Improved Limits on the Coupling of Ultralight Bosonic Dark Matter to Photons from Optical Atomic Clock Comparisons.

We present improved constraints on the coupling of ultralight bosonic dark matter to photons based on long-term measurements of two optical frequency ratios. In these optical clock comparisons, we relate the frequency of the ^{2}S_{1/2}(F=0)↔^{2}F_{7/2}(F=3) electric-octupole (E3) transition in ^{171}Yb^{+} to that of the ^{2}S_{1/2}(F=0)↔^{2}D_{3/2}(F=2) electric-quadrupole (E2) transition of the same ion, and to that of the ^{1}S_{0}↔^{3}P_{0} transition in ^{87}Sr. Measurements of the first frequency ratio ν_{E3}/ν_{E2} are performed via interleaved interrogation of both transitions in a single ion. The comparison of the single-ion clock based on the E3 transition with a strontium optical lattice clock yields the second frequency ratio ν_{E3}/ν_{Sr}. By constraining oscillations of the fine-structure constant α with these measurement results, we improve existing bounds on the scalar coupling d_{e} of ultralight dark matter to photons for dark matter masses in the range of about (10^{-24}-10^{-17}) eV/c^{2}. These results constitute an improvement by more than an order of magnitude over previous investigations for most of this range. We also use the repeated measurements of ν_{E3}/ν_{E2} to improve existing limits on a linear temporal drift of α and its coupling to gravity.

Generation of three CRISPR/Cas9 edited human induced pluripotent stem cell lines (DHMi005-A-5, DHMi005-A-6 and DHMi005-A-7) carrying a Holt-Oram Syndrome patient-specific TBX5 mutation with known cardiac phenotype and a FLAG-tag after exon 9 of the TBX5 gene.

TBX5 is a transcription factor (TF) playing essential role during cardiogenesis. It is well known that TF mutations possibly result in non- or additional binding of the DNA due to conformational changes of the protein. We introduced a Holt-Oram Syndrome (HOS) patient-specific TBX5 mutation c.920_C > A heterozygously in a healthy induced pluripotent stell cell (iPSC) line. This TBX5 mutation results in conformational changes of the protein and displayed ventricular septal defects in the patient itself. Additionally we introduced a FLAG-tag on the TBX5 mutation-carrying allele. The resulting heterozygous TBX5-FLAG iPSC lines are a powerful tool to investigate altered TF activity bonding.

Vertebrates' roadkill in the southern region of the Atlantic Forest, Paraná coast - Brazil.

Being a significant global biodiversity hotspot, the Atlantic Forest has been drastically reduced by human activities. Among the anthropic activities that most affect the biodiversity of this biome is the construction and operation of roads and highways. Between harmful effects of these infrastructures, wildlife roadkill is currently considered one of the biggest causes of mortality of wild vertebrates. This study evaluated patterns of vertebrates' roadkill on two roads in the coastal region of the largest continuous remnant of the Brazilian Atlantic Forest. For twelve months, we carry out weekly samples with a motor vehicle at a constant speed of 40 km/h to search for carcasses along the roads. All carcasses found were georeferenced and identified to the lowest possible taxonomic level. Then, using Siriema v.2.0 software, we analyzed roadkill aggregation and the spatial distribution of hotspots of wildlife roadkill. In 43 sampling days, 209 road-killed animals were registered (average roadkill rate of 0.105 and 0.111 animals/kilometer/day for PR-407 e PR-508, respectively). Extrapolating the rates found, we estimate that about 1,773 animals can be roadkill every year on these roads. The most affected groups were birds (33.01%) and amphibians (30.62%), followed by reptiles (19.13%) and mammals (17.33%). Warmer months had the highest roadkill rates. We found two critical roadkill hotspots for the PR-407 (kilometer 11.7 to 12.5 and kilometer 14.7 to 16.7). For the PR-508, we found a critical point of 5.2 km (kilometer 5 to 10.2). As a short-term measure, we recommend installing speed reducers in the identified stretches and implementing environmental education campaigns with residents and tourists, especially during the summer months, aiming to mitigate the roadkill on both roads. However, due to the importance and environmental fragility of the area, we emphasize the need for running periodic road ecology and local wildlife population viability studies in the medium and long term.

