Modeling many-particle mechanical effects of an interacting Rydberg gas

In a recent work [Phys. Rev. Lett. 98, 023004 (2007)] we have investigated the influence of attractive van der Waals interaction on the pair distribution and Penning ionization dynamics of ultracold Rydberg gases. Here we extend this description to atoms initially prepared in Rydberg states exhibiting repulsive interaction. We present calculations based on a Monte Carlo algorithm to simulate the dynamics of many atoms under the influence of both repulsive and attractive longrange interatomic forces. Redistribution to nearby states induced by black body radiation is taken into account, changing the effective interaction potentials. The model agrees with experimental observations, where the ionization rate is found to increase when the excitation laser is blue-detuned from the atomic resonance

Physical activity monitoring in Alzheimer’s disease during sport interventions: a multi-methodological perspective

IntroductionAssessment methods for physical activity and fitness are of upmost importance due to the possible beneficial effect of physical conditioning on neurodegenerative diseases. The implementation of these methods can be challenging when examining elderly or cognitively impaired participants. In the presented study, we compared three different assessment methods for physical activity from the Dementia-MOVE trial, a 6-months intervention study on physical activity in Alzheimer’s disease. The aim was to determine the comparability of physical activity assessments in elderly participants with cognitive impairment due to Alzheimer’s disease.Material or methods38 participants (mean age 70 ± 7 years) with early-stage Alzheimer’s disease (mean MoCA 18.84 ± 4.87) were assessed with (1) fitness trackers for an average of 12 (± 6) days, (2) a written diary on daily activities and (3) a questionnaire on physical activity at three intervention timepoints. For comparison purposes, we present a transformation and harmonization method of the physical assessment output parameters: Metabolic equivalent of task (MET) scores, activity intensity minutes, calorie expenditure and moderate-to-vigorous physical activity (MVPA) scores were derived from all three modalities. The resulting parameters were compared for absolute differences, correlation, and their influence by possible mediating factors such as cognitive state and markers from cerebrospinal fluid.ResultsParticipants showed high acceptance and compliance to all three assessment methods. MET scores and MVPA from fitness trackers and diaries showed high overlap, whilst results from the questionnaire suggest that participants tended to overestimate their physical activity in the long-term retrospective assessment. All activity parameters were independent of the tested Alzheimer’s disease parameters, showing that not only fitness trackers, but also diaries can be successfully applied for physical activity assessment in a sample affected by early-stage Alzheimer’s disease.DiscussionOur results show that fitness trackers and physical activity diaries have the highest robustness, leading to a highly comparable estimation of physical activity in people with Alzheimer’s disease. As assessed parameters, it is recommendable to focus on MET, MVPA and on accelerometric sensor data such as step count, and less on activity calories and different activity intensities which are dependent on different variables and point to a lower reliability

Observation of mesoscopic crystalline structures in a two-dimensional Rydberg gas

The ability to control and tune interactions in ultracold atomic gases has paved the way towards the realization of new phases of matter. Whereas experiments have so far achieved a high degree of control over short-ranged interactions, the realization of long-range interactions would open up a whole new realm of many-body physics and has become a central focus of research. Rydberg atoms are very well-suited to achieve this goal, as the van der Waals forces between them are many orders of magnitude larger than for ground state atoms. Consequently, the mere laser excitation of ultracold gases can cause strongly correlated many-body states to emerge directly when atoms are transferred to Rydberg states. A key example are quantum crystals, composed of coherent superpositions of different spatially ordered configurations of collective excitations. Here we report on the direct measurement of strong correlations in a laser excited two-dimensional atomic Mott insulator using high-resolution, in-situ Rydberg atom imaging. The observations reveal the emergence of spatially ordered excitation patterns in the high-density components of the prepared many-body state. They have random orientation, but well defined geometry, forming mesoscopic crystals of collective excitations delocalised throughout the gas. Our experiment demonstrates the potential of Rydberg gases to realise exotic phases of matter, thereby laying the basis for quantum simulations of long-range interacting quantum magnets.Comment: 10 pages, 7 figure

Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and mice

With molecular treatments coming into reach for spinocerebellar ataxia type 3 (SCA3), easily accessible, cross-species validated biomarkers for human and preclinical trials are warranted, particularly for the preataxic disease stage. We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in ataxic and preataxic subjects of two independent multicentric SCA3 cohorts and in a SCA3 knock-in mouse model. Ataxic SCA3 subjects showed increased levels of both NfL and pNfH. In preataxic subjects, NfL levels increased with proximity to the individual expected onset of ataxia, with significant NfL elevations already 7.5 years before onset. Cross-sectional NfL levels correlated with both disease severity and longitudinal disease progression. Blood NfL and pNfH increases in human SCA3 were each paralleled by similar changes in SCA3 knock-in mice, here also starting already at the presymptomatic stage, closely following ataxin-3 aggregation and preceding Purkinje cell loss in the brain. Blood neurofilaments, particularly NfL, might thus provide easily accessible, cross-species validated biomarkers in both ataxic and preataxic SCA3, associated with earliest neuropathological changes, and serve as progression, proximity-to-onset and, potentially, treatment-response markers in both human and preclinical SCA3 trials.Acknowledgements: This work was supported by the Horizon 2020 research and innovation programme (grant 779257 Solve-RD to MS and RS), the National Ataxia Foundation (grant to CW and MS), the Wilhelm Vaillant Stiftung (grant to CW), the EU Joint Programme—Neurodegenerative Disease Research (JPND) through participating national funding agencies, and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643417. BM was supported in part from the grant NKFIH 119540. HJ was funded by the Medical Faculty of the University of Heidelberg. CB was funded by the University of Basel (PhD Program in Health Sciences). The funding sources had no role in the study design, data collection, data analysis, data interpretation or writing of the manuscript

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Prospective randomized trial to investigate the effect of fibrin glue on the development of postoperative lymphatic fistulas after axillary lymph node dissection in patients with malignant melanoma

Maligne Melanome sind bösartige Tumoren mit weltweit zunehmender Inzidenz. Nur in frühen Stadien sind maligne Melanome kurativ behandelbar. Am häufigsten ist eine Metastasierung in die für die jeweiligen Regionen zuständigen, drainierenden regionalen Lymphknoten, den sogenannten Wächter-Lymphknoten. Bei Nachweis eines Lymphknotenbefalles im primären lymphogenen Abstromgebiet des Primarius ist die radikale Dissektion aller dort befindlichen Lymphknoten indiziert. Nach einer radikalen axillären Lymphknotendissektion können postoperative Komplikationen, wie Lymphfisteln, Lymphozelen, Lymphödeme und Seromformationen, mit einer verlängerten Drainageliegedauer, einer verzögerten Wundheilung und letztlich einem erhöhtem Risiko für die Entstehung von Wundinfektionen verbunden sein. Diese Komplikationen stellen eine nicht unwesentliche Herausforderung für den Chirurgen dar und bedingen teilweise einen erheblich verlängerten Krankenhausaufenthalt. In mehreren publizierten Studien, die allerdings nur relativ geringe Fallzahlen betrachteten, wurde untersucht, ob durch die intraoperative Applikation eines Fibrinklebers in die operativ entstandene Wundhöhle eine Senkung der Drainageliegedauer sowie eine Verringerung der Inzidenz postoperativer Komplikationen und somit eine signifikante Verkürzung des Krankenhausaufenthaltes erreicht werden kann. Wegen der unterschiedlichen, zum Teil widersprüchlichen Aussagen der publizierten Arbeiten war das Ziel dieser Studie, mit Hilfe einer prospektiv randomisierten, klinischen, einfach-verblindeten Studie den Effekt eines herkömmlichen Fibrinklebers auf die Inzidenz postoperativer Lymphfisteln nach radikaler axillärer Lymphadenektomie zu evaluieren. Von September 2003 bis einschließlich Juli 2005 wurde bei 58 Patienten eine radikale axilläre Lymphadenektomie durchgeführt. Bei 29 Patienten (Fibringruppe) wurde vor Wundverschluss die Wunde intraoperativ mit einem Fibrinkleber (Tissucol® Duo S 2 ml Immuno) über einen Sprühapplikator benetzt. Bei den anderen 29 Patienten (Kontrollgruppe) erfolgte nur die bei allen Patienten standardisiert durchgeführte Wundspülung mit Ringer-Lösung. Von allen Patienten wurden: 1\. die Drainageliegedauer, 2\. das Drainagegesamtvolumen, 3\. die Krankenhausverweildauer und 4\. die postoperativen Komplikationen erfasst. Nach Auswertung der Ergebnisse war festzustellen, dass die intraoperative Applikation von 2 ml Tissucol® Duo S Immuno weder einen Einfluss auf die Drainageliegedauer (5 vs. 5 Tage) noch auf das Drainagegesamtvolumen (503 vs. 410 ml) sowie auf die Rate postoperativer Komplikationen hatte. Eine signifikante Verkürzung der Krankenhausverweildauer (7 vs. 6 Tage) konnte durch die intraoperative Fibrinapplikation ebenfalls nicht erreicht werden.The world wide incidence of malignant melanoma – the most malignant tumor of the skin - is rising. Metastases of the tumor occurs frequently in the corresponding draining area of the lymph nodes. In the regional node basin the sentinel node plays a key role in the course of the disease. Only in early stages curative treatment of the tumor is possible. In case of lymph node metastases in the regional node basin a radical lymph node dissection of the regional node area is indicated. Following radical axillary lymph node dissection postoperative complications such as lymph fistulas, edema or seroma may occur, thus resulting in a prolonged placement of wound drains, diminished wound healing and finally an increased risk of minor or major wound infections. The described complications can challenge the treating surgeon and can be a reason for a prolonged hospital stay of the patient. Because of different published results concerning the described problem we conducted a blinded prospective trial to study the influence of a commercial available fibrin glue on the incidence of postoperative lymph fistula after radical axillary lymph node dissection. From Sept. 2003 to July 2005 in 58 patients a radical axillary lymph node dissection was performed. In 29 patients prior to wound closure fibrin glue (Tissucol® Duo S 2cc Immuno) were sprayed into the wound. In the other group of 29 patients only wound irrigation with ringer solution was performed. In all patients we recognized the 1\. length of drainage 2\. drainage volume 3\. lentgh of hospital stay 4\. postoperative complications. After statistical evaluation of the obtained results it appaered, that the intraoperative application of 2 cc Tissucol® Duo S Immuno did not influence the lentgh of drainage (5 vs 5 days), the drainage volume (503 cc vs 410 cc) or the rate of postoperative complications. In addtion to this a significant reduction of the hospital stay was not achieved

