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"Lloyd, Paul S"
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Dietary Advice and Fruit-Eating in Late Tudor and Early Stuart England
This article investigates an apparent contradiction between the growth in the popularity of fruit-eating in late Tudor and early Stuart England, and the generally held contemporary medical view that many types of unprocessed fruits were inappropriate to a healthful diet. The first section analyzes a broad range of household accounts and other sources of evidence to determine the extent to which fruit formed part of the daily fare of the English population. The second section looks at the advice offered in a broad cross-section of dietaries and botanical works with regard to the eating of fruit. Finally, as the manners in which fruits were eaten are discussed, it will become clear that they could often be accommodated within the humoral body, and that there was less of a discrepancy between dietary advice and fruit-eating than may seem to be the case.
Journal Article
The best horror of the year. Volume ten
A group of mountain climbers, caught in the dark, fights to survive their descent; An American band finds more than they bargained for in Mexico while scouting remote locations for a photo shoot; A young student's exploration into the origins of a mysterious song leads him on a winding, dangerous path through the US's deep south; A group of kids scaring each other with ghost stories discovers alarming consequences. The Best Horror of the Year showcases the previous year's best offerings in horror short fiction. This edition includes award-winning and critically acclaimed authors Mark Morris, Kaaron Warren, John Langan, Carole Johnstone, Brian Hodge, and others. For more than three decades, award-winning editor and anthologist Ellen Datlow has had her finger on the pulse of the latest and most terrifying in horror writing. Night Shade Books is proud to present the tenth volume in this annual series, a new collection of stories to keep you up at night.
BOOK
Troubled Geographies
\"Tap[s] the power of new geospatial technologies . . . explore[s] the intersection of geography, religion, politics, and identity in Irish history.\"— International Social Science Review
Ireland's landscape is marked by fault lines of religious, ethnic, and political identity that have shaped its troubled history. Troubled Geographies maps this history by detailing the patterns of change in Ireland from 16th century attempts to \"plant\" areas of Ireland with loyal English Protestants to defend against threats posed by indigenous Catholics, through the violence of the latter part of the 20th century and the rise of the \"Celtic Tiger.\" The book is concerned with how a geography laid down in the 16th and 17th centuries led to an amalgam based on religious belief, ethnic/national identity, and political conviction that continues to shape the geographies of modern Ireland. Troubled Geographies shows how changes in religious affiliation, identity, and territoriality have impacted Irish society during this period. It explores the response of society in general and religion in particular to major cultural shocks such as the Famine and to long term processes such as urbanization.
\"Makes a strong case for a greater consideration of spatial information in historical analysis?a message that is obviously appealing for geographers.\"— Journal of Interdisciplinary History
\"A book like this is useful as a reminder of the struggles and the sacrifices of generations of unrest and conflict, albeit that, on a global scale, the Irish troubles are just one of a myriad of disputes, each with their own history and localized geography.\"— Journal of Historical Geography
eBook
Delayed Win
Sen. Hubert H. Humphrey has won a delayed victory in the Ohio presidential primary election, defeating Sen. George McGovern to win the state's 38 at-large delegate votes to the Democratic National Convention.
Newspaper Article
A MyD88-dependent IFNyR-CCR2 signaling circuit is required for mobilization of monocytes and host defense against systemic bacterial challenge
Monocytes are mobilized to sites of infection via interaction between the chemokine MCP-1 and its receptor CCR2, at which point they differentiate into macrophages that mediate potent antimicrobial effects. In this study we investigated the mechanisms by which monocytes are mobilized in response to systemic challenge with the intracellular bacterium Francisella tularensis. We found that mice deficient in MyD88, interferon-7 （IFNT）R oJ CCR2 all had defects in the expansion of splenic monocyte populations upon E tularensis challenge, and in contro of F. tularensis infection. Interestingly, MyD88-deficient mice were defective in production of IFNγ, and IFNyR deficient mice exhibited defective production of MCP-1, the ligand for CCR2. Transplantation of IFNγR-deficien bone marrow （BM） into wild-type mice further suggested that mobilization of monocytes in response to F. tularensis challenge required IFNγR expression on BM-derived cells. These studies define a critical host defense circuit wherein MyD88-dependent IFNγ production signals via IFNγR expressed on BM-derived cells, resulting in MCP-1 production and activation of CCR2-dependent mobilization of monocytes in the innate immune response to systemic E tularensis challenge.
Journal Article
A three-talk model for shared decision making: multistage consultation process
Objectives To revise an existing three-talk model for learning how to achieve shared decision making, and to consult with relevant stakeholders to update and obtain wider engagement.Design Multistage consultation process.Setting Key informant group, communities of interest, and survey of clinical specialties.Participants 19 key informants, 153 member responses from multiple communities of interest, and 316 responses to an online survey from medically qualified clinicians from six specialties.Results After extended consultation over three iterations, we revised the three-talk model by making changes to one talk category, adding the need to elicit patient goals, providing a clear set of tasks for each talk category, and adding suggested scripts to illustrate each step. A new three-talk model of shared decision making is proposed, based on “team talk,” “option talk,” and “decision talk,” to depict a process of collaboration and deliberation. Team talk places emphasis on the need to provide support to patients when they are made aware of choices, and to elicit their goals as a means of guiding decision making processes. Option talk refers to the task of comparing alternatives, using risk communication principles. Decision talk refers to the task of arriving at decisions that reflect the informed preferences of patients, guided by the experience and expertise of health professionals.Conclusions The revised three-talk model of shared decision making depicts conversational steps, initiated by providing support when introducing options, followed by strategies to compare and discuss trade-offs, before deliberation based on informed preferences.
Journal Article
Electron paramagnetic resonance microscopy using spins in diamond under ambient conditions
Magnetic resonance spectroscopy is one of the most important tools in chemical and bio-medical research. However, sensitivity limitations typically restrict imaging resolution to ~ 10 µm. Here we bring quantum control to the detection of chemical systems to demonstrate high-resolution electron spin imaging using the quantum properties of an array of nitrogen-vacancy centres in diamond. Our electron paramagnetic resonance microscope selectively images electronic spin species by precisely tuning a magnetic field to bring the quantum probes into resonance with the external target spins. This provides diffraction limited spatial resolution of the target spin species over a field of view of 50 × 50 µm
2
with a spin sensitivity of 10
4
spins per voxel or ∼100 zmol. The ability to perform spectroscopy and dynamically monitor spin-dependent redox reactions at these scales enables the development of electron spin resonance and zepto-chemistry in the physical and life sciences.
Electron paramagnetic resonance spectroscopy has important scientific and medical uses but improving the resolution of conventional methods requires cryogenic, vacuum environments. Simpson et al. show nitrogen vacancy centres can be used for sub-micronmetre imaging with improved sensitivity in ambient conditions.
Journal Article
Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells
The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib is FDA approved for the treatment of BRCA-mutated breast, ovarian and pancreatic cancers. Olaparib inhibits PARP1/2 enzymatic activity and traps PARP1 on DNA at single-strand breaks, leading to replication-induced DNA damage that requires BRCA1/2-dependent homologous recombination repair. Moreover, DNA damage response pathways mediated by the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia mutated and Rad3-related (ATR) kinases are hypothesised to be important survival pathways in response to PARP-inhibitor treatment. Here, we show that olaparib combines synergistically with the ATR-inhibitor AZD6738 (ceralasertib), in vitro, leading to selective cell death in ATM-deficient cells. We observe that 24 h olaparib treatment causes cells to accumulate in G2-M of the cell cycle, however, co-administration with AZD6738 releases the olaparib-treated cells from G2 arrest. Selectively in ATM-knockout cells, we show that combined olaparib/AZD6738 treatment induces more chromosomal aberrations and achieves this at lower concentrations and earlier treatment time-points than either monotherapy. Furthermore, single-agent olaparib efficacy in vitro requires PARP inhibition throughout multiple rounds of replication. Here, we demonstrate in several ATM-deficient cell lines that the olaparib and AZD6738 combination induces cell death within 1–2 cell divisions, suggesting that combined treatment could circumvent the need for prolonged drug exposure. Finally, we demonstrate in vivo combination activity of olaparib and AZD6738 in xenograft and PDX mouse models with complete ATM loss. Collectively, these data provide a mechanistic understanding of combined PARP and ATR inhibition in ATM-deficient models, and support the clinical development of AZD6738 in combination with olaparib.
Journal Article