Erratum: Observation of the hyperfine spectrum of antihydrogen.

This corrects the article DOI: 10.1038/nature23446.

Nitrate-Stimulated Release of Naturally Occurring Sedimentary Uranium.

Groundwater uranium (U) concentrations have been measured above the U.S. EPA maximum contaminant level (30 µg/L) in many U.S. aquifers, including in areas not associated with anthropogenic contamination by milling or mining. In addition to carbonate, nitrate has been correlated to uranium groundwater concentrations in two major U.S. aquifers. However, to date, direct evidence that nitrate mobilizes naturally occurring U from aquifer sediments has not been presented. Here, we demonstrate that the influx of high-nitrate porewater through High Plains alluvial aquifer silt sediments bearing naturally occurring U(IV) can stimulate a nitrate-reducing microbial community capable of catalyzing the oxidation and mobilization of U into the porewater. Microbial reduction of nitrate yielded nitrite, a reactive intermediate, which was further demonstrated to abiotically mobilize U from the reduced alluvial aquifer sediments. These results indicate that microbial activity, specifically nitrate reduction to nitrite, is one mechanism driving U mobilization from aquifer sediments in addition to previously described bicarbonate-driven desorption from mineral surfaces, such as Fe(III) oxides.

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.

Effective temperature for an intermittent bistable potential.

Thermodynamics of far-from-equilibrium systems often require measurement of effective parameters such as temperature. Whether such approach is valid for the general case of resetting protocols, active systems, or of confined systems under time-varying fields is still under investigation. We report on the effect of switching ON-OFF of an asymmetric bistable potential to the mean first passage time (MFPT) of a probed particle to go from one potential minima to the other. Experimental results coupled with numerical simulations shows the potential becoming more symmetric at slow switching. Moreover, the MFPT deviates from equilibrium condition with an effective temperature, Teff < T, at slow switching but approaches room temperature, T, at fast switching. For each switching rate, we quantify how far the system is from equilibrium by measuring deviation from a detailed balance like relation and the net circulation of flux present in phase-space. Both analysis suggest equilibrium condition are met at high switching.

An improved limit on the charge of antihydrogen from stochastic acceleration.

Antimatter continues to intrigue physicists because of its apparent absence in the observable Universe. Current theory requires that matter and antimatter appeared in equal quantities after the Big Bang, but the Standard Model of particle physics offers no quantitative explanation for the apparent disappearance of half the Universe. It has recently become possible to study trapped atoms of antihydrogen to search for possible, as yet unobserved, differences in the physical behaviour of matter and antimatter. Here we consider the charge neutrality of the antihydrogen atom. By applying stochastic acceleration to trapped antihydrogen atoms, we determine an experimental bound on the antihydrogen charge, Qe, of |Q| < 0.71 parts per billion (one standard deviation), in which e is the elementary charge. This bound is a factor of 20 less than that determined from the best previous measurement of the antihydrogen charge. The electrical charge of atoms and molecules of normal matter is known to be no greater than about 10(-21)e for a diverse range of species including H2, He and SF6. Charge-parity-time symmetry and quantum anomaly cancellation demand that the charge of antihydrogen be similarly small. Thus, our measurement constitutes an improved limit and a test of fundamental aspects of the Standard Model. If we assume charge superposition and use the best measured value of the antiproton charge, then we can place a new limit on the positron charge anomaly (the relative difference between the positron and elementary charge) of about one part per billion (one standard deviation), a 25-fold reduction compared to the current best measurement.

Excitable dynamics of Physarum polycephalum plasmodial nodes under chemotaxis.

Recent results show that the chemotactic response of uni-cellular decentralized systems such as amoeboid and mammalian cells, is excitable. The same observation has not yet been reported for multi-nucleated decentralized biological systems. Here we present experimental results that shows the Physarum polycephalum plasmodial nodes spatio-temporal chemotactic dynamics as an excitable response. We found a highly optimized signal synthesis method wherein the Physarum nodes employ two intensity thresholds to properly navigate the chemoattractant field and generate corresponding spike dynamics in the node count. The node spike dynamics was found to correspond to the polarized-depolarized transition in the Physarum polycephalum morphology. Validation of our experimental observations via Brownian lattice simulations yields the same quantitative results with our experiments.

A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies.

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.

Resonant quantum transitions in trapped antihydrogen atoms.

