Neurodegenerative diseases are highly prevalent but poorly understood, and with few treatment options despite decades of intense research, attention has recently shifted toward other mediators of ...neurological disease that may present future targets for therapeutic research. One such mediator is the gut microbiome, which communicates with the brain through the gut-brain axis and has been implicated in various neurological disorders. Alterations in the gut microbiome have been associated with numerous neurological and other diseases, and restoration of the dysbiotic gut has been shown to improve disease conditions. One method of restoring a dysbiotic gut is via fecal microbiota transplantation (FMT), recolonizing the "diseased" gut with normal microbiome. Fecal microbiota transplantation is a treatment method traditionally used for
infections, but it has recently been used in neurodegenerative disease research as a potential treatment method. This review aims to present a summary of neurodegenerative research that has used FMT, whether as a treatment or to investigate how the microbiome influences pathogenesis.
We present 2603 spectra of 462 nearby Type Ia supernovae (SNe Ia), including 2065 previously unpublished spectra, obtained during 1993-2008 through the Center for Astrophysics Supernova Program. ...Based on nebular spectra of 27 SNe Ia, we find no relation between the FWHM of the iron emission feature at ~4700A and delta msub 15(B) after removing the two low-luminosity SN 1986G and SN 1991bg, suggesting that the peak luminosity is not strongly dependent on the kinetic energy of the explosion for most SNe Ia. Finally, we confirm the correlation of velocity shifts in some nebular lines with the intrinsic B-V color of SNe Ia at maximum light, although several outliers suggest a possible non-monotonic behavior for the largest blue-shifts.
Summary Background Apremilast, a small-molecule inhibitor of phosphodiesterase 4, works intracellularly to modulate proinflammatory and anti-inflammatory mediator production, and doses of 20 mg twice ...daily have shown efficacy in the treatment of moderate to severe plaque psoriasis in a 12-week phase 2 study. We assessed the clinical efficacy and safety of different doses of apremilast in the treatment of patients with moderate to severe plaque psoriasis. Methods In this phase 2b, multicentre, randomised, placebo-controlled, dose-ranging study, patients (aged ≥18 years) with moderate to severe psoriasis were randomly assigned (in a 1:1:1:1 ratio) to receive oral placebo or apremilast 10, 20, or 30 mg twice daily at 35 US and Canadian sites between Sept 24, 2008, and Oct 21, 2009. At week 16, patients in the placebo group were assigned apremilast 20 or 30 mg twice daily until week 24. Randomisation was generated with a permuted-block randomisation list via interactive voice response system. For the first 16 weeks, treatment assignment was concealed from both investigators and participants. During weeks 16–24, investigators and participants all knew that treatment was active, but the dose was concealed. The primary endpoint was the proportion of patients achieving at least 75% reduction from baseline psoriasis area and severity index (PASI-75) at week 16. Analyses were by intention to treat; missing values were imputed by last-observation-carried-forward. This trial is registered with ClinicalTrials.gov , number NCT00773734. Findings 89 patients were randomly assigned apremilast 10 mg, 87 apremilast 20 mg, and 88 apremilast 30 mg twice daily; 88 were assigned placebo. At week 16, PASI-75 was achieved in five patients (6%) assigned placebo, ten (11%) assigned apremilast 10 mg, 25 (29%) assigned 20 mg, and 36 (41%) assigned 30 mg. Apremilast 10 mg did not differ significantly from placebo in achievement of the endpoint (odds ratio 2·10; 95% CI 0·69–6·42); for both apremilast 20 mg (6·69; 2·43–18·5; p<0·0001) and apremilast 30 mg (11·5; 4·24–31·2; p<0·0001), the differences from placebo were significant. Most adverse events (96%) were mild or moderate; at least 5% of patients had nausea, upper respiratory tract infection, diarrhoea, nasopharyngitis, headache, arthralgia (placebo), gastroenteritis, or dyspepsia. Eight serious adverse events occurred (three each, placebo and apremilast 20 mg; two, apremilast 30 mg); none were judged to be related to apremilast. Apremilast had no apparent effect on the results of haematological, urinalysis, immunological or inflammation, serum chemistry, or electrocardiographic tests. Interpretation Apremilast, given orally at 20 or 30 mg twice daily, seems to be efficacious, safe, and tolerable for patients with moderate to severe plaque psoriasis. Our results support continuing, longer-term studies. Funding Celgene Corporation.
