Observation of the effect of gravity on the motion of antimatter.

Einstein's general theory of relativity from 19151 remains the most successful description of gravitation. From the 1919 solar eclipse2 to the observation of gravitational waves3, the theory has passed many crucial experimental tests. However, the evolving concepts of dark matter and dark energy illustrate that there is much to be learned about the gravitating content of the universe. Singularities in the general theory of relativity and the lack of a quantum theory of gravity suggest that our picture is incomplete. It is thus prudent to explore gravity in exotic physical systems. Antimatter was unknown to Einstein in 1915. Dirac's theory4 appeared in 1928; the positron was observed5 in 1932. There has since been much speculation about gravity and antimatter. The theoretical consensus is that any laboratory mass must be attracted6 by the Earth, although some authors have considered the cosmological consequences if antimatter should be repelled by matter7-10. In the general theory of relativity, the weak equivalence principle (WEP) requires that all masses react identically to gravity, independent of their internal structure. Here we show that antihydrogen atoms, released from magnetic confinement in the ALPHA-g apparatus, behave in a way consistent with gravitational attraction to the Earth. Repulsive 'antigravity' is ruled out in this case. This experiment paves the way for precision studies of the magnitude of the gravitational acceleration between anti-atoms and the Earth to test the WEP.

Laser cooling of antihydrogen atoms.

The photon-the quantum excitation of the electromagnetic field-is massless but carries momentum. A photon can therefore exert a force on an object upon collision1. Slowing the translational motion of atoms and ions by application of such a force2,3, known as laser cooling, was first demonstrated 40 years ago4,5. It revolutionized atomic physics over the following decades6-8, and it is now a workhorse in many fields, including studies on quantum degenerate gases, quantum information, atomic clocks and tests of fundamental physics. However, this technique has not yet been applied to antimatter. Here we demonstrate laser cooling of antihydrogen9, the antimatter atom consisting of an antiproton and a positron. By exciting the 1S-2P transition in antihydrogen with pulsed, narrow-linewidth, Lyman-α laser radiation10,11, we Doppler-cool a sample of magnetically trapped antihydrogen. Although we apply laser cooling in only one dimension, the trap couples the longitudinal and transverse motions of the anti-atoms, leading to cooling in all three dimensions. We observe a reduction in the median transverse energy by more than an order of magnitude-with a substantial fraction of the anti-atoms attaining submicroelectronvolt transverse kinetic energies. We also report the observation of the laser-driven 1S-2S transition in samples of laser-cooled antihydrogen atoms. The observed spectral line is approximately four times narrower than that obtained without laser cooling. The demonstration of laser cooling and its immediate application has far-reaching implications for antimatter studies. A more localized, denser and colder sample of antihydrogen will drastically improve spectroscopic11-13 and gravitational14 studies of antihydrogen in ongoing experiments. Furthermore, the demonstrated ability to manipulate the motion of antimatter atoms by laser light will potentially provide ground-breaking opportunities for future experiments, such as anti-atomic fountains, anti-atom interferometry and the creation of antimatter molecules.

SubSol-HIe is an AMPK-dependent hypoxia-responsive subnucleus of the nucleus tractus solitarius that coordinates the hypoxic ventilatory response and protects against apnoea in mice.

Functional magnetic resonance imaging (fMRI) suggests that the hypoxic ventilatory response is facilitated by the AMP-activated protein kinase (AMPK), not at the carotid bodies, but within a subnucleus (Bregma -7.5 to -7.1 mm) of the nucleus tractus solitarius that exhibits right-sided bilateral asymmetry. Here, we map this subnucleus using cFos expression as a surrogate for neuronal activation and mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic cells by Cre expression via the tyrosine hydroxylase promoter. Comparative analysis of brainstem sections, relative to controls, revealed that AMPK-α1/α2 deletion inhibited, with right-sided bilateral asymmetry, cFos expression in and thus activation of a neuronal cluster that partially spanned three interconnected anatomical nuclei adjacent to the area postrema: SolDL (Bregma -7.44 mm to -7.48 mm), SolDM (Bregma -7.44 mm to -7.48 mm) and SubP (Bregma -7.48 mm to -7.56 mm). This approximates the volume identified by fMRI. Moreover, these nuclei are known to be in receipt of carotid body afferent inputs, and catecholaminergic neurons of SubP and SolDL innervate aspects of the ventrolateral medulla responsible for respiratory rhythmogenesis. Accordingly, AMPK-α1/α2 deletion attenuated hypoxia-evoked increases in minute ventilation (normalised to metabolism), reductions in expiration time, and increases sigh frequency, but increased apnoea frequency during hypoxia. The metabolic response to hypoxia in AMPK-α1/α2 knockout mice and the brainstem and spinal cord catecholamine levels were equivalent to controls. We conclude that within the brainstem an AMPK-dependent, hypoxia-responsive subnucleus partially spans SubP, SolDM and SolDL, namely SubSol-HIe, and is critical to coordination of active expiration, the hypoxic ventilatory response and defence against apnoea.

