Ex-vivo perfusion bioassay : an excellent technique to measure the bioactivity of inhalable insulin coated microcrystals

Purpose: To measure the bioactivity of inhalable insulin coated microcrystals using a perfusion bioassay that measures its vasodilatory effect on smooth muscle arterial tissue. Methods: The bioactivity of an insulin protein coated microcrystal (PCMC), a potential candidate for pulmonary drug delivery and commercial insulin was determined on a Danish Myo Tech P110 pressure myograph system. 12 week old Mesenteric resistance arteries from Male Wistar rats were isolated and immersed in a physiological salt solution (PSS) and attached to 2 opposing hollow glass micro-cannula (outer diameter 80 microns). The PSS was gradually warmed to 37°C (at a pressure less than 5mm Hg) for 1hr. Subsequently the pressure was increased up to 40mm Hg over a period 15 minutes and equilibrated for a further 15 minutes after gassing with 95%O2 / 5%CO2 to achieve a pH of 7.4 at 37°C. After normalisation by two washes of 123mM KCl and exposure to 1-10mM noradrenaline the arteries were exposed intraluminally to each insulin preparation by gradual infusion directly into the lumen via a fetal microcannulae inserted to the tip of the glass mounting cannula, at a constant pressure. Results: The preliminary results (full cummulative response curve yet to be determined) demonstrate insulin mediated relaxation to noradrenaline preconstriction. The level of constriction drops from 100% to 42% as the concentration of insulin increases from -11 to -9 Log M for the PCMC compared with a drop from 100 % to 65% for the commercial insulin preparation. However the more potent vasodilatory effect found for the insulin PCMC is more likely to be a result of variance introduced in each dilution step than a real increase in potency. Conclusion: The perfusion bioassay technique provides an excellent method of measuring insulin bioactivity and indicates the insulin loaded on the microcrystal support is fully active

Clinicians’ Perceptions of The Health Status of Formerly Detained Immigrants

Background In the past decade, the U.S. immigration detention system regularly detained more than 30,000 people; in 2019 prior to the pandemic, the detention population exceeded 52,000 people. Inhumane detention conditions have been documented by internal government watchdogs, news media and human rights groups, finding over-crowding, poor hygiene and sanitation and poor and delayed medical care, as well as verbal, physical and sexual abuse. Methods This study surveyed health professionals across the United States who had provided care for immigrants who were recently released from immigration detention to assess clinician perceptions about the adverse health impact of immigration detention on migrant populations based on real-life clinical encounters. There were 150 survey responses, of which 85 clinicians observed medical conditions attributed to detention. Results These 85 clinicians reported seeing a combined 1300 patients with a medical issue related to their time in detention, including patients with delayed access to medical care or medicine in detention, patients with new or acute health conditions including infection and injury attributed to detention and patients with worsened chronic conditions or special needs conditions. Clinicians also provided details regarding sentinel cases, categorized into the following themes: Pregnant women, Children, Mentally Ill, COVID-19, and Other serious health issue. Conclusions This is the first survey, to our knowledge, of health care professionals treating individuals upon release from detention. Due to the lack of transparency by federal entities and limited access to detainees, this survey serves as a source of credible information about conditions experienced within immigration detention facilities and is a means of corroborating immigrant testimonials and media reports. These findings can help inform policy discussions regarding systematic changes to the delivery of healthcare in detention, quality assurance and transparent reporting

Identifying Trends in Masterplanning: A Typological Classification System

This document is the Accepted Manuscript version of the following article: Robert Adam, and Claire Jamieson, ‘Identifying trends in masterplanning: A typological classification system’, URBAN DESIGN International, Vol. 19 (4): 274-290, December 2014. The final publication is available at Springer via https://doi.org/10.1057/udi.2013.24.This article reports research carried out to develop a new typological method for the analysis of masterplans. This quantitative method of analysis can be used to produce comparative data that will help in the comparison of urban design typologies and their development over time. This article sets out the research to date, describing how the initial aims have developed from simple analysis to the creation of an analytical tool with wide applications. Comprising a detailed taxonomy of urban design features gathered from a wide database of recent and emerging masterplans, the system provides opportunities for further study such as trends, qualitative comparison against quantitative measurement, and comparison of aims and outcomes. This article will describe the methodology and process of research, while elaborating on the potential of the tool.Peer reviewedFinal Accepted Versio

Demystifying academics to enhance university-business collaborations in environmental science

In countries globally there is intense political interest in fostering effective university-business collaborations, but there has been scant attention devoted to exactly how an individual scientist's workload (i.e. specified tasks) and incentive structures (i.e. assessment criteria) may act as a key barrier to this. To investigate this an original, empirical dataset is derived from UK job specifications and promotion criteria, which distil universities' varied drivers into requirements upon academics. This work reveals the nature of the severe challenge posed by a heavily time-constrained culture; specifically, tension exists between opportunities presented by working with business and non-optional duties (e.g. administration and teaching). Thus, to justify the time to work with business, such work must inspire curiosity and facilitate future novel science in order to mitigate its conflict with the overriding imperative for academics to publish. It must also provide evidence of real-world changes (i.e. impact), and ideally other reportable outcomes (e.g. official status as a business' advisor), to feed back into the scientist's performance appraisals. Indicatively, amid 20-50 key duties, typical full-time scientists may be able to free up to 0.5 day per week for work with business. Thus specific, pragmatic actions, including short-term and time-efficient steps, are proposed in a "user guide"to help initiate and nurture a long-term collaboration between an early- to mid-career environmental scientist and a practitioner in the insurance sector. These actions are mapped back to a tailored typology of impact and a newly created representative set of appraisal criteria to explain how they may be effective, mutually beneficial and overcome barriers. Throughout, the focus is on environmental science, with illustrative detail provided through the example of natural hazard risk modelling in the insurance sector. However, a new conceptual model of academics' behaviour is developed, fusing perspectives from literature on academics' motivations and performance assessment, which we propose is internationally applicable and transferable between sectors. Sector-specific details (e.g. list of relevant impacts and user guide) may serve as templates for how people may act differently to work more effectively together