The hydrogen atom is one of the most important and influential model systems in modern physics. Attempts to understand its spectrum are inextricably linked to the early history and development of quantum mechanics. The hydrogen atom's stature lies in its simplicity and in the accuracy with which its spectrum can be measured and compared to theory. Today its spectrum remains a valuable tool for determining the values of fundamental constants and for challenging the limits of modern physics, including the validity of quantum electrodynamics and--by comparison with measurements on its antimatter counterpart, antihydrogen--the validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we report spectroscopy of a pure antimatter atom, demonstrating resonant quantum transitions in antihydrogen. We have manipulated the internal spin state of antihydrogen atoms so as to induce magnetic resonance transitions between hyperfine levels of the positronic ground state. We used resonant microwave radiation to flip the spin of the positron in antihydrogen atoms that were magnetically trapped in the ALPHA apparatus. The spin flip causes trapped anti-atoms to be ejected from the trap. We look for evidence of resonant interaction by comparing the survival rate of trapped atoms irradiated with microwaves on-resonance to that of atoms subjected to microwaves that are off-resonance. In one variant of the experiment, we detect 23 atoms that survive in 110 trapping attempts with microwaves off-resonance (0.21 per attempt), and only two atoms that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We also describe the direct detection of the annihilation of antihydrogen atoms ejected by the microwaves.

Trapped antihydrogen.

Antimatter was first predicted in 1931, by Dirac. Work with high-energy antiparticles is now commonplace, and anti-electrons are used regularly in the medical technique of positron emission tomography scanning. Antihydrogen, the bound state of an antiproton and a positron, has been produced at low energies at CERN (the European Organization for Nuclear Research) since 2002. Antihydrogen is of interest for use in a precision test of nature's fundamental symmetries. The charge conjugation/parity/time reversal (CPT) theorem, a crucial part of the foundation of the standard model of elementary particles and interactions, demands that hydrogen and antihydrogen have the same spectrum. Given the current experimental precision of measurements on the hydrogen atom (about two parts in 10(14) for the frequency of the 1s-to-2s transition), subjecting antihydrogen to rigorous spectroscopic examination would constitute a compelling, model-independent test of CPT. Antihydrogen could also be used to study the gravitational behaviour of antimatter. However, so far experiments have produced antihydrogen that is not confined, precluding detailed study of its structure. Here we demonstrate trapping of antihydrogen atoms. From the interaction of about 10(7) antiprotons and 7 × 10(8) positrons, we observed 38 annihilation events consistent with the controlled release of trapped antihydrogen from our magnetic trap; the measured background is 1.4 ± 1.4 events. This result opens the door to precision measurements on anti-atoms, which can soon be subjected to the same techniques as developed for hydrogen.

Verification Testing to Confirm VO2max in Altitude-Residing, Endurance-Trained Runners.

We sought to explore the utility of the verification trial to confirm individual attainment of 'true' VO2max in altitude-residing, endurance-trained runners during treadmill exercise. 24 elite endurance-trained men and women runners (age=21.5±3.3 yr, ht=174.8±9.3 cm, body mass=60.5±6.7 kg, PR 800 m 127.5±13.1 s) completed a graded exercise test (GXT) trial (VO2max=60.0±5.8 mL·kg(-1)·min(-1)), and returned 20 min after incremental exercise to complete a verification trial (VO2max=59.6±5.7 mL·kg(-1)·min(-1)) of constant load, supramaximal exercise. The incidence of 'true' VO2max confirmation using the verification trial was 24/24 (100%) with all participants revealing differences in VO2max≤3% (the technical error of our equipment) between the GXT and verification trials. These findings support use of the verification trial to confirm VO2max attainment in altitude-residing, endurance-trained runners.

Social jetlag, obesity and metabolic disorder: investigation in a cohort study.

BACKGROUND: Obesity is one of the leading causes of preventable death worldwide. Circadian rhythms are known to control both sleep timing and energy homeostasis, and disruptions in circadian rhythms have been linked with metabolic dysfunction and obesity-associated disease. In previous research, social jetlag, a measure of chronic circadian disruption caused by the discrepancy between our internal versus social clocks, was associated with elevated self-reported body mass index, possibly indicative of a more generalized association with obesity and metabolic dysfunction. METHODS: We studied participants from the population-representative Dunedin Longitudinal Study (N=1037) to determine whether social jetlag was associated with clinically assessed measurements of metabolic phenotypes and disease indicators for obesity-related disease, specifically, indicators of inflammation and diabetes. RESULTS: Our analysis was restricted to N=815 non-shift workers in our cohort. Among these participants, we found that social jetlag was associated with numerous clinically assessed measures of metabolic dysfunction and obesity. We distinguished between obese individuals who were metabolically healthy versus unhealthy, and found higher social jetlag levels in metabolically unhealthy obese individuals. Among metabolically unhealthy obese individuals, social jetlag was additionally associated with elevated glycated hemoglobin and an indicator of inflammation. CONCLUSIONS: The findings are consistent with the possibility that 'living against our internal clock' may contribute to metabolic dysfunction and its consequences. Further research aimed at understanding that the physiology and social features of social jetlag may inform obesity prevention and have ramifications for policies and practices that contribute to increased social jetlag, such as work schedules and daylight savings time.

