KELT-6b: A P~7.9 d Hot Saturn Transiting a Metal-Poor Star with a Long-Period Companion

We report the discovery of KELT-6b, a mildly-inflated Saturn-mass planet transiting a metal-poor host. The initial transit signal was identified in KELT-North survey data, and the planetary nature of the occulter was established using a combination of follow-up photometry, high-resolution imaging, high-resolution spectroscopy, and precise radial velocity measurements. The fiducial model from a global analysis including constraints from isochrones indicates that the V=10.38 host star (BD+31 2447) is a mildly evolved, late-F star with T_eff=6102 \pm 43 K, log(g_*)=4.07_{-0.07}^{+0.04} and [Fe/H]=-0.28 \pm 0.04, with an inferred mass M_*=1.09 \pm 0.04 M_sun and radius R_star=1.58_{-0.09}^{+0.16} R_sun. The planetary companion has mass M_P=0.43 \pm 0.05 M_J, radius R_P=1.19_{-0.08}^{+0.13} R_J, surface gravity log(g_P)=2.86_{-0.08}^{+0.06}, and density rho_P=0.31_{-0.08}^{+0.07} g~cm^{-3}. The planet is on an orbit with semimajor axis a=0.079 \pm 0.001 AU and eccentricity e=0.22_{-0.10}^{+0.12}, which is roughly consistent with circular, and has ephemeris of T_c(BJD_TDB)=2456347.79679 \pm 0.00036 and P=7.845631 \pm 0.000046 d. Equally plausible fits that employ empirical constraints on the host star parameters rather than isochrones yield a larger planet mass and radius by ~4-7%. KELT-6b has surface gravity and incident flux similar to HD209458b, but orbits a host that is more metal poor than HD209458 by ~0.3 dex. Thus, the KELT-6 system offers an opportunity to perform a comparative measurement of two similar planets in similar environments around stars of very different metallicities. The precise radial velocity data also reveal an acceleration indicative of a longer-period third body in the system, although the companion is not detected in Keck adaptive optics images.Comment: Published in AJ, 17 pages, 15 figures, 6 table

KELT-6b: A P ~ 7.9 Day Hot Saturn Transiting a Metal-poor Star with a Long-period Companion

We report the discovery of KELT-6b, a mildly inflated Saturn-mass planet transiting a metal-poor host. The initial transit signal was identified in KELT-North survey data, and the planetary nature of the occulter was established using a combination of follow-up photometry, high-resolution imaging, high-resolution spectroscopy, and precise radial velocity measurements. The fiducial model from a global analysis including constraints from isochrones indicates that the V = 10.38 host star (BD+31 2447) is a mildly evolved, late-F star with T eff = 6102 ± 43 K, , and [Fe/H] = –0.28 ± 0.04, with an inferred mass M = 1.09 ± 0.04 M ☉ and radius . The planetary companion has mass MP = 0.43 ± 0.05 M Jup, radius , surface gravity , and density . The planet is on an orbit with semimajor axis a = 0.079 ± 0.001 AU and eccentricity , which is roughly consistent with circular, and has ephemeris of T c(BJDTDB) = 2456347.79679 ± 0.00036 and P = 7.845631 ± 0.000046 days. Equally plausible fits that employ empirical constraints on the host-star parameters rather than isochrones yield a larger planet mass and radius by ~4}-7}. KELT-6b has surface gravity and incident flux similar to HD 209458b, but orbits a host that is more metal poor than HD 209458 by ~0.3 dex. Thus, the KELT-6 system offers an opportunity to perform a comparative measurement of two similar planets in similar environments around stars of very different metallicities. The precise radial velocity data also reveal an acceleration indicative of a longer-period third body in the system, although the companion is not detected in Keck adaptive optics images

Kelt-4Ab: An inflated hot jupiter transiting the bright (V ∼ 10) component of a hierarchical triple

We report the discovery of KELT-4Ab, an inflated, transiting Hot Jupiter orbiting the brightest component of ahierarchical triple stellar system. The host star is an F star with Teff =6206 ± 75 K, log g =4.108 ± 0.014, [Fe/H]= -0.116+0.069+0.065, M∗ = 1.201-0.061+0.067 M⊙, and R∗ = 1.603-0.038+0.039 R⊙. The best-fit linear ephemeris is BJDTDB =2456193.29157±0.00021 + E(2.9895936±0.0000048). With a magnitude of V∼10, a planetary radius of 1.699-0.045+0.046 RJ, and a mass of 0.902-0.059+0.060 MJ, it is the brightest host among the population of inflated Hot Jupiters (RP \u3e 1.5RJ), making it a valuable discovery for probing the nature of inflated planets. In addition, its existence within a hierarchical triple and its proximity to Earth (210 pc) provide a unique opportunity for dynamical studies with continued monitoring with high resolution imaging and precision radial velocities. The projected separation between KELT-4A and KELT-4BC is 328±16 AU and the projected separation between KELT-4B and KELT-4C is 10.30±0.74 AU. Assuming face-on, circular orbits, their respective periods would be 3780±290 and 29.4±3.6 years and the astrometric motions relative to the epoch in this work of both the binary stars around each other and of the binary around the primary star would be detectable now and may provide meaningful constraints on the dynamics of the system

Cell Cycle Gene Networks Are Associated with Melanoma Prognosis

BACKGROUND: Our understanding of the molecular pathways that underlie melanoma remains incomplete. Although several published microarray studies of clinical melanomas have provided valuable information, we found only limited concordance between these studies. Therefore, we took an in vitro functional genomics approach to understand melanoma molecular pathways. METHODOLOGY/PRINCIPAL FINDINGS: Affymetrix microarray data were generated from A375 melanoma cells treated in vitro with siRNAs against 45 transcription factors and signaling molecules. Analysis of this data using unsupervised hierarchical clustering and Bayesian gene networks identified proliferation-association RNA clusters, which were co-ordinately expressed across the A375 cells and also across melanomas from patients. The abundance in metastatic melanomas of these cellular proliferation clusters and their putative upstream regulators was significantly associated with patient prognosis. An 8-gene classifier derived from gene network hub genes correctly classified the prognosis of 23/26 metastatic melanoma patients in a cross-validation study. Unlike the RNA clusters associated with cellular proliferation described above, co-ordinately expressed RNA clusters associated with immune response were clearly identified across melanoma tumours from patients but not across the siRNA-treated A375 cells, in which immune responses are not active. Three uncharacterised genes, which the gene networks predicted to be upstream of apoptosis- or cellular proliferation-associated RNAs, were found to significantly alter apoptosis and cell number when over-expressed in vitro. CONCLUSIONS/SIGNIFICANCE: This analysis identified co-expression of RNAs that encode functionally-related proteins, in particular, proliferation-associated RNA clusters that are linked to melanoma patient prognosis. Our analysis suggests that A375 cells in vitro may be valid models in which to study the gene expression modules that underlie some melanoma biological processes (e.g., proliferation) but not others (e.g., immune response). The gene expression modules identified here, and the RNAs predicted by Bayesian network inference to be upstream of these modules, are potential prognostic biomarkers and drug targets

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Clinical practice recommendations for management of lateropulsion after stroke determined by a Delphi expert panel

Objective: People exhibiting post-stroke lateropulsion actively push their body across the midline to the more affected side and/or resist weight shift toward the less affected side. Despite its prevalence and associated negative rehabilitation outcomes, no clinical practice guidelines exist for the rehabilitation of poststroke lateropulsion. We aimed to develop consensus-based clinical practice recommendations for managing post-stroke lateropulsion using an international expert panel. Design: This Delphi panel process conformed with Guidance on Conducting and Reporting Delphi Studies recommendations. Participants: Panel members had demonstrated clinical and/or scientific background in the rehabilitation of people with post-stroke lateropulsion. Main Measures: The process consisted of four electronic survey rounds. Round One consisted of 13 open questions. Subsequent rounds ascertained levels of agreement with statements derived from Round One. Consensus was defined a priori as ≥75% agreement (agree or strongly agree), or ≥70% agreement after excluding ‘unsure’ responses. Results: Twenty participants completed all four rounds. Consensus was achieved regarding a total of 119 recommendations for rehabilitation approaches and considerations for rehabilitation delivery, positioning, managing fear of falling and fatigue, optimal therapy dose, and discharge planning. Statements for which ‘some agreement’ (50%–74% agreement) was achieved and those for which recommendations remain to be clarified were recorded. Conclusions: These recommendations build on existing evidence to guide the selection of interventions for post-stroke lateropulsion. Future research is required to elaborate specific rehabilitation strategies, consider the impact of additional cognitive and perceptual impairments, describe positioning options, and detail optimal therapy dose for people with lateropulsion

Post-stroke lateropulsion terminology: Pushing for agreement amongst experts

Post-stroke lateropulsion is prevalent. The global inconsistency in terminology used to describe the condition presents obstacles in accurately comparing research results, reaching consensus on use of measurement tools, agreeing upon a consistent approach to rehabilitation, and translating research to clinical practice. Commencing in 2021, 20 international experts undertook a Delphi Process that aimed to compile clinical practice recommendations for the rehabilitation of lateropulsion. As a part of the process, the panel agreed to aim to reach consensus regarding terminology used to describe the condition. Improved understanding of the condition could lead to improved management, which will enhance patient outcomes after stroke and increase efficiency of healthcare resource utilisation. While consensus was not reached, the panel achieved some agreement that ‘lateropulsion’ is the preferred term to describe the phenomenon of ‘active pushing of the body across the midline toward the more affected side, and / or actively resisting weight shift toward the less affected side’. This group recommends that ‘lateropulsion\u27 is used in future research and in clinical practice