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.

"Why them, why me, why us?" The experiences of parents of children with lysosomal acid lipase deficiency: an interpretative phenomenological analysis study.

BACKGROUND: Lysosomal acid lipase deficiency (LALD) is an ultra-rare, inherited metabolic disease within the category of lysosomal storage disorders, affecting an infant's ability to metabolise cholesterol. Developments in treatment, including Enzyme Replacement Therapy, have proven successful, with some children living for a number of years with treatment, although the future still remains unknown. The aim of this study was to explore the lived experiences of parents of children with LALD. MAIN TEXT: Participants were recruited from across the United Kingdom between 2020 and 2021. Eight parents (five mothers and three fathers) whose child had a confirmed diagnosis of LALD were interviewed. Data collected from the semi-structured interviews were audio-record, transcribed and analysed using Interpretative Phenomenological Analysis (IPA). Three superordinate and nine subordinate themes emerged from the data: (1) Uncertainty-a double-edged sword (plunged into an uncertain world, living life with worry and walking the tightrope of stability), (2) Powerless against a shared battle with LALD (a helpless parent, a joint battle, protection against distress and a vulnerable parent needing help) and 3) Accepting a life with LALD (coming to terms with a diagnosis of LALD and a hidden condition). CONCLUSIONS: The findings of this study highlight that the diagnosis of LALD proves to be a very challenging and emotionally distressing time in parents' lives, with increased uncertainty about what the future will hold for their child. This study signified the importance of healthcare pathways and service provisions to support parents and their children throughout diagnosis and beyond.

The photoprotective properties of α-tocopherol phosphate against long-wave UVA1 (385 nm) radiation in keratinocytes in vitro.

UVA1 radiation (340-400 nm), especially longwave UVA1 (> 370 nm), is often ignored when assessing sun protection due to its low sunburning potential, but it generates reactive oxygen species (ROS) and is poorly attenuated by sunscreens. This study aimed to investigate if α-tocopherol phosphate, (α-TP) a promising new antioxidant, could protect against long-wave UVA1 induced cell death and scavenge UVA1 induced ROS in a skin cell model. HaCaT keratinocyte cell viability (24 h) was assessed with Alamar Blue and Neutral Red assays. The metabolism of α-TP into α-T, assessed using mass spectrometry, and the compound's radical scavenging efficacy, assessed by the dichlorodihydrofluorescein (H2DCFDA) ROS detection assay, was monitored in HaCaTs. The mechanism of α-TP ROS scavenging was determined using non-cell based DPPH and ORAC assays. In HaCaT keratinocytes, irradiated with 226 J/cm2 UVA1 in low-serum (2%, starved) cell culture medium, pretreatment with 80 µM α-TP significantly enhanced cell survival (88%, Alamar Blue) compared to control, whereas α-T pre-treatment had no effect survival (70%, Alamar Blue). Pre-treatment of cells with 100 µM α-TP or 100 µM α-T before 57 J/cm2 UVA1 also significantly reduced ROS generation over 2 h (24.1% and 23.9% respectively) compared to the control and resulted in α-TP bioconversion into α-T. As α-TP displayed weak antioxidant activity in the cell-free assays thus its photoprotection was assigned to its bioconversion to α-T by cellular phosphatases. Through this mechanism α-TP prevented long-wave UVA1 induced cell death and scavenged UVA1 induced ROS in skin cells when added to the starved cell culture medium before UVA1 exposure by bioconversion into α-T.

Sympathetic cooling of positrons to cryogenic temperatures for antihydrogen production.

The positron, the antiparticle of the electron, predicted by Dirac in 1931 and discovered by Anderson in 1933, plays a key role in many scientific and everyday endeavours. Notably, the positron is a constituent of antihydrogen, the only long-lived neutral antimatter bound state that can currently be synthesized at low energy, presenting a prominent system for testing fundamental symmetries with high precision. Here, we report on the use of laser cooled Be+ ions to sympathetically cool a large and dense plasma of positrons to directly measured temperatures below 7 K in a Penning trap for antihydrogen synthesis. This will likely herald a significant increase in the amount of antihydrogen available for experimentation, thus facilitating further improvements in studies of fundamental symmetries.

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.

The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I.