Clusterin regulates ß-amyloid toxicity via Dickkopf-1-driven induction of the wnt-PCP-JNK pathway.

Although the mechanism of Aß action in the pathogenesis of Alzheimer's disease (AD) has remained elusive, it is known to increase the expression of the antagonist of canonical wnt signalling, Dickkopf-1 (Dkk1), whereas the silencing of Dkk1 blocks Aß neurotoxicity. We asked if clusterin, known to be regulated by wnt, is part of an Aß/Dkk1 neurotoxic pathway. Knockdown of clusterin in primary neurons reduced Aß toxicity and DKK1 upregulation and, conversely, Aß increased intracellular clusterin and decreased clusterin protein secretion, resulting in the p53-dependent induction of DKK1. To further elucidate how the clusterin-dependent induction of Dkk1 by Aß mediates neurotoxicity, we measured the effects of Aß and Dkk1 protein on whole-genome expression in primary neurons, finding a common pathway suggestive of activation of wnt-planar cell polarity (PCP)-c-Jun N-terminal kinase (JNK) signalling leading to the induction of genes including EGR1 (early growth response-1), NAB2 (Ngfi-A-binding protein-2) and KLF10 (Krüppel-like factor-10) that, when individually silenced, protected against Aß neurotoxicity and/or tau phosphorylation. Neuronal overexpression of Dkk1 in transgenic mice mimicked this Aß-induced pathway and resulted in age-dependent increases in tau phosphorylation in hippocampus and cognitive impairment. Furthermore, we show that this Dkk1/wnt-PCP-JNK pathway is active in an Aß-based mouse model of AD and in AD brain, but not in a tau-based mouse model or in frontotemporal dementia brain. Thus, we have identified a pathway whereby Aß induces a clusterin/p53/Dkk1/wnt-PCP-JNK pathway, which drives the upregulation of several genes that mediate the development of AD-like neuropathologies, thereby providing new mechanistic insights into the action of Aß in neurodegenerative diseases.

The incidence of V˙O2 plateau at V˙O2max in a cardiac-diseased population.

We sought to determine the incidence of V˙O(2) plateau at V˙O(2)max in a cardiovascular-diseased (CVD) population using 4 different sampling intervals (15-breath moving average, 15 s, 30 s, and 60 s) and 3 different V˙O(2) plateau criteria (≤50 mL · min(-1), ≤80 mL · min(-1), and ≤150 mL · min(-1)). A total of 69 people (62 ± 10 yrs.) with recently diagnosed CVD performed a maximal exercise test (10:07 ± 2:24 min) on a treadmill. The test was classified as maximal (n = 57, 2 430 ± 605 mL · min(-1)) if self-terminated due to fatigue or classified as symptom-limited (n = 12, 1 683 ± 438 mL · min(-1)) if symptoms presented. Chi-square analysis revealed a significant (p < 0.05) effect of sampling interval on incidence of V˙O(2) plateau at V˙O(2)max across all 3 V˙O(2) plateau criteria. The sampling interval had an increasingly stronger influence on the incidence of V˙O(2) plateau at V˙O(2)max with smaller criterion thresholds as evidenced by the Cramer's V statistics: [≤50 mL · min(-1) (Cramer's V = 0.548, p < 0.05], ≤80 mL · min(-1) [Cramer's V = 0.489, p < 0.05], ≤150 mL · min(-1) [Cramer's V = 0.214, p < 0.05]. Incidence of V˙O(2) plateau at V˙O(2)max in CVD individuals is significantly influenced by the sampling interval applied. Based on our findings we recommend a15 breath moving average and V˙O(2) plateau criterion of ≤50 mL · min(-1).

Comparison of intensities and rest periods for VO2max verification testing procedures.

We sought to determine the incidence of 'true' VO2max confirmation with the verification procedure across different protocols. 12 active participants (men n=6, women n=6) performed in random order 4 different maximal graded exercises tests (GXT) and verification bout protocols on 4 separate days. Conditions for the rest period and verification bout intensity were: A - 105% intensity, 20 min rest; B - 105% intensity, 60 min rest; C - 115% intensity, 20 min rest; D - 115% intensity, 60 min rest. VO2max confirmation (difference between peak VO2 GXT and verification trial<±3%) using the verification trial was 12/12 (100%), 12/12 (100%), 8/12 (66.70%), and 7/12 (58.33%) for protocols A, B, C, and D. There was a significant (p<0.05) effect of verification intensity on VO2max confirmation across all exercise test conditions (intensity effect within recovery 20 min (χ(2) (1)=4.800, p<0.05), intensity effect within recovery 60 min (χ(2) (1)=6.316, p<0.05)). No significant effect was found for incidence of VO2max confirmation with different rest periods. We recommend the use of 105% of the maximal GXT workload and 20 min rest periods when using verification trials to confirm VO2max in normally active populations.

