Dopamine boosts intention and action awareness in Parkinson’s disease

Dopaminergic deficiency in Parkinson’s disease (PD) has been associated with underactivation of the supplementary motor area and a reduction of voluntary actions. In these patients, awareness of intention to act has been shown to be delayed. However, delayed awareness of intention to act has also been shown in patients with hyperdopaminergic states and an excess of unwilled movements, as in Tourette’s, and in patients with functional movement disorders. Hence, the role of dopamine in the awareness of intention and action remains unclear. 36 PD patients were tested ON and OFF dopaminergic medication and compared with 35 healthy age-matched controls. In addition, 17 PD patients with subthalamic deep brain stimulation (DBS) were tested ON medication and ON and OFF stimulation. Participants judged either the moment a self-generated action was performed, or the moment the urge to perform the action was felt, using the “Libet method”. Temporal judgments of intention and action awareness were comparable between unmedicated PD patients and controls. Dopaminergic medication boosted anticipatory awareness of both intentions and actions in PD patients, relative to an unmedicated condition. The difference between ON/OFF DBS was not statistically reliable. Functional improvement of motor ability in PD through dopaminergic supplementation leads to earlier awareness of both intention, and of voluntary action

Transmission spectroscopy of the ultra-hot Jupiter MASCARA-4 b: Disentangling the hydrostatic and exospheric regimes of ultra-hot Jupiters

Ultra-hot Jupiters (UHJs), rendering the hottest planetary atmospheres, offer great opportunities of detailed characterisation with high-resolution spectroscopy. MASCARA-4 b is a recently discovered close-in gas giant belonging to this category. In order to refine system and planet parameters, we carried out radial velocity measurements and transit photometry with the CORALIE spectrograph and EulerCam at the Swiss 1.2m Euler telescope. We observed two transits of MASCARA-4 b with the high-resolution spectrograph ESPRESSO at ESO's Very Large Telescope. We searched for atomic, ionic, and molecular species via individual absorption lines and cross-correlation techniques. These results are compared to literature studies on UHJs characterised to date. With CORALIE and EulerCam observations, we updated the mass of MASCARA-4 b (1.675 +/- 0.241 Jupiter masses) as well as other system and planet parameters. In the transmission spectrum derived from ESPRESSO observations, we resolve excess absorption by H$\alpha$, H$\beta$, Na D1 & D2, Ca+ H & K, and a few strong individual lines of Mg, Fe and Fe+. We also present the cross-correlation detection of Mg, Ca, Cr, Fe and Fe+. The absorption strength of Fe+ significantly exceeds the prediction from a hydrostatic atmospheric model, as commonly observed in other UHJs. We attribute this to the presence of Fe+ in the exosphere due to hydrodynamic outflows. This is further supported by the positive correlation of absorption strengths of Fe+ with the H$\alpha$ line. Comparing transmission signatures of various species in the UHJ population allows us to disentangle the hydrostatic regime (as traced via the absorption by Mg and Fe) from the exospheres (as probed by H$\alpha$ and Fe+) of the strongly irradiated atmospheres.Comment: 13 pages, 9 figures, accepted to A&

Subthalamic and nigral neurons are differentially modulated during parkinsonian gait

