Educational and practice gaps in the management of volar melanocytic lesions.

BACKGROUND: The benign and malignant patterns of acral melanocytic naevi (AMN) and acral melanomas (AM) have been defined in a series of retrospective studies. A three-step algorithm was developed to determine when to biopsy acral melanocytic lesions. This algorithm has only been applied to a Japanese population. OBJECTIVES: Our study aimed to review the current management strategy of acral melanocytic lesions and to investigate the utility of the three-step algorithm in a predominately Caucasian cohort. METHODS: A retrospective search of the pathology and image databases at Mayo Clinic was performed between the years 2006 and 2016. Only cases located on a volar surface with dermoscopic images were included. Two dermatologists reviewed all dermoscopic images and assigned a global dermoscopic pattern. Clinical and follow-up data were gathered by chart review. All lesions with known diameter and pathological diagnosis were used for the three-step algorithm. RESULTS: Regular fibrillar and ridge patterns were more likely to be biopsied (P = 0.01). The majority of AMN (58.1%) and AM (60%) biopsied were due to physician-deemed concerning dermoscopic patterns. 39.2% of these cases were parallel furrow, lattice-like or regular fibrillar. When patients were asked to follow-up within a 3- to 6-month period, only 16.7% of the patients returned within that interval. The three-step algorithm would have correctly identified four of five AM for biopsy, missing a 6 mm, multicomponent, invasive melanoma. CONCLUSION: We found one major educational gap in the recognition of low-risk lesions with high rates of biopsy of the fibrillary pattern. Recognizing low-risk dermoscopic patterns could reduce the rate of biopsy of AMN by 23.3%. We identified two major practice gaps, poor patient compliance with follow-up and the potential insensitivity of the three-step algorithm to small multicomponent acral melanocytic lesions.

The stochastic nature of larval connectivity among nearshore marine populations.

Many nearshore fish and invertebrate populations are overexploited even when apparently coherent management structures are in place. One potential cause of mismanagement may be a poor understanding and accounting of stochasticity, particularly for stock recruitment. Many of the fishes and invertebrates that comprise nearshore fisheries are relatively sedentary as adults but have an obligate larval pelagic stage that is dispersed by ocean currents. Here, we demonstrate that larval connectivity is inherently an intermittent and heterogeneous process on annual time scales. This stochasticity arises from the advection of pelagic larvae by chaotic coastal circulations. This result departs from typical assumptions where larvae simply diffuse from one site to another or where complex connectivity patterns are created by transport within spatially complicated environments. We derive a statistical model for the expected variability in larval settlement patterns and demonstrate how larval connectivity varies as a function of different biological and physical processes. The stochastic nature of larval connectivity creates an unavoidable uncertainty in the assessment of fish recruitment and the resulting forecasts of sustainable yields.

Glycosylphosphatidylinositol anchors of Plasmodium falciparum: molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis.

Induction of proinflammatory cytokine responses by glycosylphosphatidylinositols (GPIs) of intraerythrocytic Plasmodium falciparum is believed to contribute to malaria pathogenesis. In this study, we purified the GPIs of P. falciparum to homogeneity and determined their structures by biochemical degradations and mass spectrometry. The parasite GPIs differ from those of the host in that they contain palmitic (major) and myristic (minor) acids at C-2 of inositol, predominantly C18:0 and C18:1 at sn-1 and sn-2, respectively, and do not contain additional phosphoethanolamine substitution in their core glycan structures. The purified parasite GPIs can induce tumor necrosis factor alpha release from macrophages. We also report a new finding that adults who have resistance to clinical malaria contain high levels of persistent anti-GPI antibodies, whereas susceptible children lack or have low levels of short-lived antibody response. Individuals who were not exposed to the malaria parasite completely lack anti-GPI antibodies. Absence of a persistent anti-GPI antibody response correlated with malaria-specific anemia and fever, suggesting that anti-GPI antibodies provide protection against clinical malaria. The antibodies are mainly directed against the acylated phosphoinositol portion of GPIs. These results are likely to be valuable in studies aimed at the evaluation of chemically defined structures for toxicity versus immunogenicity with implications for the development of GPI-based therapies or vaccines.

The ELFIN Mission.

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E < 40% and a fluxgate magnetometer (FGM) on a ∼72 cm boom that measures magnetic field waves (e.g., EMIC waves) in the range from DC to 5 Hz Nyquist (nominally) with <0.3 nT/sqrt(Hz) noise at 1 Hz. The spinning satellites (Tspin ∼ 3 s) are equipped with magnetorquers (air coils) that permit spin-up or -down and reorientation maneuvers. Using those, the spin axis is placed normal to the orbit plane (nominally), allowing full pitch-angle resolution twice per spin. An energetic particle detector for ions (EPDI) measures 250 keV - 5 MeV ions, addressing secondary science. Funded initially by CalSpace and the University Nanosat Program, ELFIN was selected for flight with joint support from NSF and NASA between 2014 and 2018 and launched by the ELaNa XVIII program on a Delta II rocket (with IceSatII as the primary). Mission operations are currently funded by NASA. Working under experienced UCLA mentors, with advice from The Aerospace Corporation and NASA personnel, more than 250 undergraduates have matured the ELFIN implementation strategy; developed the instruments, satellite, and ground systems and operate the two satellites. ELFIN's already high potential for cutting-edge science return is compounded by concurrent equatorial Heliophysics missions (THEMIS, Arase, Van Allen Probes, MMS) and ground stations. ELFIN's integrated data analysis approach, rapid dissemination strategies via the SPace Environment Data Analysis System (SPEDAS), and data coordination with the Heliophysics/Geospace System Observatory (H/GSO) optimize science yield, enabling the widest community benefits. Several storm-time events have already been captured and are presented herein to demonstrate ELFIN's data analysis methods and potential. These form the basis of on-going studies to resolve the primary mission science objective. Broad energy precipitation events, precipitation bands, and microbursts, clearly seen both at dawn and dusk, extend from tens of keV to >1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.

Chemical contrast in X-ray microscopy and spatially resolved XANES spectroscopy of organic specimens.

The scanning transmission x-ray microscope at the National Synchrotron Light Source has been used to record x-ray absorption near-edge structure (XANES) spectra from 0.01-square-micrometer regions of organic specimens. The spectral features observed reflect the molecular structure of the dominant absorbing atoms and provide the contrast mechanism for high-resolution imaging with chemical sensitivity. This technique was used with x-ray energies near the carbon K absorption edge to identify and map separate phases in various polymer blends and to map the DNA distribution in chromosomes with a spatial resolution of 55 nanometers.

In Vivo Reflectance Confocal Microscopy: Emerging Role in Noninvasive Diagnosis and Monitoring of Eczematous Dermatoses. / Microscopia confocal de reflectancia in vivo: papel emergente en el diagnóstico no invasivo, así como en el seguimiento de las dermatosis eccematosas.

Dermatologic diagnosis and monitoring have been dependent largely on visual grading. A skin biopsy is performed in case of diagnostic uncertainty, but can be traumatic, and results are delayed due to time for specimen transport and processing. Biopsies also destroy specimens, prohibiting lesion evolution monitoring. In vivo reflectance confocal microscopy (RCM) offers a diagnostic alternative to skin biopsy. RCM captures real-time, high-resolution images, and has been piloted for the evaluation of various dermatologic conditions. Identification of unique RCM features may distinguish dermatoses with similar clinical morphologies. Allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) are diagnosed by patch testing that currently uses a subjective scoring system. RCM has increasingly been studied for early detection and severity grading of CD. Common RCM features shared by ACD and ICD are stratum corneum disruption, vesicle formation, exocytosis, spongiosis, and parakeratosis. Features unique to ACD are vasodilation, increased epidermal thickness, intercellular edema, and acanthosis. Features unique to ICD are detached corneocytes and targetoid keratinocytes. This review summarizes the use of RCM in evaluating contact eccematous conditions and aims to spark future research and interest in this promising tool.

From model cell line to in vivo gene expression: disease-related intestinal gene expression in IBD.

