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This book provides a fascinating re-evaluation of the social history of the Second World War and the 20th century making of the modern self. Using the wartime diaries of nine individuals, the book illuminates the impact of war on attitudes to citizenship, the changing relationships between men and women, and the search for meaning in a wartime context of limitless violence. The diaries from which this book is derived were written by some of the unusually self-reflective and public-spirited people who agreed to write intimate journals about their daily activity for the social research organisation, Mass Observation. Each in their way is vivid, interesting and surprising. One of the nine diarists discussed is Nella Last, whose published diaries have been a source of delight and fascination for thousands of readers. A central insight underpins the book: in seeking to make the best of our own lives, each of us makes selective use of the resources of our shared culture in a unique way; in so doing, we contribute, however modestly, to molecular processes of historical change. The book resists nostalgic contrasts between the presumed dutiful citizenship of wartime Britain and contemporary anti-social individualism, pointing instead to longer-run processes of change, rooted as much in struggles for personal autonomy in the private sphere, as in the politics of active citizenship in public life.

In high-temperature superconductivity, the process that leads to the formation of Cooper pairs, the fundamental charge carriers in any superconductor, remains mysterious. We used a femtosecond laser pump pulse to perturb superconducting Bi₂Sr₂CaCu₂08+δ and studied subsequent dynamics using time and angle-resolved photoemission and infrared reflectivity probes. Gap and quasiparticle population dynamics revealed marked dependencies on both excitation density and crystal momentum. Close to the d-wave nodes, the superconducting gap was sensitive to the pump intensity, and Cooper pairs recombined slowly. Far from the nodes, pumping affected the gap only weakly, and recombination processes were faster. These results demonstrate a new window into the dynamical processes that govern quasiparticle recombination and gap formation in cuprates.

It is generally held that >100 TeV emission from astrophysical objects unambiguously demonstrates the presence of PeV protons or nuclei, due to the unavoidable Klein–Nishina suppression of inverse Compton emission from electrons. However, in the presence of inverse Compton dominated cooling, hard high-energy electron spectra are possible. We show that the environmental requirements for such spectra can naturally be met in spiral arms, and in particular in regions of enhanced star formation activity, the natural locations for the most promising electron accelerators: powerful young pulsars. Leptonic scenarios are applied to gamma-ray sources recently detected by the High-Altitude Water Cherenkov Observatory (HAWC) and the Large High Altitude Air Shower Observatory (LHAASO). We show that these sources can indeed be explained by inverse Compton emission.

Invasive melanoma is the deadliest type of skin cancer, with 101,110 expected cases to be diagnosed in 2021. Recurrent BRAF and NRAS mutations are well documented in melanoma. Biologic implications of gene fusions and the efficacy of therapeutically targeting them remains unknown. Retrospective review of patient samples that underwent next-generation sequencing of the exons of 592 cancer-relevant genes and whole transcriptome sequencing for the detection of gene fusion events and gene expression profiling. Expression of PDL1 and ERK1/2 was assessed by immunohistochemistry (IHC). There were 33 (2.6%) cases with oncogenic fusions (14 novel), involving BRAF, RAF1, PRKCA, TERT, AXL, and FGFR3. MAPK pathway-associated genes were over-expressed in BRAF and RAF1 fusion-positive tumors in absence of other driver alterations. Increased expression in tumors with PRKCA and TERT fusions was concurrent with MAPK pathway alterations. For a subset of samples with available tissue, increased phosphorylation of ERK1/2 was observed in BRAF, RAF1, and PRKCA fusion-positive tumors. Oncogenic gene fusions are associated with transcriptional activation of the MAPK pathway, suggesting they could be therapeutic targets with available inhibitors. Additional analyses to fully characterize the oncogenic effects of these fusions may support biomarker driven clinical trials.

Presbyterian Healthcare Services, based in Albuquerque, New Mexico, is the state's only private, not-for-profit integrated healthcare system. It was founded in 1908 as a sanitorium for tuberculosis patients who came to the arid Southwest in search of a cure. Today, Presbyterian is thriving as a twenty-first-century integrated healthcare system, serving one in three New Mexicans in its statewide hospital system; it also includes a 440,000-member health plan and a 700-plus provider medical group. Presbyterian remains dedicated to its singular purpose of improving the health of the patients, members, and communities it serves. Just as Presbyterian has progressed and grown during its 106-year history, its governance system has evolved over time. Presbyterian has always believed that the New Mexico communities it serves deserve not just good governance but great governance and relies on strong structure and processes to lead it to superior outcomes. The ebb and flow of change, our ability to learn from trial and error, and our commitment to success in spite of obstacles make up the story of Presbyterian's strong governance system.

