Interpreting History Through Fiction

In ‘Interpreting History Through Fiction: Three Writers Discuss their Methods’, creative historical authors Thom Conroy, Joanna Grochowicz and Cristina Sanders engage in a conversation about the intersection of history and fiction. Arising from a session of the 2021 New Zealand Historical Association Conference entitled ‘Learning History Through Fiction’, the three-way dialogue interrogates the role of learning history from creative texts, navigates the fact/fiction balance in creative historical writing, explores concerns about the potential for harm in historical fiction, outlines the authors' own motives for adopting a creative approach to history, and examines what Hilary Mantel calls the ‘readerly contract’ in historical fiction. The conversation does not seek consensus nor finality in the answers offered to the questions the authors have put to one another. Rather, the authors allow contradictions and disagreements to remain intact, thus conveying their collective sense of open-endedness regarding creative approaches to history. This open-endedness is intentional, as the answers that arise from dialogue are intended to be as provisional and contingent as the evolving genre of historical fiction itself

Punitive restoration and restorative justice.

Criminal justice policy faces the twin challenges of improving our crime reduction efforts while increasing public confidence. These challenges are exacerbated by the fact that at least some measures popular with the public are counterproductive to greater crime reduction. How to achieve greater crime reduction without sacrificing public confidence? While restorative justice approaches offer a promising alternative to traditional sentencing with the potential to achieve these goals, they suffer from several serious obstacles, not least their relatively limited applicability, flexibility, and public support. Punitive restoration is a new and distinctive idea about restorative justice modeled on an important principle of stakeholding, which states that those who have a stake in penal outcomes should have a say about them. Punitive restoration is restorative insofar as it aims to achieve the restoration of rights infringed or threatened by criminal offences. Punitive restoration is punitive insofar as the available options for this agreement are more punitive than found in most restorative justice approaches, such as the option of some form of hard treatment. Punitive restoration sheds new light on how we may meet the twin challenges of improving our efforts to reduce reoffending without sacrificing public confidence, demonstrating how restorative practices can be embedded deeper within the criminal justice system

Minimal in vivo efficacy of iminosugars in a lethal Ebola virus guinea pig model

The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated. A pilot study treating infected animals three times within an 8 hour period was promising with 1 of 4 infected NB-DNJ treated animals surviving and the remaining three showing improved clinical signs. MON-DNJ showed no protective effects when EBOV-infected guinea pigs were treated. On histopathological examination, animals treated with NB-DNJ had reduced lesion severity in liver and spleen. However, a second study, in which NB-DNJ was administered at equally-spaced 8 hour intervals, could not confirm drug-associated benefits. Neither was any antiviral effect of iminosugars detected in an EBOV glycoprotein pseudotyped virus assay. Overall, this study provides evidence that NB-DNJ and MON-DNJ do not protect guinea pigs from a lethal EBOV-infection at the dose levels and regimens tested. However, the one surviving animal and signs of improvements in three animals of the NB-DNJ treated cohort could indicate that NB-DNJ at these levels may have a marginal beneficial effect. Future work could be focused on the development of more potent iminosugars

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Observation of tW production in the single-lepton channel in pp collisions at root s=13 TeV

A measurement of the cross section of the associated production of a single top quark and a W boson in final states with a muon or electron and jets in proton-proton collisions at root s = 13 TeV is presented. The data correspond to an integrated luminosity of 36 fb(-1) collected with the CMS detector at the CERN LHC in 2016. A boosted decision tree is used to separate the tW signal from the dominant t (t) over bar background, whilst the subleading W+jets and multijet backgrounds are constrained using data-based estimates. This result is the first observation of the tW process in final states containing a muon or electron and jets, with a significance exceeding 5 standard deviations. The cross section is determined to be 89 +/- 4 (stat) +/- 12 (syst) pb, consistent with the standard model.Peer reviewe

Optical Imaging of Tumor Response to Hyperbaric Oxygen Treatment and Irradiation in an Orthotopic Mouse Model of Head and Neck Squamous Cell Carcinoma

PURPOSE: Hyperbaric oxygen therapy (HBOT) is used in the treatment of radiation-induced tissue injury but its effect on (residual) tumor tissue is indistinct and therefore investigated in this study. PROCEDURES: Orthotopic FaDu tumors were established in mice, and the response of the (irradiated) tumors to HBOT was monitored by bioluminescence imaging. Near infrared fluorescence imaging using AngioSense750 and Hypoxisense680 was applied to detect tumor vascular permeability and hypoxia. RESULTS: HBOT treatment resulted in accelerated growth of non-irradiated tumors, but mouse survival was improved. Tumor vascular leakiness and hypoxia were enhanced after HBOT, whereas histological characteristics, epithelial-to-mesenchymal transition markers, and metastatic incidence were not influenced. CONCLUSIONS: Squamous cell carcinoma responds to HBOT with respect to tumor growth, vascular permeability, and hypoxia, which may have implications for its use in cancer patients. The ability to longitudinally analyze tumor characteristics highlights the versatility and potential of optical imaging methods in oncological research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11307-015-0834-8) contains supplementary material, which is available to authorized users