Instrumental Music Guide: Grades 5-9

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Real-world keystroke dynamics are a potentially valid biomarker for clinical disability in multiple sclerosis

Background: Clinical measures in multiple sclerosis (MS) face limitations that may be overcome by utilising smartphone keyboard interactions acquired continuously and remotely during regular typing. Objective: The aim of this study was to determine the reliability and validity of keystroke dynamics to assess clinical aspects of MS. Methods: In total, 102 MS patients and 24 controls were included in this observational study. Keyboard interactions were obtained with the Neurokeys keyboard app. Eight timing-related keystroke features were assessed for reliability with intraclass correlation coefficients (ICCs); construct validity by analysing group differences (in fatigue, gadolinium-enhancing lesions on magnetic resonance imaging (MRI), and patients vs controls); and concurrent validity by correlating with disability measures. Results: Reliability was moderate in two (ICC = 0.601 and 0.742) and good to excellent in the remaining six features (ICC = 0.760–0.965). Patients had significantly higher keystroke latencies than controls. Latency between key presses correlated the highest with Expanded Disability Status Scale (r = 0.407) and latency between key releases with Nine-Hole Peg Test and Symbol Digit Modalities Test (ρ = 0.503 and r = −0.553, respectively), ps < 0.001. Conclusion: Keystroke dynamics were reliable, distinguished patients and controls, and were associated with clinical disability measures. Consequently, keystroke dynamics are a promising valid surrogate marker for clinical disability in MS

The recurrence of disease activity after ocrelizumab discontinuation in multiple sclerosis

Introduction: Ocrelizumab (OCR) is a highly effective treatment of multiple sclerosis (MS), and B cell repopulation profiles suggest that it might be used as an immune reconstitution therapy. However, data on disease recurrence after stopping treatment with OCR are scarce. Our objective was to evaluate the recurrence of disease activity after OCR discontinuation.Methods: In this multicenter retrospective cohort study, we included MS patients who discontinued OCR, without switching to another treatment, for twelve months or more, after having received at least one full dosage of 600 mg. We defined focal inflammation as the occurrence of a clinical relapse or significant MRI activity (≥3 new T2 lesions or ≥2 contrast-enhancing lesions). Results: We included 53 MS patients; 41 relapsing remitting (RRMS), 5 secondary progressive (SPMS) and 7 primary progressive (PPMS) patients. Median follow-up period after OCR discontinuation was 16 months. We only observed focal inflammation after discontinuation in RRMS patients; 2.4 % (1/41) patients presented with significant MRI activity and matching clinical symptoms, and 7.3 % (3/41) patients presented with a suspected clinical relapse without radiological activity: a total of 9.8 % (4/41) at a median time of 17 months after the last infusion. Discussion: We found focal inflammation after discontinuation of OCR in 4 (9.8 %) of the RRMS patients, of which 1 was radiologically confirmed. Our observations highlight that recurrence of focal inflammation seems low but discontinuation may not be appropriate for everyone. Further larger studies are important to determine the immune reconstitution therapy potential of OCR.</p

Health costs in anthroposophic therapy users: a two-year prospective cohort study

BACKGROUND: Anthroposophic therapies (counselling, special medication, art, eurythmy movement, and rhythmical massage) aim to stimulate long-term self-healing processes, which theoretically could lead to a reduction of healthcare use. In a prospective two-year cohort study, anthroposophic therapies were followed by a reduction of chronic disease symptoms and improvement of quality of life. The purpose of this analysis was to describe health costs in users of anthroposophic therapies. METHODS: 717 consecutive outpatients from 134 medical practices in Germany, starting anthroposophic therapies for chronic diseases, participated in a prospective cohort study. We analysed direct health costs (anthroposophic therapies, physician and dentist consultations, psychotherapy, medication, physiotherapy, ergotherapy, hospital treatment, rehabilitation) and indirect costs (sick leave compensation) in the pre-study year and the first two study years. Costs were calculated from resource utilisation, documented by patient self-reporting. Data were collected from January 1999 to April 2003. RESULTS: Total health costs in the first study year (bootstrap mean 3,297 Euro; 95% confidence interval 95%-CI 3,157 Euro to 3,923 Euro) did not differ significantly from the pre-study year (3,186 Euro; 95%-CI 3,037 Euro to 3,711 Euro), whereas in the second year, costs (2,771 Euro; 95%-CI 2,647 Euro to 3,256 Euro) were significantly reduced by 416 Euro (95%-CI 264 Euro to 960 Euro) compared to the pre-study year. In each period hospitalisation and sick-leave together amounted to more than half of the total health costs. Anthroposophic therapies and medication amounted to 3%, 15%, and 8% of total health costs in the pre-study year, first year, and second study year, respectively. The cost reduction in the second year was largely accounted for by a decrease of inpatient hospitalisation, leading to a hospital cost reduction of 519 Euro (95%-CI 377 Euro to 904 Euro) compared to the pre-study year. CONCLUSION: In patients starting anthroposophic therapies for chronic disease, total health costs did not increase in the first year, and were reduced in the second year. This reduction was largely explained by a decrease of inpatient hospitalisation. Within the limits of a pre-post design, study findings suggest that anthroposophic therapies are not associated with a relevant increase in total health costs