Generation of two CRISPR/Cas edited human induced pluripotent stem cell lines (DHMi005-A-3 and DHMi005-A-4) carrying a FLAG-tag after exon 9 of the TBX5 gene.

Although TBX5 plays a major role during human cardiogenesis and initiates and controls limb development, many of its interactions with genomic DNA and the resulting biological consequences are not well known. Existing anti-TBX5-antibodies work very inefficiently in certain applications such as ChIP-Seq analysis. To circumvent this drawback, we introduced a FLAG-tag sequence into the TBX5 locus at the end of exon 9 prior to the stop codon by CRISPR/Cas9. The expressed TBX5-FLAG fusion protein can effectively be precipitated by anti-FLAG antibodies. Therefore, these gene-edited iPSC lines represent powerful cellular in vitro tools to unravel TBX5:DNA interactions in detail.

Human biomonitoring guidance values (HBM-GVs) for priority substances under the HBM4EU initiative - New values derivation for deltamethrin and cyfluthrin and overall results.

The European Initiative HBM4EU aimed to further establish human biomonitoring across Europe as an important tool for determining population exposure to chemicals and as part of health-related risk assessments, thus making it applicable for policy advice. Not only should analytical methods and survey design be harmonized and quality assured, but also the evaluation of human biomonitoring data. For the health-related interpretation of the data within HBM4EU, a strategy for deriving health-based human biomonitoring guidance values (HBM-GVs) for both the general population and workers was agreed on. On this basis, HBM-GVs for exposure biomarkers of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), phthalates (diethyl hexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), butyl benzyl phthalate (BBzP), and bis-(2-propylheptyl) phthalate (DPHP)), bisphenols A and S, pyrethroids (deltamethrin and cyfluthrin), solvents (1-methyl-2-pyrrolidone (NMP), 1-ethylpyrrolidin-2-one (NEP), N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC)), the heavy metal cadmium and the mycotoxin deoxynivalenol (DON) were developed and assigned a level of confidence. The approach to HBM-GV derivations, results, and limitations in data interpretation with special focus on the pyrethroids are presented in this paper.

Stop black and white thinking: Russula subgenus Compactae (Russulaceae, Russulales) in Europe revised.

Russula subgenus Compactae is a group of ectomycorrhizal basidiomycetes, usually with large pileate fruitbodies. European members of the group are characterised by the absence of bright colours on the surfaces of their pilei, the context turning grey to black after cutting, the abundance of short lamellulae in the hymenophore, and spores with an inamyloid suprahilar spot and with low reticulate ornamentation. Our multi-locus phylogenetic study confirmed that this morphological delimitation corresponds to a well-supported clade. Within this clade, 16 species are recognised in Europe, of which five belong to the R. albonigra lineage and were described in a previous study, while eleven are fully described in this study. The application of the names R. acrifolia, R. adusta, R. anthracina, R. atramentosa, R. densissima, R. nigricans and R. roseonigra is based on the position of sequences retrieved from types or authentic material. Based on type sequences, R. fuliginosa is synonymised with R. anthracina and two varieties of R. anthracina are considered synonyms of R. atramentosa. The application of the name R. densifolia is based on a morphological match with the traditional species interpretation and the neotype specimen. Three species are described as new, R. marxmuelleriana sp. nov., R. picrophylla sp. nov. and R. thuringiaca sp. nov. This study recognises three major lineages and two species with isolated positions within the European Compactae and a morphological barcode was assigned to the species using an analysis of 23 selected characters. A search of publicly available sequences from the UNITE database revealed that the majority of species are host tree generalists and widely distributed in temperate and Mediterranean areas of Europe. Russula adusta is the only species so far proven to form ectomycorrhiza exclusively with conifers. Citation: De Lange R, Kleine J, Hampe F, et al. 2023. Stop black and white thinking: Russula subgenus Compactae (Russulaceae, Russulales) in Europe revised. Persoonia 51: 152-193. doi: 10.3767/persoonia.2023.51.04.

Erratum: Coherent Excitation of the Highly Forbidden Electric Octupole Transition in

This corrects the article DOI: 10.1103/PhysRevLett.125.163001.

Establishment of an induced pluripotent stem cell line DHMi005-A from a healthy male proband.