Injection-induced basement seismicity beneath the Raton Basin: constraints from refined fault architectures and basin structure.

Intraplate earthquakes induced by anthropogenic fluid injection present unexpected seismic risk to previously quiescent or low seismicity-rate regions. Despite many studies of induced seismicity, there are relatively few with detailed openly accessible constraints on the interaction between seismic sources and subsurface structures. In this study of the Raton Basin, we refine source observations from a dense nodal array and constrain basin structure using teleseismic receiver functions. The cross-correlation-based relocated hypocentres and a new set of focal mechanisms light up active fault segments and show clear spatiotemporal patterns. The geometric complexity of reactivated fault clusters appears greatest near higher rate injection wells. Simpler normal fault structure is found farther from injection wells and near abrupt structural transitions suggested by receiver functions. While less induced seismicity in the crystalline basement is expected when injection is >1 km from the top of the basement (like Raton), our receiver function analysis identified a basin thickness ~3 km beneath the nodal array and lateral variations in sedimentary structures. Our results explain potential fluid connectivity between the injection depths focused at ~1-1.5 km below the surface and basement fault activity that begins at ~3 km and reaches peak activity at ~4-8 km depths. This article is part of the theme issue 'Induced seismicity in coupled subsurface systems'.

Observation of the 1S-2P Lyman-α transition in antihydrogen.

In 1906, Theodore Lyman discovered his eponymous series of transitions in the extreme-ultraviolet region of the atomic hydrogen spectrum1,2. The patterns in the hydrogen spectrum helped to establish the emerging theory of quantum mechanics, which we now know governs the world at the atomic scale. Since then, studies involving the Lyman-α line-the 1S-2P transition at a wavelength of 121.6 nanometres-have played an important part in physics and astronomy, as one of the most fundamental atomic transitions in the Universe. For example, this transition has long been used by astronomers studying the intergalactic medium and testing cosmological models via the so-called 'Lyman-α forest'3 of absorption lines at different redshifts. Here we report the observation of the Lyman-α transition in the antihydrogen atom, the antimatter counterpart of hydrogen. Using narrow-line-width, nanosecond-pulsed laser radiation, the 1S-2P transition was excited in magnetically trapped antihydrogen. The transition frequency at a field of 1.033 tesla was determined to be 2,466,051.7 ± 0.12 gigahertz (1σ uncertainty) and agrees with the prediction for hydrogen to a precision of 5 × 10-8. Comparisons of the properties of antihydrogen with those of its well-studied matter equivalent allow precision tests of fundamental symmetries between matter and antimatter. Alongside the ground-state hyperfine4,5 and 1S-2S transitions6,7 recently observed in antihydrogen, the Lyman-α transition will permit laser cooling of antihydrogen8,9, thus providing a cold and dense sample of anti-atoms for precision spectroscopy and gravity measurements10. In addition to the observation of this fundamental transition, this work represents both a decisive technological step towards laser cooling of antihydrogen, and the extension of antimatter spectroscopy to quantum states possessing orbital angular momentum.

Erratum: Observation of the hyperfine spectrum of antihydrogen.

This corrects the article DOI: 10.1038/nature23446.

Characterization of the 1S-2S transition in antihydrogen.