Crohn's disease (CD) and ulcerative colitis (UC) are subforms of inflammatory bowel diseases (IBD). Genetic and environmental factors influencing the onset and course of the diseases have been recently identified. This study uses a two-step approach to detect genes involved in the pathogenesis of IBD by microarray analysis and real-time PCR (RT-PCR). In a first step, microarray expression screening was used to obtain tumour necrosis factor-alpha (TNF-alpha) induction profiles of two human cell lines to represent the tissue cell types involved in IBD. In a second step, a subset of differentially expressed genes was examined by real-time PCR in intestinal biopsy samples of normal controls (NC) compared with UC and CD patients, as well as to a cohort of patients suffering from intestinal diseases other than IBD. Data were obtained from 88 CD, 88 UC, 53 non-IBD patients (inflammatory control), DC and 45 NC individuals. The experimental design enabled the identification of disease-specific expressed genes. DnaJ (Hsp40) homologue, subfamily B, member 5 (DNAJB5) was downregulated in intestinal biopsy samples of the UC cohort compared with NC. A difference in JUNB expression levels was observed by comparing biopsy samples from inflamed and non-inflamed areas of UC patients. Transcript expression differences between IBD and control cohorts were found by examining histamine N-methyltransferase (HNMT), interleukin-1A (IL-1A) and proplatelet basic protein (PPBP) expression. The experimental procedure represents an approach to identify disease-relevant genes, which is applicable to any disease where appropriate model systems are available.

Microbiological analysis of food contact surfaces in child care centers.

A study of six child care centers was conducted to assess the microbiological quality of three food contact surfaces (one food serving surface and two food preparation surfaces) and one non-food contact surface (diaper changing surface) to determine the effectiveness of cleaning and sanitization procedures within the facilities. Aerobic plate counts (APCs) and Escherichia coli/coliform counts of 50-cm(2) areas on all surfaces were determined using standard microbiological swabbing methods. Samples were taken three times a day (preopening, lunchtime, and following final cleanup) twice per month for 8 months in each child care center (n = 288 sampling times). Mean log APCs over the survey period were 1.32, 1.71, 1.34, 1.96, 1.50, and 1.81 log CFU/50 cm(2) for the six centers. Mean log coliform counts were 0.15, 0.40, 0.33, 1.41, 0.28, and 1.12 CFU/50 cm(2) for the same centers. Coliforms were detected in 283 of 1,149 (24.7%) samples, with counts ranging from 1 to 2,000 CFU/50 cm(2), while E. coli was detected in 18 of 1,149 (1.6%) samples, with counts ranging from 1 to 35 CFU/50 cm(2). The findings of this study demonstrated that the extent of bacterial contamination was dependent on the center, time of day, and the area sampled. While no direct correlation between contamination and illness can be made, given the high risk of food-borne illness associated with children, microbial contamination of food contact or non-food contact surfaces is an aspect of food safety that requires more attention. Emphasis on training and the development of modified standard sanitation operating procedures for child care centers are needed to reduce potential hazards.

Etanercept in the treatment of palmoplantar pustulosis.

INTRODUCTION: Palmoplantar pustulosis (PPP) is a chronic, recurrent and difficult to treat skin condition characterized by the presence of pustules, erythema, and hyperkeratosis on palms and soles. METHODS: Fifteen subjects with PPP were randomized (2:1) to receive subcutaneous injections of either etanercept 50 mg or a placebo twice a week for 3 months. All subjects then received the etanercept 50 mg injections twice a week for an additional 3 months. RESULTS: Etanercept was well tolerated by subjects with PPP. The decrease in median Palmoplantar Pustulosis Area and Severity Index (PPPASI) score from baseline to 24 weeks was statistically significant for subjects treated with etanercept for 24 weeks (P = 0.038, n = 10) but not for subjects in the placebo/etanercept cross-over group (P = 0.125, n = 5). Comparison of changes in PPPASI from baseline to week 12 was not statistically significant for subjects assigned to etanercept or to placebo. Some subjects treated with etanercept presented good clinical improvements in PPP severity whereas others showed an increase in PPP severity. CONCLUSION: This study showed that etanercept was well tolerated in subjects with PPP and suggests that some PPP subjects might benefit from etanercept therapy. Larger studies are needed to assess PPP response to etanercept including the influence of smoking and the presence or absence of psoriasis outside palms and soles.

