Queer Touch Between Holy Women: Julian of Norwich, Margery Kempe, Birgitta of Sweden, and the Visitation

Under embargo until: 2021-12-17This essay takes a new approach to the well-known meeting between two late-medieval English visionary women, Margery Kempe and the anchoress Julian of Norwich, as described in The Book of Margery Kempe. In this analysis their conversation subtly evokes a long history of women concentrating their subversive power through intimate, spiritual exchange, a history reaching back to the Biblical Visitation scene and expressed in its medieval artistic and literary instantiations. A queer reading illuminates the way that such female same-sex relationships challenge patriarchal systems by offering a privileged access to God outside clerical supervision. By examining Margery and Julian’s encounter, Luke’s Visitation passage, its depiction in a late-medieval Book of Hours, and comparing two different Middle English translations of a Visitation vision in Birgitta of Sweden’s Revelations, the full transgressive effect of queer touch between women—or even its unspoken possibility—emerges.acceptedVersio

Visually Driven Activation in Macaque Areas V2 and V3 without Input from the Primary Visual Cortex

Creating focal lesions in primary visual cortex (V1) provides an opportunity to study the role of extra-geniculo-striate pathways for activating extrastriate visual cortex. Previous studies have shown that more than 95% of neurons in macaque area V2 and V3 stop firing after reversibly cooling V1 [1], [2], [3]. However, no studies on long term recovery in areas V2, V3 following permanent V1 lesions have been reported in the macaque. Here we use macaque fMRI to study area V2, V3 activity patterns from 1 to 22 months after lesioning area V1. We find that visually driven BOLD responses persist inside the V1-lesion projection zones (LPZ) of areas V2 and V3, but are reduced in strength by ∼70%, on average, compared to pre-lesion levels. Monitoring the LPZ activity over time starting one month following the V1 lesion did not reveal systematic changes in BOLD signal amplitude. Surprisingly, the retinotopic organization inside the LPZ of areas V2, V3 remained similar to that of the non-lesioned hemisphere, suggesting that LPZ activation in V2, V3 is not the result of input arising from nearby (non-lesioned) V1 cortex. Electrophysiology recordings of multi-unit activity corroborated the BOLD observations: visually driven multi-unit responses could be elicited inside the V2 LPZ, even when the visual stimulus was entirely contained within the scotoma induced by the V1 lesion. Restricting the stimulus to the intact visual hemi-field produced no significant BOLD modulation inside the V2, V3 LPZs. We conclude that the observed activity patterns are largely mediated by parallel, V1-bypassing, subcortical pathways that can activate areas V2 and V3 in the absence of V1 input. Such pathways may contribute to the behavioral phenomenon of blindsight

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2–69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m−2 i.v. day 1 and gemcitabine 1000 mg m−2 i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20–46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

Macrophage-Specific ApoE Gene Repair Reduces Diet-Induced Hyperlipidemia and Atherosclerosis in Hypomorphic Apoe Mice

Apolipoprotein (apo) E is best known for its ability to lower plasma cholesterol and protect against atherosclerosis. Although the liver is the major source of plasma apoE, extra-hepatic sources of apoE, including from macrophages, account for up to 10% of plasma apoE levels. This study examined the contribution of macrophage-derived apoE expression levels in diet-induced hyperlipidemia and atherosclerosis.Hypomorphic apoE (Apoe(h/h)) mice expressing wildtype mouse apoE at ∼2-5% of physiological levels in all tissues were derived by gene targeting in embryonic stem cells. Cre-mediated gene repair of the Apoe(h/h) allele in Apoe(h/h)LysM-Cre mice raised apoE expression levels by 26 fold in freshly isolated peritoneal macrophages, restoring it to 37% of levels seen in wildtype mice. Chow-fed Apoe(h/h)LysM-Cre and Apoe(h/h) mice displayed similar plasma apoE and cholesterol levels (55.53±2.90 mg/dl versus 62.70±2.77 mg/dl, n = 12). When fed a high-cholesterol diet (HCD) for 16 weeks, Apoe(h/h)LysM-Cre mice displayed a 3-fold increase in plasma apoE and a concomitant 32% decrease in plasma cholesterol when compared to Apoe(h/h) mice (602.20±22.30 mg/dl versus 888.80±24.99 mg/dl, n = 7). On HCD, Apoe(h/h)LysM-Cre mice showed increased apoE immunoreactivity in lesional macrophages and liver-associated Kupffer cells but not hepatocytes. In addition, Apoe(h/h)LysM-Cre mice developed 35% less atherosclerotic lesions in the aortic root than Apoe(h/h) mice (167×10(3)±16×10(3) µm(2) versus 259×10(3)±56×10(3) µm(2), n = 7). This difference in atherosclerosis lesions size was proportional to the observed reduction in plasma cholesterol.Macrophage-derived apoE raises plasma apoE levels in response to diet-induced hyperlipidemia and by such reduces atherosclerosis proportionally to the extent to which it lowers plasma cholesterol levels