Respiratory outcomes in Mucopolysaccharidosis Type I (MPS I), have mainly focused on upper airway obstruction, with the evolution of the restrictive lung disease being poorly documented. We report the long-term pulmonary function outcomes and examine the potential factors affecting these in 2 cohorts of MPS I patients, those who have undergone Haematopoietic Stem Cell Transplantation (HSCT) and those treated with Enzyme Replacement Therapy (ERT). The results were stratified using the American Thoracic Society (ATS) guidelines. 66 patients, capable of adequately performing testing, were identified by a retrospective case note review, 46 transplanted (45 Hurler, 1 Non-Hurler) and 20 having ERT (17 Non-Hurler and 3 Hurler diagnosed too late for HSCT). 5 patients died; 4 in the ERT group including the 3 Hurler patients. Overall 14% of patients required respiratory support (non-invasive ventilation (NIV) or supplemental oxygen)) at the end of follow up. Median length of follow-up was 12.2 (range = 4.9-32) years post HSCT and 14.34 (range = 3.89-20.4) years on ERT. All patients had restrictive lung disease. Cobb angle and male sex were significantly associated with more severe outcomes in the HSCT cohort, with 49% having severe to very severe disease. In the 17 Non-Hurler ERT treated patients there was no variable predictive of severity of disease with 59% having severe to very severe disease. During the course of follow up 67% of the HSCT cohort had no change or improved pulmonary function as did 52% of the ERT patients. However, direct comparison between therapeutic modalities was not possible. This initial evidence would suggest that a degree of restrictive lung disease is present in all treated paediatrically diagnosed MPS I and is still a significant cause of morbidity, though further stratification incorporating diffusing capacity for carbon monoxide (DLCO) is needed.

Glycerin suppositories used prophylactically in premature infants (supp): A pilot randomized controlled trial.

BACKGROUND: Glycerin suppositories are often used to facilitate meconium evacuation in premature infants. The evidence for this practice is inconclusive. The purpose of this study was to assess the feasibility of a multicenter randomized controlled trial on the effectiveness of this treatment strategy. STUDY DESIGN: We conducted an external pilot study for a multicenter randomized controlled trial of premature infants randomized to glycerin suppositories or placebo procedure. Participants were included if they were gestational age of 24 weeks 0 days to 31 weeks 6 days and/or birthweight of 500 to 1500 grams. We excluded infants with life-threatening congenital anomalies, contraindications to receiving suppositories, or signs of clinical instability. Outcomes included cost, recruitment, and treatment-related adverse events. RESULT: A total of 109 were screened, 79 were initially eligible, and 34 consented to participate. Four of these infants were excluded prior to randomization due to thrombocytopenia, 30 were randomized, and 26 reached full enteral feeds. Three infants (10%) experienced rectal bleeding 5 to 43 days after completing study treatments. An anal fissure was noted in two of these patients. There were no cases of rectal perforation but one infant assigned to active treatment developed necrotizing enterocolitis. CONCLUSIONS: Conducting a multicenter randomized controlled trial on the use of glycerin suppositories in premature infants is feasible. Minor modifications to the study protocol are needed to increase participant recruitment and simplify the administration of study treatments.

Characterisation and optimisation of foams for varicose vein sclerotherapy.

BACKGROUND: Foam sclerotherapy is the process of using an aqueous foam to deliver surfactant to a varicose vein to damage vein wall endothelial cells, causing the vein to spasm, collapse and ultimately be re-absorbed into the body. Aqueous foams are complex fluids that can exhibit a significant yield stress and high effective viscosity which depend on their composition, particularly the bubble size and liquid fraction. OBJECTIVE: To characterise the properties of foams used for varicose vein sclerotherapy and determine their effectiveness in the displacement of blood during sclerotherapy. METHODS: Foams are modelled as yield stress fluids and their flow profiles in a model vein are predicted. Values of the yield stress are determined from experimental data for three different foams using the Sauter mean of the bubble size distribution. Along with the measured liquid fraction of the foams, this information is collected into a Bingham number which entirely characterises the process of sclerotherapy. RESULTS: Polydispersity in bubble size has a strong effect on the yield stress of a foam and the Sauter mean of the size distribution better captures the effects of a few large bubbles. Reducing the polydispersity increases the yield stress, and a higher yield stress results in a larger plug region moving along the vein, which is more effective in displacing blood. The width of the plug region is proportional to the Bingham number, which also has a quadratic dependence on the liquid fraction of the foam. Assuming typical values for the rate of injection of a foam, we predict that for a vein of diameter 5 mm, the most effective foams have low liquid fraction, a narrow size distribution, and a Bingham number B ≈ 4.5. CONCLUSIONS: The Sauter mean radius provides the most appropriate measure of the bubble size for sclerotherapy and the Bingham number then provides a simple measure of the efficacy of foam sclerotherapy in a vein of a given size, and explains the ability of different foams to remove varicose veins. Foams containing small bubbles, with a narrow size distribution, and a low liquid fraction are beneficial for sclerotherapy.

The Ethics and Welfare Implications of Keeping Western European Hedgehogs (erinaceus Europaeus) in Captivity.

