Multispecies Ion Acceleration in 3D Magnetic Reconnection with Hybrid-Kinetic Simulations.

Magnetic reconnection drives multispecies particle acceleration broadly in space and astrophysics. We perform the first 3D hybrid simulations (fluid electrons, kinetic ions) that contain sufficient scale separation to produce nonthermal heavy-ion acceleration, with fragmented flux ropes critical for accelerating all species. We demonstrate the acceleration of all ion species (up to Fe) into power-law spectra with similar indices, by a common Fermi acceleration mechanism. The upstream ion velocities influence the first Fermi reflection for injection. The subsequent onsets of Fermi acceleration are delayed for ions with lower charge-mass ratios (Q/M), until growing flux ropes magnetize them. This leads to a species-dependent maximum energy/nucleon ∝(Q/M)^{α}. These findings are consistent with in situ observations in reconnection regions, suggesting Fermi acceleration as the dominant multispecies ion acceleration mechanism.

Syntheses and Cytotoxicities of Quinazolinone-Based Conjugates.

Two novel series of quinazolinone-based hybrids, including quinazolinone-1,3,4-oxadiazoles (10a-l) and quinazolinone-1,3,4-oxadiazole-benzimidazoles (8a-e), were designed and synthesized and their cytotoxic activities against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7), were evaluated. The cytotoxic assays revealed that 10i with a lipophilic 4-fluoro-phenyl moiety at the C-2 position of the quinazolinone ring displayed good cytotoxicities against the A549 and MCF-7 cell lines, while 8b-d with the thioether-linked benzimidazole moiety incorporated on the right side of the oxadiazole ring induced comparable stronger activities toward the MCF-7 cell line, relative to the simple two-heterocycle-containing hybrid 10i. These novel quinazolinone-based hybrids could be considered as lead compounds that merit further optimization and development as anti-cancer agents.

Medical school dermatology education: a scoping review.

Dermatological diseases are widespread and have a significant impact on the quality of life of patients; however, access to appropriate care is often limited. Improved early training during medical school represents a potential upstream solution. This scoping review explores dermatology education during medical school, with a focus on identifying the factors associated with optimizing the preparation of future physicians to provide care for patients with skin disease. A literature search was conducted using online databases (Embase, MEDLINE, CINAHL and Scopus) to identify relevant studies. The Joanna Briggs Institute methodological framework for scoping reviews was used, including quantitative and qualitative data analysis following a grounded theory approach. From 1490 articles identified, 376 articles were included. Most studies were from the USA (46.3%), UK (16.2%), Germany (6.4%) and Canada (5.6%). Only 46.8% were published as original articles, with a relatively large proportion either as letters (29.2%) or abstracts (12.2%). Literature was grouped into three themes: teaching content, delivery and assessment. Core learning objectives were country dependent; however, a common thread was the importance of skin cancer teaching and recognition that diversity and cultural competence need greater fostering. Various methods of delivery and assessment were identified, including computer-aided and online, audiovisual, clinical immersion, didactic, simulation and peer-led approaches. The advantages and disadvantages of each need to be weighed when deciding which is most appropriate for a given learning outcome. The broader teaching-learning ecosystem is influenced by (i) community health needs and medical school resources, and (ii) the student and their ability to learn and perform. Efforts to optimize dermatology education may use this review to further investigate and adapt teaching according to local needs and context.

MMS SITL Ground Loop: Automating the Burst Data Selection Process.

Global-scale energy flow throughout Earth's magnetosphere is catalyzed by processes that occur at Earth's magnetopause (MP). Magnetic reconnection is one process responsible for solar wind entry into and global convection within the magnetosphere, and the MP location, orientation, and motion have an impact on the dynamics. Statistical studies that focus on these and other MP phenomena and characteristics inherently require MP identification in their event search criteria, a task that can be automated using machine learning so that more man hours can be spent on research and analysis. We introduce a Long-Short Term Memory (LSTM) Recurrent Neural Network model to detect MP crossings and assist studies of energy transfer into the magnetosphere. As its first application, the LSTM has been implemented into the operational data stream of the Magnetospheric Multiscale (MMS) mission. MMS focuses on the electron diffusion region of reconnection, where electron dynamics break magnetic field lines and plasma is energized. MMS employs automated burst triggers onboard the spacecraft and a Scientist-in-the-Loop (SITL) on the ground to select intervals likely to contain diffusion regions. Only low-resolution survey data is available to the SITL, which is insufficient to resolve electron dynamics. A strategy for the SITL, then, is to select all MP crossings. Of all 219 SITL selections classified as MP crossings during the first five months of model operations, the model predicted 166 (76%) of them, and of all 360 model predictions, 257 (71%) were selected by the SITL. Most predictions that were not classified as MP crossings by the SITL were still MP-like, in that the intervals contained mixed magnetosheath and magnetospheric plasmas. The LSTM model and its predictions are public to ease the burden of arduous event searches involving the MP, including those for EDRs. For MMS, this helps free up mission operation costs by consolidating manual classification processes into automated routines.