In prostate cancer (PCa) the laminin binding integrin (LBI) α6β1 is involved in the extra capsular and muscle invasion of cohesive tumor clusters in part through dissemination via peripheral nerves expressing laminin. This invasion results in part due to the posttranslational modification (PTM) of the α6β1 integrin (α6) by the serine protease urokinase plasminogen activator (uPA, PLAU) and its cognate receptor (uPAR, PLAUR). The cleavage results in a tumor specific variant form of the α6 integrin called α6pβ1 (α6p). This leads to altered biophysical adhesive properties of the cohesive cancer clusters. This PTM occurs early in progression from indolent and confined tumors to aggressive and invasive phenotypes. Current strategies have the capability to detect aggressive cancers that have invaded, but are unreliable for identification of tumors that have an early signature of invasiveness. Therefore, an identification of a reliable diagnostic method that stratifies confined and indolent (low risk) tumors that lack migratory capability from one that will progress to early invasive phenotypes will aid informed and objective decisions for specific treatment strategies.Utilizing an emerging technique of multiplex immunohistochemistry (IHC) detection of primary antibodies specific for protein biomarkers within a single formalin fixed paraffin embedded (FFPE), LBI protein interactions and associations were detected within prostate tissue samples. The interaction of LBI biomarkers with uPAR, the essential cell-cell adhesion protein E-cadherin were detected. In addition, associations with the pathway regulating tumor suppressor protein PTEN in concert with the transcription factor ERG in human prostate tissue samples were also detected. These interactions were detected in tissues exhibiting various stages of PCa disease progression. These protein interactions and associations were also the basis for generating image analysis algorithms to quantify protein expression. Using brightfield multiplex and standard DAB IHC image analysis, two separate quantitation algorithms were created and tested utilizing multiplex chromogen and IHC DAB detections. One quantitative algorithm allowed differentiation of individual chromogenic stain intensities and co-incidence of LBIs and E-cadherin biomarkers within focal regions of interest in PCa tissues. The results also displayed increased ratio of α6 integrin and E-cadherin cell-cell co-distribution in early pre-malignant events compared to aggressive tumors. The other algorithm designed identified specific localization patterns of α6 integrin in association of PTEN and ERG status. This indicated that localization of α6β1 integrin correlating to PTEN and ERG status could be used as an indicator of PCa aggressiveness.In this study, the role of the α6β1 integrin cleavage plays in cohesive tumor invasion through muscle was characterized. A CRISPR Cas9 mouse model muscle invasion assay with DU145 prostate tumor cells injected with a transfected uncleavable α6 mutant (α6AA) exhibited significantly reduced tumor onset and extravasation (6 weeks) while mice injected with cells with a transient knockout of α3β1 integrin (α3) increased tumor burden and invasion sites in xenograft tissues. Analysis of xenograft sample tissue confirmed a significant decrease in tumor burden and reduced muscle invasion. Overall, these results suggest a loss of α3 integrin plays a role in aggressive tumor burden and muscle invasion in PCa via the cleavage of α6β1 integrin. Also, the results indicate a blockage of the α6β1 integrin cleavage demonstrate a promising mechanism to inhibit the progression of aggressive disease.

In June 1939 the social research organization Mass-Observation sent a directive to its panellists designed to solicit information on what it called \"the nexus of social attitudes and behaviour which make up the 'class' complex\". The responses, sent in by nearly 400 people from all parts of Britain, provide a rich source for understanding the experience of class on the eve of World War II. This article examines the responses, particularly in light of Pierre Bourdieu's analysis of cultural distinction, which conceptualises culture as false consciousness of class. Rather than confirming Bourdieu's view of high culture as intrinsically anti-democratic, the Mass Observers appear to exemplify a modernity which linked reflexive self-exploration to participation in public affairs and, for many, engagement with high culture. Their reflections suggest the potentially emancipatory effects of literature, the arts and intellectual life in general. (Quotes from original text)

ObjectivesGentamicin and vancomycin are narrow-therapeutic-index antibiotics with potential for high toxicity requiring dose individualisation and continuous monitoring. Clinical decision support (CDS) tools have been effective in reducing gentamicin and vancomycin dosing errors. Online dose calculators for these drugs were implemented in a London National Health Service hospital. This study aimed to evaluate the impact of these calculators on the accuracy of gentamicin and vancomycin initial doses.MethodsThe study used a pre–postintervention design. Data were collected using electronic patient records and paper notes. Random samples of gentamicin and vancomycin initial doses administered during the 8 months before implementation of the calculators were assessed retrospectively against hospital guidelines. Following implementation of the calculators, doses were assessed prospectively. Any gentamicin dose not within ±10% and any vancomycin dose not within ±20% of the guideline-recommended dose were considered incorrect.ResultsThe intranet calculator pages were visited 721 times (gentamicin=333; vancomycin=388) during the 2-month period following the calculators’ implementation. Gentamicin dose errors fell from 61.5% (120/195) to 44.2% (95/215), p<0.001. Incorrect vancomycin loading doses fell from 58.1% (90/155) to 32.4% (46/142), p<0.001. Incorrect vancomycin first maintenance doses fell from 55.5% (86/155) to 33.1% (47/142), p<0.001. Loading and first maintenance vancomycin doses were both incorrect in 37.4% (58/155) of patients before and 13.4% (19/142) after calculator implementation, p<0.001.ConclusionsThis study suggests that gentamicin and vancomycin dose calculators significantly improved the prescribing of initial doses of these agents. Therefore, healthcare organisations should consider using such CDS tools to support the prescribing of these high-risk drugs.