GDF15 linked to maternal risk of nausea and vomiting during pregnancy.

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1-4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with ß-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

Age and the anaesthetist: considerations for the individual anaesthetist and workforce planning: Guidelines about the ageing anaesthetic workforce from the Association of Anaesthetists: Guidelines for the ageing anaesthetic workforce from the Association of Anaesthetists.

There is clear evidence of a growing workforce gap and this is compounded by demographic data that show the current workforce is ageing. Within the current workforce, more doctors are taking voluntary early retirement and the loss of these experienced clinicians from departments can have wide-ranging effects. Older doctors are at risk of age-related health problems (e.g. sight, musculoskeletal, menopause) and are more susceptible to the effects of fatigue, which may increase the risk of error and or complaint. The purpose of this working party and advocacy campaign was to address concerns over the number of consultants retiring at the earliest opportunity and whether a different approach could extend the working career of consultant anaesthetists and SAS doctors. This could be viewed as 'pacing your career'. The earlier this is considered in a clinician's career the greater the potential mitigation on individuals.

Realizing Einstein's Mirror: Optomechanical Damping with a Thermal Photon Gas.

Einstein described the damping and thermalization of the center-of-mass motion of a mirror placed inside a blackbody cavity by collisions with thermal photons. While the time for damping even a microscale or nanoscale object is so long that it is not experimentally viable, we show that this damping is feasible using the high-intensity light from an amplified thermal light source with a well-defined chemical potential. We predict this damping of the center-of-mass motion will occur on timescales of tens of seconds for small optomechanical systems.

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.

Quantum Spectrometry for Arbitrary Noise.

We present a technique for recovering the spectrum of a non-Markovian bosonic bath and/or non-Markovian noises coupled to a harmonic oscillator. The treatment is valid under the conditions that the environment is large and hot compared to the oscillator, and that its temporal autocorrelation functions are symmetric with respect to time translation and reflection-criteria which we consider fairly minimal. We model a demonstration of the technique as deployed in the experimental scenario of a nanosphere levitated in a Paul trap, and show that it would effectively probe the spectrum of an electric field noise source from 10^{2} to 10^{6} Hz with a resolution inversely proportional to the measurement time. This technique may be deployed in quantum sensing, metrology, computing, and in experimental probes of foundational questions.

Field Evaluation of a Portable Whispering Gallery Mode Accelerometer.

An accelerometer utilising the optomechanical coupling between an optical whispering gallery mode (WGM) resonance and the motion of the WGM cavity itself was prototyped and field-tested on a vehicle. We describe the assembly of this portable, battery operated sensor and the field-programmable gate array automation. Pre-trial testing using an electrodynamic shaker demonstrated linear scale-factors with <0.3% standard deviation ( ± 6 g range where g = 9.81 ms - 2 ), and a strong normalised cross-correlation coefficient (NCCC) of r ICP / WGM = 0.997 when compared with an integrated circuit piezoelectric (ICP) accelerometer. A noise density of 40 µ g Hz - 1 / 2 was obtained for frequencies of 2⁻7 kHz, increasing to 130 µ g Hz - 1 / 2 at 200 Hz, and 250 µ g Hz - 1 / 2 at 100 Hz. A reduction in the cross-correlation was found during the trial, r ICP / WGM = 0.36, which we attribute to thermal fluctuations, mounting differences, and the noisy vehicle environment. The deployment of this hand-fabricated sensor, shown to operate and survive during ±60 g shocks, demonstrates important steps towards the development of a chip-scale device.

AAGBI: Consent for anaesthesia 2017: Association of Anaesthetists of Great Britain and Ireland.

Previous guidelines on consent for anaesthesia were issued by the Association of Anaesthetists of Great Britain and Ireland in 1999 and revised in 2006. The following guidelines have been produced in response to the changing ethical and legal background against which anaesthetists, and also intensivists and pain specialists, currently work, while retaining the key principles of respect for patients' autonomy and the need to provide adequate information. The main points of difference between the relevant legal frameworks in England and Wales and Scotland, Northern Ireland and the Republic of Ireland are also highlighted.

Simultaneous cooling of coupled mechanical oscillators using whispering gallery mode resonances.

We demonstrate simultaneous center-of-mass cooling of two coupled oscillators, consisting of a microsphere-cantilever and a tapered optical fiber. Excitation of a whispering gallery mode (WGM) of the microsphere, via the evanescent field of the taper, provides a transduction signal that continuously monitors the relative motion between these two microgram objects with a sensitivity of 3 pm. The cavity enhanced optical dipole force is used to provide feedback damping on the motion of the micron-diameter taper, whereas a piezo stack is used to damp the motion of the much larger (up to 180 µm in diameter), heavier (up to 1.5 × 10(-7) kg) and stiffer microsphere-cantilever. In each feedback scheme multiple mechanical modes of each oscillator can be cooled, and mode temperatures below 10 K are reached for the dominant mode, consistent with limits determined by the measurement noise of our system. This represents stabilization on the picometer level and is the first demonstration of using WGM resonances to cool the mechanical modes of both the WGM resonator and its coupling waveguide.

Nonlinear Dynamics and Strong Cavity Cooling of Levitated Nanoparticles.

Optomechanical systems explore and exploit the coupling between light and the mechanical motion of macroscopic matter. A nonlinear coupling offers rich new physics, in both quantum and classical regimes. We investigate a dynamic, as opposed to the usually studied static, nonlinear optomechanical system, comprising a nanosphere levitated in a hybrid electro-optical trap. The cavity offers readout of both linear-in-position and quadratic-in-position (nonlinear) light-matter coupling, while simultaneously cooling the nanosphere, for indefinite periods of time and in high vacuum. We observe the cooling dynamics via both linear and nonlinear coupling. As the background gas pressure was lowered, we observed a greater than 1000-fold reduction in temperature before temperatures fell below readout sensitivity in the present setup. This Letter opens the way to strongly coupled quantum dynamics between a cavity and a nanoparticle largely decoupled from its environment.

Free Nano-Object Ramsey Interferometry for Large Quantum Superpositions.

We propose an interferometric scheme based on an untrapped nano-object subjected to gravity. The motion of the center of mass (c.m.) of the free object is coupled to its internal spin system magnetically, and a free flight scheme is developed based on coherent spin control. The wave packet of the test object, under a spin-dependent force, may then be delocalized to a macroscopic scale. A gravity induced dynamical phase (accrued solely on the spin state, and measured through a Ramsey scheme) is used to reveal the above spatially delocalized superposition of the spin-nano-object composite system that arises during our scheme. We find a remarkable immunity to the motional noise in the c.m. (initially in a thermal state with moderate cooling), and also a dynamical decoupling nature of the scheme itself. Together they secure a high visibility of the resulting Ramsey fringes. The mass independence of our scheme makes it viable for a nano-object selected from an ensemble with a high mass variability. Given these advantages, a quantum superposition with a 100 nm spatial separation for a massive object of 10^{9} amu is achievable experimentally, providing a route to test postulated modifications of quantum theory such as continuous spontaneous localization.

Differences in Eccentricity Index and Systolic-Diastolic Ratio in Extremely Low-Birth-Weight Infants with Bronchopulmonary Dysplasia at Risk of Pulmonary Hypertension.

OBJECTIVE: To compare the left ventricular eccentricity index (EI) and tricuspid valve systolic-diastolic (SD) ratio in infants at risk of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). STUDY DESIGN: Review of echocardiograms performed on infants born at ≤ 28 weeks' postmenstrual age, categorized into the following three cohorts: BPD and PH (n = 13); BPD only (n = 16); and controls (n = 59). EI was measured from a parasternal short axis 2D image. The SD ratio was measured from the continuous wave Doppler tracing. Groups were compared using Kruskal-Wallis and Wilcoxon rank sum tests. RESULT: EI and SD ratios were successfully measured in all infants. There were no differences between controls and BPD cohort. In contrast, the BPD and PH cohort had increased systolic EI (1.46 vs. 1.00-1.01), diastolic EI (1.47 vs. 1.00), and SD ratio (1.12 vs. 0.97-1.00) compared with controls and BPD only cohort (p ≤ 0.01 for all). CONCLUSION: The EI and SD ratio may be useful as a screening tool for PH in this population.

Health surveillance for occupational asthma in the UK.

BACKGROUND: Periodic health surveillance (HS) of workers can identify early cases of occupational asthma. Information about its uptake and its content in the UK is lacking. AIMS: To identify the overall levels of uptake and quality of HS for occupational asthma within three high-risk industry sectors in the UK. METHODS: A telephone survey of employers, and their occupational health (OH) professionals, carried out in three sectors with exposures potentially capable of causing occupational asthma (bakeries, wood working and motor vehicle repair). RESULTS: A total of 457 organizations participated (31% response rate). About 77% employed <10 people, 17% between 10 and 50 and 6% >50. Risk assessments were common (67%) and 14% carried out some form of HS for occupational asthma, rising to 19% if only organizations reporting asthma hazards and risks were considered. HS was carried out both by in-house (31%) and external providers (69%). Organizational policies were often used to define HS approaches (80%), but infrequently shared with the OH provider. OH providers described considerable variation in practice. Record keeping was universal, but worker-held records were not reported. HS tools were generally developed in-house. Lung function was commonly measured, but only limited interpretation evident. Referral of workers to local specialist respiratory services was variable. CONCLUSIONS: This study provided new insights into the real world of HS for occupational asthma. We consider that future work could and should define simpler, more practical and evidence-based approaches to HS to ensure maximal consistency and use of high-quality approaches.

Parallel reconstruction in accelerated multivoxel MR spectroscopy.

PURPOSE: To develop the simultaneous acquisition of multiple voxels in localized MR spectroscopy (MRS) using sensitivity encoding, allowing reduced total scan time compared to conventional sequential single voxel (SV) acquisition methods. METHODS: Dual volume localization was used to simultaneously excite voxels in both hemispheres. Receiver coil sensitivity profiles were used to unfold the data. To demonstrate the method, MRS voxels in the left and right hippocampus were measured at 3 tesla (T) and the left and right motor cortices at 7T. Spectra were compared to conventional SV acquisitions. Spectra were also recorded from the lesion and contralateral hemisphere of a patient with a low-grade oligodendroglioma at 7T. RESULTS: It was possible to generate signal in two voxels simultaneously and separate the signal originating from the different locations, with spectral results almost identical to those observed using conventional single voxel methods. The method results in an increased chemical shift displacement artifact, which might be improved by advanced pulse designs, and a noise increase due to the unfolding g-factor, which was larger at 3T than 7T. CONCLUSION: The simultaneous acquisition of voxels for MRS is possible by using modulated slice-selective pulses and receive coil sensitivity profiles to unfold the resulting signals.

Cavity cooling a single charged levitated nanosphere.

Optomechanical cavity cooling of levitated objects offers the possibility for laboratory investigation of the macroscopic quantum behavior of systems that are largely decoupled from their environment. However, experimental progress has been hindered by particle loss mechanisms, which have prevented levitation and cavity cooling in a vacuum. We overcome this problem with a new type of hybrid electro-optical trap formed from a Paul trap within a single-mode optical cavity. We demonstrate a factor of 100 cavity cooling of 400 nm diameter silica spheres trapped in vacuum. This paves the way for ground-state cooling in a smaller, higher finesse cavity, as we show that a novel feature of the hybrid trap is that the optomechanical cooling becomes actively driven by the Paul trap, even for singly charged nanospheres.

Peri-operative management of the surgical patient with diabetes 2015: Association of Anaesthetists of Great Britain and Ireland.

Diabetes affects 10-15% of the surgical population and patients with diabetes undergoing surgery have greater complication rates, mortality rates and length of hospital stay. Modern management of the surgical patient with diabetes focuses on: thorough pre-operative assessment and optimisation of their diabetes (as defined by a HbA1c < 69 mmol.mol(-1) ); deciding if the patient can be managed by simple manipulation of pre-existing treatment during a short starvation period (maximum of one missed meal) rather than use of a variable-rate intravenous insulin infusion; and safe use of the latter when it is the only option, for example in emergency patients, patients expected not to return to a normal diet immediately postoperatively, and patients with poorly controlled diabetes. In addition, it is imperative that communication amongst healthcare professionals and between them and the patient is accurate and well informed at all times. Most patients with diabetes have many years of experience of managing their own care. The purpose of this guideline is to provide detailed guidance on the peri-operative management of the surgical patient with diabetes that is specific to anaesthetists and to ensure that all current national guidance is concordant.

Trapping cold ground state argon atoms.

We trap cold, ground state argon atoms in a deep optical dipole trap produced by a buildup cavity. The atoms, which are a general source for the sympathetic cooling of molecules, are loaded in the trap by quenching them from a cloud of laser-cooled metastable argon atoms. Although the ground state atoms cannot be directly probed, we detect them by observing the collisional loss of cotrapped metastable argon atoms and determine an elastic cross section. Using a type of parametric loss spectroscopy we also determine the polarizability of the metastable 4s[3/2](2) state to be (7.3±1.1)×10(-39) C m(2)/V. Finally, Penning and associative losses of metastable atoms in the absence of light assisted collisions, are determined to be (3.3±0.8)×10(-10) cm(3) s(-1).

Anatomy and biomechanics of gluteus maximus and the thoracolumbar fascia at the sacroiliac joint.

Biomechanical models predict that recruitment of gluteus maximus (GMax) will exert a compressive force across the sacroiliac joint (SIJ), yet this muscle requires morphologic assessment. The aims of this study were to document GMax's proximal attachments and assess their capacity to generate forces including compressive force at the SIJ. In 11 embalmed cadaver limbs, attachments of GMax crossing the SIJ were dissected and their fascicle orientation, length and attachment volume documented. The physiological cross-sectional area (PCSA) of each attachment was calculated along with its estimated maximum force at the SIJ and lumbar spine. GMax fascicles originated from the gluteus medius fascia, ilium, thoracolumbar fascia, erector spinae aponeurosis, sacrum, coccyx, dorsal sacroiliac and sacrotuberous ligaments in all specimens. Their mean fascicle orientation ranged from 32 to 45° below horizontal and mean length from 11 to 18 cm. The mean total PCSA of GMax was 26 cm(2) (range 16-36), of which 70% crossed the SIJ. The average maximum force predicted to be generated by GMax's total attachments crossing each SIJ was 891 N (range 572-1,215), of which 70% (702 N: range 450-1,009) could act perpendicular to the plane of the SIJ. The capacity of GMax to generate an extensor moment at lower lumbar segments was estimated at 4 Nm (range 2-9.5). GMax may generate compressive forces at the SIJ through its bony and fibrous attachments. These may assist effective load transfer between lower limbs and trunk.

Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep.

Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline-treated group. The results show that cortisol overexposure before birth programmes pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.

Attainment of metabolic goals in the integrated UK islet transplant program with locally isolated and transported preparations.

The objective was to determine whether metabolic goals have been achieved with locally isolated and transported preparations over the first 3 years of the UK's nationally funded integrated islet transplant program. Twenty islet recipients with C-peptide negative type 1 diabetes and recurrent severe hypoglycemia consented to the study, including standardized meal tolerance tests. Participants received a total of 35 infusions (seven recipients: single graft; 11 recipients: two grafts: two recipients: three grafts). Graft function was maintained in 80% at [median (interquartile range)] 24 (13.5-36) months postfirst transplant. Severe hypoglycemia was reduced from 20 (7-50) episodes/patient-year pretransplant to 0.3 (0-1.6) episodes/patient-year posttransplant (p < 0.001). Resolution of impaired hypoglycemia awareness was confirmed [pretransplant: Gold score 6 (5-7); 24 (13.5-36) months: 3 (1.5-4.5); p < 0.03]. Target HbA1c of <7.0% was attained/maintained in 70% of recipients [pretransplant: 8.0 (7.0-9.6)%; 24 (13.5-36) months: 6.2 (5.7-8.4)%; p < 0.001], with 60% reduction in insulin dose [pretransplant: 0.51 (0.41-0.62) units/kg; 24 (13.5-36) months: 0.20 (0-0.37) units/kg; p < 0.001]. Metabolic outcomes were comparable 12 months posttransplant in those receiving transported versus only locally isolated islets [12 month stimulated C-peptide: transported 788 (114-1764) pmol/L (n = 9); locally isolated 407 (126-830) pmol/L (n = 11); p = 0.32]. Metabolic goals have been attained within the equitably available, fully integrated UK islet transplant program with both transported and locally isolated preparations.

Single-shot coherent Rayleigh-Brillouin scattering using a chirped optical lattice.

We present a method for obtaining coherent Rayleigh-Brillouin scattering (CRBS) spectra on timescales of hundreds of nanoseconds using rapidly chirped, pulsed, optical lattices. This enables us to transfer the spectral profile to a temporal profile which can be easily recorded on a single shot of an oscilloscope. These spectra are demonstrated to have sufficient signal-to-noise ratio to study CRBS models over a wide range of gas densities.