A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse.

As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.

Primary Retrograde Tibiotalocalcaneal Nailing in an Elderly Osteoporotic Patient With Ankle Fracture: A Case Report.

Introduction: Ankle fractures are a common orthopedic injury traditionally treated with open reduction and internal fixation or conservative management. One complication introduced with open reduction and internal fixation is the requirement for non or partial weight bearing in the post-operative period. This requirement poses a unique challenge for patients who may not comply with these weight-bearing restrictions. This case is the first known article that specifically illustrates the validity and effectiveness of retrograde tibiotalocalcaneal (TTC) nailing for patients who are unlikely to follow weight-bearing restrictions. Case Report: An 83-year-old Caucasian female with idiopathic mild mental retardation and Alzheimer's presented with a minimally displaced trimalleolar ankle fracture and was treated at a single urban hospital with a retrograde TTC nail secondary to her inability to adhere to weight-bearing restrictions post-operatively. Pertinent demographic, clinical, radiographic, and surgical data were collected. The patient had minimal post-operative pain, was able to bear weight on the day of surgery, and had no post-operative complications. Conclusion: This case report demonstrates that the use of a TTC nail is a safe and effective mode of fixation for ankle fractures in patient populations who may not adhere to weight-bearing restrictions post-operatively. The main benefits of fixation with a TTC nail are the ability to weight bear as tolerated post-operatively and decreased wound complications while having similar functional outcomes to open reduction and internal fixation. We suggest the use of TTC nails for ankle fractures in select patients who may not adhere to weight-bearing restrictions post-operatively.

Differences Between Patients With Diabetes Mellitus and Those Without in Cases of Necrotizing Fasciitis.

Purposes This study aims to evaluate further differences between patients with diabetes and those without who have been diagnosed with necrotizing fasciitis (NF) to assist clinicians in improving morbidity and mortality. Methods All patients diagnosed with NF of an extremity were retrospectively reviewed and divided into two groups based on a diagnosis of diabetes. Patient charts were reviewed to obtain multiple variables, which were compared between groups. Results From 2015 to 2021, 115 patients underwent surgical intervention due to concern for NF of an extremity with 92 patients included for data computation. Patients with diabetes had an average Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score of 9.02 compared to 7.24 (p=0.02). Patients with diabetes had a significantly higher rate of undergoing amputation when diagnosed with NF (p<0.0001). The mortality rate for diabetes and non-diabetes cohorts were 30.9% and 18.9%, respectively (p=0.2). Conclusion This study demonstrated that patients with diabetes with confirmed NF of an extremity had a significantly higher LRINEC score were more likely to undergo an amputation primarily, and were more likely to have a polymicrobial infection compared to those without. The overall mortality rate of NF was 26.1%.

Outpatient Surgery for Rib Fracture Fixation: A Report of Three Cases.

Rib fractures are common injuries observed in trauma patients that will often heal without operative intervention. However, patients can infrequently have continued pain. Operative fixation of these symptomatic rib fractures has traditionally led to the patient requiring hospital admission for observation and pain control. The purpose of this study was to review three cases of outpatient rib fracture, open reduction and internal fixation (ORIF) surgery. Three patients with symptomatic rib fractures treated with ORIF at a single urban level one trauma center underwent outpatient same-day surgery. Pertinent demographic, clinical, radiographic, and surgical data were collected. All patients had decreased preoperative pain and no complications. This case series demonstrates that outpatient surgery for rib fracture ORIF can be performed safely in a select patient population. Additionally, it has similar efficacy as inpatient operative fixation with the main added benefit being decreased costs to both the patient and the healthcare system. We suggest that outpatient operative fixation of rib fractures should be considered for select patients.

Autoresonant excitation of antiproton plasmas.

We demonstrate controllable excitation of the center-of-mass longitudinal motion of a thermal antiproton plasma using a swept-frequency autoresonant drive. When the plasma is cold, dense, and highly collective in nature, we observe that the entire system behaves as a single-particle nonlinear oscillator, as predicted by a recent theory. In contrast, only a fraction of the antiprotons in a warm plasma can be similarly excited. Antihydrogen was produced and trapped by using this technique to drive antiprotons into a positron plasma, thereby initiating atomic recombination.