In 1928, Dirac published an equation 1 that combined quantum mechanics and special relativity. Negative-energy solutions to this equation, rather than being unphysical as initially thought, represented a class of hitherto unobserved and unimagined particles-antimatter. The existence of particles of antimatter was confirmed with the discovery of the positron 2 (or anti-electron) by Anderson in 1932, but it is still unknown why matter, rather than antimatter, survived after the Big Bang. As a result, experimental studies of antimatter3-7, including tests of fundamental symmetries such as charge-parity and charge-parity-time, and searches for evidence of primordial antimatter, such as antihelium nuclei, have high priority in contemporary physics research. The fundamental role of the hydrogen atom in the evolution of the Universe and in the historical development of our understanding of quantum physics makes its antimatter counterpart-the antihydrogen atom-of particular interest. Current standard-model physics requires that hydrogen and antihydrogen have the same energy levels and spectral lines. The laser-driven 1S-2S transition was recently observed 8 in antihydrogen. Here we characterize one of the hyperfine components of this transition using magnetically trapped atoms of antihydrogen and compare it to model calculations for hydrogen in our apparatus. We find that the shape of the spectral line agrees very well with that expected for hydrogen and that the resonance frequency agrees with that in hydrogen to about 5 kilohertz out of 2.5 × 1015 hertz. This is consistent with charge-parity-time invariance at a relative precision of 2 × 10-12-two orders of magnitude more precise than the previous determination 8 -corresponding to an absolute energy sensitivity of 2 × 10-20 GeV.

AMPK facilitates the hypoxic ventilatory response through non-adrenergic mechanisms at the brainstem.

We recently demonstrated that the hypoxic ventilatory response (HVR) is facilitated by the AMP-activated protein kinase (AMPK) in catecholaminergic neural networks that likely lie downstream of the carotid bodies within the caudal brainstem. Here, we further subcategorise the neurons involved, by cross-comparison of mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic (TH-Cre) or adrenergic (PNMT-Cre) neurons. As expected, the HVR was markedly attenuated in mice with AMPK-α1/α2 deletion in catecholaminergic neurons, but surprisingly was modestly augmented in mice with AMPK-α1/α2 deletion in adrenergic neurons when compared against a variety of controls (TH-Cre, PNMT-Cre, AMPK-α1/α2 floxed). Moreover, AMPK-α1/α2 deletion in catecholaminergic neurons precipitated marked hypoventilation and apnoea during poikilocapnic hypoxia, relative to controls, while mice with AMPK-α1/α2 deletion in adrenergic neurons entered relative hyperventilation with reduced apnoea frequency and duration. We conclude, therefore, that AMPK-dependent modulation of non-adrenergic networks may facilitate increases in ventilatory drive that shape the classical HVR, whereas AMPK-dependent modulation of adrenergic networks may provide some form of negative feedback or inhibitory input to moderate HVR, which could, for example, protect against hyperventilation-induced hypocapnia and respiratory alkalosis.

Observation of the hyperfine spectrum of antihydrogen.

The observation of hyperfine structure in atomic hydrogen by Rabi and co-workers and the measurement of the zero-field ground-state splitting at the level of seven parts in 1013 are important achievements of mid-twentieth-century physics. The work that led to these achievements also provided the first evidence for the anomalous magnetic moment of the electron, inspired Schwinger's relativistic theory of quantum electrodynamics and gave rise to the hydrogen maser, which is a critical component of modern navigation, geo-positioning and very-long-baseline interferometry systems. Research at the Antiproton Decelerator at CERN by the ALPHA collaboration extends these enquiries into the antimatter sector. Recently, tools have been developed that enable studies of the hyperfine structure of antihydrogen-the antimatter counterpart of hydrogen. The goal of such studies is to search for any differences that might exist between this archetypal pair of atoms, and thereby to test the fundamental principles on which quantum field theory is constructed. Magnetic trapping of antihydrogen atoms provides a means of studying them by combining electromagnetic interaction with detection techniques that are unique to antimatter. Here we report the results of a microwave spectroscopy experiment in which we probe the response of antihydrogen over a controlled range of frequencies. The data reveal clear and distinct signatures of two allowed transitions, from which we obtain a direct, magnetic-field-independent measurement of the hyperfine splitting. From a set of trials involving 194 detected atoms, we determine a splitting of 1,420.4 ± 0.5 megahertz, consistent with expectations for atomic hydrogen at the level of four parts in 104. This observation of the detailed behaviour of a quantum transition in an atom of antihydrogen exemplifies tests of fundamental symmetries such as charge-parity-time in antimatter, and the techniques developed here will enable more-precise such tests.

Observation of the 1S-2S transition in trapped antihydrogen.

