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Science engagement can be a daunting prospect. This is especially true for scientists whose work involves animal models, and particularly nonhuman primates. Here, we show that openly explaining our rationale for our neuroscience work involving nonhuman primates — and the legal and ethical regulations that govern animal experimentation — increased public support and understanding, which is crucial for this essential research to continue.

Highlights • A non-human primate protective head cap that promotes wound healing after cranial implants. • Use of the head cap reduced wound dehiscence and the need to re-suture surgical wounds. • The head cap is easily adjustable to cover most primate cranial implants. • The head cap facilitates primate cranial implant wound management in neuroscience., Background Neuroscience studies with macaque monkeys may require cranial implants to stabilize the head or gain access to the brain for scientific purposes. Wound management that promotes healing after the cranial implant surgery in non-human primates can be difficult as it is not necessarily possible to cover the wound margins. New method Here, we developed an easily modifiable head cap that protects the sutured skin margins after cranial implant surgery and contributes to wound healing. The protective head cap was developed in response to monkeys picking at sutured skin margins around an implant, complicating healing. The user-friendly protective cap, made from Klarity- R™ Sheet (3.2 mm thick with 36 % or 42 % perforation) is affixed to the implant post-surgically. Once secured and while the monkey is still anesthetized, the plastic sheeting is molded around the implant. The protective head cap restricts the monkey’s finger access to its’ wound margins while allowing air to circulate to promote wound healing. Results and comparison with existing methods Across two UK primate facilities, the protective head cap promoted wound healing. In monkeys that did not wear the head cap, re-suturing was necessary in ∼30 % of cases. In contrast, none of the monkeys that wore the head cap required re-suturing. The monkeys wearing the head cap also had reduced numbers of days of prescribed antibiotics and analgesia. Conclusion This bespoken, easily adaptable, protective head cap supports postoperative wound healing, and enhances the welfare of monkeys involved in neuroscience research.

The frontal cortex and temporal lobes together regulate complex learning and memory capabilities. Here, we collected resting-state functional and diffusion-weighted MRI data before and after male rhesus macaque monkeys received extensive training to learn novel visuospatial discriminations (reward-guided learning). We found functional connectivity changes in orbitofrontal, ventromedial prefrontal, inferotemporal, entorhinal, retrosplenial, and anterior cingulate cortices, the subicular complex, and the dorsal, medial thalamus. These corticocortical and thalamocortical changes in functional connectivity were accompanied by related white matter structural alterations in the uncinate fasciculus, fornix, and ventral prefrontal tract: tracts that connect (sub)cortical networks and are implicated in learning and memory processes in monkeys and humans. After the well-trained monkeys received fornix transection, they were impaired in learning new visuospatial discriminations. In addition, the functional connectivity profile that was observed after the training was altered. These changes were accompanied by white matter changes in the ventral prefrontal tract, although the integrity of the uncinate fasciculus remained unchanged. Our experiments highlight the importance of different communication relayed among corticocortical and thalamocortical circuitry for the ability to learn new visuospatial associations (learning-to-learn) and to make reward-guided decisions.SIGNIFICANCE STATEMENTFrontal neural networks and the temporal lobes contribute to reward-guided learning in mammals. Here, we provide novel insight by showing that specific corticocortical and thalamocortical functional connectivity is altered after rhesus monkeys received extensive training to learn novel visuospatial discriminations. Contiguous white matter fiber pathways linking these gray matter structures, namely, the uncinate fasciculus, fornix, and ventral prefrontal tract, showed structural changes after completing training in the visuospatial task. Additionally, different patterns of functional and structural connectivity are reported after removal of subcortical connections within the extended hippocampal system, via fornix transection. These results highlight the importance of both corticocortical and thalamocortical interactions in reward-guided learning in the normal brain and identify brain structures important for memory capabilities after injury.

Distributed brain networks govern adaptive decision‐making, new learning and rapid updating of information. However, the functional contribution of the rhesus macaque monkey parvocellular nucleus of the mediodorsal thalamus (MDpc) in these key higher cognitive processes remains unknown. This study investigated the impact of MDpc damage in cognition. Preoperatively, animals were trained on an object‐in‐place scene discrimination task that assesses rapid learning of novel information within each session. Bilateral neurotoxic (NMDA and ibotenic acid) MDpc lesions did not impair new learning unless the monkey had also sustained damage to the magnocellular division of the MD (MDmc). Contralateral unilateral MDpc and MDmc damage also impaired new learning, while selective unilateral MDmc damage produced new learning deficits that eventually resolved with repeated testing. In contrast, during food reward (satiety) devaluation, monkeys with either bilateral MDpc damage or combined MDpc and MDmc damage showed attenuated food reward preferences compared to unoperated control monkeys; the selective unilateral MDmc damage left performance intact. Our preliminary results demonstrate selective dissociable roles for the two adjacent nuclei of the primate MD, namely, MDpc, as part of a frontal cortical network, and the MDmc, as part of a frontal‐temporal cortical network, in learning, memory and the cognitive control of behavioural choices after changes in reward value. Moreover, the functional cognitive deficits produced after differing MD damage show that the different subdivisions of the MD thalamus support distributed neural networks to rapidly and fluidly incorporate task‐relevant information, in order to optimise the animals’ ability to receive rewards.

Highlights • Refining training for monkeys in neuroscience is essential to optimise their welfare. • Refinements still produce high quality science. • Pair- or group-training monkeys helps acclimate them quicker to transport devices. • Commencing positive reinforcement training on arrival facilitates acclimation. • Negative reinforcement techniques used effectively are also sometimes necessary., Background Neuroscience research using macaques remains fundamental in our endeavours to understand how the human brain functions. Applying the refinement principle of the 3Rs is essential to optimise the monkeys’ welfare and still produces high quality science. New method Here we document refinements in our training methods for acclimation to transport devices (i.e. primate chair or transport box) while working with 46 male rhesus macaques. Our training methods always used positive reinforcement training (PRT). However, PRT was sometimes combined with negative reinforcement training (NRT), but not pole and collar techniques, to successfully transfer each monkey from its home enclosure to its transport device. Results and comparison with existing methods Training monkeys in pairs or groups, and starting their PRT training upon arrival within the unit reduced the days required to acclimate them. While the use of PRT is essential to establish a positive relationship with monkeys, NRT techniques are sometimes necessary, and are most effective when withdrawn immediately once the monkey makes the desired response, to reduce the days of acclimation. Once acclimatised to their chair, monkeys succeeded within 10 days to present their head voluntarily for neck-plating using PRT. Space reducers inside the chairs also facilitated head presentations for some monkeys. Conclusions Acclimating (shaping) the monkeys to transport devices can be a stressful experience for monkeys and trainers. The adaptations to our training substantially reduced the days spent on this stage. We view this reduction in days as an effective implementation of the 3Rs (refinement) in monkey neuroscience research.

Foundational attitudes towards quantum theory have recently thrown off much of the old philosophical baggage largely associated with Niels Bohr to which Einstein famously objected, including the central ‘collapse of the wavefunction’ concept. A ‘neo-Copenhagen’ interpretation, it is suggested, has arisen. This development is placed in its historical context and contrasted to philosophical allegations of anti-realism. The neo-Copenhagen interpretation remains wedded to Heisenberg's uncertainty and observer-dependent values of particles. However a discussion of Nick Herbert's ‘rainbow analogy’ suggests that subatomic particles are emergent from a ‘nonlocal’ level of reality outside the domain of space and time. Critical realism recognizes that emergent systems have an irreducibly ontologically character, and in its combination of epistemological relativism and ontological realism, provides a basis for the proposition that realists who support Einstein's objections must now recognize that their reali...

That the Homo sapiens brain has structural and functional complexity, cognitive sophistication, and inventive toolmaking capabilities far beyond other known species is incontrovertible. What is debatable is who—or what—is, idiomatically, in the driver’s seat. While we typically assign that role to ourselves, a closer inspection of that perspective uncovers some questionable assumptions about how we define ubiquitous concepts such as self and mind—terminological conventions that intuitively appear concrete, but have no innate physical existence; rather, these and related linguistic devices are referential descriptions of our experience as self-aware beings. Here, I propose that the self-organizing brain itself (which evolved as a result of a surprisingly limited series of genetic errors and mutations in our distant ancestors) is at the helm; that it is also the source of the intentionally generated trends in human toolmaking over the millennia; and, ultimately, that neuroprosthetics are the result of the brain applying its toolmaking acumen to treat and augment itself. I therefore present a compact history of prosthetics and early treatments that foresaw neuroprosthetics; a current review of current neuroprosthetics; and future neuroprosthetics, including neurobiohybrids and bionanoprotonics.

This White Paper follows the first one produced in 2017 by the IEEE Symbiotic Autonomous Systems Initiative (SAS)1 , extending it to address updated technologies and cover additional topics due to the evolution of science and technology. Additional white papers will follow because this is an area in continuous development. The first examples of symbioses are already available in a number of areas, and even now, these are impacting our economic system and way of life. The IEEE SAS Initiative takes a 360° view based on technology and standardization—the foundation of IEEE—and invites all interested constituencies to contribute complementary point of views, including economic, regulatory, and sociocultural perspectives. The transformation fostered by technology evolution in all paths of life requires planning and education by current and future players. Another goal of the initiative is to consider the future of education, given that these symbioses transform its meaning, making it both shared and distributed. In this respect, the aims of this White Paper are to further develop the ideas presented in the first white paper: (1) to highlight impacts that are clearly identifiable today, and (2) to indicate emerging issues, thus providing a starting point to those involved in making public policy to understand the technical fundamentals, their evolution and their potential implications. Note that this White Paper is intended to be self-contained, without requiring the reader to read the previous white paper.

A sermon given by a London senior social worker on All Saints' Day 1986, during the Spode House conference ‘The Catholic Church and Aids’.

A patient with an apparent abnormality of cortisol binding globulin (CBG) is reported. Investigations showed that while the plasma CBG binding capacity (equivalent to the plasma CBG concentration) was normal, the binding affinity was reduced by a factor of four. The significance of this observation is discussed with regard to its possible role in the development of the adrenocortical hyperfunction also seen in this patient.

SUMMARY The effect of glucose or insulin administration in a group of five patients with partial lipodystrophy and three with total lipodystrophy was studied. In only one patient was the glucose tolerance curve abnormal. Mean fasting serum insulin, growth hormone, free fatty acids (FFA) and triglycerides were all significantly elevated. The serum insulin response to glucose was grossly elevated. Insulin resistance was present. The serum insulin was shown to be immunologically normal, Exogenous insulin disappeared at a normal rate from the circulation, suggesting that the elevated insulin levels in the fasting state and after glucose were due to hypersecretion. Serum growth hormone levels failed to suppress normally after glucose. Serum FFA fell after glucose or insulin administration. In one patient treated with propranolol unusual insulin responses to the administration of glucose were observed. A working hypothesis capable of explaining the metabolic changes in lipodystrophy is proposed.

SUMMARY A 46XY individual with incomplete male pseudohermaphroditism was studied. The phenotype was distinctive, with a masculine habitus despite a small phallus, gynaecomastia and diminished virilization. Plasma levels of testosterone, oestrogens, gonadotrophins and sex-hormone binding globulin were elevated. It is proposed that this syndrome is a variant of Type I incomplete male pseudohermaphroditism.

SUMMARY Basal free fatty acid (FFA) turnover was found to be elevated or at the upper limit of normal in a patient with total lipodystrophy. The decrease in plasma FFA concentration which occurred after intravenous administration of insulin was shown to be primarily due to a fall in the inflow of FFA into the circulation. These results provide support for the suggestion that adipocytes in total lipodystrophy are able to synthesize triglyceride, but that they are unable to store it because of rapid lipolysis.

SUMMARY Eight patients with treated Addison's disease were studied whilst receiving different doses of fludrocortisone together with a constant intake of glucocorticoid. Plasma renin activity (PRA), blood pressure, pulse rate and plasma potassium and urea concentrations were measured after 2-week periods on each dose. In two patients, PRA measurements indicated that mineralocorticoid replacement therapy had been inadequate. In four others, PRA remained normal throughout the study, even after fludrocortisone had been discontinued, suggesting that the drug was unnecessary for the maintenance of normal sodium balance in these patients. Asymptomatic fludrocortisone overdosage was indicated by a low plasma potassium concentration, but not by PRA measurements which failed in this study to distinguish between adequate and excessive mineralocorticoid replacement.

SUMMARY A patient with partial lipodystrophy is described in whom hypertriglyceridaemia was accompanied by marked hyperinsulinaemia. The hyperlipidaemia was due to increased plasma levels of very low density lipoprotein (VLDL). Kinetic studies, performed after injection of autologous radioiodinated VLDL, indicated that the raised VLDL levels were associated with over-production of this lipoprotein. Administration of diazoxide led to a substantial fall in serum insulin levels, accompanied by reduction in VLDL production and in serum triglyceride concentration. The possible role of insulin in inducing hyperlipidaemia by causing over-production of VLDL is discussed.

SUMMARY The production of ACTH, gastrin and glucagon by a pancreatic islet cell tumour is reported. The tumour contained at least two distinct cell types on electron microscopy. The fulminating hypercorticism was efficiently controlled with metyrapone and aminoglutethimide, but streptozotocin was not an effective anti-tumour agent.

Publisher Summary The chapter discusses one of the most important features that is the growth in the size of the testes as the seminiferous tubular system develops under the influence of pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) . The androgenic effect on somatic growth is most obvious when the sexual signs of puberty are well established, the peak height velocity being reached about two years after the first signs of sexual development. The signs of precocious sexual growth depend on the nature of the lesion. Paramount is the size of the testes. Precocious true puberty is associated with symmetrical enlargement of the testes. The premature secretion of adrenal androgen, as in congenital adrenal hyperplasia, leaves the testes in their small prepubertal state. The very rare androgen-producing tumor of the testis will be revealed by a palpable lump in one testis, the other being infantile. The rare cases of ectopic LH secretion have some increase in the testicular bulk that may be confused with the early more complete growth of true puberty. In all forms of premature androgen excess, it seems that penile growth is more marked than that seen in normal puberty. Depending on the intensity and duration of androgen secretion, the height age will be advanced beyond the chronological age, and more important, the bone age will be in advance of the height age so that premature fusion of the epiphyses occurs.

This chapter presents the studies on multi-system involvement in active chronic hepatitis and primary biliary cirrhosis. 63 patients have been studied. They were classified into four groups on the basis of clinical, biochemical, and histological criteria. Of the 24 patients with active chronic hepatitis, 41% patients had keratoconjunctivitis sicca, and 38% patients also had xerostomia. Rheumatoid arthritis was found in only 4% patients. In the primary biliary cirrhosis group, 73% patients had keratoconjunctivitis sicca, 61% patients had xerostomia, and 6% patients had rheumatoid arthritis. In the group with cryptogenic cirrhosis, there were fewer patients with keratocon. Renal tubular acidosis is an inability of the renal tubule to acidify urine out of proportion to any reduction in glomerular filtration rate. Renal tubular acidosis might be present clinically as an overt type in which the urine pH is greater than 6, despite a systemic metabolic acidosis. Ulcerative colitis, peripheral neuropathy, sensory and motor, and auto-immune thyroid disease were found in various patients as was observed in other series.