We generated an induced pluripotent stem cell (iPSC) line from a healthy male 29-year-old proband. Adipose fibroblasts (AFs) were reprogrammed using Sendai virus. Generated iPSCs showed typical stem cell morphology. From passage 9 on, iPSCs were free of virus. Pluripotency in the iPSCs was verified and spontaneous differentiation showed expression of all three germ layers. Karyotyping indicated no anomalies for the generated iPSCs. Many patient-specific iPSCs are generated from subcutaneous fat fibroblasts obtained during surgical procedure. The described control iPSC line was generated equally and therefore serves as an ideal control for adipose-fibroblast-based patient-specific iPSC lines in disease modeling.

Excitation of an Electric Octupole Transition by Twisted Light.

We study the coherent excitation of the ^{2}S_{1/2}→^{2}F_{7/2} electric octupole (E3) transition by twisted light modes with a single ^{171}Yb^{+} ion in the dark center of a vortex beam. The intensity distribution of the beam is mapped as a function of the ion's position by measuring the light shift on an auxiliary electric quadrupole transition. In the center of the vortex beam, we observe excitation of the E3 transition with a fivefold reduced light shift in comparison to excitation by plane wave radiation for the same Rabi frequency. We measure the excitation probabilities for Laguerre-Gaussian twisted light modes of first and second order for different polarization patterns at various orientations of the ion quantization axis with respect to the beam propagation vector. We compare the experimental results with theoretical predictions and find good qualitative agreement.

Establishment of a patient-specific induced pluripotent stem cell line DHMi004-A from a male Holt-Oram syndrome patient with verified TBX5 mutation.

The Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder, mostly based on mutations in the TBX5 gene. Patients show malformation of at least one upper limb along with congenital heart defects. The established induced pluripotent stem cell (iPSC) line was generated from a patient displaying pronounced and typical features of HOS and carrying a single-nucleotide change c.920_C>A leading to an amino acid change from proline to threonine at amino acid position 85, which appeared de novo. Adipose fibroblasts from the patient were reprogrammed using Sendai virus. Pluripotency of the iPSCs was fully demonstrated.

Lifetime of the

We report a measurement of the radiative lifetime of the ^{2}F_{7/2} level of ^{171}Yb^{+} that is coupled to the ^{2}S_{1/2} ground state via an electric octupole transition. The radiative lifetime is determined to be 4.98(25)×10^{7} s, corresponding to 1.58(8) yr. The result reduces the relative uncertainty in this exceptionally long excited state lifetime by 1 order of magnitude with respect to previous experimental estimates. Our method is based on the coherent excitation of the corresponding transition and avoids limitations through competing decay processes. The explicit dependence on the laser intensity is eliminated by simultaneously measuring the resonant Rabi frequency and the induced quadratic Stark shift. Combining the result with information on the dynamic differential polarizability permits a calculation of the transition matrix element to infer the radiative lifetime.

Improved Limits for Violations of Local Position Invariance from Atomic Clock Comparisons.

We compare two optical clocks based on the ^{2}S_{1/2}(F=0)→^{2}D_{3/2}(F=2) electric quadrupole (E2) and the ^{2}S_{1/2}(F=0)→^{2}F_{7/2}(F=3) electric octupole (E3) transition of ^{171}Yb^{+} and measure the frequency ratio ν_{E3}/ν_{E2}=0.932829404530965376(32), improving upon previous measurements by an order of magnitude. Using two caesium fountain clocks, we find ν_{E3}=642121496772645.10(8) Hz, the most accurate determination of an optical transition frequency to date. Repeated measurements of both quantities over several years are analyzed for potential violations of local position invariance. We improve by factors of about 20 and 2 the limits for fractional temporal variations of the fine structure constant α to 1.0(1.1)×10^{-18}/yr and of the proton-to-electron mass ratio µ to -8(36)×10^{-18}/yr. Using the annual variation of the Sun's gravitational potential at Earth Φ, we improve limits for a potential coupling of both constants to gravity, (c^{2}/α)(dα/dΦ)=14(11)×10^{-9} and (c^{2}/µ)(dµ/dΦ)=7(45)×10^{-8}.