The spectrum of the hydrogen atom has played a central part in fundamental physics over the past 200 years. Historical examples of its importance include the wavelength measurements of absorption lines in the solar spectrum by Fraunhofer, the identification of transition lines by Balmer, Lyman and others, the empirical description of allowed wavelengths by Rydberg, the quantum model of Bohr, the capability of quantum electrodynamics to precisely predict transition frequencies, and modern measurements of the 1S-2S transition by Hänsch to a precision of a few parts in 1015. Recent technological advances have allowed us to focus on antihydrogen-the antimatter equivalent of hydrogen. The Standard Model predicts that there should have been equal amounts of matter and antimatter in the primordial Universe after the Big Bang, but today's Universe is observed to consist almost entirely of ordinary matter. This motivates the study of antimatter, to see if there is a small asymmetry in the laws of physics that govern the two types of matter. In particular, the CPT (charge conjugation, parity reversal and time reversal) theorem, a cornerstone of the Standard Model, requires that hydrogen and antihydrogen have the same spectrum. Here we report the observation of the 1S-2S transition in magnetically trapped atoms of antihydrogen. We determine that the frequency of the transition, which is driven by two photons from a laser at 243 nanometres, is consistent with that expected for hydrogen in the same environment. This laser excitation of a quantum state of an atom of antimatter represents the most precise measurement performed on an anti-atom. Our result is consistent with CPT invariance at a relative precision of about 2 × 10-10.

Streamlined CRISPR genome engineering in wild-type bacteria using SIBR-Cas.

CRISPR-Cas is a powerful tool for genome editing in bacteria. However, its efficacy is dependent on host factors (such as DNA repair pathways) and/or exogenous expression of recombinases. In this study, we mitigated these constraints by developing a simple and widely applicable genome engineering tool for bacteria which we termed SIBR-Cas (Self-splicing Intron-Based Riboswitch-Cas). SIBR-Cas was generated from a mutant library of the theophylline-dependent self-splicing T4 td intron that allows for tight and inducible control over CRISPR-Cas counter-selection. This control delays CRISPR-Cas counter-selection, granting more time for the editing event (e.g. by homologous recombination) to occur. Without the use of exogenous recombinases, SIBR-Cas was successfully applied to knock-out several genes in three wild-type bacteria species (Escherichia coli MG1655, Pseudomonas putida KT2440 and Flavobacterium IR1) with poor homologous recombination systems. Compared to other genome engineering tools, SIBR-Cas is simple, tightly regulated and widely applicable for most (non-model) bacteria. Furthermore, we propose that SIBR can have a wider application as a simple gene expression and gene regulation control mechanism for any gene or RNA of interest in bacteria.

Of Mice and Men and Plethysmography Systems: Does LKB1 Determine the Set Point of Carotid Body Chemosensitivity and the Hypoxic Ventilatory Response?

Our recent studies suggest that the level of liver kinase B1 (LKB1) expression in some way determines carotid body afferent discharge during hypoxia and to a lesser extent during hypercapnia. In short, phosphorylation by LKB1 of an as yet unidentified target(s) determines a set point for carotid body chemosensitivity. LKB1 is the principal kinase that activates the AMP-activated protein kinase (AMPK) during metabolic stresses, but conditional deletion of AMPK in catecholaminergic cells, including therein carotid body type I cells, has little or no effect on carotid body responses to hypoxia or hypercapnia. With AMPK excluded, the most likely target of LKB1 is one or other of the 12 AMPK-related kinases, which are constitutively phosphorylated by LKB1 and, in general, regulate gene expression. By contrast, the hypoxic ventilatory response is attenuated by either LKB1 or AMPK deletion in catecholaminergic cells, precipitating hypoventilation and apnea during hypoxia rather than hyperventilation. Moreover, LKB1, but not AMPK, deficiency causes Cheyne-Stokes-like breathing. This chapter will explore further the possible mechanisms that determine these outcomes.

Associations with sub-optimal clinic attendance and reasons for missed appointments among heterosexual women and men living with HIV in London.

Poor engagement in HIV care is associated with poorer health outcomes and increased mortality. Our survey examined experiential and circumstantial factors associated with clinic attendance among women (n = 250) and men (n = 106) in London with heterosexually-acquired HIV. While no associations were found for women, among men, sub-optimal attendance was associated with insecure immigration status (25.6% vs. 1.8%), unstable housing (32.6% vs. 10.2%) and reported effect of HIV on daily activities (58.7% vs. 40.0%). Among women and men on ART, it was associated with missing doses of ART (OR = 2.96, 95% CI:1.74-5.02), less belief in the necessity of ART (OR = 0.56, 95% CI:0.35-0.90) and more concern about ART (OR = 3.63, 95% CI:1.45-9.09). Not wanting to think about being HIV positive was the top reason for ever missing clinic appointments. It is important to tackle stigma and the underlying social determinants of health to improve HIV prevention, and the health and well-being of people living with HIV.

