Laboratory Study of Collisionless Magnetic Reconnection.

A concise review is given on the past two decades' results from laboratory experiments on collisionless magnetic reconnection in direct relation with space measurements, especially by the Magnetospheric Multiscale (MMS) mission. Highlights include spatial structures of electromagnetic fields in ion and electron diffusion regions as a function of upstream symmetry and guide field strength, energy conversion and partitioning from magnetic field to ions and electrons including particle acceleration, electrostatic and electromagnetic kinetic plasma waves with various wavelengths, and plasmoid-mediated multiscale reconnection. Combined with the progress in theoretical, numerical, and observational studies, the physics foundation of fast reconnection in collisionless plasmas has been largely established, at least within the parameter ranges and spatial scales that were studied. Immediate and long-term future opportunities based on multiscale experiments and space missions supported by exascale computation are discussed, including dissipation by kinetic plasma waves, particle heating and acceleration, and multiscale physics across fluid and kinetic scales.

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.

Mating allocations in Holstein combining genomic information and linear programming optimization at the herd level.

In this study, we explored mating allocation in Holstein using genomic information for 24,333 Holstein females born in Denmark, Finland, and Sweden. We used 2 data sets of bulls: the top 50 genotyped bulls and the top 25 polled genotyped bulls on the Nordic total merit scale. We used linear programming to optimize economic scores within each herd, considering genetic level, genetic relationship, semen cost, the economic impact of genetic defects, polledness, and ß-casein. We found that it was possible to reduce genetic relationships and eliminate expression of genetic defects with minimal effect on the genetic level in total merit index. Compared with maximizing only Nordic total merit index, the relative frequency of polled offspring increased from 13.5 to 22.5%, and that of offspring homozygous for ß-casein (A2A2) from 66.7 to 75.0% in one generation, without any substantial negative impact on other comparison criteria. Using only semen from polled bulls, which might become necessary if dehorning is banned, considerably reduced the genetic level. We also found that animals carrying the polled allele were less likely to be homozygous for ß-casein (A2A2) and more likely to be carriers of the genetic defect HH1. Hence, adding economic value to a monogenic trait in the economic score used for mating allocation sometimes negatively affected another monogenetic trait. We recommend that the comparison criteria used in this study be monitored in a modern genomic mating program.

Future Exploration of the Outer Heliosphere and Very Local Interstellar Medium by Interstellar Probe.

A detailed overview of the knowledge gaps in our understanding of the heliospheric interaction with the largely unexplored Very Local Interstellar Medium (VLISM) are provided along with predictions of with the scientific discoveries that await. The new measurements required to make progress in this expanding frontier of space physics are discussed and include in-situ plasma and pick-up ion measurements throughout the heliosheath, direct sampling of the VLISM properties such as elemental and isotopic composition, densities, flows, and temperatures of neutral gas, dust and plasma, and remote energetic neutral atom (ENA) and Lyman-alpha (LYA) imaging from vantage points that can uniquely discern the heliospheric shape and bring new information on the interaction with interstellar hydrogen. The implementation of a pragmatic Interstellar Probe mission with a nominal design life to reach 375 Astronomical Units (au) with likely operation out to 550 au are reported as a result of a 4-year NASA funded mission study.

Cognitive impairment in REM-sleep behaviour disorder and individuals at risk of Parkinson's disease.

BACKGROUND: Mild cognitive impairment (MCI) is commonly present at the time of Parkinson's Disease (PD) diagnosis, but its prevalence amongst individuals at increased risk of PD is unclear. METHODS: Cognition was assessed using the Montreal Cognitive Assessment (MoCA) in 208 participants in the PREDICT-PD study, and 25 participants with REM-sleep behaviour disorder (RBD). Prevalence of MCI level I was determined in all participants, and level II MCI in the RBD sub-group. RESULTS: Total MoCA scores were worse in the higher risk than the lower risk group defined as those below the 15th percentile of risk (p = 0.009), and in the RBD group compared to all healthy participants (p < 0.001). The prevalence of MCI level I was 12.8% in the lower-risk, 21.9% in the higher-risk (within the highest 15th percentile) and 64% in RBD participants; 66% of RBD participants had MCI level II with multi-domain MCI, but particularly attention and memory deficits. CONCLUSIONS: Cognitive impairment is increased in different groups at higher risk of PD, particularly in the subgroup formally diagnosed with RBD.

National compliance with UK wide guidelines for usage of valproate in women of childbearing potential.