Marine spatial planning makes room for offshore aquaculture in crowded coastal waters.

Marine spatial planning (MSP) seeks to reduce conflicts and environmental impacts, and promote sustainable use of marine ecosystems. Existing MSP approaches have successfully determined how to achieve target levels of ocean area for particular uses while minimizing costs and impacts, but they do not provide a framework that derives analytical solutions in order to co-ordinate siting of multiple uses while balancing the effects of planning on each sector in the system. We develop such a framework for guiding offshore aquaculture (bivalve, finfish, and kelp farming) development in relation to existing sectors and environmental concerns (wild-capture fisheries, viewshed quality, benthic pollution, and disease spread) in California, USA. We identify > 250,000 MSP solutions that generate significant seafood supply and billions of dollars in revenue with minimal impacts (often < 1%) on existing sectors and the environment. We filter solutions to identify candidate locations for high-value, low-impact aquaculture development. Finally, we confirm the expectation of substantial value of our framework over conventional planning focused on maximizing individual objectives.

Materials characterization of explanted polypropylene hernia meshes.

Hernia repair with prosthetic mesh significantly decreases the rate of recurrence compared with traditional, primary suture repair by reducing the tension on the edges of the wound. However, there are several complications associated with the use of mesh that may be due to the chronic inflammatory reaction to the mesh or a loss of compliance after degradation of the material. Mesh contraction and migration can also occur, sometimes resulting in a recurrent hernia. Based on the chemical structure of the polypropylene mesh material and the physiological conditions to which it is subjected, it is possible that oxidation is responsible for these changes in material properties. Oxidation would result in surface cracking, decreased melting temperature, loss of mass, and reduced compliance of the material. The objective of this study was to identify physiochemical changes in the surface and bulk properties of explanted polypropylene hernia meshes compared to pristine polypropylene mesh materials. Several characterization techniques were utilized, including scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and compliance testing. Overall, the results supported our hypothesis that oxidation is involved with the degradation of polypropylene hernia mesh materials.

Use of porcine dermal collagen as a prosthetic mesh in a contaminated field for ventral hernia repair: a case report.

Chronic infection of a prosthetic mesh implant is a severe complication of ventral hernia repair, and mesh explantation is usually required in these cases. Biologic mesh implants have a possible role in ventral hernia repair in this setting. Here we present a case of chronic mesh infection following ventral hernia repair and the use of a biologic mesh to repair the existing defect following explantation of the infected mesh. Analysis of the explant material demonstrated possible oxidative degradation of the original polypropylene. A review of the literature follows.

Depression: Loss of Reinforcers or Loss of Reinforcer Effectiveness? - Republished Article.

A number of behavior therapists have proposed that depression results when a discriminative stimulus or reinforcer for behavior is removed. It is proposed here that the depressed person's general loss of interest in his environment suggests that there is a loss of reinforcer effectiveness. The manner in which environmental events, including the loss of a reinforcer, may result in this general loss of reinforcer effectiveness is discussed. The possible evolutionary significance of depression is also briefly discussed.

Attitudes to outcomes measured in clinical trials of cardiovascular prevention.