Opting into breast screening over the age of 70 years: seeking evidence to support informed choice.

AIM: To provide evidence specific to the Scottish population regarding the risk-benefit balance of women >70 years opting into continued breast screening, which may be used as a basis for patient information documentation. MATERIALS AND METHODS: The present study consisted of a parallel, retrospective data analysis of breast cancer mortality data for breast cancer cases diagnosed between 2009 and 2013 (n=22,013) followed up to 31/12/18, and breast screening programme data from 2010 and 2015 (n=47,235). Screening outcome measures included recall for assessment, oncome of assessment, and tumour features. Tumours were classified as high, intermediate, or low risk according to grade and presence of invasion. Mortality data were linked to age at diagnosis and cause of death was recorded. RESULTS: The proportion of all deaths due breast cancer is inversely related to age at diagnosis. From 77 years, women are more likely to die with breast cancer, than directly due to breast cancer. Mammographic screening accurately identifies breast cancer in older women; however, many of the cancers detected were considered intermediate or low risk. CONCLUSIONS: Harms may outweigh the benefits of continued breast screening in older women. This information should be available to all older women.

Elevated and sustained anti-feeding effect of Scalibor® deltamethrin collar against the sand fly Phlebotomus perniciosus in dogs confirmed for 1 year following treatment.

Dogs are reservoir hosts for Leishmania infantum, a protozoan parasite transmitted by phlebotomine sand flies. The anti-feeding and fast-killing efficacy of Scalibor® deltamethrin collars against experimental Phlebotomus perniciosus challenges on dogs was determined over 1 year. Two groups of 8 dogs each were fitted with placebo (control) or deltamethrin collars (treated) on Day 0 and exposed to sand flies approximately every 28 days up to Day 364. After each exposure, anti-feeding and fast-killing efficacy rates were determined by comparing blood-fed or live insects, respectively, in the treated vs. the control group. Blood-fed and live sand flies were significantly less in treated dogs as compared to control dogs at each assessment. The anti-feeding efficacy rate exceeded 90% except on Day 337 (89%) but increased again (96%) on Day 364. Fast killing efficacy was <74% over the study when considering all flies. However, this value increased cumulatively to 98% when only blood-fed flies were compared between groups. Scalibor® collars are highly effective at preventing P. perniciosus blood-feeding and in fast-killing flies taking a blood meal for up to 1 year after application. These strong and long-lasting effects are an important strategic component for L. infantum transmission control.

Hospital admissions in infants with Down syndrome: a record-linked population-based cohort study in Wales.

BACKGROUND: Despite recent advances, mortality in children with Down syndrome remains five times higher than in the general population. This study aims to describe the burden, patterns and causes of hospital admissions in infants with Down syndrome, and compare this with infants without Down syndrome in a population-based cohort. METHODS: This study used data from the Wales Electronic Cohort for Children, a cohort of all children born in Wales between 1990 and 2012. The cohort was generated from routine administrative data, linked to create an anonymised data set within the Secure Anonymised Information Linkage databank. This analysis is based on all infants born between January 2003 and January 2012 who were followed to their first birthday, a move out of Wales, death, or until 31 October 2012 (end of follow-up). Infants with Down syndrome were identified using the Congenital Anomaly Register and Information Service in Wales. Multivariable Cox regression was used to compare the time to first hospital admission. Admission codes were used to identify the commonest indications for hospitalisation and to determine the presence of other congenital anomalies. RESULTS: We included 324 060 children, 356 of whom had Down syndrome. Of infants with Down syndrome, 80.3% had at least one hospital inpatient admission during the first year of life, compared with 32.9% of infants without Down syndrome. These first admissions were earlier [median of 6 days interquartile range (IQR) (3, 72) compared with 45 days [IQR 6, 166)] and longer [median of 4 days (IQR 1, 15) compared with 1 day (IQR 0, 3)] than in infants without Down syndrome. The most common causes of admissions were congenital abnormalities, respiratory diseases, conditions originating in the perinatal period and infectious diseases. The presence of other congenital abnormalities increased hospitalisations in all infants, but more so in infants with Down syndrome who spent a median of 21 days in hospital (IQR 11, 47) during their first year of life. CONCLUSION: Infants with Down syndrome are at high risk for early, more frequent and longer hospital admissions. Congenital heart disease and respiratory infections remain a major burden in this population. More research is needed to understand how to better manage these conditions particularly in the first month of life when most admissions occur.

