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The belief of poet Gajanan Madhav Muktibodh that poetry can resolve the disjuncture between aesthetic and political realms is significant to interpretations of the literary production of mid-20th-century India. This article examines the use of affects in Muktibodh's poetry translated into English, that both mark such disjunction and attempt to resolve it. It analyses affects for how they foreground the codependency of modernity and modernism. To this end, the article understands modernity through relative periodization as a phenomenon that continually causes change either through transitions towards capitalism, or alternatively through authoritative, surveillance-based forms of governance. The losses caused by such modernity require rehabilitation, which in Muktibodh's poetry takes place through a modernist aesthetic. Thus, the article offers a reading that interprets Muktibodh's modernism as aiming to reconcile his creative-aesthetic freedom with the sociopolitical realities of the losses caused by modernity, and as inspired by the urge to overcome loss. [ABSTRACT FROM AUTHOR]

Chronic bone infection caused by Staphylococcus aureus biofilms in children and adults is characterized by reduced antibiotic sensitivity. In this study, we assessed 'heat-targeted, on-demand' antibiotic delivery for S. aureus killing by combining ciprofloxacin (CIP)-laden low-temperature sensitive liposomes (LTSLs) with local high-intensity focused ultrasound (HIFU) induced bone heating in a rat model of bone infection. CIP-LTSLs were prepared using the thin-film hydration and extrusion method. Bone infection was established by surgically implanting an orthopedic K-wire colonized with methicillin-resistant S. aureus (MRSA) strain into rat's femurs. For bone heating, ultrasound-guided HIFU exposures were performed to achieve a local temperature of 40–42 °C (∼15 min) concurrently with intravenous injection of CIP-LTSLs or CIP. CIP biodistribution was determined spectrophotometrically and therapeutic efficacy was determined by bacteriological, histological and scanning electron microscopy (SEM) analyses. CIP-LTSLs in the range of 183.5 nm ± 1.91 showed an encapsulation efficiency of >70% at 37 °C and a complete release at ∼42 °C. The metal implantation method yielded medullary osteomyelitis characterized by suppurative changes (bacterial and pus pockets) by day 10 in bones and adjoining muscle tissues. HIFU heating significantly improved CIP delivery from LTSLs in bones, resulting in a significant reduction in MRSA load compared to HIFU and CIP alone groups. These were also verified by histology and SEM, wherein a distinct reduction in S. aureus population in the infected metal wires and tissues from the combinatorial therapy was noted. HIFU improved CIP delivery to bones, achieving clearance of hard-to-treat MRSA biofilms. [ABSTRACT FROM AUTHOR]

Classical Swine Fever (CSF) is a contagious viral disease of pigs which is endemic in several parts of the world, including India. Prophylactic vaccination using live attenuated vaccine is the preferred method of control. However, there is significant inter-individual variation in the antibody response to vaccination. In this study, we measured the E2 antibody blocking percentage after 21 days of CSF vaccination in a mixed pig population consisting of Landrace, indigenous Ghurrah pigs, and their crossbreds. A Genome Wide Association Study (GWAS) carried out using single-SNP and haplotype based methods detected a 1.6 Mb region on SSC2 (28.92−30.52 Mb) as significantly associated with antibody response to CSF vaccination. The significant region and 1 Mb flanking sequences encompass 3 genes – EIF3M, DNAJC24 and ARL14EP, which code for proteins involved in Pestivirus replication and host immune response system. Our results combined with previous studies on immune response of pigs present this region as a suitable candidate for future functional investigations. [ABSTRACT FROM AUTHOR]

Educational stakeholders are keen to know the magnitude and importance of different interventions. However, the way evidence is communicated to support understanding of the effectiveness of an intervention is controversial. Typically studies in education have used the standardised mean difference as a measure of the impact of interventions. This measure, commonly known as the effect size, is problematic, in terms of how it is interpreted and understood. In this study, we propose a "gain index" as an alternative metric for quantifying and communicating the effectiveness of an intervention. This is estimated as the difference in the percentage of children who make positive gains between the intervention and control groups. Analysis of four randomized controlled trials in education supports the expectation that most children make progress due to normal school activities, which is independent of the intervention. This study elaborates a method to illustrate how trials with a positive gain index and with a higher percentage of pupils with positive gain in the intervention group can be used to communicate which trials are effective in improving educational outcomes. [ABSTRACT FROM AUTHOR]

In education, multisite trials involve randomization of pupils into intervention and comparison groups within schools. Most analytical models in multisite educational trials ignore that the impact of an intervention may be school dependent. This study investigates the impact of statistical models on the uncertainty associated with an effect size using comparable outcomes and covariates from ten multisite educational trials funded by the UK's Education Endowment Foundation. Ordinary least squares (OLS) models often assume that the pupil's outcomes within schools are independent, which is not always true. Multilevel models address this limitation by incorporating heterogeneity between schools to account for intra-school dependency. This inflates the confidence interval of an effect size obtained from the multilevel models than from an OLS model. For a multisite trial, the heterogeneity between schools also includes the differences in the expected impact of intervention between schools. Ignoring this additional school-by-intervention variation in a multisite trial could affect both its interpretation and conclusions. A robust approach to estimate the confidence intervals for effect size from multisite trials is by treating effect size as a parameter with its distribution. This paper is important for evaluating evidence from multisite trials by accounting for all sources of variability. [ABSTRACT FROM AUTHOR]

Educational researchers advocate the use of an effect size and its confidence interval to assess the effectiveness of interventions instead of relying on a p-value, which has been blamed for lack of reproducibility of research findings and the misuse of statistics. The aim of this study is to provide a framework, which can provide direct evidence of whether an intervention works for the study participants in an educational trial as the first step before generalizing evidence to the wider population. A hierarchical Bayesian model was applied to ten cluster and multisite educational trials funded by the Education Endowment Foundation in England, to estimate the effect size and associated credible intervals. The use of posterior probability is proposed as an alternative to p-values as a simple and easily interpretable metric of whether an intervention worked or not. The probability of at least one month's progression or any other appropriate threshold is proposed to use in education outcomes instead of using a threshold of zero to determine a positive impact. The results show that the probability of at least one month's progress ranges from 0.09 for one trial, GraphoGame Rime, to 0.94 for another, the Improving Numeracy and Literacy trial. [ABSTRACT FROM AUTHOR]

The epithelial cells of the mammary gland secrete extracellular nanovesicles known as exosomes that carry and protect microRNAs and other various signaling biomolecules. Milk exosomes are stable during processing and remain protected from digestion in the gastrointestinal tract in order to reach specific target cells including peripheral tissues by crossing biological barriers. Milk exosomal microRNAs have their role as growth-promoting factor, in immunological programming, improving allergy tolerance and epigenetic controller of other mRNAs. However, in contrast, many translational evidence indicated that excessive consumption of bovine milk and continuous exposure of these exosomal microRNAs may be responsible for chronic inflammatory diseases of contemporary societies. Milk exosomes have potential preventive impact on necrotizing enterocolitis, ulcerative colitis, and inflammatory bowel diseases and may be targeted as preventive medicine or in therapeutic diets and also have potential as a nano-vehicle for drug delivery for chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Oral cancers are one of the commonly diagnosed tumors worldwide in human and veterinary patients. Most oral cancers are surgically resected; however, obtaining an adequate margin of safety in patients without compromising their quality of life is often challenging. Herein, we investigated the ability of non-invasive focused ultrasound (FUS) to thermally ablate a biopsy confirmed canine oral cancer. Materials and Methods: A male canine patient with a large neurilemmoma (schwannoma) mass on the left maxilla, with evidence of thinning and loss of alveolar bone and pressure necrosis, was treated with FUS ablation instead of the traditional maxillectomy procedure. FUS ablations were performed in three sessions over three weeks. Tumor remission was determined with computed tomography and histopathological examination of the treated site. Additionally, the anti-tumor immune effects of FUS were assessed by flow cytometry analysis of blood and tumor samples. Results: Complete tumor remission was noted at the treated site. Treatment related adverse events were primarily thermal burns of the buccal mucosa, which were managed with periodic hyperbaric oxygen therapy and surgical coverage of the underlying exposed bones with gingival flaps. Enhanced proliferation of adaptive immunity cells (e.g., T-cells) was observed in tumor and blood samples. Conclusion: Our limited investigation in a canine oral cancer patient suggests that FUS may avoid the need for large-scale resection of bony tissues, thus potentially improving quality of life. [ABSTRACT FROM AUTHOR]

Immunotherapy to treat cancer is now an established clinical approach. Immunotherapy can be applied systemically, as done with checkpoint blockade antibodies, but it can also be injected directly into identified tumors, in a strategy of in situ vaccination (ISV). ISV is designed to stimulate a strong local antitumor immune response involving both innate and adaptive immune cells, and through this generate a systemic antitumor immune response against metastatic tumors. A variety of ISVs have been utilized to generate an immunostimulatory tumor microenvironment (TME). These include attenuated microorganisms, recombinant proteins, small molecules, physical disruptors of TME (alternating magnetic and focused ultrasound heating, photothermal therapy, and radiotherapy), and more recently nanoparticles (NPs). NPs are attractive and unique since they can load multiple drugs or other reagents to influence immune and cancer cell functions in the TME, affording a unique opportunity to stimulate antitumor immunity. Here, we describe the NP-ISV therapeutic mechanisms, review chemically synthesized NPs (i.e., liposomes, polymeric, chitosan-based, inorganic NPs, etc.), biologically derived NPs (virus and bacteria-based NPs), and energy-activated NP-ISVs in the context of their use as local ISV. Data suggests that NP-ISVs can enhance outcomes of immunotherapeutic regimens including those utilizing tumor hyperthermia and checkpoint blockade therapies. [ABSTRACT FROM AUTHOR]

FDA approval of anti-CTLA4 in 2011 for melanoma immunotherapy was paradigm shifting and dramatically accelerated cancer immunotherapy research. The investment and effort have been exceptionally large, with a commensurate impressive pace of discovery. Historical and current research has validated the following key points: tumors are recognized by the immune system; tumors develop an immunosuppressive environment which suppresses the antitumor immune response; successful immunotherapy must overcome that tumor-mediated immunosuppression. While cancer immunotherapy research expanded, a parallel effort developing nanoparticles (NP) for cancer diagnosis and therapy also received major investment and expanded. Initially the two efforts appeared to have minimal synergy. Systemically administered nanoparticles are rapidly ingested by phagocytic leukocytes, and therefore nanotechnologists developed strategies to avoid NP ingestion by leukocytes in order to accomplish nanoparticle accumulation in tumors rather than liver and spleen. Recently, nanotechnology and cancer immunotherapy have increasingly merged since phagocytic leukocytes are the key to reversing the local tumor immunosuppression and the tendency of NP to be phagocytosed can be exploited to manipulate phagocytes for immunotherapy. This review focuses on in situ vaccination (ISV), an immunotherapy approach that can utilize direct injection of immunostimulatory reagents, including NPs, into tumors to disrupt the local immunosuppression, stimulate effective immune response against the treated tumor, and most importantly, generate a systemic antitumor immune response to eliminate metastatic tumors. While there are many specific options for using NP for ISV (reviewed further in this special issue), this review focuses on immunology concepts needed to understand and design successful NP ISV approaches. [ABSTRACT FROM AUTHOR]