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Although much has been written on Descartes’ thought on animals, not so much has originated in, or has taken full account of, Descartes’ views on (human) emotions. I explore here the extent to which the latter can contribute to the debate on whether he embraced, and to which extent, the doctrine of the bete machine. I first try to show that Descartes’ views on emotions can help offer new support to the skeptical position without necessarily creating new tensions with other central aspects of his philosophy. And second, I sketch the type of theory of animal passions which Descartes could have accepted. The general conclusion I draw is not that Descartes did not hold the view of the bete machine but rather that we can find within his thought a solid stream of ideas, which became stronger towards the end of his life, that points in the opposite direction.

Objective To compare alfaxalone as continuous intravenous (IV) infusion with intermittent IV injections for maintenance of anaesthesia in ponies undergoing castration. Study design Prospective, randomized, ‘blinded’ clinical study. Animals A group of 33 entire male Welsh ponies undergoing field castration. Methods After preanaesthetic medication with IV detomidine (10 μg kg−1) and butorphanol (0.05 mg kg−1), anaesthesia was induced with IV diazepam (0.05 mg kg−1) followed by alfaxalone (1 mg kg−1). After random allocation, anaesthesia was maintained with either IV alfaxalone 2 mg kg−1 hour−1 (group A; n = 16) or saline administered at equal volume (group S; n = 17). When necessary, additional alfaxalone (0.2 mg kg−1) was administered IV. Ponies were breathing room air. Using simple descriptive scales, surgical conditions and anaesthesia recovery were scored. Total amount of alfaxalone, ponies requiring additional alfaxalone and time to administration, time from induction to end of infusion and end of infusion to standing were noted. Indirect arterial blood pressure, pulse and respiratory rates, end-expiratory carbon dioxide partial pressure and arterial haemoglobin oxygen saturation were recorded every 5 minutes. Data were analysed using Student t, Mann–Whitney U and chi-square tests, where appropriate (p Results Total amount of alfaxalone administered after induction of anaesthesia (0.75 ± 0.27 versus 0.17 ± 0.23 mg kg−1; p Conclusion and clinical relevance Continuous IV infusion and intermittent administration of alfaxalone provided similar anaesthesia quality and surgical conditions in ponies undergoing field castration. Less alfaxalone is required when used intermittently.

The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbit[7]uril (CB[7])-PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB[7] and an N-terminal aromatic residue on one specific protein drug, insulin, further results in altering of its pharmacological properties in vivo by extending activity in a manner dependent on molecular weight of the attached PEG chain. Supramolecular modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other molecules or polymers, for applications in formulation or therapy.

Background An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease following bacille Calmette–Guérin (BCG) vaccination. Methods In this study, 5,726 infants vaccinated with BCG at birth were enrolled. Host responses in blood collected at 10 weeks of age were compared between infants who developed pulmonary TB disease during 2 years of follow-up (cases) and those who remained healthy (controls). Results Comprehensive gene expression and cellular and soluble marker analysis failed to identify a correlate of risk. We showed that distinct host responses after BCG vaccination may be the reason: two major clusters of gene expression, with different myeloid and lymphoid activation and inflammatory patterns, were evident when all infants were examined together. Cases from each cluster demonstrated distinct patterns of gene expression, which were confirmed by cellular assays. Conclusions Distinct patterns of host responses to Mycobacterium bovis BCG suggest that novel TB vaccines may also elicit distinct patterns of host responses. This diversity should be considered in future TB vaccine development. Electronic supplementary material The online version of this article (doi:10.1186/s12916-016-0617-3) contains supplementary material, which is available to authorized users.

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

We use the asymptotic expansion of the heat trace to express all residues of spectral zeta functions as regularized sums over the spectrum. The method extends to those spectral zeta functions that are localized by a bounded operator., Comment: 12 pages, highly simplified, improved convergence

When aiming to apply mathematical results of non-commutative geometry to physical problems the question arises how they translate to a context in which only a part of the spectrum is known. In this article we aim to detect when a finite-dimensional triple is the truncation of the Dirac spectral triple of a spin manifold. To that end, we numerically investigate the restriction that the higher Heisenberg equation [A. H. Chamseddine, A. Connes, and V. Mukhanov, Journal of High Energy Physics, 98 (2014)] places on a truncated Dirac operator. We find a bounded perturbation of the Dirac operator on the Riemann sphere that induces the same Chern class., Comment: This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Journal of Mathematical Physics 61, 033507 (2020) and may be found at https://doi.org/10.1063/1.5131864

Noble metal catalysts possess outstanding catalytic behaviors in organic reactions, photocatalysis, electrocatalysis and many other applications. Peptide fibrils are used for the controllable nanostructuring of metal nanoparticles with specific sizes, shapes and high-surface area structures. The degradation of these fibrils with O2-plasma yields interconnected networks of nanoparticles, similar to metallic nanowires. Herein, platinum nanoparticles (Pt-NPs) were synthesized by reduction using VUV excimer radiation. The particle size was characterized by dynamic light scattering (DLS). Due to agglomeration, the metal nanoparticles were stabilized using poly(vinyl pyrrolidone) (PVP) and the same synthesis procedure. The influence of the polymer PVP molecular weight (Mwt), PVP concentration (Cp) and VUV irradiation time on platinum nanoparticle size was investigated. Small (2���3 nm) Pt-NPs are formed in the case of PVP with Mwt = 10 000 g mol���1. With increasing PVP Mwt, decreasing PVP concentration and shorter irradiation times, larger sized nanoparticles appear. The applicability of templated platinum nanoparticles, both the PVP-stabilized and non-stabilized Pt-NPs, immobilized via electrostatic interactions on the solid phase-synthesized aniline-GGAAKLVFF (AFP) peptide fibrils was investigated to serve as possible electrode material. The plasma treatment of the nanoparticle-fibril-assemblies was also studied as a novel technique. The Pt-NPs-AFP fibrils and the PVP-stabilized-Pt-NPs-AFP fibrils nanohybrids were employed to modify electrodes and then subjected to O2-plasma treatment. These O2-plasma treated/modified electrodes exhibited high electrocatalytic activities towards oxygen reduction in cyclic voltammetry measurements. Thus, the aforementioned nanocomposites hold great potential for polymer electrolyte fuel cells and other electrochemical applications in miniature devices and microfluidic chips.

An insulin delivery system that self-regulates blood glucose levels has the potential to limit hypoglycemic events and improve glycemic control. Glucose-responsive insulin delivery systems have been developed by coupling glucose oxidase with a stimuli-responsive biomaterial. However, the challenge of achieving desirable release kinetics (i.e., insulin release within minutes after glucose elevation and duration of release on the order of weeks) still remains. Here, we develop a glucose-responsive delivery system using encapsulated glucose-responsive, acetalated-dextran nanoparticles in porous alginate microgels. The nanoparticles respond rapidly to changes in glucose concentrations while the microgels provide them with protection and stability, allowing for extended glucose-responsive insulin release. This system reduces blood sugar in a diabetic mouse model at a rate similar to naked insulin and responds to a glucose challenge 3 days after administration similarly to a healthy animal. With 2 doses of microgels containing 60 IU/kg insulin each, we are able to achieve extended glycemic control in diabetic mice for 22 days., National Cancer Institute (Grant P30-CA14051)

To determine the prevalence of pectinate ligament dysplasia in a large group of Welsh springer spaniels; to investigate associations between pectinate ligament dysplasia and age, sex and intraocular pressure and between intraocular pressure and age and sex; and to investigate progression of pectinate ligament dysplasia in individual dogs.In a prospective study, gonioscopy was performed in both eyes of 227 Welsh springer spaniels and intraocular pressure measured by rebound tonometry. Eyes were classified as "unaffected" if 0% of the iridocorneal angle was affected with pectinate ligament dysplasia (grade 0), "mildly affected" if20% was affected (grade 1), "moderately affected" if 20 to 90% was affected (grade 2) and "severely affected" if90% was affected (grade 3). In a retrospective study, progression of pectinate ligament dysplasia over time was investigated for 65 dogs.One hundred and thirty-nine of 227 dogs (61·2%) were affected by pectinate ligament dysplasia (grades 1 to 3) and 82/227 (36·2%) were moderately or severely affected. There was a significant association between pectinate ligament dysplasia and age. There were no associations between pectinate ligament dysplasia and intraocular pressure or pectinate ligament dysplasia and sex. Thirty-five of 65 dogs (53·8%) demonstrated progression of pectinate ligament dysplasia.Prevalence of pectinate ligament dysplasia was high despite widespread screening and selection against the condition. Our data indicate that gonioscopic features of pectinate ligament dysplasia can progress in the Welsh springer spaniel. Dogs deemed unaffected at an early age may subsequently be diagnosed with pectinate ligament dysplasia.

Objectives To investigate the effects of MK‐467 on sedation quality, and cardiopulmonary and pharmacokinetic variables in horses sedated intravenously (IV) with romifidine. Study design Experimental, randomized, crossover design. Animals Seven healthy mares. Methods Romifidine (80 μg kg −1 ; R) and MK‐467 (200 μg kg −1 ; MK) were administered IV alone and in combination (R + MK). Levels of sedation and borborygmi were scored. Heart rate (HR), direct arterial blood pressure (ABP) and respiratory rate ( f R ) were recorded. Arterial and venous blood gas analyses were performed and venous plasma drug concentrations were measured. Pharmacokinetic parameters were calculated. Linear mixed modelling for repeated measures, contrasts of least square means by Bonferroni correction tests, one‐way anova for repeated measures with Bonferroni multiple comparison tests and paired Student's t ‐tests were used to compare results within and between treatments as appropriate. Significance was set at p Results After R, ABP increased and HR and f R decreased significantly. After R + MK, HR, f R , systolic and mean ABP decreased. MK alone increased both HR and f R . After R, ABP was significantly higher than after R + MK. HR and f R were significantly higher after MK than after R and R + MK. Areas under the curve for sedation time were similar after R and R + MK. Intestinal activity decreased markedly after R and less after R + MK. Volume of distribution and clearance of romifidine were significantly higher and area under the concentration time curve extrapolated to infinity significantly lower after R + MK than after R. Conclusions Combined romifidine and MK‐467 prevented the cardiovascular changes commonly seen with romifidine but did not affect sedation quality. Clinical relevance Combined IV romifidine and MK‐467 can be used to attenuate the cardiovascular effects of romifidine, such as in horses with colic or undergoing general anaesthesia.

Grazing management plays an important role in grassland conservation. Given that grasshoppers are key components in the grassland food web, various studies have been conducted to investigate the effects of grazing by large herbivores on grasshoppers at population and community levels. However, grazing effects on grasshopper fitness and abundance remain poorly understood. Here, using a field experiment in a meadow steppe, we examined the effects of sheep grazing, with different intensities, on grasshopper (Euchorthippus unicolor) fitness and abundance. Results showed that female grasshopper’s survival rate, mean survival time, and egg production were positively associated with increasing grazing intensities. The positive relationships are likely due to changes in plant nitrogen content and microhabitat induced by large herbivore grazing activities for grasshoppers. Moreover, there were strong positive associations between the fitness and abundance of female grasshoppers, and between female and total grasshopper abundance, which are responsible for an increase in overall grasshopper abundance. These findings improve our understanding about the role of grasshopper fitness in explaining their abundance in response to grazing management. Our study also suggests that measuring grasshopper fitness should be considered for species conservation in management practices of moderate grazing.

Antimicrobial resistance (AMR) is a global health concern and the inappropriate use of antibiotics in animals and humans is considered a contributing factor. A cross-sectional survey to assess the knowledge, attitudes and practices of veterinarians regarding AMR and antimicrobial stewardship was conducted in Nigeria. A total of 241 respondents completed an online survey. Only 21% of respondents correctly defined the term antimicrobial stewardship and 59.8% were unaware of the guidelines provided by the Nigeria AMR National Action Plan. Over half (51%) of the respondents indicated that prophylactic antibiotic use was appropriate when farm biosecurity was poor. Only 20% of the respondents conducted antimicrobial susceptibility testing (AST) frequently, and the unavailability of veterinary laboratory services (82%) and the owner&rsquo, s inability to pay (72%) were reported as key barriers to conducting AST. The study findings suggest strategies focusing on the following areas may be useful in improving appropriate antibiotic use and antimicrobial stewardship among veterinarians in Nigeria: increased awareness of responsible antimicrobial use among practicing and newly graduated veterinarians, increased dissemination of regularly updated antibiotic use guidelines, increased understanding of the role of good biosecurity and vaccination practices in disease prevention, and increased provision of laboratory services and AST at affordable costs.

The cooking ability of three (03) parboiled varieties (IR 841, Oroukokey and Burkina ) was evaluated. The method used consisted of four (04) steps: (i) Experimental determination of rice cooking parameters, (ii) evaluation of the three cooking rice methods, (iii) physical quality assessment of the three cooked rice samples and (iv) validation of the best rice cooking method by the women processors. At the laboratory level, results obtained show that for 5 g of every rice variety tested, the variety IR 841 cooked more quickly than the two other varieties with a cooking time of 24±2 min for IR 841 and 31.25±1.25min and 29±1min respectively for the Oroukokey and Burkina varieties. As for the swelling capacity, the Oroukokey varieties and Burkina swelled more (3.31±0.15% and 3.77±0.34% respectively) than IR 841 variety (2.99±0.22%). Results of the three cooking methods tested with the restaurants, showed that the double cooking and the steam cooking was the most suitable method for cooking of IR 841 whereas the direct cooking method was most preferred for the Oroukokey and Burkina varieties. In conclusion, the double cooking methods was recommended for IR 841while direct cooking method was recommended for the Oroukokey and Burkina varieties. Keywords: IR 841, Oroukokey , Burkina , local, appropriate preparation.

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

Nature Chemistry 9, 937–943 (2017); published online 22 September 2017; corrected after print 24 November 2017. In the version of this Perspective originally published, the affiliations for authors Zhen Gu and Sanjoy Dutta were not correct, they should have read: Zhen Gu3,4,5, Sanjoy Dutta6 3Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27695, USA.

A study of what Descartes calls emotions in his Passions of the Soul (1649) suggests that, rather than just a theory of passions—as Descartes himself explicitly claims to be proposing—he was in practice putting forward a more comprehensive theory of passions-emotions, a unified theory which would be closer to what today should properly be called Descartes’ theory of emotions. I try here to make explicit the grounds of this unity by showing that emotions both (1) fit within the functional account Descartes attributes to what he calls passions; and (2) complement the intentionality of passions by expanding it to new objects. In order to show this I offer also a tentative distinction, functionally and intentionally, between passions and emotions in general, on one hand, and, on the other, between the two apparent types of emotions Descartes refers to in the treatise—interior or internal [interieure] and intellectual [intellectuelle] emotions.

Since its discovery and isolation, exogenous insulin has dramatically changed the outlook for patients with diabetes. However, even when patients strictly follow an insulin regimen, serious complications can result as patients experience both hyperglycemic and hypoglycemic states. Several chemically or genetically modified insulins have been developed that tune the pharmacokinetics of insulin activity for personalized therapy. Here, we demonstrate a strategy for the chemical modification of insulin intended to promote both long-lasting and glucose-responsive activity through the incorporation of an aliphatic domain to facilitate hydrophobic interactions, as well as a phenylboronic acid for glucose sensing. These synthetic insulin derivatives enable rapid reversal of blood glucose in a diabetic mouse model following glucose challenge, with some derivatives responding to repeated glucose challenges over a 13-h period. The best-performing insulin derivative provides glucose control that is superior to native insulin, with responsiveness to glucose challenge improved over a clinically used long-acting insulin derivative. Moreover, continuous glucose monitoring reveals responsiveness matching that of a healthy pancreas. This synthetic approach to insulin modification could afford both long-term and glucose-mediated insulin activity, thereby reducing the number of administrations and improving the fidelity of glycemic control for insulin therapy. The described work is to our knowledge the first demonstration of a glucose-binding modified insulin molecule with glucose-responsive activity verified in vivo.