'A habitual disposition to the good': on reason, virtue and realism

Amidst the crisis of instrumental reason, a number of contemporary political philosophers including Jürgen Habermas have sought to rescue the project of a reasonable humanism from the twin threats of religious fundamentalism and secular naturalism. In his recent work, Habermas defends a post-metaphysical politics that aims to protect rationality against encroachment while also accommodating religious faith within the public sphere. This paper contends that Habermas’ post-metaphysical project fails to provide a robust alternative either to the double challenge of secular naturalism and religious fundamentalism or to the ruthless instrumentalism that underpins capitalism. By contrast with Habermas and also with the ‘new realism’ of contemporary political philosophers such as Raymond Geuss or Bernard Williams, realism in the tradition of Plato and Aristotle can defend reason against instrumental rationality and blind belief by integrating it with habit, feeling and even faith. Such metaphysical–political realism can help develop a politics of virtue that goes beyond communitarian thinking by emphasising plural modes of association (not merely ‘community’), substantive ties of sympathy and the importance of pursuing goodness and mutual flourishing

WHODAS 2.0 in prodromal Huntington disease : measures of functioning in neuropsychiatric disease

We thank the PREDICT-HD sites, the study participants, the National Research Roster for Huntington Disease Patients and Families, the Huntington’s Disease Society of America and the Huntington Study Group. This research was supported by the National Center for Advancing Translational Sciences, and the National Institutes of Health (NIH), through Grant 2 UL1 TR000442-06. This research is supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke (NS040068), CHDI Foundation, Inc (A3917), Cognitive and Functional Brain Changes in Preclinical Huntington’s Disease (HD) (5R01NS054893), 4D Shape Analysis for Modeling Spatiotemporal Change Trajectories in Huntington’s (1U01NS082086), Functional Connectivity in Pre-manifest Huntington’s Disease (1U01NS082083), and Basal Ganglia Shape Analysis and Circuitry in Huntington’s Disease (1U01NS082085).Peer reviewedPublisher PD

Low luminosity Type II supernovae - IV. SN 2020cxd and SN 2021aai, at the edges of the sub-luminous supernovae class

Photometric and spectroscopic data for two Low Luminosity Type IIP Supernovae (LL SNe IIP) 2020cxd and 2021aai are presented. SN 2020cxd was discovered 2 d after explosion at an absolute magnitude of Mr = -14.02 ± 0.21 mag, subsequently settling on a plateau which lasts for ∼120 d. Through the luminosity of the late light curve tail, we infer a synthesized 56Ni mass of (1.8 ± 0.5) × 10-3 M⊙. During the early evolutionary phases, optical spectra show a blue continuum ($T\, \gt$8000 K) with broad Balmer lines displaying a P Cygni profile, while at later phases, Ca ii, Fe ii, Sc ii, and Ba ii lines dominate the spectra. Hydrodynamical modelling of the observables yields $R\, \simeq$ 575 R⊙ for the progenitor star, with Mej = 7.5 M⊙ and $E\, \simeq$ 0.097 foe emitted during the explosion. This low-energy event originating from a low-mass progenitor star is compatible with both the explosion of a red supergiant (RSG) star and with an Electron Capture Supernova arising from a super asymptotic giant branch star. SN 2021aai reaches a maximum luminosity of Mr = -16.57 ± 0.23 mag (correcting for AV = 1.92 mag), at the end of its remarkably long plateau (∼140 d). The estimated 56Ni mass is (1.4 ± 0.5) × 10-2 M⊙. The expansion velocities are compatible with those of other LL SNe IIP (few 103 km s-1). The physical parameters obtained through hydrodynamical modelling are $R\, \simeq$ 575 R⊙, Mej = 15.5 M⊙, and E = 0.4 foe. SN 2021aai is therefore interpreted as the explosion of an RSG, with properties that bridge the class of LL SNe IIP with standard SN IIP events.GV acknowledges INAF for funding his PhD fellowship within the PhD School in Astronomy at the University of Padova. MLP acknowledges support from the plan ‘programma ricerca di ateneo UNICT 2020-22 linea 2” of the University of Catania. AR acknowledges support from ANID BECAS/DOCTORADO NACIONAL 21202412. NER acknowledges partial support from MIUR, PRIN 2017 (grant 20179ZF5KS), from the Spanish MICINN grant PID2019-108709GB-I00 and FEDER funds, and from the programme Unidad de Excelencia María de Maeztu CEX2020-001058-M. LG acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación (MCIN), the Agencia Estatal de Investigación (AEI) 10.13039/501100011033, and the European Social Fund (ESF) ‘Investing in your future’ under the 2019 Ramón y Cajal programme RYC2019-027683-I and the PID2020-115253GA-I00 HOSTFLOWS project, from Centro Superior de Investigaciones Científicas (CSIC) under the PIE project 20215AT016, and the programme Unidad de Excelencia María de Maeztu CEX2020-001058-M. TMB acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación (MCIN), the Agencia Estatal de Investigación (AEI) 10.13039/501100011033 under the PID2020-115253GA-I00 HOSTFLOWS project, and from Centro Superior de Investigaciones Científicas (CSIC) under the PIE project 20215AT016, and the programme Unidad de Excelencia María de Maeztu CEX2020-001058-M. Y-ZC is funded by China Postdoctoral Science Foundation (grant no. 2021M691821

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

Pharmacist services for non-hospitalised patients

We are very grateful to the Chief Scientist Office, Scottish Government, for funding this review (CZH/4/1041). The authors wish to thank the members of Cochrane Effective Practice and Organisation of Care (EPOC) Group who supported this review, particularly Ms Tamara Rader and Mr Paul Miller for conducting the searches, and Ms Julia Worswick for her continued and good‐natured assistance throughout the update. We are very grateful to Dr Imran Omar for providing additional technical support. We thank Ms Caroline Burnett, Ms Andrea Fraser, Mrs Bev Smith and Ms Lynn McKenzie for their administrative and clerical support of this review. We thank the referees whose comments improved the reporting and interpretation of this review. These include: External referees: Yoon K Loke; Newton Opiyo; Internal editor: Carmel Hughes; Statistical editor: Sofia Massa; Contact editor: Gillian Leng; Managing editor: Daniela Gonçalves‐Bradley We also thank National Institute for Health Research, via Cochrane Infrastructure funding to the EPOC Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.Peer reviewedPublisher PD

Lunar Surface Systems Supportability Technology Development Roadmap

The Lunar Surface Systems Supportability Technology Development Roadmap is a guide for developing the technologies needed to enable the supportable, sustainable, and affordable exploration of the Moon and other destinations beyond Earth. Supportability is defined in terms of space maintenance, repair, and related logistics. This report considers the supportability lessons learned from NASA and the Department of Defense. Lunar Outpost supportability needs are summarized, and a supportability technology strategy is established to make the transition from high logistics dependence to logistics independence. This strategy will enable flight crews to act effectively to respond to problems and exploit opportunities in an environment of extreme resource scarcity and isolation. The supportability roadmap defines the general technology selection criteria. Technologies are organized into three categories: diagnostics, test, and verification; maintenance and repair; and scavenge and recycle. Furthermore, "embedded technologies" and "process technologies" are used to designate distinct technology types with different development cycles. The roadmap examines the current technology readiness level and lays out a four-phase incremental development schedule with selection decision gates. The supportability technology roadmap is intended to develop technologies with the widest possible capability and utility while minimizing the impact on crew time and training and remaining within the time and cost constraints of the program

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Neuroblastoma Cell Lines Contain Pluripotent Tumor Initiating Cells That Are Susceptible to a Targeted Oncolytic Virus

Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers.Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice.These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus

Sequence Conservation and Functional Constraint on Intergenic Spacers in Reduced Genomes of the Obligate Symbiont Buchnera

Analyses of genome reduction in obligate bacterial symbionts typically focus on the removal and retention of protein-coding regions, which are subject to ongoing inactivation and deletion. However, these same forces operate on intergenic spacers (IGSs) and affect their contents, maintenance, and rates of evolution. IGSs comprise both non-coding, non-functional regions, including decaying pseudogenes at varying stages of recognizability, as well as functional elements, such as genes for sRNAs and regulatory control elements. The genomes of Buchnera and other small genome symbionts display biased nucleotide compositions and high rates of sequence evolution and contain few recognizable regulatory elements. However, IGS lengths are highly correlated across divergent Buchnera genomes, suggesting the presence of functional elements. To identify functional regions within the IGSs, we sequenced two Buchnera genomes (from aphid species Uroleucon ambrosiae and Acyrthosiphon kondoi) and applied a phylogenetic footprinting approach to alignments of orthologous IGSs from a total of eight Buchnera genomes corresponding to six aphid species. Inclusion of these new genomes allowed comparative analyses at intermediate levels of divergence, enabling the detection of both conserved elements and previously unrecognized pseudogenes. Analyses of these genomes revealed that 232 of 336 IGS alignments over 50 nucleotides in length displayed substantial sequence conservation. Conserved alignment blocks within these IGSs encompassed 88 Shine-Dalgarno sequences, 55 transcriptional terminators, 5 Sigma-32 binding sites, and 12 novel small RNAs. Although pseudogene formation, and thus IGS formation, are ongoing processes in these genomes, a large proportion of intergenic spacers contain functional sequences

IL-7 Promotes CD95-Induced Apoptosis in B Cells via the IFN-γ/STAT1 Pathway

Interleukin-7 (IL-7) concentrations are increased in the blood of CD4+ T cell depleted individuals, including HIV-1 infected patients. High IL-7 levels might stimulate T cell activation and, as we have shown earlier, IL-7 can prime resting T cell to CD95 induced apoptosis as well. HIV-1 infection leads to B cell abnormalities including increased apoptosis via the CD95 (Fas) death receptor pathway and loss of memory B cells. Peripheral B cells are not sensitive for IL-7, due to the lack of IL-7Ra expression on their surface; however, here we demonstrate that high IL-7 concentration can prime resting B cells to CD95-mediated apoptosis via an indirect mechanism. T cells cultured with IL-7 induced high CD95 expression on resting B cells together with an increased sensitivity to CD95 mediated apoptosis. As the mediator molecule responsible for B cell priming to CD95 mediated apoptosis we identified the cytokine IFN-γ that T cells secreted in high amounts in response to IL-7. These results suggest that the lymphopenia induced cytokine IL-7 can contribute to the increased B cell apoptosis observed in HIV-1 infected individuals