Valproate (VPA) is an effective treatment for epilepsy and also used in bipolar disorder. However, VPA is associated with a significant risk of birth defects and developmental disorders if used during pregnancy. This has led to the introduction of measures to reduce the use of valproate in women of childbearing potential such as the 'Prevent' pregnancy prevention program (PPP) and the completion of an annual risk acknowledgement form (ARAF). The aim of the current audit was to assess compliance with the guidance. An audit tool was made available to neurologists registered with the Association of British Neurologists (ABN) and to epilepsy nurse specialists via the Epilepsy Nurses Association (ESNA) in the UK. Data were collected between November 2020 and March 2021. The main indication for valproate was generalised epilepsy (55.8%), followed by focal (22.5%). For most, there was documentation that the woman had been informed about the risks associated with taking valproate during pregnancy (93.1%) and the need to be on highly effective contraception or that this was not deemed appropriate (92.2%). A signed ARAF was available in the notes for 81.2% although only 66% were <12 months old. Although information had been made available for most women, there were still individuals where this was not documented. Further work is needed to facilitate identification of women taking valproate and implementation of a digital ARAF. For clinicians, the audit highlights a need to carefully counsel women about the teratogenic risks of continuing to take valproate versus the risk of deteriorating seizure control if the drug is withdrawn. This is particularly true of women with focal epilepsy, where there may be safer, equally effective, alternative anti-seizure medication (ASM). The aim should be to create a partnership of trust between the patient and clinician in order to arrive at the best clinical decision for that individual.

Serum TK1 protein and C-reactive protein correlate to treatment response and predict survival in dogs with hematologic malignancies.

Thymidine kinase 1 (TK1), involved in DNA precursor synthesis, is used as a serum biomarker in cancer diagnostics in both human and veterinary medicine. We investigated the utility of serum TK1 protein (TK1p) and TK1 activity (TK1a) determinations for prognosis and monitoring of canine hematological malignancies. The combination of TK1p or TK1a with canine C-reactive protein (CRP) determinations was also investigated. Serum samples from 51 client-owned dogs with naive hematological malignancies and from 149 healthy subjects were included. Serum TK1p levels were determined using a prototype TK1-ELISA, TK1a using the [3H]-dThd phosphorylation assay, and CRP using an immunoturbidimetric assay. Mean TK1p in sera from dogs with tumors was significantly higher than from healthy dogs (mean ± SD = 3.9 ± 5.9 vs. 0.45 ± 0.15 ng/mL). Similarly, TK1a in hematological malignancies was significantly higher than in healthy dogs (mean ± SD = 15.1 ± 31.3 vs. 0.96 ± 0.33 pmol/min/mL). The receiver-operating characteristic indicated that a combination of TK1p or TK1a with CRP gave higher sensitivity than either biomarker alone for the prognosis of hematological malignancies. Median pretreatment TK1p and TK1a levels were significantly higher than in dogs in remission and correlated with clinical outcome. Kaplan-Meier curve analysis showed that naive dogs with high TK1p, TK1a, and CRP had significantly shorter survival. This study present two new polyclonal antibodies used in an ELISA system to determine TK1p. The study also show that combining TK1p or TK1a with CRP gave higher sensitivity than either biomarker alone. Monitoring patients in the study while undergoing chemotherapy, suggests that the TK1 + CRP combination could be useful in a biomarker panel, possibly aiding the prognosis and therapy monitoring of hematological malignancies in dogs.

Mating allocations in Nordic Red Dairy Cattle using genomic information.

In this study, we compared mating allocations in Nordic Red Dairy Cattle using genomic information. We used linear programming to optimize different economic scores within each herd, considering genetic level, semen cost, the economic impact of recessive genetic defects, and genetic relationships. We selected 9,841 genotyped females born in Denmark, Finland, or Sweden in 2019 for mating allocations. We used 2 different pedigree relationship coefficients, the first tracing the pedigree 3 generations back from the parents of the potential mating and the second based on all available pedigree information. We used 3 different genomic relationship coefficients, 1 SNP-by-SNP genomic relationship and 2 based on shared genomic segments. We found high correlations (≥0.83) between the pedigree and genomic relationship measures. The mating results showed that it was possible to reduce the different genetic relationships between parents with minimal effect on genetic level. Including the cost of known recessive genetic defects eliminated expression of genetic defects. It was possible to reduce genomic relationships between parents with pedigree measures, but it was best done with genomic measures. Linear programming maximized the economic score for all herds studied within seconds, which means that it is suitable for implementation in mating software to be used by advisors and farmers.

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.

Impact of preoperative breast MRI on 10-year survival of patients included in the Swedish randomized multicentre POMB trial.

