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

Development of a core descriptor set for parastomal hernia repair

Aim: Parastomal hernia repair is a poorly evidenced area, with uncertainty around the optimum management. There is considerable heterogeneity within the patient cohort, and currently there is no standardization of patient descriptors in the reporting of parastomal hernia repair. The aim of this study was to develop a core descriptor set of key patient characteristics for patients undergoing surgical repair of a parastomal hernia for reporting in all parastomal hernia research. Method: A longlist of descriptors was generated from a review of the existing literature. The longlist was discussed with patients with lived experience of parastomal hernia repair. Colorectal, general and hernia surgeons took part in a three‐round international modified Delphi process using a nine‐point Likert scale to rank the importance of descriptors. Items meeting predetermined thresholds were included in the final set and discussed and ratified at the consensus meeting. Results: Seventy seven respondents completed round one, with 23 (29.8%) completing round three. Eighty six descriptors were rated across the three rounds, with 52 descriptors shortlisted. The consensus meeting ratified a final core descriptor set with 19 descriptors across eight domains: anatomy, contamination, disease, previous treatment, risk factors, symptoms, pathway and other hernia. Conclusion: The core descriptor set reflects characteristics that are important to surgeons when reporting on parastomal hernia repair. The use of this agreed core descriptor set may aid the reporting of future studies

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

Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis

Background Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy. Methods We conducted a meta-analysis of individual participant data from randomised controlled trials of statin therapy that participated in the CTT Collaboration. All double-blind randomised controlled trials of statin therapy of at least 2 years’ scheduled duration and with at least 1000 participants were eligible for inclusion in this meta-analysis. All recorded diabetes-related adverse events, treatments, and measures of glycaemia were sought from eligible trials. Meta-analyses assessed the effects of allocation to statin therapy on new-onset diabetes (defined by diabetes-related adverse events, use of new glucose-lowering medications, glucose concentrations, or HbA1c values) and on worsening glycaemia in people with diabetes (defined by complications of glucose control, increased use of glucose-lowering medication, or HbA1c increase of ≥0·5%). Standard inverse-variance-weighted meta-analyses of the effects on these outcomes were conducted according to a prespecified protocol. Findings Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123 940 participants, 25 701 [21%] with diabetes; median follow-up of 4·3 years), and four trials compared more versus less intensive statin therapy (30 724 participants, 5340 [17%] with diabetes, median follow-up of 4·9 years). Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39 179 participants assigned to receive a statin [1·3% per year] vs 2214 of 39 266 participants assigned to receive placebo [1·2% per year]; rate ratio [RR] 1·10, 95% CI 1·04–1·16), and allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4·8% per year] vs 905 of 9859 participants assigned to receive placebo [3·5% per year]; 1·36, 1·25–1·48). For each trial, the rate of new-onset diabetes among participants allocated to receive placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than the low-intensity or moderate-intensity trials. Consequently, the main determinant of the magnitude of the absolute excesses in the two types of trial was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy. In participants without baseline diabetes, mean glucose increased by 0·04 mmol/L with both low-intensity or moderate-intensity (95% CI 0·03–0·05) and high-intensity statins (0·02–0·06), and mean HbA1c increased by 0·06% (0·00–0·12) with low-intensity or moderate-intensity statins and 0·08% (0·07–0·09) with high-intensity statins. Among those with a baseline measure of glycaemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution. The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time. Among participants with baseline diabetes, the RRs for worsening glycaemia were 1·10 (1·06–1·14) for low-intensity or moderate-intensity statin therapy and 1·24 (1·06–1·44) for high-intensity statin therapy compared with placebo. Interpretation Statins cause a moderate dose-dependent increase in new diagnoses of diabetes that is consistent with a small upwards shift in glycaemia, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes. Importantly, however, any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in these trials. These findings should further inform clinical guidelines regarding clinical management of people taking statin therapy. Funding British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council

Long-Term Maternal Metabolic and Cardiovascular Phenotypes after a Pregnancy Complicated by Mild Gestational Diabetes Mellitus or Obesity

Objective: To evaluate the association of mild gestational diabetes (GDM) and obesity with metabolic and cardiovascular markers 5-10 years after pregnancy. Study Design: This was a secondary analysis of 5-10 year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/HOMA-IR, and cardiovascular markers VEGF, VCAM-1, CD40L, GDF-15, and ST-2. Multivariable linear regression estimated the association of GDM and obesity with biomarkers. Results: Of 951 participants in the parent study, 642(68%) were included. Lower 1/HOMA-IR were observed in treated and untreated GDM groups, compared with non-GDM (mean differences −0.24, 95%CI −0.36–−0.12 and −0.15, 95%CI −0.28–−0.03, respectively). Lower VCAM-1 (angiogenesis) was observed in treated GDM group (mean difference −0.11, 95%CI −0.19–−0.03). GDM was not associated with IGI or other biomarkers. Obesity was associated with lower 1/HOMA-IR (mean difference −0.42, 95%CI −0.52–−0.32), but not other biomarkers. Conclusion: Five to ten years after delivery, prior GDM and obesity are associated with more insulin resistance but not insulin secretion or consistent cardiovascular dysfunction

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