BACKGROUND: Selecting outcome measures in cardiovascular prevention trials should be informed by their importance to selected populations. Major vascular event outcomes are usually prioritized in these trials with considerably less attention paid to cognitive and functional outcomes. AIM: To examine views on importance of outcome measures used in clinical trials. DESIGN: Cross-sectional survey. METHODS: Of 367 individuals approached, 280 (76%) participated: outpatients attending cardiovascular prevention clinics (n = 97), active retirement groups members (n = 75), medical students (n = 108). Participants were asked to rank, in order of importance, outcome measures, which may be included in cardiovascular prevention trials. Results were compared between two groups: <65s (n = 157) and ≥65s (n = 104). RESULTS: When asked what outcomes were most important to measure in cardiovascular prevention trials, respondents reported: death (31.6%) stroke (28.5%), dementia (26.9%), myocardial infarction (MI) (7.9%) and requiring nursing home (NH) care (5.1%). When asked the most relevant outcomes regarding successful ageing respondents reported; maintaining independence (32.4%), avoiding major illness (24.3%), good family life (23.6%), living as long as possible (15.8%), avoiding NH care (3.1%) and contributing to society (0.8%) as most important. When asked what outcome concerned them most about the future, respondents reported: dementia (32.6%), dependence (30.4%), death (12.8%), stroke (12.5%), cancer (6.2%) requiring NH care (4.8%) and MI (0.7%). Maintaining independence was considered most important in younger and older cohorts. CONCLUSION: Cognitive and functional outcomes are important patient-relevant outcomes, sometimes more important than major vascular events. Incorporating these outcomes into trials may encourage patient participation and adherence to preventative regimens.

Occurrence of novel branched-chain fatty acids in Refsum's disease.

Two novel branched-chain fatty acids, which appear to be unsaturated analogs of phytanic acid, have been observed in sera and urine of patients with Refsum's disease. They occur in both phospholipids and neutral lipids, and have been isolated and characterized.

HIV-1 subtype E progression among northern Thai couples: traditional and non-traditional predictors of survival.

BACKGROUND: In the continuing effort to introduce antiretroviral therapy in resource-limited settings, there is a need to understand differences between natural history of HIV in different populations and to identify feasible clinical measures predictive of survival. METHODS: We examined predictors of survival among 836 heterosexuals who were infected with HIV subtype CRF01_AE in Thailand. RESULTS: From 1993 to 1999, 269 (49.4%) men and 65 (25.7%) women died. The median time from the estimated seroconversion to death was 7.8 years (95% confidence interval 7.0-9.1). Men and women with enrolment CD4 counts <200 cells/microl had about 2 and 11 times greater risk of death than those with CD4 counts of 200-500 and >500, respectively. Measurements available in resource-limited settings, including total lymphocyte count (TLC), anaemia, and low body mass index (BMI), also predicted survival. Men with two or more of these predictors had a median survival of 0.8 (0.5-1.8) years, compared with 2.7 (1.9-3.3) years for one predictor and 4.9 (4.1-5.2) years for no predictors. CONCLUSIONS: The time from HIV infection to death appears shorter among this Thai population than among antiretroviral naive Western populations. CD4 count and viral load (VL) were strong, independent predictors of survival. When CD4 count and VL are unavailable, individuals at high risk for shortened HIV survival may be identified by a combination of low TLC, anaemia, and low BMI. This combination of accessible clinical measures of the disease stage may be useful for medical management in resource-limited settings.

Bioanalytic applications of mass spectrometry.

Mass spectrometry has suddenly expanded out of research and assay laboratories into biology, medicine and therapeutics. Electrospray ionization and matrix-assisted laser desorption/ionization yield increased mass-range and sensitivity, leading to novel applications and sparking new analyzer designs, software, and robotics.

Kinetic equivalence of stable-isotope-labeled and unlabeled phenytoin.

Stable isotope labeling (SIL) of a drug results in a higher molecular weight than that of the unlabeled drug. SIL tracer doses can be quantitated separately from unlabeled drug by gas chromatography-mass spectrometry (GC-MS) without exposing the patient to radiation. The higher molecular weight of SIL drug could cause a higher energy of activation for (and slowing of) metabolic reactions ("isotope effect"). To evaluate possible isotope effect, three dogs and three men were infused with a mixture containing equal amounts of SIL (2-13C-1,3-15N2) and unlabeled phenytoin (PHT). Plasma and urine were collected at regular intervals. Concentrations of SIL and unlabeled PHT and HPPH (the major metabolite of PHT) were determined by GC-MS. Within each subject there was no trend for concentrations of SIL PHT or HPPH to be higher or lower than concentrations of their unlabeled analogs (greater than 0.20 to 0.90). There was no difference in the distribution and elimination half-lifes (t 1/2s), volume of distribution, volume of central compartment, or clearance of the two forms of PHT. Thus, no isotope effect was found.