BACKGROUND: The value of preoperative breast MRI as an adjunct technique regarding its effect on re-excision rates has been a subject of discussion. No survival data regarding preoperative breast MRI are available from randomized studies. METHODS: Ten-year follow-up of the POMB randomized multicentre study was analysed, evaluating MRI and its effect on disease-free survival (DFS) and overall survival (OS). Patients with newly diagnosed breast cancer were randomized to either preoperative MRI or conventional imaging. Kaplan-Meier plots were used to analyse DFS and OS, and Cox regression to estimate hazard ratios (HRs). RESULTS: A total of 440 patients, aged 56 years or less, with newly diagnosed breast cancer were randomized to either preoperative MRI (220) or conventional imaging (220; control). Median follow-up for each group was 10 years. DFS rates were 85.5 and 80.0 per cent for the MRI and control groups respectively (P = 0.099). The risk of relapse or death was 46 per cent higher in the control group (HR 1.46, 95 per cent c.i. 0.93 to 2.29). OS rates after 10 years were 90.9 and 88.6 per cent in the MRI and control groups respectively (P = 0.427). The risk of death was 27 per cent higher in the control group (HR 1.27, 0.71 to 2.29). Locoregional, distant, and contralateral recurrence outcomes combined were increased in the control group (P = 0.048). A subgroup analysis of patients with breast cancer stages I-III showed that preoperative MRI improved DFS compared with conventional imaging, but this did not reach statistical significance (P = 0.057). CONCLUSION: After 10 years of follow-up, preoperative breast MRI as an adjunct to conventional imaging resulted in slightly, but non-significantly, improved DFS and OS. Registration number: NCT01859936 (http://www.clinicaltrials.gov).

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.

Standard procedures for the diagnostic pathway of sleep-related epilepsies and comorbid sleep disorders: an EAN, ESRS and ILAE-Europe consensus review.

BACKGROUND AND PURPOSE: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2). METHODS: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library. RESULTS: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control. CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.

Preferences regarding antibiotic treatment and the role of antibiotic resistance: A discrete choice experiment.

OBJECTIVES: To identify preferences of the Swedish public regarding antibiotic treatment characteristics and the relative weight of antibiotic resistance in their treatment choices. METHODS: A questionnaire including a discrete choice experiment questionnaire was answered by 378 Swedish participants. Preferences of the general public regarding five treatment characteristics (attributes) were measured: contribution to antibiotic resistance, cost, side effects, failure rate and treatment duration. Latent class analysis models were used to determine attribute-level estimates and heterogeneity in preferences. Relative importance of the attributes and willingness to pay for antibiotics with a lower contribution to antibiotic resistance were calculated from the estimates. RESULTS: All attributes influenced participants' preferences for antibiotic treatment. For the majority of participants, contribution to antibiotic resistance was the most important attribute. Younger respondents found contribution to antibiotic resistance more important in their choice of antibiotic treatments. Choices of respondents with lower numeracy, higher health literacy and higher financial vulnerability were influenced more by the cost of the antibiotic treatment. Older respondents with lower financial vulnerability and health literacy, and higher numeracy found side effects to be most important. CONCLUSIONS: All attributes can be considered as potential drivers of antibiotic use by lay people. Findings also suggest that the behaviour of lay people may be influenced by concerns over the rise of antibiotic resistance. Therefore, stressing individual responsibility for antibiotic resistance in clinical and societal communication has the potential to affect personal decision making.

Association of genomically enhanced and parent average breeding values with cow performance in Nordic dairy cattle.

This study compared the abilities of virgin heifer genomically enhanced breeding values (GEBV) and parent average breeding values (PA) to predict future cow performance. To increase confidence in genomic technology among farmers, a clear demonstration of the relationship between genomic predictions and future phenotypes is needed. We analyzed 12 different traits in first parity, including production, conformation, fertility, and other functional traits. Phenotype data were obtained from national milk recording schemes and breeding values from the Nordic Cattle Genetic Evaluation. Direct genomic breeding values were calculated using genomic BLUP and combined with traditional breeding values, using bivariate blending. The data covered 14,862 Red Dairy Cattle, 17,145 Holstein, and 7,330 Jersey genotyped virgin heifers born between 2013 and 2015 in Denmark, Finland, and Sweden. Phenotypes adjusted for systematic environmental effects were used as measures of cow performance. Two methods were used to compared virgin heifer GEBV and PA regarding their ability to predict future cow performance: (1) correlations between breeding values and adjusted phenotypes, (2) ranking cows into 4 quartiles for their virgin heifer GEBV or PA, and calculating actual cow performance for each quartile. We showed that virgin heifer GEBV predicted cow performance significantly better than PA for the vast majority of analyzed traits. The correlations with adjusted phenotypes were 38 to 136% higher for GEBV than for PA in Red Dairy Cattle, 42 to 194% higher for GEBV in Holstein, and 11 to 78% higher for GEBV in Jersey. The relative change between GEBV bottom and top quartiles compared with that between PA bottom and top quartiles ranged from 9 to 261% for RDC, 42 to 138% for Holstein, and 4 to 90% for Jersey. Hence, farmers in Denmark, Finland, and Sweden can have confidence in using genomic technology on their herds.