Cutaneous manifestation of IgG4-related disease mimicking dermatitis artefacta.

Dermatitis artefacta is a self-inflicted cutaneous disease presenting as sharply delineated ulcers, usually in accessible sites such as the head and neck. IgG4-related disease (IgG4-RD) is a recently recognised immune-mediated condition causing a fibroinflammatory process, resulting in the formation of tumefactive lesions in various organs, rarely presenting primarily in the skin. We report a case of cutaneous IgG4-RD clinically presenting as dermatitis artefacta.

Entrepreneurial patent management in pharmaceutical startups.

Startups fill an increasingly important role as innovators in the pharmaceutical industry, and patenting is typically central to their success. This article aims to explore patent management in pharmaceutical startups. The results show that startups need to deal with several challenges related to patenting and an 'entrepreneurial' approach to patent management is called for. Resource constraints, venture capital provision, exits and other conditions and events must be readily considered in the patent management process to build a successful pharmaceutical venture, something that could benefit the pharmaceutical industry as a whole.

Wavelength dependency for UVA-induced suppression of recall immunity in humans.

BACKGROUND: Ultraviolet (UV) A radiation, which has both mutagenic and immune suppressive effects on the skin, is increasingly recognised as a key contributor to cutaneous carcinogenesis. Whilst short wavelength UVB (290-320 nm) is well-recognised as an environmental health hazard, the dangers of UVA (320-400 nm) are relatively unexplored. OBJECTIVE: Using the nickel model of recall immunity in healthy human volunteers, we determined the wavelength dependency for UV-induced immunosuppression across the UVA spectrum. METHODS: Dose-response curves were established for local suppression of contact hypersensitivity responses to nickel at 7 wavelengths between 331 and 392 nm. RESULTS: We found a broad peak of UVA immune suppressive effectiveness at 364-385 nm. Whilst we had previously found linear dose-responses for UVB-induced immunosuppression in this model, long wavelength UVA caused bell-shaped, Gaussian dose-responses, suggesting different chromophores and mechanisms of immunosuppression for UVB and UVA. CONCLUSION: The immunosuppressive peak induced by longwave UVA has not been described previously for any species and being close to the border with visible light indicates an unexpected role for these long wavebands in human health and disease.

Sporotrichoid Mycobacterium marinum infection of the face following a cat scratch.

Mycobacterium marinum infections in humans uncommonly affect the face and are not known to be associated with cat scratches. We describe a 24-year-old woman who presented with a 3-month history of multiple tender, occasionally discharging cystic nodules involving the left side of her face in a sporotrichoid distribution. She had suffered a cat scratch to her left lower eyelid 3 weeks before the onset of the eruption and owned multiple tropical fish tanks. She was systemically well and had no lymphadenopathy. She had a background history of a 4.5-mm-thick nodular melanoma of her temple treated by wide local excision and negative sentinel lymph node biopsy 4 years prior. Skin biopsies showed multiple variably sized granulomas surrounded by thick cuffs of lymphocytes involving the superficial and deep dermis with no organisms seen on Ziehl-Neelsen, peroidic acid-Schiff and methenamine silver stains. Laboratory investigations showed a mildly raised erythrocyte sedimentation rate but normal full blood count and C-reactive protein. Fluid from the left cheek grew an acid-fast bacillus identified as Mycobacterium marinum. The skin eruption cleared after 5-month treatment with oral clarithromycin 500 mg twice daily and rifampicin 600 mg daily.

A UVB wavelength dependency for local suppression of recall immunity in humans demonstrates a peak at 300 nm.

UVB radiation is a potent environmental carcinogen that not only causes mutations in the skin but also profoundly suppresses skin immune responses. Although this UVB-induced suppression of antitumor immunity has a key role in skin cancer development, the wavelengths within UVB causing greatest in vivo immunosuppression in humans are as yet unknown. We have identified a wavelength dependency for immunosuppression in humans across the UVB spectrum. We established linear dose-response curves for UV-induced local suppression of recall contact hypersensitivity responses at four wavelengths between 289 and 322 nm and found peak immune suppressive effectiveness at 300 nm and no detectable suppression at 322 nm within a physiologically relevant dose range.

Anomalous flow deflection at earth's low-Alfvén-Mach-Number bow shock.

Earth's magnetosphere is an obstacle to the supersonic solar wind and the bow shock is formed in the front side of it. In ordinary hydrodynamics, the flow decelerated at the shock is diverted around the obstacle symmetrically about the Earth-Sun line, which is indeed observed in the magnetosheath most of the time. Here we show a case under a very low-density solar wind in which duskward flow was observed in the dawnside magnetosheath. A Rankine-Hugoniot test shows that the magnetic effect is crucial for this "wrong flow" to appear. A full three-dimensional magnetohydrodynamics (MHD) simulation of the situation confirming this interpretation and earlier simulations is also performed. It is illustrated that in addition to the "wrong flow" feature, various peculiar characteristics appear in the global picture of the MHD flow interaction with the obstacle.

Tail reconnection triggering substorm onset.

