Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet

Human Auditory Cortical Activation during Self-Vocalization

During speaking, auditory feedback is used to adjust vocalizations. The brain systems mediating this integrative ability have been investigated using a wide range of experimental strategies. In this report we examined how vocalization alters speech-sound processing within auditory cortex by directly recording evoked responses to vocalizations and playback stimuli using intracranial electrodes implanted in neurosurgery patients. Several new findings resulted from these high-resolution invasive recordings in human subjects. Suppressive effects of vocalization were found to occur only within circumscribed areas of auditory cortex. In addition, at a smaller number of sites, the opposite pattern was seen; cortical responses were enhanced during vocalization. This increase in activity was reflected in high gamma power changes, but was not evident in the averaged evoked potential waveforms. These new findings support forward models for vocal control in which efference copies of premotor cortex activity modulate sub-regions of auditory cortex

Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy : a position paper

Chimeric antigen receptor (CAR) T-cell therapy is one of the most promising emerging treatments for B-cell malignancies. Recently, two CAR T-cell products (axicabtagene ciloleucel and tisagenlecleucel) have been approved for patients with aggressive B-cell lymphoma and acute lymphoblastic leukemia; many other CAR-T constructs are in research for both hematological and non-hematological diseases. Most of the patients receiving CAR-T therapy will develop fever at some point after infusion, mainly due to cytokine release syndrome (CRS). The onset of CRS is often indistinguishable from an infection, which makes management of these patients challenging. In addition to the lymphodepleting chemotherapy and CAR T cells, the treatment of complications with corticosteroids and/or tocilizumab increases the risk of infection in these patients. Data regarding incidence, risk factors and prevention of infections in patients receiving CAR-T cell therapy are scarce. To assist in patient care, a multidisciplinary team from hospitals designated by the Spanish Ministry of Health to perform CAR-T therapy prepared these recommendations. We reviewed the literature on the incidence, risk factors, and management of infections in adult and pediatric patients receiving CAR-T cell treatment. Recommendations cover different areas: monitoring and treatment of hypogammaglobulinemia, prevention, prophylaxis, and management of bacterial, viral, and fungal infections as well as vaccination prior and after CAR-T cell therapy

Development of an Affimer-antibody combined immunological diagnosis kit for glypican-3

Glypican-3 (GPC3) is a promising new marker for hepatocellular carcinoma, but the reported values for serum GPC3 differ markedly between currently available kits. Here we isolated Affimer non-antibody binding proteins against GPC3 by phage display and developed a new sandwich chemiluminescence immunoassay (CLIA) combining an Affimer with a monoclonal antibody (Affimer-MAb CLIA). The proposed CLIA assay demonstrated a wide linear range  0.03–600 ng/mL) with a good linear correlation coefficient (0.9999), a high detection limitation (0.03 ng/mL) and specificity (0–0.002%) for detection of GPC3. The accuracy, hook effect and stability were demonstrated to be satisfactory. The mean level of GPC3 in serum was higher (>8.5 fold, P < 0.001) in hepatocellular carcinoma patients compared to healthy and other liver disease individuals. A poor correlation (correlation coefficients ranged from −0.286 to 0.478) was observed through pairwise comparison within different kits. However, only this newly developed CLIA test showed high specificity and correlated with the “gold standard” GPC3-immunohistochemistry. This study indicates that Affimer-MAb CLIA can be used to generate a sensitive immunodiagnostic kit, which offers the potential for a highly specific clinically-relevant detection system

Best Treatment Option for Patients With Refractory Aggressive B-Cell Lymphoma in the CAR-T Cell Era: Real-World Evidence From GELTAMO/GETH Spanish Groups

Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4-6 months, p <= 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44-0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31-0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria

Inadequate glucose control in type 2 diabetes is associated with impaired lung function and systemic inflammation: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Inadequate glucose control may be simultaneously associated with inflammation and decreased lung function in type 2 diabetes. We evaluated if lung function is worse in patients with inadequate glucose control, and if inflammatory markers are simultaneously increased in these subjects.</p> <p>Methods</p> <p>Subjects were selected at the Colombian Diabetes Association Center in Bogotá. Pulmonary function tests were performed and mean residual values were obtained for forced expiratory volume (FEV₁₎, forced vital capacity (FVC) and FEV₁/FVC, with predicted values based on those derived by Hankinson et al. for Mexican-Americans. Multiple least-squares regression was used to adjust for differences in known determinants of lung function. We measured blood levels of glycosylated hemoglobin (HBA_1c), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), fibrinogen, ferritin, and C-reactive protein (C-RP).</p> <p>Results</p> <p>495 diabetic patients were studied, out of which 352 had inadequate control (HBA_1c> 7%). After adjusting for known determinants of lung function, those with inadequate control had lower FEV₁(-75.4 mL, IC95%: -92, -59; P < 0.0001) and FVC (-121 mL, IC95%: -134, -108; P < 0,0001) mean residuals, and higher FEV₁/FVC (0.013%, IC95%: 0.009, 0.018, P < 0.0001) residuals than those with adequate control, as well as increased levels of all inflammatory markers (P < 0.05), with the exception of IL-6.</p> <p>Conclusions</p> <p>Subjects with type 2 diabetes and inadequate control had lower FVC and FEV₁than predicted and than those of subjects with adequate control. It is postulated that poorer pulmonary function may be associated with increased levels of inflammatory mediators.</p

Extrapulmonary tuberculosis, human immunodeficiency virus, and foreign birth in North Carolina, 1993 – 2006

<p>Abstract</p> <p>Background</p> <p>The proportion of extrapulmonary tuberculosis (EPTB) reported in the United States has been gradually increasing. HIV infection and foreign birth are increasingly associated with tuberculosis and understanding their effect on the clinical presentation of tuberculosis is important.</p> <p>Methods</p> <p>Case-control study of 6,124 persons with tuberculosis reported to the North Carolina Division of Public health from January 1, 1993 to December 31, 2006. Multivariate logistic regression was used to obtain adjusted odds ratios measuring the associations of foreign birth region and US born race/ethnicity, by HIV status, with EPTB.</p> <p>Results</p> <p>Among all patients with tuberculosis, 1,366 (22.3%) had EPTB, 563 (9.2%) were HIV co-infected, and 1,299 (21.2%) were foreign born. Among HIV negative patients, EPTB was associated with being foreign born (adjusted ORs 1.36 to 5.09, depending on region of birth) and with being US born, Black/African American (OR 1.84; 95% CI 1.42, 2.39). Among HIV infected patients, EPTB was associated with being US born, Black/African American (OR 2.60; 95% CI 1.83, 3.71) and with foreign birth in the Americas (OR 5.12; 95% CI 2.84, 9.23).</p> <p>Conclusion</p> <p>Foreign born tuberculosis cases were more likely to have EPTB than US born tuberculosis cases, even in the absence of HIV infection. Increasing proportions of foreign born and HIV-attributable tuberculosis cases in the United States will likely result in a sustained burden of EPTB. Further research is needed to explore why the occurrence and type of EPTB differs by region of birth and whether host genetic and/or bacterial variation can explain these differences in EPTB.</p

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P= 2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those re-ceiving tisa-cel. Efficacy was not significantly different between both products

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P =0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P =0.003, and 42% vs. 16%, P <0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P =0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P =0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P =0.195), 51% and 47% (P =0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98