EAC-1A: A novel large-volume lunar regolith simulant.

The European Astronaut Centre (EAC) is currently constructing the European Lunar Exploration Laboratory (LUNA), a large training and operations facility to be located adjacent to EAC at the DLR (German Aerospace Centre) campus in Cologne, Germany. With an estimated representative lunar testbed area of approximately 660 m2, a large volume of lunar regolith simulant material is needed for this purpose. In this study, a basanitic sandy silt from a quarry located in the Siebengebirge Volcanic Field is evaluated as a large-volume source of material. The focus of this project has been to conduct a physical and chemical characterisation of the fine-grained material to be used in LUNA; the European Astronaut Centre lunar regolith simulant 1 (EAC-1 A). The physical characterisation tests undertaken include sphericity, density measurements, cohesion and static angle of repose, with mineralogical investigations via petrographical analysis with optical microscope and SEM, XRF, XRD and DSC measurements. The results of the EAC-1A tests are compared to published data on existing widely used lunar regolith simulants, namely JSC-1A, JSC-2A, NU-LHT-3M, DNA and FJS-1.

Risk factors for pancreatitis following endoscopic retrograde cholangiopancreatography.

The aim of this study was to assess whether sex, age, ASA grade, previous history of acute pancreatitis, diabetes, hyperlipidaemia, hypercalcaemia, kidney disease and liver cirrhosis influence the risk for developing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). A total of 15 800 ERCP procedures retrieved from the Swedish National Quality Register for Gallstone Surgery and ERCP (GallRiks) for 2006-2014 were identified and cross-checked with the National Patient Register. Women, patients aged less than 65 years, patients with hyperlipidaemia and those with a previous history of acute pancreatitis had a significantly increased risk of PEP, whereas patients with diabetes had a significantly decreased risk. Risk of pancreatitis following ERCP.

Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study).

BACKGROUND: One-fifth of patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) have invasive breast cancer (IBC) on definitive histology. Sentinel lymph node dissection (SLND) is performed in almost half of women having surgery for DCIS in Sweden. The aim of the present study was to try to minimize unnecessary SLND by injecting superparamagnetic iron oxide (SPIO) nanoparticles at the time of primary breast surgery, enabling SLND to be performed later, if IBC is found in the primary specimen. METHODS: Women with DCIS at high risk for the presence of invasion undergoing breast conservation, and patients with DCIS undergoing mastectomy were included. The primary outcome was whether this technique could reduce SLND. Secondary outcomes were number of SLNDs avoided, detection rate and procedure-related costs. RESULTS: This was a preplanned interim analysis of 189 procedures. IBC was found in 47 and a secondary SLND was performed in 41 women. Thus, 78·3 per cent of patients avoided SLND (P < 0·001). At reoperation, SPIO plus blue dye outperformed isotope and blue dye in detection of the sentinel node (40 of 40 versus 26 of 40 women; P < 0·001). Costs were reduced by a mean of 24·5 per cent in women without IBC (€3990 versus 5286; P < 0·001). CONCLUSION: Marking the sentinel node with SPIO in women having surgery for DCIS was effective at avoiding unnecessary SLND in this study. Registration number: ISRCTN18430240 (http://www.isrctn.com).

Doxorubicin effects on leukemia and breast cancer cells in culture on the TK1 protein levels using AroCell TK 210 ELISA: a tool for drug development.

In this study changes in thymidine kinase 1 (TK1) levels after 24 hours of Doxorubicin (Dox) exposure of CEM and MDA MB-231 cells were determined using the commercially available AroCell TK 210 ELISA test. In cell extracts, TK1 levels increased twofold with 1 µM Dox in both cell lines, while the TK1 levels in the culture media increased with 5 and 10 µM of Dox only in case of CEM cells. In conclusion, this study reveals that the TK 210 ELISA can measure changes in intra- and extracellular TK1 levels apparently related to the mechanism of cytotoxicity of anti-cancer agents.

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.