We present a near-infrared spectral sequence of the electromagnetic counterpart to the binary neutron star merger GW170817 detected by Advanced Laser Interferometer Gravitational-wave Observatory ...(LIGO)/Virgo. Our data set comprises seven epochs of J+H spectra taken with FLAMINGOS-2 on Gemini-South between 1.5 and 10.5 days after the merger. In the initial epoch, the spectrum is dominated by a smooth blue continuum due to a high-velocity, lanthanide-poor blue kilonova component. Starting the following night, all of the subsequent spectra instead show features that are similar to those predicted in model spectra of material with a high concentration of lanthanides, including spectral peaks near 1.07 and 1.55 m. Our fiducial model with 0.04 M of ejecta, an ejection velocity of v = 0.1c, and a lanthanide concentration of Xlan = 10−2 provides a good match to the spectra taken in the first five days, although it over-predicts the late-time fluxes. We also explore models with multiple fitting components, in each case finding that a significant abundance of lanthanide elements is necessary to match the broad spectral peaks that we observe starting at 2.5 days after the merger. These data provide direct evidence that binary neutron star mergers are significant production sites of even the heaviest r-process elements.
We present 645 optical spectra of 73 supernovae (SNe) of Types IIb, Ib, Ic, and broad-lined Ic. All of these types are attributed to the core collapse of massive stars, with varying degrees of intact ...H and He envelopes before explosion. The SNe in our sample have a mean redshift left angle bracketczright angle bracket = 4200 km s super(-1). Most of these spectra were gathered at the Harvard-Smithsonian Center for Astrophysics (CfA) between 2004 and 2009. For 53 SNe, these are the first published spectra. The data coverage ranges from mere identification (1-3 spectra) for a few SNe to extensive series of observations (10-30 spectra) that trace the spectral evolution for others, with an average of 9 spectra per SN. For 44 SNe of the 73 SNe presented here, we have well-determined dates of maximum light to determine the phase of each spectrum. Our sample constitutes the most extensive spectral library of stripped-envelope SNe to date. We provide very early coverage (as early as 30 days before V-band max) for photospheric spectra, as well as late-time nebular coverage when the innermost regions of the SN are visible (as late as 2 yr after explosion, while for SN 1993J, we have data as late as 11.6 yr). This data set has homogeneous observations and reductions that allow us to study the spectroscopic diversity of these classes of stripped SNe and to compare these to SNe-gamma-ray bursts. We undertake these matters in follow-up papers.
Background IL-23 expression is increased in psoriatic lesions and might regulate TH 17 T-cell counts in patients with psoriasis. Objectives We sought to test a novel IL-23–specific therapeutic agent ...for the treatment of psoriasis. Methods In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti–IL-23–specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis. A total of 24 patients were randomized to receive a single dose of placebo or 10, 30, 100, or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis Area and Severity Index (PASI). Additionally, histologic analysis and gene expression in skin biopsy specimens from guselkumab-treated patients were compared with those from placebo-treated patients. Results At week 12, 50% (10 mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients, respectively, achieved a 75% improvement in PASI scores from baseline compared with 0% of placebo-treated patients. Improvements in PASI scores were generally maintained through week 24 in all guselkumab-treated patients. The proportion of patients experiencing an adverse event was comparable between the combined guselkumab (13/20 65.0%) and placebo (2/4 50.0%) groups through week 24. Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases in epidermal thickness and T-cell and dendritic cell expression in guselkumab-treated patients compared with values seen in placebo-treated patients. At week 12, significant reductions in psoriasis gene expression and serum IL-17A levels were observed in guselkumab-treated patients. Conclusion IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis.
ABSTRACT Supernovae (SNe) embedded in dense circumstellar material (CSM) may show prominent emission lines in their early-time spectra (≤10 days after the explosion), owing to recombination of the ...CSM ionized by the shock-breakout flash. From such spectra ("flash spectroscopy"), we can measure various physical properties of the CSM, as well as the mass-loss rate of the progenitor during the year prior to its explosion. Searching through the Palomar Transient Factory (PTF and iPTF) SN spectroscopy databases from 2009 through 2014, we found 12 SNe II showing flash-ionized (FI) signatures in their first spectra. All are younger than 10 days. These events constitute 14% of all 84 SNe in our sample having a spectrum within 10 days from explosion, and 18% of SNe II observed at ages <5 days, thereby setting lower limits on the fraction of FI events. We classified as "blue/featureless" (BF) those events having a first spectrum that is similar to that of a blackbody, without any emission or absorption signatures. It is possible that some BF events had FI signatures at an earlier phase than observed, or that they lack dense CSM around the progenitor. Within 2 days after explosion, 8 out of 11 SNe in our sample are either BF events or show FI signatures. Interestingly, we found that 19 out of 21 SNe brighter than an absolute magnitude MR = −18.2 belong to the FI or BF groups, and that all FI events peaked above MR = −17.6 mag, significantly brighter than average SNe II.
ABSTRACT
The hydrogen-poor supernova (SN) PTF11rka (z = 0.0744), reported by the Palomar Transient Factory, was observed with various telescopes starting a few days after the estimated explosion time ...of 2011 December 5 UT and up to 432 rest-frame days thereafter. The rising part of the light curve was monitored only in the RPTF filter band, and maximum in this band was reached ∼30 rest-frame days after the estimated explosion time. The light curve and spectra of PTF11rka are consistent with the core-collapse explosion of a ∼10 M⊙ carbon–oxygen core evolved from a progenitor of main-sequence mass 25–40 M⊙, that liberated a kinetic energy Ek≈4 × 1051 erg, expelled ∼8 M⊙ of ejecta, and synthesized ∼0.5 M⊙ of 56Ni. The photospheric spectra of PTF11rka are characterized by narrow absorption lines that point to suppression of the highest ejecta velocities (≳ 15 000 km s−1). This would be expected if the ejecta impacted a dense, clumpy circumstellar medium. This in turn caused them to lose a fraction of their energy (∼5 × 1050 erg), less than 2 per cent of which was converted into radiation that sustained the light curve before maximum brightness. This is reminiscent of the superluminous SN 2007bi, the light-curve shape and spectra of which are very similar to those of PTF11rka, although the latter is a factor of 10 less luminous and evolves faster in time. PTF11rka is in fact more similar to gamma-ray burst SNe in luminosity, although it has a lower energy and a lower Ek/Mej ratio.
Recent high-resolution spectra of the Type Ia supernova SN 2006X have revealed the presence of time-variable and blueshifted Na I D features, interpreted by Patat et al. as originating in ...circumstellar material within the progenitor system. The variation seen in SN 2006X induces relatively large changes in the total Na I D equivalent width (EW ~ 0.5 A in just over two weeks) that would be detectable at lower resolutions. We have used a large data set comprising 2400 low-resolution spectra of 450 Type Ia supernovae (SNe Ia) obtained by the CfA Supernova Program to search for variable Na I D features. Out of the 31 SNe Ia (including SN 2006X) in which we could have detected similar EW variations, only one other (SN 1999cl) shows variable Na I D features, with an even larger change over a similar ~10 day timescale (EW = 1.66 ± 0.21 A). Interestingly, both SN 1999cl and SN 2006X are the two most highly reddened objects in our sample, raising the possibility that the variability is connected to dusty environments.
We present an analysis of 507 spectra of 173 stripped-envelope (SE) supernovae (SNe) discovered by the untargeted Palomar Transient Factory (PTF) and intermediate PTF (iPTF) surveys. Our sample ...contains 55 Type IIb SNe (SNe IIb), 45 Type Ib SNe (SNe Ib), 56 Type Ic SNe (SNe Ic), and 17 Type Ib/c SNe (SNe Ib/c). We have compared the SE SN subtypes via measurements of the pseudo-equivalent widths (pEWs) and velocities of the He I λλ5876, 7065 and O I λ7774 absorption lines. Consistent with previous work, we find that SNe Ic show higher pEWs and velocities in O I λ7774 compared to SNe IIb and Ib. The pEWs of the He I λλ5876, 7065 lines are similar in SNe Ib and IIb after maximum light. The He I λλ5876, 7065 velocities at maximum light are higher in SNe Ib compared to SNe IIb. We identify an anticorrelation between the He I λ7065 pEW and O I λ7774 velocity among SNe IIb and Ib. This can be interpreted as a continuum in the amount of He present at the time of explosion. It has been suggested that SNe Ib and Ic have similar amounts of He, and that lower mixing could be responsible for hiding He in SNe Ic. However, our data contradict this mixing hypothesis. The observed difference in the expansion rate of the ejecta around maximum light of SNe Ic (Vm = √2Ek/Mej ≈ 15 000 km s−1Vm=2Ek/Mej≈15 000 km s−1${V_{\rm{m}}} = \sqrt {2{E_{\rm{k}}}/{M_{{\rm{ej}}} \approx 1{\rm{5 \, 000 \, km }} \, {{\rm{s}}^{ - 1}}$) and SNe Ib (Vm ≈ 9000 km s−1) would imply an average He mass difference of ∼1.4 M⊙, if the other explosion parameters are assumed to be unchanged between the SE SN subtypes. We conclude that SNe Ic do not hide He but lose He due to envelope stripping.
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