Magnetospheric substorms explosively release solar wind energy previously stored in Earth's magnetotail, encompassing the entire magnetosphere and producing spectacular auroral displays. It has been unclear whether a substorm is triggered by a disruption of the electrical current flowing across the near-Earth magnetotail, at approximately 10 R(E) (R(E): Earth radius, or 6374 kilometers), or by the process of magnetic reconnection typically seen farther out in the magnetotail, at approximately 20 to 30 R(E). We report on simultaneous measurements in the magnetotail at multiple distances, at the time of substorm onset. Reconnection was observed at 20 R(E), at least 1.5 minutes before auroral intensification, at least 2 minutes before substorm expansion, and about 3 minutes before near-Earth current disruption. These results demonstrate that substorms are likely initiated by tail reconnection.

Segmental haemangiomas of infancy: A review of 14 cases.

Haemangiomas of infancy are the commonest benign tumour in childhood, with the majority being a localized subtype, only requiring therapy in specific locations. The segmental subtype, however, confers a higher complication rate, an association with the PHACE syndrome and poorer prognosis. This retrospective case series of 14 infants with segmental haemangiomas aimed to further define the variety of clinical presentations, complication rates, and response to treatment in this subset of patients. We found in our series that 71% of infants with segmental haemangiomas develop at least one complication related to the lesion. Systemic corticosteroids prevented the further growth as well as reduced the pain and ulceration of the segmental haemangiomas in all of those treated. Early recognition and early treatment to arrest the growth of segmental haemangiomas will reduce morbidity and complications associated with these haemangiomas. Corticosteroid use, however, needs to be considered against the high incidence of side-effects such as secondary hypertension (40%), cushingoid features (40%) and growth suppression (67%). In our experience, these infants benefit from multidisciplinary team involvement for the assessment of associated syndromes, and to follow up and avoid complications associated with systemic therapy.

Melanin differentially protects from the initiation and progression of threshold UV-induced erythema depending on UV waveband.

BACKGROUND/PURPOSE: This study aimed to determine the relationship between various measures of constitutive skin pigmentation and erythema caused by solar-simulated UV (ssUV), 290 and 310 nm UV. METHODS: Skin pigmentation was assessed clinically by skin typing as well as objectively by measurement of the melanin index (MI) by reflectance spectroscopy. Subjects having Fitzpatrick skin types I-IV were exposed to graded doses of ssUV and either narrowband 310 nm (n=70) or 290 nm (n=69) UV, and assessed 24 h after exposure. Minimal erythema dose (MED) was assessed visually as the lowest dose that caused minimally perceptible erythema. Susceptibility to further development of erythema with higher exposure doses was measured by the gradient of erythema dose-response curves. This was determined by linear regression using reflectance spectrometry data beyond the MED. RESULTS: Although there was considerable variation within each skin type, MI and ssUV MED increased with increasing Fitzpatrick skin type. MI correlated with ssUV MED and 310 nm UV MED, but not 290 nm UV MED. There was also a significant negative correlation between MI and erythema dose-response gradients caused by ssUV, 310 and 290 nm UV. CONCLUSION: Melanin situated near the basal epidermis may not protect from the initial development of threshold erythema caused by 290 nm UV because it penetrates poorly past the stratum corneum and is not well absorbed by melanin in vivo compared with 310 nm UV. Higher erythemal 290 nm UV doses may reach basal epidermal melanin, which may then afford protection against further 290 nm UV erythema.

Spectral and dose dependence of ultraviolet radiation-induced immunosuppression.

Ultraviolet radiation (UV) wavelength and dose dependence has been demonstrated for a number of cutaneous endpoints such as erythema, pigment darkening, DNA damage, and photocarcinogenesis. More recently, a number of in-vitro and in-vivo models of UV immunosuppression have implicated UVA (320-400 nm) in immune protection as well as immune suppression. While the wavelength dependencies for immunosuppression within UVB have been well established in mice, the exact role of specific UVA wavelengths has been less clear. Moreover, in humans, the spectral dependence of UV immunosuppression is even less well established. This review firstly outlines the established UV action spectra for a variety of cutaneous effects. The waveband and dose dependence of UV immunosuppression and its mechanisms are explored with a focus on in-vivo models. Finally, since UV immunosuppression along with DNA damage is thought to play a central role in the development of skin cancer, a clearer understanding of the immunosuppressive potential of discrete UV wavebands will allow a more rational approach to our understanding and prevention of skin cancer.

Angular gyrus syndrome mimicking depressive pseudodementia.

A 67-year-old left-handed woman with a diagnosis of pseudodementia was being treated for depression with little benefit. Neuropsychological evaluations revealed features of angular gyrus syndrome, namely, agraphia, alexia, Gerstmann's syndrome and behavioural manifestations such as depression, poor memory, frustration and irritability. A computed tomographic scan showed a right occipito-temporal infarction, which had occurred 18 months earlier. The patient demonstrated aspects of language dysfunction associated with the syndrome and showed reversed lateralization of cerebral functions. Recognizing and distinguishing between angular gyrus syndrome and depression is important because the appropriate therapies differ. The use of the term pseudodementia can be misleading.