Time and \u27Manyness\u27: Temporality, Ecology, and Form in Don DeLillo\u27s Underworld

Don DeLillo’s Underworld employs formal approaches to the novel that question the limits of language. DeLillo’s novel charts an ecology of the human relation to the material world as it is created by language. He uses parataxis to demonstrate the methods whereby language receives limitation from its situation in frames of reference that are both historical and fictional. His formal techniques show how Cold War tropes inform interpretation of the material world through discourse, in terms of paranoia and knowledge, consumer capitalism and waste, and historically relevant forms of mimesis. This thesis argues that DeLillo’s emphasis on the limitation of discourse through framing encourages the reader to consider the ability of language to generate awareness of the grounds for its situatedness in time and history. The reader’s ceremonial engagement with the mimesis of the text creates the possibility for a temporality based in thought, dignity, and consequence to emerge

Assessment of Food Safety Knowledge, Attitudes and Practices of Food Service Staff in Bangladeshi Hospitals: A Cross-Sectional Study.

Food safety knowledge, attitudes and practices among hospital food service staff are crucial in the prevention of foodborne disease outbreaks, as hospitalized patients are more vulnerable to potential hazards. This study, therefore, sought to assess the food safety knowledge, attitudes and practices of food service staff in Bangladeshi hospitals. A cross-sectional study was conducted among 191 food service staff from seven different hospitals in Dhaka and Chattogram from October 2021 to March 2022 using pretested questionnaires. Multiple linear regression was used to identify the factors associated with the food safety knowledge, attitudes and practices. The findings showed moderate knowledge but high levels of attitudes and practices of food safety among hospital food handlers. Food safety knowledge was significantly higher among males, participants from private hospitals and participants working in a hospital that had a food service supervisor and dietitian in charge of food service operations. Moreover, participants from private hospitals and participants working in a hospital that had a food service supervisor and dietitian in charge of food service operations had more positive attitudes and better practices regarding food safety. Hospital management should consider these factors for enhancing food handlers' knowledge and increase training and supervision on food safety practices to reduce foodborne diseases and outbreaks

Does owning a pet protect older people against loneliness?

This article has been made available through the Brunel Open Access Publishing Fund.Pet ownership is thought to make a positive contribution to health, health behaviours and the general well-being of older people. More specifically pet ownership is often proposed as a solution to the problem of loneliness in later life and specific 'pet based' interventions have been developed to combat loneliness. However the evidence to support this relationship is slim and it is assumed that pet ownership is a protection against loneliness rather than a response to loneliness. The aim of this paper is to examine the association between pet ownership and loneliness by exploring if pet ownership is a response to, or protection against, loneliness using Waves 0-5 from the English Longitudinal Study of Ageing (ELSA)

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

Efficacy and Safety of a New 20% Immunoglobulin Preparation for Subcutaneous Administration, IgPro20, in Patients With Primary Immunodeficiency

Subcutaneous human IgG (SCIG) therapy in primary immunodeficiency (PID) offers sustained IgG levels throughout the dosing cycle and fewer adverse events (AEs) compared to intravenous immunoglobulin (IVIG). A phase I study showed good local tolerability of IgPro20, a new 20% liquid SCIG stabilized with L-proline. A prospective, open-label, multicenter, single-arm, phase III study evaluated the efficacy and safety of IgPro20 in patients with PID over 15 months. Forty-nine patients (5–72 years) previously treated with IVIG received weekly subcutaneous infusions of IgPro20. The mean serum IgG level was 12.5 g/L. No serious bacterial infections were reported. There were 96 nonserious infections (rate 2.76/patient per year). The rate of days missed from work/school was 2.06/patient per year, and the rate of hospitalization was 0.2/patient per year. Ninety-nine percent of AEs were mild or moderate. No serious, IgPro20-related AEs were reported. IgPro20 effectively protected patients with PID against infections and maintained serum IgG levels without causing unexpected AEs

Efficacy and Safety of Hizentra®, a New 20% Immunoglobulin Preparation for Subcutaneous Administration, in Pediatric Patients with Primary Immunodeficiency

Subcutaneous IgG treatment for primary immunodeficiencies (PI) is particularly well suited for children because it does not require venous access and is mostly free of systemic adverse events (AEs). In a prospective, open-label, multicenter, single-arm, Phase III study, 18 children and five adolescents with PI were switched from previous intravenous (IVIG) or subcutaneous (SCIG) IgG treatment to receive dose-equivalent, weekly subcutaneous infusions of Hizentra® for 40 weeks. Mean IgG trough levels were maintained in patients previously on SCIG, or increased in those previously on IVIG, regardless of age. No serious bacterial infections were reported during the efficacy period of the study. The rates of non-serious infections were 4.77 (children) and 5.18 (adolescents) infections per patient per year. Related AEs were observed in seven children (38.9%) and two adolescents (40%). Three serious AEs and two AEs leading to discontinuation (all unrelated) were reported in children. Hizentra® is an effective and well-tolerated treatment for pediatric patients

Germline Genetic Variants Disturbing the Let-7/LIN28 Double-Negative Feedback Loop Alter Breast Cancer Susceptibility

Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7–induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0×10−5. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk

Hacking into bacterial biofilms: a new therapeutic challenge

Microbiologists have extensively worked during the past decade on a particular phase of the bacterial cell cycle known as biofilm, in which single-celled individuals gather together to form a sedentary but dynamic community within a complex structure, displaying spatial and functional heterogeneity. In response to the perception of environmental signals by sensing systems, appropriate responses are triggered, leading to biofilm formation. This process involves various molecular systems that enable bacteria to identify appropriate surfaces on which to anchor themselves, to stick to those surfaces and to each other, to construct multicellular communities several hundreds of micrometers thick, and to detach from the community. The biofilm microbial community is a unique, highly competitive, and crowded environment facilitating microevolutionary processes and horizontal gene transfer between distantly related microorganisms. It is governed by social rules, based on the production and use of "public" goods, with actors and recipients. Biofilms constitute a unique shield against external aggressions, including drug treatment and immune reactions. Biofilm-associated infections in humans have therefore generated major problems for the diagnosis and treatment of diseases. Improvements in our understanding of biofilms have led to innovative research designed to interfere with this process

Social Networking Technology, Social Network Composition, and Reductions in Substance Use Among Homeless Adolescents

Peer-based prevention programs for homeless youth are complicated by the potential for reinforcing high-risk behaviors among participants. The goal of this study is to understand how homeless youth could be linked to positive peers in prevention programming by understanding where in social and physical space positive peers for homeless youth are located, how these ties are associated with substance use, and the role of social networking technologies (e.g., internet and cell phones) in this process. Personal social network data were collected from 136 homeless adolescents in Los Angeles, CA. Respondents reported on composition of their social networks with respect to: home-based peers and parents (accessed via social networking technology; e.g., the internet, cell phone, texting), homeless peers and agency staff (accessed face-to-face) and whether or not network members were substance-using or non-substance-using. Associations between respondent’s lifetime cocaine, heroin, and methamphetamine use and recent (previous 30 days) alcohol and marijuana use were assessed by the number of non-substance-using versus substance-using ties in multivariate linear regression models. 43% of adolescents reported a non-substance-using home-based tie. More of these ties were associated with less recent alcohol use. 62% of adolescents reported a substance-using homeless tie. More of these ties were associated with more recent marijuana use as well as more lifetime heroin and methamphetamine use. For homeless youth, who are physically disconnected from positive peers, social networking technologies can be used to facilitate the sorts of positive social ties that effective peer-based prevention programs require