Patient outcomes for hedgehog (Erinaceus europaeus) casualties are not limited to release versus euthanasia; some hedgehogs have conditions that do not preclude their ability to survive in captivity with human intervention. This research explored the welfare implications and ethical issues of keeping disabled hedgehogs in permanent captivity. Currently, there is very little in the literature and the subject is highly emotive and controversial. A questionnaire was used to assess welfare and these data contrasted with the normal behaviors, environment, and diet of free-living hedgehogs. The most convincing argument for keeping wild animals in captivity is species conservation; however, hedgehogs are not currently listed as endangered. Sixty-six datasets were obtained, representing 194 hedgehogs kept in permanent captivity. Results were mixed, i.e., many respondents providing suitable habitat features (for example, grass and soil 83.3% of respondents, shrubs and/or hedges 69.7% of respondents) observing "positive" behaviors such as foraging for natural foods (69.7% of respondents), and observing appropriate behavioral responses to humans; and some areas for concern, i.e., habitat size (22.7% of respondents reported habitats <10m2), presence of badgers (only 48.5% of respondents reported no badgers in the area), evidence of aggressive behavior (22.7% of respondents had observed non-food-related aggression between hedgehogs) and seven hedgehogs having sustained bite wounds whilst in captivity. The authors are cautious about drawing any definitive conclusions from this research, though it would appear that some of the hedgehogs in the survey had welfare comparable to their free-living counterparts.

Ten years of enzyme replacement therapy in paediatric onset mucopolysaccharidosis II in England.

The outcome of 110 patients with paediatric onset mucopolysaccharidosis II (MPS II) since the commercial introduction of enzyme replacement therapy (ERT) in England in 2007 is reported. Median length of follow up was 10 years 3 months (range = 1 y 2 m to 18 years 6 month). 78 patients were treated with ERT, 18 had no ERT or disease modifying treatment 7 had haematopoietic stem cell transplant, 4 experimental intrathecal therapy and 3 were lost to follow up. There is clear evidence of improved survival (median age of death of ERT treated (n = 16) = 15.13 years (range = 9.53 to 20.58 y), and untreated (n = 17) = 11.43 y (0.5 to 19.13 y) p = .0005). Early introduction of ERT improved respiratory outcome at 16 years, the median FVC (% predicted) of those in whom ERT initiated <8 years = 69% (range = 34-86%) and 48% (25-108) (p = .045) in those started >8 years. However, ERT appears to have minimal impact on hearing, carpal tunnel syndrome or progression of cardiac valvular disease. Cardiac valvular disease occurred in 18/46 (40%), with progression occurring most frequently in the aortic valve 13/46 (28%). The lack of requirement for neurosurgical intervention in the first 8 years of life suggests that targeted imaging based on clinical symptomology would be safe in this age group after baseline assessments. There is also emerging evidence that the neurological phenotype is more nuanced than the previously recognized dichotomy of severe and attenuated phenotypes in patients presenting in early childhood.

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.

Outcomes from 18 years of cervical spine surgery in MPS IVA: a single centre's experience.

PURPOSE: This study examines the long-term outcomes of paediatric Morquio (MPS IVA) patients undergoing cervical spine surgery and evaluates the factors that impacting this. METHODS: A retrospective review was performed on all MPS IVA patients undergoing cervical spine surgery, since the introduction of standardised neuroradiological screening. The impact of preoperative neurological status, growth, genotype and radiological status on outcome is assessed, whilst long-term surgical, radiological and neurological outcomes are documented. RESULTS: Twenty-six of the eighty-two MPS IVA patients (31%) reviewed underwent cervical spine surgery at a median age of 6.1 years (range, 1.45 to 15.24). Preoperatively, cord signal change was seen in 11 patients with 5 being myelopathic; however, 6 clinically manifesting patients had no overt cord signal change. Postoperatively, none of the 14 preoperatively clinically asymptomatic patients followed long term progressed neurologically during a median follow-up of 77.5 months (range = 18-161). Of the ten preoperatively clinically symptomatic patients who were followed up for the same duration, seven continued to deteriorate, two initially improved and one remained stable. Radiological follow-up performed for a median duration of 7 years (range = 0.5-16) has shown a degree of stenosis at the level immediately caudal to the termination of the graft in 76% of patients, though only one has become clinically symptomatic and required revision. CONCLUSIONS: Once clinically elicitable neurological signs become evident in patients with MPS IVA, they tend to progress despite surgical intervention. Referring clinicians should also not be falsely reassured by the lack of T2 spinal cord signal change but should consider surgical intervention in the face of new clinical symptomology or radiological signs of progressive canal stenosis or instability.

Foam flow in a model porous medium: II. The effect of trapped gas.

Gas trapping is an important mechanism in both Water or Surfactant Alternating Gas (WAG/SAG) and foam injection processes in porous media. Foams for enhanced oil recovery (EOR) can increase sweep efficiency as they decrease the gas relative permeability, and this is mainly due to gas trapping. However, gas trapping mechanisms are poorly understood. Some studies have been performed during corefloods, but little work has been carried out to describe the bubble trapping behaviour at the pore scale. We have carried out foam flow tests in a micromodel etched with an irregular hexagonal pattern. Image analysis of the foam flow allowed the bubble centres to be tracked and local velocities to be obtained. It was found that the flow in the micromodel is dominated by intermittency and localized zones of trapped gas. The quantity of trapped gas was measured both by considering the fraction of bubbles that were trapped (via velocity thresholding) and by measuring the area fraction containing immobile gas (via image analysis). A decrease in the quantity of trapped gas was observed for both increasing total velocity and increasing foam quality. Calculations of the gas relative permeability were made with the Brooks Corey equation, using the measured trapped gas saturations. The results showed a decrease in gas relative permeabilities, and gas mobility, for increasing fractions of trapped gas. It is suggested that the shear thinning behaviour of foam could be coupled to the saturation of trapped gas.

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.

Foam flow in a model porous medium: I. The effect of foam coarsening.

Foam structure evolves with time due to gas diffusion between bubbles (coarsening). In a bulk foam, coarsening behaviour is well defined, but there is less understanding of coarsening in confined geometries such as porous media. Previous predictions suggest that coarsening will cause foam lamellae to move to low energy configurations in the pore throats, resulting in greater capillary resistance when restarting flow. Foam coarsening experiments were conducted in both a model-porous-media micromodel and in a sandstone core. In both cases, foam was generated by coinjecting surfactant solution and nitrogen. Once steady state flow had been achieved, the injection was stopped and the system sealed off. In the micromodel, the foam coarsening was recorded using time-lapse photography. In the core flood, the additional driving pressure required to reinitiate flow after coarsening was measured. In the micromodel the bubbles coarsened rapidly to the pore size. At the completion of coarsening the lamellae were located in minimum energy configurations in the pore throats. The wall effect meant that the coarsening did not conform to the unconstricted growth laws. The coreflood tests also showed coarsening to be a rapid process. The additional driving pressure to restart flow reached a maximum after just 2 minutes.

IL-27: a double agent in the IL-6 family.

The cytokine interleukin (IL)-6 is a major therapeutic target for the treatment of various inflammatory and autoimmune diseases. While IL-6 receives considerable attention in studies of innate and adaptive immunity, the IL-6-related family member IL-27 is recognized increasingly for its effects on cellular proliferation, differentiation and leucocyte effector functions. Both cytokines activate responses in myeloid and stromal tissue cells, where they direct the transition from innate to adaptive immunity. However, they are identified frequently as lymphokines that control responses in T cells and B cells. In this regard, IL-27 often opposes the action of IL-6. Here, we will review the role of IL-6 and IL-27 in inflammation, with a particular focus on inflammatory arthritis, and discuss their importance in the diagnosis, stratification and treatment of autoimmune disease.

Enhanced Control and Reproducibility of Non-Neutral Plasmas.

The simultaneous control of the density and particle number of non-neutral plasmas confined in Penning-Malmberg traps is demonstrated. Control is achieved by setting the plasma's density by applying a rotating electric field while simultaneously fixing its axial potential via evaporative cooling. This novel method is particularly useful for stabilizing positron plasmas, as the procedures used to collect positrons from radioactive sources typically yield plasmas with variable densities and particle numbers; it also simplifies optimization studies that require plasma parameter scans. The reproducibility achieved by applying this technique to the positron and electron plasmas used by the ALPHA antihydrogen experiment at CERN, combined with other developments, contributed to a 10-fold increase in the antiatom trapping rate.

Rapidly Progressive White Matter Involvement in Early Childhood: The Expanding Phenotype of Infantile Onset Pompe?

Glycogen accumulation in the central nervous system of patients with classical infantile onset Pompe disease (IOPD) has been a consistent finding on the few post-mortems performed. While delays in myelination and a possible reduction in processing speed have previously been noted, it has only been recently that the potential for clinically significant progressive white matter disease has been noted. The limited reports thus far published infer that in some IOPD patients, this manifests as intellectual decline in the second decade of life. We present a CRIM negative patient, immunomodulated with rituximab and methotrexate at birth, who despite an initial good clinical response to ERT, at the age of just under 4 years, presented with evolving spasticity in the lower limbs. The investigation of which revealed progressive central nervous system involvement. Given both the earlier onset of the symptoms and consanguineous familial pedigree, extensive biochemical and genetic investigation was undertaken to ensure no alternative pathology was elucidated. In light of these findings, we review the radiology and post-mortems of previous cases and discuss the potential mechanisms that may underlie this presentation.

Erratum: Observation of the hyperfine spectrum of antihydrogen.

This corrects the article DOI: 10.1038/nature23446.