"I must do this!": A latent profile analysis approach to understanding the role of irrational beliefs and motivation regulation in mental and physical health.

In the research concerning rational emotive behaviour therapy (REBT) in sport and exercise, irrational beliefs are proposed as a risk factor for health. Concurrent to this, researchers have also indicated that autonomous and controlled motivation, as proposed in organismic integration theory could, together with irrational beliefs, determine individual health. However, research is yet to align irrational beliefs and motivation, and explore how this alignment relates to mental health. The present two study paper identifies individual subgroups, drawn from data concerning irrational beliefs, motivation, and health (psychological distress, and physical health), in a sample of exercisers (study 1) and student athletes (study 2). We examined the latent profile structure of irrational beliefs and motivation, and how these latent profiles relate to psychological distress (studies 1 and 2), and physical health (study 2). Results indicate a two class profile whereby class 1 is characterised by high irrational beliefs, low self-determined motivation, and poor health outcomes. Class 2 is characterised by low irrational beliefs, high self-determined motivation, and better health outcomes. The findings are discussed in relation to the theoretical implications for REBT and organismic integration theory, and the practical implications for key stakeholders in the health of exercise participants and athletes.

The association between use of chemsex drugs and HIV clinic attendance among gay and bisexual men living with HIV in London.

OBJECTIVES: To investigate the association between chemsex drug use and HIV clinic attendance among gay and bisexual men in London. METHODS: A cross-sectional survey of adults (> 18 years) diagnosed with HIV for > 4 months, attending seven London HIV clinics (May 2014 to August 2015). Participants self-completed an anonymous questionnaire linked to clinical data. Sub-optimal clinic attenders had missed one or more HIV clinic appointments in the past year, or had a history of non-attendance for > 1 year. RESULTS: Over half (56%) of the 570 men who identified as gay or bisexual reported taking recreational drugs in the past 5 years and 71.5% of these men had used chemsex drugs in the past year. Among men reporting chemsex drug use (past year), 32.1% had injected any drugs in the past year. Sub-optimal clinic attenders were more likely than regular attenders to report chemsex drug use (past year; 46.9% vs. 33.2%, P = 0.001), injecting any drugs (past year; 17.1% vs. 8.9%, P = 0.011) and recreational drug use (past 5 years; 65.5% vs. 48.8%, P < 0.001). One in five sub-optimal attenders had missed an HIV clinic appointment because of taking recreational drugs (17.4% vs. 1.8%, P < 0.001). In multivariable logistic regression, chemsex drug use was significantly associated with sub-optimal clinic attendance (adjusted odds ratio = 1.71, 95% confidence interval: 1.10-2.65, P = 0.02). CONCLUSIONS: Our findings highlight the importance of systematic assessment of drug use and development of tools to aid routine assessment. We suggest that chemsex drug use should be addressed when developing interventions to improve engagement in HIV care among gay and bisexual men.

Speech metrics, general disability, brain imaging and quality of life in multiple sclerosis.

BACKGROUND AND PURPOSE: Objective measurement of speech has shown promising results to monitor disease state in multiple sclerosis. In this study, we characterize the relationship between disease severity and speech metrics through perceptual (listener based) and objective acoustic analysis. We further look at deviations of acoustic metrics in people with no perceivable dysarthria. METHODS: Correlations and regression were calculated between speech measurements and disability scores, brain volume, lesion load and quality of life. Speech measurements were further compared between three subgroups of increasing overall neurological disability: mild (as rated by the Expanded Disability Status Scale ≤2.5), moderate (≥3 and ≤5.5) and severe (≥6). RESULTS: Clinical speech impairment occurred majorly in people with severe disability. An experimental acoustic composite score differentiated mild from moderate (P < 0.001) and moderate from severe subgroups (P = 0.003), and correlated with overall neurological disability (r = 0.6, P < 0.001), quality of life (r = 0.5, P < 0.001), white matter volume (r = 0.3, P = 0.007) and lesion load (r = 0.3, P = 0.008). Acoustic metrics also correlated with disability scores in people with no perceivable dysarthria. CONCLUSIONS: Acoustic analysis offers a valuable insight into the development of speech impairment in multiple sclerosis. These results highlight the potential of automated analysis of speech to assist in monitoring disease progression and treatment response.

Partial Support for an Interaction Between a Polygenic Risk Score for Major Depressive Disorder and Prenatal Maternal Depressive Symptoms on Infant Right Amygdalar Volumes.

Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother-infant dyads (44 female, 11-54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample.