Human pigmentation genes under environmental selection

Genome-wide association studies and comparative genomics have established major loci and specific polymorphisms affecting human skin, hair and eye color. Environmental changes have had an impact on selected pigmentation genes as populations have expanded into different regions of the globe

Factors associated with risky sun exposure behaviors among operating engineers

Background The objective of this study was to determine the factors associated with sun exposure behaviors among Operating Engineers (heavy equipment operators). Methods Operating Engineers (N = 498) were asked to complete a cross‐sectional survey. Linear and logistic regression analyses were used to determine health behavioral, perceptional, and demographic factors associated with sun exposure behavior (sun burns, blistering, use of sunscreen, and interest in sun protection services). Results Almost half reported two or more sunburns/summer and the median times blistering was 2 with a range of 0–100. About one‐third never used sun block, while just over one‐third rarely used sun block. Almost one‐quarter were interested in sun protection guidance. Multivariate analyses showed that perceptions of skin type, alcohol problems, fruit intake, BMI, sleep quality, age, sex, and race were significantly associated with at least one of the outcome variables ( P  < 0.05). Conclusions Operating Engineers are at high risk for skin cancer due to high rates of exposure to ultraviolet light and low rates of sun block use. Subgroups of Operating Engineers are particularly at risk for sun damage. Interventions are needed to decrease sun exposure among Operating Engineers. Am. J. Ind. Med. 55:786–792, 2012. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93541/1/22079_ftp.pd

DEVELOPMENT OF RECOMBINANT PROTEIN BASED CHEMICAL CONJUGATE MALARIA VACCINES TARGETING THE PRE-ERYTHROCYTIC STAGE, TRANSMISSION BLOCKING, OR BOTH

The development of a Plasmodium falciparum malaria vaccine is critical for future control and elimination programs. Recombinant protein based chemical conjugate vaccines, covering different parasite stages, are being developed due to complexity of the parasite and sub-optimal immunogenicity of recombinant malaria proteins in humans, respectively. Chemical conjugation of recombinant malaria proteins to carrier proteins improves their immunogenicity in animal studies. A transmission blocking vaccine comprised of the ookinete protein Pfs25 chemically conjugated to Pseudomonas aeruginosa ExoProtein A (EPA) is currently being developed for pilot scale cGMP production. Bulk lots of Pfs25 and EPA have already been produced and released following cGMP. Appropriate analytical assays are being evaluated for both in-process and bulk release of the Pfs25-EPA conjugate vaccine. One critical assay already evaluated for determining the average mass is analytical size exclusion HPLC coupled with multi-angle light scattering. Phase 1 human clinical trials are planned for 2011. Another biological target of interest is the circumsporozoite protein (CSP), the most abundant and immunogenic protein on the surface of the sporozoite. A recombinant nearly full-length CSP has been produced in the methylotrophic yeast Pichia pastoris containing a bioengineered free thiol for chemical conjugation to various carrier proteins, including a chemically conjugated form of Pfs25. This recombinant protein based chemical conjugation platform, in combination with better adjuvant selection, will improve the potential for developing an efficacious malaria vaccine

The speckled scallop, Argopecten circularis, in Aqua Hedionda Lagoon, San Diego County, California

Speckled scallops, Argopecten circularis (Sowerby, 1835), were sampled at Agua Hedionda Lagoon, Carlsbad, San Diego County from March 1984 to October 1986, to obtain basic life history data. Monthly samples of scallops were collected, measured, and released to obtain length frequency data for estimates of growth, life span, and spawning period. Subsamples of scallops were collected for determination of gonadal-somatic and adductor muscle-somatic indices. In 1984 large concentrations of speckled scallops were found on the sand-silt bottom of the lagoon, closely associated with eelgrass, Zostra marina. During the course of the study the numbers of scallops declined, until their virtual disappearance at the end of 1986. Monthly length frequency plots from 24,375 scallop measurements indicate that this is a rapidly growing species with a short life span. Gonadal- and adductor muscle-somatic indices from subsamples of 1,714 scallops indicate first spawning at age one and a relationship between temperature and spawning. Based on this study management recommendations are made for the speckled scallop. (39pp.