The anti-epileptic drug Valproic Acid (VPA) inhibits steroidogenesis in bovine theca and granulosa cells in vitro

Valproic acid (VPA) is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS)-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC) and granulosa (GC) cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml) on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P99% decrease; P<0.0001) with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05). VPA only reduced TC progesterone secretion induced by the highest (luteinizing) LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml) VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001) by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001). The potent histone deacetylase (HDAC) inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC

Feasibility study of portable technology for weight loss and HbA1c control in type 2 diabetes

Background The study investigated the feasibility of conducting a future Randomised Controlled Trial (RCT) of a mobile health (mHealth) intervention for weight loss and HbA1c reduction in Type 2 Diabetes Mellitus (T2DM). Methods The intervention was a small wearable mHealth device used over 12 weeks by overweight people with T2DM with the intent to lose weight and reduce their HbA1c level. A 4 week maintenance period using the device followed. The device records physical activity level and information about food consumption, and provides motivational feedback based on energy balance. Twenty-seven participants were randomised to receive no intervention; intervention alone; or intervention plus weekly motivational support. All participants received advice on diet and exercise at the start of the study. Weight and HbA1c levels were recorded at baseline and weeks 6, 12, and 16. Qualitative interviews were conducted with participants who received the intervention to explore their experiences of using the device and involvement in the study including the training received. Results Overall the device was perceived to be well-liked, acceptable, motivational and easy to use by participants. Some logistical changes were required during the feasibility study, including shortening of the study duration and relaxation of participant inclusion criteria. Descriptive statistics of weight and HbA1c data showed promising trends of weight loss and HbA1c reduction in both intervention groups, although this should be interpreted with caution. Conclusions A number of methodological recommendations for a future RCT emerged from the current feasibility study. The mHealth device was acceptable and promising for helping individuals with T2DM to reduce their HbA1c and lose weight. Devices with similar features should be tested further in larger studies which follow these methodological recommendations

Consensus on exercise reporting template (Cert): Modified delphi study

© 2016 American Physical Therapy Association. Background. Exercise interventions are often incompletely described in reports of clinical trials, hampering evaluation of results and replication and implementation into practice. Objective. The aim of this study was to develop a standardized method for reporting exercise programs in clinical trials: the Consensus on Exercise Reporting Template (CERT). Design and Methods. Using the EQUATOR Network’s methodological framework, 137 exercise experts were invited to participate in a Delphi consensus study. A list of 41 items was identified from a meta-epidemiologic study of 73 systematic reviews of exercise. For each item, participants indicated agreement on an 11-point rating scale. Consensus for item inclusion was defined a priori as greater than 70% agreement of respondents rating an item 7 or above. Three sequential rounds of anonymous online questionnaires and a Delphi workshop were used. Results. There were 57 (response rate=42%), 54 (response rate=95%), and 49 (response rate=91%) respondents to rounds 1 through 3, respectively, from 11 countries and a range of disciplines. In round 1, 2 items were excluded; 24 items reached consensus for inclusion (8 items accepted in original format), and 16 items were revised in response to participant suggestions. Of 14 items in round 2, 3 were excluded, 11 reached consensus for inclusion (4 items accepted in original format), and 7 were reworded. Sixteen items were included in round 3, and all items reached greater than 70% consensus for inclusion. Limitations. The views of included Delphi panelists may differ from those of experts who declined participation and may not fully represent the views of all exercise experts. Conclusions. The CERT, a 16-item checklist developed by an international panel of exercise experts, is designed to improve the reporting of exercise programs in all evaluative study designs and contains 7 categories: materials, provider, delivery, location, dosage, tailoring, and compliance. The CERT will encourage transparency, improve trial interpretation and replication, and facilitate implementation of effective exercise interventions into practice

A Systematically Improved High Quality Genome and Transcriptome of the Human Blood Fluke Schistosoma mansoni

Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research

From Sacred to Scientific: Epic Religion, Spectacular Science, and Charlton Heston’s Science Fiction Cinema

This paper analyses how long-1960s cinema responded to and framed public discourses surrounding religion and science. This approach allows for a discussion that extends beyond a critical study of the scholarly debates that surround the place of religion in science during a transitional period. Charlton Heston was an epic actor who went from literally playing God in The Ten Commandments (1956) to playing “god” as a messianic scientist in The Omega Man (1971). Best known for playing Moses, Heston became an unlikely science-based cinema star during the early 1970s. He was re-imagined as a scientist, but the religiosity of his established persona was inescapable. Heston and the science-based films he starred in capitalized upon the utopian promises of real science, and also the fears of the vocal activist counterculture. Planet of the Apes (1968), Omega Man (1971), Soylent Green (1973), and other science-based films made between 1968-1977 were bleak countercultural warnings about excessive consumerism, uncontrolled science, nuclear armament, irreversible environmental damage, and eventual human extinction. In this paper I argue that Heston’s transition from biblical epic star to science-fiction anti-hero represents the way in which the role and interpretation of science changed in post-classical cinema. Despite the shift from religious epic to science-based spectacle, religion remained a faithful component of Hollywood output indicating the ongoing connection between science and religion in US culture. I will consider the transition from sacred to science-based narratives and how religion was utilised across the production process of films that commented upon scientific advances

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements