In Infancy, It’s the Extremes of Arousal That Are ‘Sticky’: Naturalistic Data Challenge Purely Homeostatic Approaches to Studying Self-Regulation

Most theoretical models of arousal/regulatory function emphasise the maintenance of homeostasis; consistent with this, most previous research into arousal has concentrated on examining individuals’ recovery following the administration of experimentally administered stressors. Here, we take a different approach: we recorded day-long spontaneous fluctuations in autonomic arousal (indexed via electrocardiogram, heart rate variability and actigraphy) in a cohort of 82 typically developing 12-month-old infants while they were at home and awake. Based on the aforementioned models, we hypothesised that extreme high or low arousal states might be more short-lived than intermediate arousal states. Our results suggested that, contrary to this, both low- and high-arousal states were more persistent than intermediate arousal states. The same pattern was present when the data were viewed over multiple epoch sizes from 1 second to 5 minutes; over 10-15-minute time-scales, high-arousal states were more persistent than low- and intermediate states. One possible explanation for these findings is that extreme arousal states have intrinsically greater hysteresis; another is that, through ‘metastatic’ processes, small initial increases and decreases in arousal can become progressively amplified over time. Rather than exclusively studying recovery, we argue that future research into self regulation during early childhood should instead examine the mechanisms through which some states can be maintained, or even amplified, over time

Parents mimic and influence their infant’s autonomic state through dynamic affective state matching

When we see someone experiencing an emotion, and when we experience it ourselves, common neurophysiological activity occurs [1, 2]. But although inter-dyadic synchrony, concurrent and sequential [3], has been identified, its functional significance remains inadequately understood. Specifically, how do influences of partner A on partner B reciprocally influence partner A? For example, if I am experiencing an affective state and someone matches their physiological state to mine, what influence does this have on me – the person experiencing the emotion? Here, we investigated this using infant-parent dyads. We developed miniaturised microphones to record spontaneous vocalisations and wireless autonomic monitors to record heart rate, heart rate variability and movement in infants and parents concurrently in naturalistic settings. Overall, we found that infant-parent autonomic activity did not covary across the day – but that ‘high points’ of infant arousal led to autonomic changes in the parent, and that instances where the adult showed greater autonomic responsivity were associated with faster infant quieting. Parental responsivity was higher following peaks in infant negative affect than in positive affect. Overall, parents responded to increases in their child’s arousal by increasing their own. However, when the overall arousal level of the dyad was high, parents responded to elevated child arousal by decreasing their own arousal. Our findings suggest that autonomic state matching has a direct effect on the person experiencing the affective state, and that parental co-regulation may involve both connecting, and disconnecting, their own arousal state from that of the child contingent on context

Influences of environmental stressors on autonomic function in 12-month-old infants: understanding early common pathways to atypical emotion regulation and cognitive performance

Background Previous research has suggested that children exposed to more early‐life stress show worse mental health outcomes and impaired cognitive performance in later life, but the mechanisms subserving these relationships remain poorly understood. Method Using miniaturised microphones and physiological arousal monitors (electrocardiography, heart rate variability and actigraphy), we examined for the first time infants’ autonomic reactions to environmental stressors (noise) in the home environment, in a sample of 82 12‐month‐old infants from mixed demographic backgrounds. The same infants also attended a laboratory testing battery where attention‐ and emotion‐eliciting stimuli were presented. We examined how children's environmental noise exposure levels at home related to their autonomic reactivity and to their behavioural performance in the laboratory. Results Individual differences in total noise exposure were independent of other socioeconomic and parenting variables. Children exposed to higher and more rapidly fluctuating environmental noise showed more unstable autonomic arousal patterns overall in home settings. In the laboratory testing battery, this group showed more labile and short‐lived autonomic changes in response to novel attention‐eliciting stimuli, along with reduced visual sustained attention. They also showed increased arousal lability in response to an emotional stressor. Conclusions Our results offer new insights into the mechanisms by which environmental noise exposure may confer increased risk of adverse mental health and impaired cognitive performance during later life

Guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency: Guidelines from the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK

These guidelines aim to ensure that patients with adrenal insufficiency are identified and adequately supplemented with glucocorticoids during the peri-operative period. There are two major categories of adrenal insufficiency. Primary adrenal insufficiency is due to diseases of the adrenal gland (failure of the hormone-producing gland), and secondary adrenal insufficiency is due to deficient adrenocorticotropin hormone secretion by the pituitary gland, or deficient corticotropin-releasing hormone secretion by the hypothalamus (failure of the regulatory centres). Patients taking physiological replacement doses of corticosteroids for either primary or secondary adrenal insufficiency are at significant risk of adrenal crisis and must be given stress doses of hydrocortisone during the peri-operative period. Many more patients other than those with adrenal and hypothalamic-pituitary causes of adrenal failure are receiving glucocorticoids as treatment for other medical conditions. Daily doses of prednisolone of 5 mg or greater in adults and 10-15 mg.m-2 hydrocortisone equivalent or greater in children may result in hypothalamo-pituitary-adrenal axis suppression if administered for 1 month or more by oral, inhaled, intranasal, intra-articular or topical routes; this chronic administration of glucocorticoids is the most common cause of secondary adrenal suppression, sometimes referred to as tertiary adrenal insufficiency. A pragmatic approach to adrenal replacement during major stress is required; considering the evidence available, blanket recommendations would not be appropriate, and it is essential for the clinician to remember that adrenal replacement dosing following surgical stress or illness is in addition to usual steroid treatment. Patients with previously undiagnosed adrenal insufficiency sometimes present for the first time following the stress of surgery. Anaesthetists must be familiar with the symptoms and signs of acute adrenal insufficiency so that inadequate supplementation or undiagnosed adrenal insufficiency can be detected and treated promptly. Delays may prove fatal

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Versatile Coordination of Cyclopentadienyl-Arene Ligands and Its Role in Titanium-Catalyzed Ethylene Trimerization

Cationic titanium(IV) complexes with ansa-(η5-cyclopentadienyl,η6-arene) ligands were synthesized and characterized by X-ray crystallography. The strength of the metal-arene interaction in these systems was studied by variable-temperature NMR spectroscopy. Complexes with a C1 bridge between the cyclopentadienyl and arene moieties feature hemilabile coordination behavior of the ligand and consequently are active ethylene trimerization catalysts. Reaction of the titanium(IV) dimethyl cations with CO results in conversion to the analogous cationic titanium(II) dicarbonyl species. Metal-to-ligand backdonation in these formally low-valent complexes gives rise to a strongly bonded, partially reduced arene moiety. In contrast to the η6-arene coordination mode observed for titanium, the more electron-rich vanadium(V) cations [cyclopentadienyl-arene]V(NiPr2)(NC6H4-4-Me)+ feature η1-arene binding, as determined by a crystallographic study. The three different metal-arene coordination modes that we experimentally observed model intermediates in the cycle for titanium-catalyzed ethylene trimerization. The nature of the metal-arene interaction in these systems was studied by DFT calculations.

Pilot study to define criteria for Pituitary Tumors Centers of Excellence (PTCOE):results of an audit of leading international centers

Purpose: The Pituitary Society established the concept and mostly qualitative parameters for defining uniform criteria for Pituitary Tumor Centers of Excellence (PTCOEs) based on expert consensus. Aim of the study was to validate those previously proposed criteria through collection and evaluation of self-reported activity of several internationally-recognized tertiary pituitary centers, thereby transforming the qualitative 2017 definition into a validated quantitative one, which could serve as the basis for future objective PTCOE accreditation. Methods: An ad hoc prepared database was distributed to nine Pituitary Centers chosen by the Project Scientific Committee and comprising Centers of worldwide repute, which agreed to provide activity information derived from registries related to the years 2018–2020 and completing the database within 60 days. The database, provided by each center and composed of Excel® spreadsheets with requested specific information on leading and supporting teams, was reviewed by two blinded referees and all 9 candidate centers satisfied the overall PTCOE definition, according to referees’ evaluations. To obtain objective numerical criteria, median values for each activity/parameter were considered as the preferred PTCOE definition target, whereas the low limit of the range was selected as the acceptable target for each respective parameter. Results: Three dedicated pituitary neurosurgeons are preferred, whereas one dedicated surgeon is acceptable. Moreover, 100 surgical procedures per center per year are preferred, while the results indicated that 50 surgeries per year are acceptable. Acute post-surgery complications, including mortality and readmission rates, should preferably be negligible or nonexistent, but acceptable criterion is a rate lower than 10% of patients with complications requiring readmission within 30 days after surgery. Four endocrinologists devoted to pituitary diseases are requested in a PTCOE and the total population of patients followed in a PTCOE should not be less than 850. It appears acceptable that at least one dedicated/expert in pituitary diseases is present in neuroradiology, pathology, and ophthalmology groups, whereas at least two expert radiation oncologists are needed. Conclusion: This is, to our knowledge, the first study to survey and evaluate the activity of a relevant number of high-volume centers in the pituitary field. This effort, internally validated by ad hoc reviewers, allowed for transformation of previously formulated theoretical criteria for the definition of a PTCOE to precise numerical definitions based on real-life evidence. The application of a derived synopsis of criteria could be used by independent bodies for accreditation of pituitary centers as PTCOEs.</p

A strategy to characterize the LISA-Pathfinder cold gas thruster system

The cold gas micro-propulsion system that will be used during the LISA-Pathfinder mission will be one of the most important component used to ensure the "free-fall" of the enclosed test masses. In this paper we present a possible strategy to characterize the effective direction and amplitude gain of each of the 6 thrusters of this system

Free-flight experiments in LISA Pathfinder

The LISA Pathfinder mission will demonstrate the technology of drag-free test masses for use as inertial references in future space-based gravitational wave detectors. To accomplish this, the Pathfinder spacecraft will perform drag-free flight about a test mass while measuring the acceleration of this primary test mass relative to a second reference test mass. Because the reference test mass is contained within the same spacecraft, it is necessary to apply forces on it to maintain its position and attitude relative to the spacecraft. These forces are a potential source of acceleration noise in the LISA Pathfinder system that are not present in the full LISA configuration. While LISA Pathfinder has been designed to meet it's primary mission requirements in the presence of this noise, recent estimates suggest that the on-orbit performance may be limited by this `suspension noise'. The drift-mode or free-flight experiments provide an opportunity to mitigate this noise source and further characterize the underlying disturbances that are of interest to the designers of LISA-like instruments. This article provides a high-level overview of these experiments and the methods under development to analyze the resulting data.Comment: 13 pages, 5 figures. Accepted to Journal Of Physics, Conference Series. Presented at 10th International LISA Symposium, May 2014, Gainesville, FL, US