to know the important factors that affect the results, and what compromises can be made, with a genuine understanding of what the compromises will result in. This paper reports some initial findings from our attempt towards robust modelling for the design of the rotary forging process. Herein, we have taken the simple case of rotary upsetting of cylinders using a custom-designed rotary forging machine and modelled it using commercial metal-forming software QForm

Effects of visual obstruction, prey resources, and satiety on bird use of simulated airport grasslands

Grasslands represent 39%–50% of U.S. airport properties, and a recent management framework recommended exploiting both antipredator behaviours and food resources in airport grasslands to curb use by birds considered hazardous to aviation safety. We evaluated framework predictions empirically by exposing unsated and sated brown-headed cowbirds (Molothrus ater) to visually obstructive (∼13-cm vegetation height; tall), higher-risk plots versus unobstructive (height; short) plots, and relative to prey resources. We predicted that 1) unsated birds (unfed since the previous day) would be present in greater numbers and forage more in short than tall vegetation plots 24 h post-mowing because of invertebrate flush resulting from mowing; 2) unsated birds would show increasing numbers and foraging in tall plots \u3e24 h post-mowing because of decreasing food abundance and availability in short plots; and 3) sated birds would be present in greater numbers and forage more in short vegetation overall, because vigilance needs would exceed that of food needs. We evaluated effects of visual obstruction (a metric correlated with both vegetation height and insect density) on behaviours within plots via generalized linear mixed models. Unsated cowbirds showed nearly equal numbers in tall and short plots (X [SE] individuals using tall plots: 9.5 [5.1]; short plots: 9.8 [5.1], P = 1.00, Wilcoxon Signed Ranks Test), and foraged nearly equally in both plots 24 h post-mowing (tall plots: 6.9 [4.7] individuals; short plots: 6.6 [4.1] individuals, P = 0.94). Prey availability was likely enhanced within short plots within 24 h of mowing, but possibly in adjacent tall plots as well. Over the course of the experiments (8–9 days) unsated cowbirds showed no difference in numbers between plots (tall plots: 8.2 [4.9] individuals; short plots: 11.4 [4.9] individuals, P = 0.13), but foraged more in short plots (tall plots: 4.4 [3.8] individuals; short plots: 7.8 [4.2] individuals, P = 0.01); visual obstruction was significantly and negatively correlated with foraging in tall plots. Sated cowbirds selected for short plots (use of tall plots: 5.9 [4.2] individuals; short plots: 11.7 [4.6] individuals, P \u3c 0.01; foraging in tall plots: 4.1 [3.3] individuals; short plots: 8.2 [4.6] individuals, P \u3c 0.01). Our findings support recommendations for use of visually obstructive vegetation in combination with proactive control of food resources to reduce use of airport grasslands by birds that select against visually obstructive cover

Promoting mental health and wellbeing in doctoral researchers through co-designed inductions: Initial insights into implementation

In recent years, there is increasing concern in the higher education sector for doctoral researchers’ mental health and wellbeing. In response to calls for the development of prevention strategies to address this issue, this talk will present actionable strategies that could be implemented into induction programmes to support doctoral researcher mental health and wellbeing, and thus promote positive research cultures. Initially, we will outline the method and present findings from a co-design study that generated evidence to inform the design of inductions to support mental health and wellbeing in doctoral researchers (Jackman et al., 2021). Recognising the value of working in partnership with end-users and stakeholders in the design of health-promoting interventions, our findings were generated through a 9-month collaboration with 47 doctoral researchers from 24 institutions and 13 stakeholders from one university, with data collected via focus groups and follow-up surveys. After conducting thematic analysis and making further refinements based on feedback from participants, the recommended strategies were organised into five themes: peer connections; supervisor relationships; information and resources; student services advice and support; and training and development. After presenting the study findings, we will explain how actionable strategies within the five principles recommended in our research have been implemented and present initial insights into the impact of these strategies for doctoral researchers. Furthermore, given the emphasis placed on positioning equality, diversity, and inclusion at the heart of inductions for doctoral researchers in our research, we will discuss strategies employed to support often isolated communities within the doctoral researcher population, including the provision of accessible online training and blended approaches to career development opportunities to support peer connections. Our talk will conclude by providing considerations for the design of inductions and strategies to support the mental health and wellbeing of doctoral researchers from the outset of their studies

Assessment of the cortisol awakening response: Real-time analysis and curvilinear effects of sample timing inaccuracy

The cortisol awakening response (CAR) is typically measured in the domestic setting. Moderate sample timing inaccuracy has been shown to result in erroneous CAR estimates and such inaccuracy has been shown partially to explain inconsistency in the CAR literature. The need for more reliable measurement of the CAR has recently been highlighted in expert consensus guidelines where it was pointed out that less than 6% of published studies provided electronic-monitoring of saliva sampling time in the post-awakening period. Analyses of a merged data-set of published studies from our laboratory are presented. To qualify for selection, both time of awakening and collection of the first sample must have been verified by electronic-monitoring and sampling commenced within 15 min of awakening. Participants (n = 128) were young (median age of 20 years) and healthy. Cortisol values were determined in the 45 min post-awakening period on 215 sampling days. On 127 days, delay between verified awakening and collection of the first sample was less than 3 min (‘no delay’ group); on 45 days there was a delay of 4–6 min (‘short delay’ group); on 43 days the delay was 7–15 min (‘moderate delay’ group). Cortisol values for verified sampling times accurately mapped on to the typical post-awakening cortisol growth curve, regardless of whether sampling deviated from desired protocol timings. This provides support for incorporating rather than excluding delayed data (up to 15 min) in CAR analyses. For this population the fitted cortisol growth curve equation predicted a mean cortisol awakening level of 6 nmols/l (±1 for 95% CI) and a mean CAR rise of 6 nmols/l (±2 for 95% CI). We also modelled the relationship between real delay and CAR magnitude, when the CAR is calculated erroneously by incorrectly assuming adherence to protocol time. Findings supported a curvilinear hypothesis in relation to effects of sample delay on the CAR. Short delays of 4–6 min between awakening and commencement of saliva sampling resulted an overestimated CAR. Moderate delays of 7–15 min were associated with an underestimated CAR. Findings emphasize the need to employ electronic-monitoring of sampling accuracy when measuring the CAR in the domestic setting

Relationship Between Excessive Gestational Weight Gain and Neonatal Adiposity in Women With Mild Gestational Diabetes Mellitus:

To evaluate the relationships between excessive gestational weight gain, neonatal adiposity, and adverse obstetric outcomes in women with mild gestational diabetes mellitus (GDM)

Marxist keywords for performance

Theatre and performance studies is awash with scholarship that examines performance in relation to its labor processes, modes of management, financial infrastructures, and so forth. But there lacks shared critical understanding of what terms such as value or capital mean and how they can be applied when studying performance. The range of meanings given to such words as commodity, class, or the state reveals more than a slight degree of imprecision or disagreement. It indicates a lack of systematic thought and, consequently, a need to interrogate the categories used for discussing performance's political economy. Collectively written by nine people, this keywords project contributes to growing critical attention within performance studies towards political economy by defining key Marxist concepts and exploring how they can be applied to study performance

Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials

Background Whether statin therapy is as effective in women as in men is debated, especially for primary prevention. We undertook a meta-analysis of statin trials in the Cholesterol Treatment Trialists' (CTT) Collaboration database to compare the effects of statin therapy between women and men. Methods We performed meta-analyses on data from 22 trials of statin therapy versus control (n=134 537) and five trials of more-intensive versus less-intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1·0 mmol/L reduction in LDL cholesterol and effects in men and women compared with a Cox model that adjusted for non-sex differences. For subgroup analyses, we used 99% CIs to make allowance for the multiplicity of comparisons. Findings 46 675 (27%) of 174 149 randomly assigned participants were women. Allocation to a statin had similar absolute effects on 1 year lipid concentrations in both men and women (LDL cholesterol reduced by about 1·1 mmol/L in statin vs control trials and roughly 0·5 mmol/L for more-intensive vs less-intensive therapy). Women were generally at lower cardiovascular risk than were men in these trials. The proportional reductions per 1·0 mmol/L reduction in LDL cholesterol in major vascular events were similar overall for women (rate ratio [RR] 0·84, 99% CI 0·78–0·91) and men (RR 0·78, 99% CI 0·75–0·81, adjusted p value for heterogeneity by sex=0·33) and also for those women and men at less than 10% predicted 5 year absolute cardiovascular risk (adjusted heterogeneity p=0·11). Likewise, the proportional reductions in major coronary events, coronary revascularisation, and stroke did not differ significantly by sex. No adverse effect on rates of cancer incidence or non-cardiovascular mortality was noted for either sex. These net benefits translated into all-cause mortality reductions with statin therapy for both women (RR 0·91, 99% CI 0·84–0·99) and men (RR 0·90, 99% CI 0·86–0·95; adjusted heterogeneity p=0·43). Interpretation In men and women at an equivalent risk of cardiovascular disease, statin therapy is of similar effectiveness for the prevention of major vascular events.UK Medical Research Council, British Heart Foundation, Australian National Health and Medical Research Council, European Community Biomed Program

HER2 - A good addiction

Recent neoadjuvant studies have examined the effects of adding single or dual agents targeting HER2 to chemotherapy, finding unanimously that dual HER2 targeting markedly improves pathologic response. These findings have significant implications for future trial designs, particularly if the impact on pathologic response is accompanied by improved disease-free survival or overall survival