The parkinsonian gait disorder and freezing of gait are therapeutically demanding symptoms with considerable impact on quality of life. The aim of this study was to assess the role of subthalamic and nigral neurons in the parkinsonian gait control using intraoperative microelectrode recordings of basal ganglia neurons during a supine stepping task. Twelve male patients (56 ± 7 years) suffering from moderate idiopathic Parkinson's disease (disease duration 10 ± 3 years, Hoehn and Yahr stage 2), undergoing awake neurosurgery for deep brain stimulation, participated in the study. After 10 s resting, stepping at self-paced speed for 35 s was followed by short intervals of stepping in response to random 'start' and 'stop' cues. Single- and multi-unit activity was analysed offline in relation to different aspects of the stepping task (attentional 'start' and 'stop' cues, heel strikes, stepping irregularities) in terms of firing frequency, firing pattern and oscillatory activity. Subthalamic nucleus and substantia nigra neurons responded to different aspects of the stepping task. Of the subthalamic nucleus neurons, 24% exhibited movement-related activity modulation as an increase of the firing rate, suggesting a predominant role of the subthalamic nucleus in motor aspects of the task, while 8% of subthalamic nucleus neurons showed a modulation in response to the attentional cues. In contrast, responsive substantia nigra neurons showed activity changes exclusively associated with attentional aspects of the stepping task (15%). The firing pattern of subthalamic nucleus neurons revealed gait-related firing regularization and a drop of beta oscillations during the stepping performance. During freezing episodes instead, there was a rise of beta oscillatory activity. This study shows for the first time specific, task-related subthalamic nucleus and substantia nigra single-unit activity changes during gait-like movements in humans with differential roles in motor and attentional control of gait. The emergence of perturbed firing patterns in the subthalamic nucleus indicates a disrupted information transfer within the gait network, resulting in freezing of gait

Discovery of a massive giant planet with extreme density around a sub-giant star TOI-4603

We present the discovery of a transiting massive giant planet around TOI-4603, a sub-giant F-type star from NASA's Transiting Exoplanet Survey Satellite (TESS). The newly discovered planet has a radius of $1.042^{+0.038}_{-0.035}$ $R_{J}$, and an orbital period of $7.24599^{+0.00022}_{-0.00021}$ days. Using radial velocity measurements with the PARAS {and TRES} spectrographs, we determined the planet's mass to be $12.89^{+0.58}_{-0.57}$ $M_{J}$, resulting in a bulk density of $14.1^{+1.7}_{-1.6}$ g ${cm^{-3}}$. This makes it one of the few massive giant planets with extreme density and lies in the transition mass region of massive giant planets and low-mass brown dwarfs, an important addition to the population of less than five objects in this mass range. The eccentricity of $0.325\pm0.020$ and an orbital separation of $0.0888\pm0.0010$ AU from its host star suggest that the planet is likely undergoing high eccentricity tidal (HET) migration. We find a fraction of heavy elements of $0.13^{+0.05}_{-0.06}$ and metal enrichment of the planet ($Z_{P}/Z_{star}$) of $4.2^{+1.6}_{-2.0}$. Detection of such systems will offer us to gain valuable insights into the governing mechanisms of massive planets and improve our understanding of their dominant formation and migration mechanisms.Comment: accepted for publication in A&A Letter

Comparison of subthalamic unilateral and bilateral theta burst deep brain stimulation in Parkinson’s disease

High-frequency, conventional deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD) is usually applied bilaterally under the assumption of additive effects due to interhemispheric crosstalk. Theta burst stimulation (TBS-DBS) represents a new patterned stimulation mode with 5 Hz interburst and 200 Hz intraburst frequency, whose stimulation effects in a bilateral mode compared to unilateral are unknown. This single-center study evaluated acute motor effects of the most affected, contralateral body side in 17 PD patients with unilateral subthalamic TBS-DBS and 11 PD patients with bilateral TBS-DBS. Compared to therapy absence, both unilateral and bilateral TBS-DBS significantly improved (p < 0.05) lateralized Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) scores. Bilateral TBS-DBS revealed only slight, but not significant additional effects in comparison to unilateral TBS-DBS on total lateralized motor scores, but on the subitem lower limb rigidity. These results indicate that bilateral TBS-DBS has limited additive beneficial effects compared to unilateral TBS-DBS in the short term

Antihypertensive medication classes and risk of incident dementia in primary care patients: a longitudinal cohort study in the Netherlands