Resting-state connectivity in neurodegenerative disorders: Is there potential for an imaging biomarker?

Biomarkers in whichever modality are tremendously important in diagnosing of disease, tracking disease progression and clinical trials. This applies in particular for disorders with a long disease course including pre-symptomatic stages, in which only subtle signs of clinical progression can be observed. Magnetic resonance imaging (MRI) biomarkers hold particular promise due to their relative ease of use, cost-effectiveness and non-invasivity. Studies measuring resting-state functional MR connectivity have become increasingly common during recent years and are well established in neuroscience and related fields. Its increasing application does of course also include clinical settings and therein neurodegenerative diseases. In the present review, we critically summarise the state of the literature on resting-state functional connectivity as measured with functional MRI in neurodegenerative disorders. In addition to an overview of the results, we briefly outline the methods applied to the concept of resting-state functional connectivity.While there are many different neurodegenerative disorders cumulatively affecting a substantial number of patients, for most of them studies on resting-state fMRI are lacking. Plentiful amounts of papers are available for Alzheimer's disease (AD) and Parkinson's disease (PD), but only few works being available for the less common neurodegenerative diseases. This allows some conclusions on the potential of resting-state fMRI acting as a biomarker for the aforementioned two diseases, but only tentative statements for the others

Bariatric Surgery as the One Route to Achieving Donor Heart Transplantation in a Patient with a Left-Ventricular Assist Device

Bariatric and metabolic surgery is currently the most effective procedure of achieving and maintaining weight loss. In the case under discussion, a 48-year-old male patient with heart insufficiency and an implanted left-ventricular assist device (LVAD) wanted to reduce his high BMI (48.6 kg/m2), so as to qualify for the heart transplant waiting list. According to the guidelines, he underwent all the required preoperative testing, which included psychosomatic clarifications, determination of endocrinological causes, and a nutritional consultation. During laparoscopic sleeve gastrectomy, a cardiac technician was present to support the anesthetist. After inserting 3 trocars with no complications, the greater curvature was mobilized using Medtronic's bipolar electrothermal vessel-sealing instrument, LigaSure™. The resection was performed with an Ethicon™ endostapler. Postoperative monitoring showed no signs of hemorrhage. The patient's BMI on the day of surgery was 46.8 kg/m2 and consecutively fell to 26.7 kg/m2 1 year after the procedure. Follow-up appointments revealed that the patient was fit and in good health. Thus, the patient's aim of being listed on the transplant list was fulfilled, and at the time of this writing, he is ready to be matched with an organ donor. Because high-BMI patients with inserted LVADs are less likely to receive a donor graft and must remain longer on transplant waiting lists than normal-weight patients, bariatric and metabolic weight loss surgery may lead to a speedier resolution for these high-risk patients