A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer

The aim of this study was to evaluate the efficacy and tolerability of gefitinib (‘IRESSA') in Japanese patients with previously untreated stage IV non-small-cell lung cancer (NSCLC). This was a multi-institutional phase II study. Thirty-four patients with previously untreated stage IV NSCLC were enrolled between May 2003 and September 2004. Gefitinib was administered orally 250 mg once a day and was continued until there was either disease progression or severe toxicity. Objective tumour response rate was 26.5% (95% confidence interval, 11.7–41.3%). Adverse events were generally mild (National Cancer Institute-Common Toxicity Criteria grade 1 or 2) and consisted mainly of skin rash, fatigue and liver dysfunction. No pulmonary toxicity was observed. The global health status revealed that there was no change in quality of life during the study. This study found that single-agent gefitinib is active and well tolerated in chemonaive Japanese patients with advanced NSCLC

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

The Sensory Consequences of Speaking: Parametric Neural Cancellation during Speech in Auditory Cortex

When we speak, we provide ourselves with auditory speech input. Efficient monitoring of speech is often hypothesized to depend on matching the predicted sensory consequences from internal motor commands (forward model) with actual sensory feedback. In this paper we tested the forward model hypothesis using functional Magnetic Resonance Imaging. We administered an overt picture naming task in which we parametrically reduced the quality of verbal feedback by noise masking. Presentation of the same auditory input in the absence of overt speech served as listening control condition. Our results suggest that a match between predicted and actual sensory feedback results in inhibition of cancellation of auditory activity because speaking with normal unmasked feedback reduced activity in the auditory cortex compared to listening control conditions. Moreover, during self-generated speech, activation in auditory cortex increased as the feedback quality of the self-generated speech decreased. We conclude that during speaking early auditory cortex is involved in matching external signals with an internally generated model or prediction of sensory consequences, the locus of which may reside in auditory or higher order brain areas. Matching at early auditory cortex may provide a very sensitive monitoring mechanism that highlights speech production errors at very early levels of processing and may efficiently determine the self-agency of speech input

Tumor Necrosis Factor Receptor Associated Factor 6 Is Not Required for Atherogenesis in Mice and Does Not Associate with Atherosclerosis in Humans

BACKGROUND: Tumor necrosis factor receptor-associated factors (TRAFs) are important signaling molecules for a variety of pro-atherogenic cytokines including CD40L, TNF alpha, and IL1beta. Several lines of evidence identified TRAF6 as a pro-inflammatory signaling molecule in vitro and we previously demonstrated overexpression of TRAF6 in human and Murine atherosclerotic plaques. This study investigated the role of TRAF6-deficiency in mice developing atherosclerosis, a chronic inflammatory disease. METHODOLOGY/PRINCIPAL FINDINGS: Lethally irradiated low density lipoprotein receptor-deficient mice (TRAF6(+/+)/LDLR(-/-)) were reconstituted with TRAF6-deficient fetal liver cells (FLC) and consumed high cholesterol diet for 18 weeks to assess the relevance of TRAF6 in hematopoietic cells for atherogenesis. Additionally, TRAF6(+/-)/LDLR(-/-) mice received TRAF6-deficient FLC to gain insight into the role of TRAF6 deficiency in resident cells. Surprisingly, atherosclerotic lesion size did not differ between the three groups in both aortic roots and abdominal aortas. Similarly, no significant differences in plaque composition could be observed as assessed by immunohistochemistry for macrophages, lipids, smooth muscle cells, T-cells, and collagen. In accord, in a small clinical study TRAF6/GAPDH total blood RNA ratios did not differ between groups of patients with stable coronary heart disease (0.034+/-0.0021, N = 178), acute coronary heart disease (0.029+/-0.0027, N = 70), and those without coronary heart disease (0.032+/-0.0016, N = 77) as assessed by angiography. CONCLUSION: Our study demonstrates that TRAF6 is not required for atherogenesis in mice and does not associate with clinical disease in humans. These data suggest that pro- and anti-inflammatory features of TRAF6 signaling outweigh each other in the context of atherosclerosis

Simulation modeling for stratified breast cancer screening : a systematic review of cost and quality of life assumptions

BACKGROUND: The economic evaluation of stratified breast cancer screening gains momentum, but produces also very diverse results. Systematic reviews so far focused on modeling techniques and epidemiologic assumptions. However, cost and utility parameters received only little attention. This systematic review assesses simulation models for stratified breast cancer screening based on their cost and utility parameters in each phase of breast cancer screening and care. METHODS: A literature review was conducted to compare economic evaluations with simulation models of personalized breast cancer screening. Study quality was assessed using reporting guidelines. Cost and utility inputs were extracted, standardized and structured using a care delivery framework. Studies were then clustered according to their study aim and parameters were compared within the clusters. RESULTS: Eighteen studies were identified within three study clusters. Reporting quality was very diverse in all three clusters. Only two studies in cluster 1, four studies in cluster 2 and one study in cluster 3 scored high in the quality appraisal. In addition to the quality appraisal, this review assessed if the simulation models were consistent in integrating all relevant phases of care, if utility parameters were consistent and methodological sound and if cost were compatible and consistent in the actual parameters used for screening, diagnostic work up and treatment. Of 18 studies, only three studies did not show signs of potential bias. CONCLUSION: This systematic review shows that a closer look into the cost and utility parameter can help to identify potential bias. Future simulation models should focus on integrating all relevant phases of care, using methodologically sound utility parameters and avoiding inconsistent cost parameters