Total Body Photography and Sequential Digital Dermoscopy Imaging for Melanoma Surveillance in Patients Starting Natalizumab for Multiple Sclerosis

Introduction: Natalizumab is an integrin receptor antagonist that has been approved by the Food and Drug Administration to treat multiple sclerosis and Crohn’s disease. The drug has been linked to an increased risk of melanoma. This brief report highlights an innovative clinical approach for monitoring the skin of patients prescribed natalizumab. Methods: We include 2 cases from our skin oncology clinic and a literature review on the incidence of melanoma in patients prescribed natalizumab between 2004 and 2019. Results: In addition to our 2 cases, we found 193 reports of patients with melanoma who were prescribed natalizumab. We propose an innovative and proactive approach using total body photography and sequential digital dermoscopy imaging before starting and while treating patients with natalizumab. Discussion: Given the mechanism of action of natalizumab, many of the melanomas diagnosed likely arose from preexisting melanocytic nevi. Using total body photography before starting this high-risk medication and then sequential digital dermoscopy imaging will increase a dermatologist’s ability to recognize new and preexisting skin lesions that have evolved since the patient began taking natalizumab. Conclusions: Using the latest non-invasive technology to detect skin cancer supports systematic and objective monitoring of changing melanocytic growths in patients prescribed natalizumab, resulting in earlier detection of melanoma and greater cure rates

Targeted Activation of Hippocampal Place Cells Drives Memory-Guided Spatial Behavior

The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and have been proposed to form the neural basis of a cognitive map of space that supports these mnemonic functions. However, the direct influence of place cell activity on spatial navigation behavior has not yet been demonstrated. Using an ‘all-optical’ combination of simultaneous two-photon calcium imaging and two-photon optogenetics, we identified and selectively activated place cells that encoded behaviorally relevant locations in a virtual reality environment. Targeted stimulation of a small number of place cells was sufficient to bias the behavior of animals during a spatial memory task, providing causal evidence that hippocampal place cells actively support spatial navigation and memory

A method for the dynamic correction of B0-related distortions in single-echo EPI at 7 T

We propose a method to calculate field maps from the phase of each EPI in an fMRI time series. These field maps can be used to correct the corresponding magnitude images for distortion caused by inhomogeneity in the static magnetic field. In contrast to conventional static distortion correction, in which one 'snapshot’ field map is applied to all subsequent fMRI time points, our method also captures dynamic changes to B0which arise due to motion and respiration. The approach is based on the assumption that the non-B0-related contribution to the phase measured by each radio-frequency coil, which is dominated by the coil sensitivity, is stable over time and can therefore be removed to yield a field map from EPI. Our solution addresses imaging with multi-channel coils at ultra-high field (7 T), where phase offsets vary rapidly in space, phase processing is non-trivial and distortions are comparatively large. We propose using dual-echo gradient echo reference scan for the phase offset calculation, which yields estimates with high signal-to-noise ratio. An extrapolation method is proposed which yields reliable estimates for phase offsets even where motion is large and a tailored phase unwrapping procedure for EPI is suggested which gives robust results in regions with disconnected tissue or strong signal decay. Phase offsets are shown to be stable during long measurements (40 min) and for large head motions. The dynamic distortion correction proposed here is found to work accurately in the presence of large motion (up to 8.1°), whereas a conventional method based on single field map fails to correct or even introduces distortions (up to 11.2 mm). Finally, we show that dynamic unwarping increases the temporal stability of EPI in the presence of motion. Our approach can be applied to any EPI measurements without the need for sequence modification

The dynamics of apparent horizons in Robinson-Trautman spacetimes

We present an alternative scheme of finding apparent horizons based on spectral methods applied to Robinson-Trautman spacetimes. We have considered distinct initial data such as representing the spheroids of matter and the head-on collision of two non-rotating black holes. The evolution of the apparent horizon is presented. We have obtained in some cases a mass gap between the final Bondi and apparent horizon masses, whose implications were briefly commented in the light of the thermodynamics of black holes.Comment: 9 pages, 7 figure