Coherent Excitation of the Highly Forbidden Electric Octupole Transition in

We report on the first coherent excitation of the highly forbidden ^{2}S_{1/2}→^{2}F_{7/2} electric octupole (E3) transition in a single trapped ^{172}Yb^{+} ion, an isotope without nuclear spin. Using the transition in ^{171}Yb^{+} as a reference, we determine the transition frequency to be 642 116 784 950 887.6(2.4) Hz. We map out the magnetic field environment using the forbidden ^{2}S_{1/2}→^{2}D_{5/2} electric quadrupole (E2) transition and determine its frequency to be 729 476 867 027 206.8(4.4) Hz. Our results are a factor of 1×10^{5} (3×10^{5}) more accurate for the E2 (E3) transition compared to previous measurements. The results open up the way to search for new physics via precise isotope shift measurements and improved tests of local Lorentz invariance using the metastable ^{2}F_{7/2} state of Yb^{+}.

Coherent Suppression of Tensor Frequency Shifts through Magnetic Field Rotation.

We introduce a scheme to coherently suppress second-rank tensor frequency shifts in atomic clocks, relying on the continuous rotation of an external magnetic field during the free atomic state evolution in a Ramsey sequence. The method retrieves the unperturbed frequency within a single interrogation cycle and is readily applicable to various atomic clock systems. For the frequency shift due to the electric quadrupole interaction, we experimentally demonstrate suppression by more than two orders of magnitude for the ^{2}S_{1/2}→^{2}D_{3/2} transition of a single trapped ^{171}Yb^{+} ion. The scheme provides particular advantages in the case of the ^{171}Yb^{+} ^{2}S_{1/2}→^{2}F_{7/2} electric octupole (E3) transition. For an improved estimate of the residual quadrupole shift for this transition, we measure the excited state electric quadrupole moments Θ(^{2}D_{3/2})=1.95(1)ea_{0}^{2} and Θ(^{2}F_{7/2})=-0.0297(5)ea_{0}^{2} with e the elementary charge and a_{0} the Bohr radius, improving the measurement uncertainties by one order of magnitude.

Testosterone boosters: a report of a supplement's misleading labelling claims.

This paper illustrates how labelling claims of a testosterone booster supplement mislead consumers. The labelling claims misappropriate scientific terminology, exaggerate and misrepresent research as evidence for the product's purported efficacy.

Neonates and infants requiring life-long cardiac pacing: How reliable are epicardial leads through childhood?

BACKGROUND: In the literature, data is lacking on mid-term results of epicardial pacemaker implantation in neonates and infants. Our aim was to evaluate the mid-term results of epicardial pacemakers implanted in infants under 1 year of age. METHODS AND RESULTS: We conducted a retrospective review of patients who underwent pacemaker implantation between 2000 and 2017. Pacemaker and lead parameters were reviewed at discharge, 2, 4 and more than 5 years after implantation. A total of 71 patients aged 4 ±â€¯3 months and weighing 4 ±â€¯2 kg were included in the study. Indications for pacemaker implantation were: acquired AV-block (n = 44), congenital AV block (n = 22), sick sinus syndrome (n = 4) and AV block type Mobitz II (n = 1). Median follow-up time was 5 years (range: 1 month-17 years). At 5 years of follow-up, atrial lead energy threshold for pacing decreased significantly (0.72 ±â€¯0.71 µJ to 0.45 ±â€¯0.35 µJ; P < 0.001) but was stable for ventricular leads (0.57 µJ [0.05; 39.47] to 0.64 µJ [0.13; 9.45], P = 0.97). Atrial lead impedance increased significantly (569 ±â€¯137 Ω to 603 ±â€¯134 Ω, P < 0.001), whereas ventricular lead impedance decreased (603 ±â€¯202 Ω to 490 ±â€¯150 Ω, P < 0.001) after 5 years. Repeat operations were required for generator change (n = 55), lead exchange (n = 17) and infection (n = 1). At 2, 5 and 10 years, atrial lead survival was 96%, 91% and 76% and ventricular lead survival was 94%, 82% and 75%, respectively (P = 0.45). CONCLUSION: Stable pacing thresholds after 5 years indicated that epicardial pacemakers are safe for infants under 1 year of age until at least school enrolment age. However, due to stimulation at higher heart rates in infancy, battery depletion is a frequent occurrence.

Development and validation of a measurement system for continuously monitoring postoperative reservoir levels.