Protocol of a randomized controlled trial of sun protection interventions for operating engineers

Abstract Background Skin cancer are increasing and some types of skin cancer are among the most lethal cancers yet are easily preventable. However, sun protection interventions are rarely implemented among outdoor workers. Our prior work shows that Michigan Operating Engineers (heavy equipment operators) spend an average of 4–5 hours in the sun, about one-third reported getting sun burned at least once a summer, and over half burned more than once a summer. About three-quarters of the sample never or only sometimes used sun block. Methods/design Using the Health Belief Model as a guide, this randomized controlled trial (RCT) will test the efficacy of four sun protection interventions targeting Operating Engineers: a) education only; b) education and mailed sunscreen; c) education and text message reminders; and, d) education, mailed sunscreen, and text message reminders. Participations in the study will be offered during regularly scheduled safety trainings at the Local 324 Training Center. Pre- and post-intervention surveys will be collected to determine changes in sunscreen use and sun burning, the primary dependent variables. The analyses will include: a) paired t-tests to determine changes over time (from pre-intervention to post–intervention) in outcome variables (sunscreen use and burning) separately in the 4 intervention groups, b) Repeated Measures Analysis of Variance (RM-ANOVA) to compare the changes in outcomes across the 4 groups, and c) t-tests on change scores as follow-ups to the RM-ANOVA to determine exactly which groups differ from each other. Discussion Based on the outcome of this study, we will develop a RO1 for wider scale testing and dissemination in conjunction with the International Training Center which services North America (including the US, Mexico, and Canada). Wide scale dissemination of an efficacious sun protection intervention has the potential to substantially impact skin cancer rates among this population. The ultimate goal is for high reach, high efficacy, and low cost. Trial registration NCT01804595http://deepblue.lib.umich.edu/bitstream/2027.42/112879/1/12889_2013_Article_5170.pd

Real-time PCR quantification of the canine filaggrin orthologue in the skin of atopic and non-atopic dogs: a pilot study

Canine atopic dermatitis (AD) is a common inflammatory skin disease associated with defects in the epidermal barrier, particularly in West Highland white terriers (WHWTs). It shares many similarities with human AD, and so may be a useful animal model for this disease. Epidermal dysfunction in human AD can be caused by mutations in the gene encoding the epidermal protein filaggrin (FLG) and, in some atopic patients, be associated with altered FLG mRNA and protein expression in lesional and/or non-lesional skin. In experimental models of canine AD, mRNA expression of the orthologous canine filaggrin gene may be reduced in non-lesional skin compared with healthy controls. However, there is no published data on canine filaggrin mRNA expression in the skin of dogs with naturally-occurring AD. Hence, the aim of this pilot study was to develop a reverse transcriptase real-time PCR assay to compare filaggrin mRNA expression in the skin of atopic (n = 7) and non-atopic dogs (n = 5) from five breeds, including eight WHWTs.Overall, filaggrin mRNA expression in non-lesional atopic skin was decreased compared to non-lesional non-atopic skin (two fold change); however this difference was only statistically significant in the subgroup of WHWTs (P = 0.03).Although limited by the small sample size, these results indicate that, comparable to some cases of human AD, altered filaggrin mRNA expression may exist in the skin of some atopic dogs with naturally-occurring disease. Additional studies, including larger sample numbers, will be necessary to confirm this finding and to investigate whether mutations in the filaggrin gene exist and contribute to epidermal lesions of AD in dogs

Deep Learning Discovery of Demographic Biomarkers in Echocardiography

Deep learning has been shown to accurately assess 'hidden' phenotypes and predict biomarkers from medical imaging beyond traditional clinician interpretation of medical imaging. Given the black box nature of artificial intelligence (AI) models, caution should be exercised in applying models to healthcare as prediction tasks might be short-cut by differences in demographics across disease and patient populations. Using large echocardiography datasets from two healthcare systems, we test whether it is possible to predict age, race, and sex from cardiac ultrasound images using deep learning algorithms and assess the impact of varying confounding variables. We trained video-based convolutional neural networks to predict age, sex, and race. We found that deep learning models were able to identify age and sex, while unable to reliably predict race. Without considering confounding differences between categories, the AI model predicted sex with an AUC of 0.85 (95% CI 0.84 - 0.86), age with a mean absolute error of 9.12 years (95% CI 9.00 - 9.25), and race with AUCs ranging from 0.63 - 0.71. When predicting race, we show that tuning the proportion of a confounding variable (sex) in the training data significantly impacts model AUC (ranging from 0.57 to 0.84), while in training a sex prediction model, tuning a confounder (race) did not substantially change AUC (0.81 - 0.83). This suggests a significant proportion of the model's performance on predicting race could come from confounding features being detected by AI. Further work remains to identify the particular imaging features that associate with demographic information and to better understand the risks of demographic identification in medical AI as it pertains to potentially perpetuating bias and disparities.Comment: 2450 words, 2 figure, 3 table