A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis

© 2016 cThe Author(s). Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases

Practical mammography

‘Digital health’ is an overarching concept that currently lacks theoretical definition and common terminology. For instance, this broad and emerging field includes all of the following terms within its lexicon: mHealth, Wireless Health, Health 2.0, eHealth, e-Patient(s), Healthcare IT/Health IT, Big Data, Health Data, Cloud Computing, Quantified Self, Wearable Computing, Gamification, and Telehealth/Telemedicine [1]. However, whilst a definition is difficult to provide, in this overview it is considered that digital health is the use of digital media to transform the way healthcare provision is conceived and delivered. We consider it does this through three basic features

New times, new politics: history and memory during the final years of the CPGB

This article examines the relationship between collective memory, historical interpretation and political identity. It focuses on the dissolution of the Communist Party of Great Britain (CPGB) as constructed through collective narrative memory, and on Marxist interpretations of history. The divisions within the party and the wider Marxist community, stretching from 1956 until 1991, were often framed around questions of historical interpretation. The events of 1989–1991 created an historical and mnemonic crisis for CPGB members who struggled to reconcile their past identities with their present situation. Unlike the outward-facing revisionism of other political parties, this was an intensely personal affair. The solution for many was to emphasise the need to find new ways to progress socialist aims, without relying on a discredited grand narrative. In contrast, other Communist parties, such as the Communist Party of Britain, which had been established (or ‘re-established’) in 1988, fared rather better. By adhering to the international party line of renewal and continued struggle, the party was able to hold its narrative together, condemning the excesses of totalitarian regimes, while reaffirming the need for international class struggle

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com

Discovery of the peculiar supernova 1998bw in the error box of GRB980425

The discovery of X-ray, optical and radio afterglows of gamma-ray bursts (GRBs) and the measurements of the distances to some of them have established that these events come from Gpc distances and are the most powerful photon emitters known in the Universe, with peak luminosities up to 10^52 erg/s. We here report the discovery of an optical transient, in the BeppoSAX Wide Field Camera error box of GRB980425, which occurred within about a day of the gamma-ray burst. Its optical light curve, spectrum and location in a spiral arm of the galaxy ESO 184-G82, at a redshift z = 0.0085, show that the transient is a very luminous type Ic supernova, SN1998bw. The peculiar nature of SN1998bw is emphasized by its extraordinary radio properties which require that the radio emitter expand at relativistical speed. Since SN1998bw is very different from all previously observed afterglows of GRBs, our discovery raises the possibility that very different mechanisms may give rise to GRBs, which differ little in their gamma-ray properties.Comment: Under press embargo at Nature (submitted June 10, 1998

How and When Socially Entrepreneurial Nonprofit Organizations Benefit From Adopting Social Alliance Management Routines to Manage Social Alliances?

Social alliance is defined as the collaboration between for-profit and nonprofit organizations. Building on the insights derived from the resource-based theory, we develop a conceptual framework to explain how socially entrepreneurial nonprofit organizations (SENPOs) can improve their social alliance performance by adopting strategic alliance management routines. We test our framework using the data collected from 203 UK-based SENPOs in the context of cause-related marketing campaign-derived social alliances. Our results confirm a positive relationship between social alliance management routines and social alliance performance. We also find that relational mechanisms, such as mutual trust, relational embeddedness, and relational commitment, mediate the relationship between social alliance management routines and social alliance performance. Moreover, our findings suggest that different types of social alliance motivation can influence the impact of social alliance management routines on different types of the relational mechanisms. In general, we demonstrate that SENPOs can benefit from adopting social alliance management routines and, in addition, highlight how and when the social alliance management routines–social alliance performance relationship might be shaped. Our study offers important academic and managerial implications, and points out future research directions