Background: Hypertension is a modifiable risk factor for dementia affecting over 70% of individuals older than 60. Lowering dementia risk through preferential treatment with antihypertensive medication (AHM) classes that are otherwise equivalent in indication could offer a cost-effective, safe, and accessible approach to reducing dementia incidence globally. Certain AHM-classes have been associated with lower dementia risk, potentially attributable to angiotensin-II-receptor (Ang-II) stimulating properties. Previous study results have been inconclusive, possibly due to heterogeneous methodology and limited power. We aimed to comprehensively investigate associations between AHM (sub-)classes and dementia risk using large-scale continuous, real-world prescription and outcome data from primary care. Methods: We used data from three Dutch General Practice Registration Networks. Primary endpoints were clinical diagnosis of incident all-cause dementia and mortality. Using Cox regression analysis with time-dependent covariates, we compared the use of angiotensin-converting enzyme inhibitors (ACEi) to angiotensin receptor blockers (ARBs), beta blockers, calcium channel blockers (CCBs), and diuretics; and Ang-II-stimulating- to Ang-II-inhibiting AHM. Findings: Of 133,355 AHM-using participants, 5877 (4.4%) developed dementia, and 14,079 (10.6%) died during a median follow-up of 7.6 [interquartile range = 4.1–11.0] years. Compared to ACEi, ARBs [HR = 0.86 (95% CI = 0.80–0.92)], beta blockers [HR = 0.81 (95% CI = 0.75–0.87)], CCBs [HR = 0.77 (95% CI = 0.71–0.84)], and diuretics [HR = 0.65 (95% CI = 0.61–0.70)] were associated with significantly lower dementia risks. Regarding competing risk of death, beta blockers [HR = 1.21 (95% CI = 1.15–1.27)] and diuretics [HR = 1.69 (95% CI = 1.60–1.78)] were associated with higher, CCBs with similar, and ARBs with lower [HR = 0.83 (95% CI = 0.80–0.87)] mortality risk. Dementia [HR = 0.88 (95% CI = 0.82–0.95)] and mortality risk [HR = 0.86 (95% CI = 0.82–0.91)] were lower for Ang-II-stimulating versus Ang-II-inhibiting AHM. There were no interactions with sex, diabetes, cardiovascular disease, and number of AHM used. Interpretation: Among patients receiving AHM, ARBs, CCBs, and Ang-II-stimulating AHM were associated with lower dementia risk, without excess mortality explaining these results. Extensive subgroup and sensitivity analyses suggested that confounding by indication did not importantly influence our findings. Dementia risk may be influenced by AHM-classes’ angiotensin-II-receptor stimulating properties. An RCT comparing BP treatment with different AHM classes with dementia as outcome is warranted. Funding: Netherlands Organisation for Health, Research and Development (ZonMw); Stoffels-Hornstra Foundation

TESS Duotransit Candidates from the Southern Ecliptic Hemisphere

Discovering transiting exoplanets with long orbital periods allows us to study warm and cool planetary systems with temperatures similar to the planets in our own Solar system. The TESS mission has photometrically surveyed the entire Southern Ecliptic Hemisphere in Cycle 1 (August 2018 - July 2019), Cycle 3 (July 2020 - June 2021) and Cycle 5 (September 2022 - September 2023). We use the observations from Cycle 1 and Cycle 3 to search for exoplanet systems that show a single transit event in each year - which we call duotransits. The periods of these planet candidates are typically in excess of 20 days, with the lower limit determined by the duration of individual TESS observations. We find 85 duotransit candidates, which span a range of host star brightnesses between 8 < $T_{mag}$ < 14, transit depths between 0.1 per cent and 1.8 per cent, and transit durations between 2 and 10 hours with the upper limit determined by our normalisation function. Of these candidates, 25 are already known, and 60 are new. We present these candidates along with the status of photometric and spectroscopic follow-up.Comment: 25 pages, 16 figures, submitted to Monthly Notices of the Royal Astronomical Societ

The NORDeHEALTH 2022 Patient Survey: Cross-Sectional Study of National Patient Portal Users in Norway, Sweden, Finland, and Estonia

Background: Although many surveys have been conducted on patients accessing their own health records in recent years, there is a limited amount of nationwide cross-country data available on patients’ views and preferences. To address this gap, an international survey of patient users was conducted in the Nordic eHealth project, NORDeHEALTH. Objective: We aimed to investigate the sociodemographic characteristics and experiences of patients who accessed their electronic health records (EHRs) through national patient portals in Norway, Sweden, Finland, and Estonia. Methods: A cross-sectional web-based survey was distributed using the national online health portals. The target participants were patients who accessed the national patient portals at the start of 2022 and who were aged ≥15 years. The survey included a mixture of close-ended and free-text questions about participant sociodemographics, usability experience, experiences with health care and the EHR, reasons for reading health records online, experience with errors, omissions and offense, opinions about security and privacy, and the usefulness of portal functions. In this paper, we summarized the data on participant demographics, past experience with health care, and the patient portal through descriptive statistics. Results: In total, 29,334 users completed the survey, of which 9503 (32.40%) were from Norway, 13,008 (44.35%) from Sweden, 4713 (16.07%) from Finland, and 2104 (7.17%) from Estonia. National samples were comparable according to reported gender, with about two-thirds identifying as women (19,904/29,302, 67.93%). Age distributions were similar across the countries, but Finland had older users while Estonia had younger users. The highest attained education and presence of health care education varied among the national samples. In all 4 countries, patients most commonly rated their health as “fair” (11,279/29,302, 38.48%). In Estonia, participants were more often inclined to rate their health positively, whereas Norway and Sweden had the highest proportion of negative health ratings. Across the whole sample, most patients received some care in the last 2 years (25,318/29,254, 86.55%). Mental health care was more common (6214/29,254, 21.24%) than oncological care (3664/29,254, 12.52%). Overall, most patients had accessed their health record “2 to 9 times” (11,546/29,306, 39.4%), with the most frequent users residing in Sweden, where about one-third of patients accessed it “more than 20 times” (4571/13,008, 35.14%). Conclusions: This is the first large-scale international survey to compare patient users’ sociodemographics and experiences with accessing their EHRs. Although the countries are in close geographic proximity and demonstrate similar advancements in giving their residents online records access, patient users in this survey differed. We will continue to investigate patients’ experiences and opinions about national patient-accessible EHRs through focused analyses of the national and combined data sets from the NORDeHEALTH 2022 Patient Survey

Separated twins or just siblings? A multi-planet system around an M dwarf including a cool sub-Neptune

We report the discovery of two TESS sub-Neptunes orbiting the early M dwarf TOI-904 (TIC 261257684). Both exoplanets, TOI-904 b and c, were initially observed in TESS sector 12 with twin sizes of 2.49R$_\oplus$ and 2.31R$_\oplus$, respectively. Through observations in five additional sectors in the TESS primary mission and the first and second extended missions, the orbital periods of both planets were measured to be 10.887$\pm$0.001 and 83.999$\pm$0.001 days, respectively. Reconnaissance radial velocity measurements (taken with EULER/CORALIE) and high resolution speckle imaging with adaptive optics (obtained from SOAR/HRCAM and Gemini South/ZORRO) show no evidence of an eclipsing binary or a nearby companion, which together with the low false positive probabilities calculated with the statistical validation software TRICERATOPS establish the planetary nature of these candidates. The outer planet, TOI-904 c, is the longest-period M dwarf exoplanet found by TESS, with an estimated equilibrium temperature of 217K. As the three other validated planets with comparable host stars and orbital periods were observed by Kepler around much dimmer stars (J$_{mag}$ $>$ 12), TOI-904 c, orbiting a brighter star (J$_{mag}$ $=$ 9.6), is the coldest M dwarf planet easily accessible for atmospheric follow-up. Future mass measurements and transmission spectroscopy of the similar sized planets in this system could determine whether they are also similar in density and composition, suggesting a common formation pathway, or whether they have distinct origins.Comment: 18 pages, 6 figures, Accepted by the Astrophysical Journal Letter