Development of the Home Cooking EnviRonment and Equipment Inventory Observation form (Home-CookERITM): An Assessment of Content Validity, Face Validity, and Inter-Rater Agreement

Introduction: Quantifying Home Cooking EnviRonments has applications in nutrition epidemiology, health promotion, and nutrition interventions. This study aimed to develop a tool to quantify household cooking environments and establish its content validity, face validity, and inter-rater agreement. Methods: The Home Cooking EnviRonment and equipment Inventory observation form (Home-CookERI™) was developed as a 24-question (91-item) online survey. Items included domestic spaces and resources for storage, disposal, preparation, and cooking of food or non-alcoholic beverages. Home-CookERITM was piloted to assess content validity, face validity, and usability with six Australian experts (i.e., dietitians, nutrition researchers, chefs, a food technology teacher, and a kitchen designer) and 13 laypersons. Pilot participants provided feedback in a 10 min telephone interview. Home-CookERI™ was modified to an 89-item survey in line with the pilot findings. Inter-rater agreement was examined between two trained raters in 33 unique Australian households. Raters were required to observe each item before recording a response. Home occupants were instructed to only assist with locating items if asked. Raters were blinded to each other’s responses. Inter-rater agreement was calculated by Cohen’s Kappa coefficient (κ) for each item. To optimize κ, similar items were grouped together reducing the number of items to 81. Results: Home-CookERITM had excellent content and face validity with responding participants; all 24 questions were both clear and relevant (X2 (1, n = 19; 19.0, p = 0.392)). Inter-rater agreement for the modified 81-item Home-CookERI™ was almost-perfect to perfect for 46% of kitchen items (n = 37 items, κ = 0.81–1), moderate to substantial for 28% (n = 23, κ = 0.51–0.8), slight to fair for 15% (n = 12, κ = 0.01–0.5), and chance or worse for 11% of items (n = 9, κ ≤ 0.0). Home-CookERITM was further optimized by reduction to a 77-item version, which is now available to researchers. Conclusion: Home-CookERI™ is a comprehensive tool for quantifying Australian household cooking environments. It has excellent face and content validity and moderate to perfect inter-rater agreement for almost three-quarters of included kitchen items. To expand Home-CookERI™ applications, a home occupant self-completion version is planned for validatio

Mapping the Asymmetric Thick Disk: III. The Kinematics and Interaction with the Galactic Bar

In the first two papers of this series, Larsen et al (2010a,b) describe our faint CCD survey in the inner Galaxy and map the over-density of Thick Disk stars in Quadrant I (Q1) to 5 kpc or more along the line of sight. The regions showing the strongest excess are above the density contours of the bar in the Galactic disk. In this third paper on the asymmetric Thick Disk, we report on radial velocities and derived metallicity parameters for over 4000 stars in Q1, above and below the plane and in Q4 above the plane. We confirm the corresponding kinematic asymmetry first reported by Parker et al. (2004), extended to greater distances and with more spatial coverage. The Thick Disk stars in Q1 have a rotational lag of 60 -- 70 km/s relative to circular rotation, and the Metal-Weak Thick Disk stars have an even greater lag of 100 km/s. Both lag their corresponding populations in Q4 by approximately 30 km/s. Interestingly, the Disk stars in Q1 also appear to participate in the rotational lag by about 30 km/s. The enhanced rotational lag for the Thick Disk in Q1 extends to 4 kpc or more from the Sun. At 3 to 4 kpc, our sight lines extend above the density contours on the near side of the bar, and as our lines of sight pass directly over the bar the rotational lag appears to decrease. This is consistent with a "gravitational wake" induced by the rotating bar in the Disk which would trap and pile up stars behind it. We conclude that a dynamical interaction with the stellar bar is the most probable explanation for the observed kinematic and spatial asymmetries

IAT-TiMeS: Intra-Arterial Thrombectomy Transfer Metric Study in Texas

Objective: We aim to report intra-arterial thrombectomy transfer metrics for ischemic stroke patients that were transferred to hub hospitals for possible intra-arterial thrombectomy in multiple geographic regions throughout the state of Texas and to identify potential barriers and delays in the intra-arterial thrombectomy transfer process. Method: We prospectively collected data from 8 participating Texas comprehensive stroke/thrombectomy capable centers from 7 major regions in the State of Texas. We collected baseline clinical and imaging data related to the pre-transfer evaluation, transfer metrics, and post-transfer clinical and imaging data. Results: A total of 103 acute ischemic stroke patients suspected/confirmed to have large vessel occlusions between December 2016 to May 2019 that were transferred to hubs as possible intra-arterial thrombectomy candidates were enrolled. A total of 56 (54%) patients were sent from the spoke to the hub via ground ambulance with 47 (46%) patients traveling via air ambulance. The median spoke arrival to hub arrival time was 174 min, median spoke arrival to departure from spoke was 131 min, and median travel time was 39 min. The spoke arrival time to transfer initiation was 68 min. CT-perfusion obtained at the spoke and earlier initiation of transfer were statistically associated with shorter transfer times. Conclusion: Transfer of intra-arterial thrombectomy patients in Texas may take over 4 h from spoke arrival to hub arrival. This time may be shortened by earlier transfer initiation and acceptance

Hot Streaks in Artistic, Cultural, and Scientific Careers

The hot streak, loosely defined as winning begets more winnings, highlights a specific period during which an individual's performance is substantially higher than her typical performance. While widely debated in sports, gambling, and financial markets over the past several decades, little is known if hot streaks apply to individual careers. Here, building on rich literature on lifecycle of creativity, we collected large-scale career histories of individual artists, movie directors and scientists, tracing the artworks, movies, and scientific publications they produced. We find that, across all three domains, hit works within a career show a high degree of temporal regularity, each career being characterized by bursts of high-impact works occurring in sequence. We demonstrate that these observations can be explained by a simple hot-streak model we developed, allowing us to probe quantitatively the hot streak phenomenon governing individual careers, which we find to be remarkably universal across diverse domains we analyzed: The hot streaks are ubiquitous yet unique across different careers. While the vast majority of individuals have at least one hot streak, hot streaks are most likely to occur only once. The hot streak emerges randomly within an individual's sequence of works, is temporally localized, and is unassociated with any detectable change in productivity. We show that, since works produced during hot streaks garner significantly more impact, the uncovered hot streaks fundamentally drives the collective impact of an individual, ignoring which leads us to systematically over- or under-estimate the future impact of a career. These results not only deepen our quantitative understanding of patterns governing individual ingenuity and success, they may also have implications for decisions and policies involving predicting and nurturing individuals with lasting impact

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

Defecting or not defecting: how to "read" human behavior during cooperative games by EEG measurements

Understanding the neural mechanisms responsible for human social interactions is difficult, since the brain activities of two or more individuals have to be examined simultaneously and correlated with the observed social patterns. We introduce the concept of hyper-brain network, a connectivity pattern representing at once the information flow among the cortical regions of a single brain as well as the relations among the areas of two distinct brains. Graph analysis of hyper-brain networks constructed from the EEG scanning of 26 couples of individuals playing the Iterated Prisoner's Dilemma reveals the possibility to predict non-cooperative interactions during the decision-making phase. The hyper-brain networks of two-defector couples have significantly less inter-brain links and overall higher modularity - i.e. the tendency to form two separate subgraphs - than couples playing cooperative or tit-for-tat strategies. The decision to defect can be "read" in advance by evaluating the changes of connectivity pattern in the hyper-brain network

Bioengineered small extracellular vesicles deliver multiple SARS‐CoV‐2 antigenic fragments and drive a broad immunological response

The COVID‐19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS‐CoV‐2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long‐lived protective immunity. Here we report the design and preclinical testing of small extracellular vesicles (sEVs) as a multi‐subunit vaccine. Cell lines were engineered to produce sEVs containing either the SARS‐CoV‐2 Spike receptor‐binding domain, or an antigenic region from SARS‐CoV‐2 Nucleocapsid, or both in combination, and we tested their ability to evoke immune responses in vitro and in vivo. B cells incubated with bioengineered sEVs were potent activators of antigen‐specific T cell clones. Mice immunised with sEVs containing both sRBD and Nucleocapsid antigens generated sRBD‐specific IgGs, nucleocapsid‐specific IgGs, which neutralised SARS‐CoV‐2 infection. sEV‐based vaccines allow multiple antigens to be delivered simultaneously resulting in potent, broad immunity, and provide a quick, cheap, and reliable method to test vaccine candidates

Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release

The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon‐induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS‐CoV‐2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS‐CoV‐2 viral titres. We investigate the potential viral proteins involved in abrogating tetherin function and find that SARS‐CoV‐2 ORF3a reduces tetherin localisation within biosynthetic organelles where Coronaviruses bud, and increases tetherin localisation to late endocytic organelles via reduced retrograde recycling. We also find that expression of Spike protein causes a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS‐CoV‐2 and highlight the multiple distinct mechanisms by which SARS‐CoV‐2 subverts tetherin function

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

Mitochondrially-targeted APOBEC1 is a potent mtDNA mutator affecting mitochondrial function and organismal fitness in Drosophila

Abstract: Somatic mutations in the mitochondrial genome (mtDNA) have been linked to multiple disease conditions and to ageing itself. In Drosophila, knock-in of a proofreading deficient mtDNA polymerase (POLG) generates high levels of somatic point mutations and also small indels, but surprisingly limited impact on organismal longevity or fitness. Here we describe a new mtDNA mutator model based on a mitochondrially-targeted cytidine deaminase, APOBEC1. mito-APOBEC1 acts as a potent mutagen which exclusively induces C:G>T:A transitions with no indels or mtDNA depletion. In these flies, the presence of multiple non-synonymous substitutions, even at modest heteroplasmy, disrupts mitochondrial function and dramatically impacts organismal fitness. A detailed analysis of the mutation profile in the POLG and mito-APOBEC1 models reveals that mutation type (quality) rather than quantity is a critical factor in impacting organismal fitness. The specificity for transition mutations and the severe phenotypes make mito-APOBEC1 an excellent mtDNA mutator model for ageing research