Absence of Inhibin Alpha and Retinoblastoma Protein Leads to Early Sertoli Cell Dysfunction

Sertoli cells, the support cells of mammalian spermatogenesis, are regulated by a number of nuclear factors and express retinoblastoma (RB) tumor suppressor protein. We hypothesized that RB is an important mediator of Sertoli cell tumorigenesis in inhibin α knockout (Inha KO) mice. In our previous mouse studies, we found that conditional knockout (cKO) of Rb in Sertoli cells caused progressive Sertoli cell dysfunction. Initially, loss of RB had no gross effect on Sertoli cell function as the mice were fertile with normal testis weights at 6 weeks of age, but by 10–14 weeks of age, mutant mice demonstrated severe Sertoli cell dysfunction and infertility. Although double knockout (dKO) of Rb and Inha did not result in exacerbation of the tumorigenic phenotype of Inha-null mice, we found that the dKO mice demonstrate an acceleration of Sertoli cell dysfunction compared to Rb cKO mice. Specifically, in contrast to Rb cKO mice, Inha/Rb dKO mice showed signs of Sertoli cell dysfunction as early as 4 weeks of age. These results demonstrate that RB is not essential for Sertoli cell tumorigenesis in Inha KO mice but that loss of Inha accelerates the infertility phenotype of Rb cKO mice

NuSTAR and Chandra observations of new X-ray transients in the central parsec of the Galaxy

We report NuSTAR and Chandra observations of two X-ray transients, SWIFT J174540.7$-$290015 (T15) and SWIFT J174540.2$-$290037 (T37), which were discovered by the Neil Gehrels Swift Observatory in 2016 within $r\sim1$ pc of Sgr A*. NuSTAR detected bright X-ray outbursts from T15 and T37, likely in the soft and hard states, with 3-79~keV luminosities of $8\times10^{36}$ and $3\times10^{37}$ erg/s, respectively. No X-ray outbursts have previously been detected from the two transients and our Chandra ACIS analysis puts an upper limit of $L_X \lesssim 2 \times10^{31}$ erg/s on their quiescent 2-8 keV luminosities. No pulsations, significant QPOs, or type I X-ray bursts were detected in the NuSTAR data. While T15 exhibited no significant red noise, the T37 power density spectra are well characterized by three Lorentzian components. The declining variability of T37 above $\nu \sim 10$ Hz is typical of black hole (BH) transients in the hard state. NuSTAR spectra of both transients exhibit a thermal disk blackbody, X-ray reflection with broadened Fe atomic features, and a continuum component well described by Comptonization models. Their X-ray reflection spectra are most consistent with high BH spin ($a_{*} \gtrsim 0.9$) and large disk density ($n_e\sim10^{21}$ cm$^{-3}$). Based on the best-fit ionization parameters and disk densities, we found that X-ray reflection occurred near the inner disk radius, which was derived from the relativistic broadening and thermal disk component. These X-ray characteristics suggest the outbursting BH-LMXB scenario for both transients and yield the first BH spin measurements from X-ray transients in the central 100 pc region.Comment: 15 pages, 7 figures, accepted for publication in Ap

A Measurement of the CMB Temperature Power Spectrum and Constraints on Cosmology from the SPT-3G 2018 TT/TE/EE Data Set

We present a sample-variance-limited measurement of the temperature power spectrum ($TT$) of the cosmic microwave background (CMB) using observations of a $\sim\! 1500 \,\mathrm{deg}^2$ field made by SPT-3G in 2018. We report multifrequency power spectrum measurements at 95, 150, and 220GHz covering the angular multipole range $750 \leq \ell < 3000$. We combine this $TT$ measurement with the published polarization power spectrum measurements from the 2018 observing season and update their associated covariance matrix to complete the SPT-3G 2018 $TT/TE/EE$ data set. This is the first analysis to present cosmological constraints from SPT $TT$, $TE$, and $EE$ power spectrum measurements jointly. We blind the cosmological results and subject the data set to a series of consistency tests at the power spectrum and parameter level. We find excellent agreement between frequencies and spectrum types and our results are robust to the modeling of astrophysical foregrounds. We report results for $\Lambda$CDM and a series of extensions, drawing on the following parameters: the amplitude of the gravitational lensing effect on primary power spectra $A_\mathrm{L}$, the effective number of neutrino species $N_{\mathrm{eff}}$, the primordial helium abundance $Y_{\mathrm{P}}$, and the baryon clumping factor due to primordial magnetic fields $b$. We find that the SPT-3G 2018 $T/TE/EE$ data are well fit by $\Lambda$CDM with a probability-to-exceed of $15\%$. For $\Lambda$CDM, we constrain the expansion rate today to $H_0 = 68.3 \pm 1.5\,\mathrm{km\,s^{-1}\,Mpc^{-1}}$ and the combined structure growth parameter to $S_8 = 0.797 \pm 0.042$. The SPT-based results are effectively independent of Planck, and the cosmological parameter constraints from either data set are within $<1\,\sigma$ of each other. (abridged)Comment: 35 Pages, 17 Figures, 11 Table