Following cardiac surgical procedures, multiple drainage systems remain in place inside the patient's chest to prevent the development of pericardial effusion or pneumothorax. Therefore, postoperative bleeding must be diligently observed. Currently, observation of the exudate rate is performed through periodical visual inspection of the reservoir. To improve postoperative monitoring, a measurement system based on load cells was developed to automatically detect bleeding rates. A reservoir retaining bracket was instrumented with a load cell. The signal was digitized by a microcontroller and then processed and displayed on customized software written in LabView. In cases where bleeding rates reach critical levels, the device will automatically sound an alarm. Additionally, the bleeding rate is displayed on the screen with the status of the alarm, as well as the fluid level of the reservoir. These data are all logged to a file. The measurement system has been validated for gain stability and drift, as well as for sensor accuracy, with different in vitro examinations. Additionally, performance of the measurement device was tested in a clinical pilot study on patients recovering from cardiac surgical procedures. The in vitro investigation showed that the monitoring device had excellent gain and drift stability, as well as sensor accuracy, with a resolution of 2.6 mL/h for the bleeding rate. During the clinical examination, bleeding rates of all patients were correctly measured. Continuously recording drainage volume using the developed system was comparable to manual measurements performed every 30 min by a nurse. Implementation of continuous digital measurements could improve patient safety and reduce the workload of medical professionals working in intensive care units.

Regions of open water and melting sea ice drive new particle formation in North East Greenland.

Atmospheric new particle formation (NPF) and growth significantly influences the indirect aerosol-cloud effect within the polar climate system. In this work, the aerosol population is categorised via cluster analysis of aerosol number size distributions (9-915 nm, 65 bins) taken at Villum Research Station, Station Nord (VRS) in North Greenland during a 7 year record (2010-2016). Data are clustered at daily averaged resolution; in total, we classified six categories, five of which clearly describe the ultrafine aerosol population, one of which is linked to nucleation events (up to 39% during summer). Air mass trajectory analyses tie these frequent nucleation events to biogenic precursors released by open water and melting sea ice regions. NPF events in the studied regions seem not to be related to bird colonies from coastal zones. Our results show a negative correlation (r = -0.89) between NPF events and sea ice extent, suggesting the impact of ultrafine Arctic aerosols is likely to increase in the future, given the likely increased sea ice melting. Understanding the composition and the sources of Arctic aerosols requires further integrated studies with joint multi-component ocean-atmosphere observation and modelling.

Efficacy and safety of a fixed-dose combination of ibuprofen and caffeine in the management of moderate to severe dental pain after third molar extraction.

BACKGROUND: Ibuprofen is an effective analgesic treatment with a ceiling effect at doses above 400 mg. This study compared the combination of ibuprofen 400 mg and caffeine 100 mg with ibuprofen 400 mg monotherapy, caffeine and placebo in the analgesic treatment of moderate to severe acute dental pain following third molar extraction. METHODS: Phase III, active-/placebo-controlled, double-blind, single-centre, two-stage, parallel-group study in adult patients with at least moderate baseline pain intensity. Primary endpoint was defined as the time-weighted sum of pain relief and pain intensity difference over 8 h (SPRID0-8 h), secondary endpoints included duration of pain relief, time to meaningful pain relief and more. RESULTS: N = 748 patients were enrolled and N = 562 treated. Mean baseline pain intensity was 7.7 on a 0-10 numerical rating scale. Analysis of SPRID0-8 h demonstrated superior analgesic effects for a single dose of ibuprofen/caffeine versus ibuprofen, caffeine and placebo over 8 h, rescue medication in this stage was requested by more patients on ibuprofen (32.5%) than on ibuprofen/caffeine (16.0%). Median time to meaningful pain relief was shorter for ibuprofen/caffeine (1.13 h) compared with ibuprofen (1.78 h; p = 0.0001). More patients on ibuprofen/caffeine than on ibuprofen reported meaningful pain relief. Adverse events were infrequent and mostly mild or moderate across treatment groups. Tolerability was rated as 'very good' or 'excellent' by most patients in both treatment groups. CONCLUSION: This study demonstrated clinically relevant superiority of ibuprofen/caffeine over monotherapy with ibuprofen in patients with acute dental pain. All treatments were well tolerated. SIGNIFICANCE: This trial showed superior efficacy of 400/100 mg ibuprofen/caffeine, compared to 400 mg ibuprofen alone, for treating acute pain, reflecting that caffeine is an effective analgesic adjuvant. Data on efficacy of 400 mg ibuprofen combined with caffeine for the treatment of acute pain were not available yet.