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Background Solar radiation causes skin damage through the generation of reactive oxygen species (ROS). While UV filters effectively reduce UV‐induced ROS, they cannot prevent VIS‐induced (400‐760 nm) oxidative stress. Therefore, potent antioxidants are needed as additives to sunscreen products. Methods We investigated VIS‐induced ROS formation and the photoprotective effects of the Nrf2 inducer Licochalcone A (LicA). Results Visible spectrum of 400‐500 nm dose‐dependently induced ROS in cultured human fibroblasts at doses equivalent to 1 hour of sunshine on a sunny summer day (150 J/cm2). A pretreatment for 24 hours with 1 µmol/L LicA reduced ROS formation to the level of unirradiated cells while UV filters alone were ineffective, even at SPF50+. In vivo, topical treatment with a LicA‐containing SPF50 + formulation significantly prevented the depletion of intradermal carotenoids by VIS irradiation while SPF50 + control did not protect. Conclusion LicA may be a useful additive antioxidant for sunscreens.

Post-inflammatory hyperpigmentation (PIH) is a major cosmetic concern especially in individuals with darker skin complexion. Unfortunately, treatment with anti-inflammatory ingredients alone does not prevent the development of hyperpigmented spots. Recently, isobutylamido-thiazolyl-resorcinol (Thiamidol) was described as a very potent inhibitor of human tyrosinase. The objective of this research was to investigate the potential of this compound to prevent PIH induced by epidermal wounding (suction blister) and related to acne.Suction blister-induced PIH was treated with a formulation containing Thiamidol or a vehicle for 3 months, and the changes in hyperpigmentation were monitored by spectroscopic measurements. The effect of skin care formulations containing Thiamidol on acne-related PIH was investigated in two studies, a vehicle-controlled, double-blinded, randomized clinical study and a clinical observational study. Both studies had a duration of 3 months and included assessments such as clinical photography, clinical grading and melanin index measurements.Already after 2 weeks of treatment, suction blister sites treated with Thiamidol were significantly lighter than control sites and improved throughout the treatment period. Subjects´ self-grading demonstrated that Thiamidol significantly improved the visibility of acne-induced hyperpigmentation compared to the vehicle treatment. A skin care regimen with Thiamidol significantly improved acne-related PIH over 12 weeks shown by Mexameter measurements, expert grading, self-grading and clinical photography.Thiamidol represents a safe and effective ingredient for cosmetic products against post-inflammatory hyperpigmentation.L’hyperpigmentation post-inflammatoire (Post-Inflammatory Hyperpigmentation, PIH) est une préoccupation d’ordre esthétique majeure, en particulier chez les personnes dont le teint est plus foncé. Malheureusement, un traitement par des ingrédients anti-inflammatoires seuls n’empêche pas le développement de taches hyperpigmentées. Récemment, l’isobutylamido-thiazolyl-résorcinol (Thiamidol) a été décrit comme un inhibiteur très puissant de la tyrosinase humaine. L’objectif de cette investigation était d’étudier le potentiel de ce composé pour prévenir la PIH induite par une plaie épidermique (bulle de succion) et liée à l’acné. MÉTHODES: La PIH induite par la bulle de succion a été traitée avec une formulation contenant du Thiamidol ou un véhicule pendant 3 mois et les changements dans l’hyperpigmentation ont été surveillés par le biais de mesures spectroscopiques. L’effet des formulations pour soins de la peau contenant du Thiamidol visant à traiter la PIH liée à l’acné a été étudié au cours de deux études : une étude clinique randomisée, en double aveugle, contrôlée par véhicule et une étude clinique observationnelle. Les deux études avaient une durée de 3 mois et comportaient des évaluations telles que la photographie médicale, l’évaluation par les médecins et les mesures de l’indice de mélanine. RÉSULTATS: Après 2 semaines de traitement seulement, les sites de bulles de succion traités par du Thiamidol étaient significativement plus clairs que les sites-témoins et avaient montré une amélioration tout au long de la période de traitement. L’auto-évaluation des sujets a démontré que le Thiamidol améliorait significativement la visibilité de l’hyperpigmentation induite par l’acné par rapport au traitement par véhicule. Un programme de soins de la peau contenant du Thiamidol a significativement amélioré la PIH liée à l’acné sur 12 semaines, comme l’ont démontré les mesures de Mexameter, l’évaluation par des experts, l’auto-évaluation des sujets et la photographie médicale.Le Thiamidol représente un ingrédient sûr et efficace pour les produits cosmétiques contre l’hyperpigmentation post-inflammatoire.

Tyrosinase is the rate-limiting enzyme of melanin production and, accordingly, is the most prominent target for inhibiting hyperpigmentation. Numerous tyrosinase inhibitors have been identified, but most of those lack clinical efficacy because they were identified using mushroom tyrosinase as the target. Therefore, we used recombinant human tyrosinase to screen a library of 50,000 compounds and compared the active screening hits with well-known whitening ingredients. Hydroquinone and its derivative arbutin only weakly inhibited human tyrosinase with a half-maximal inhibitory concentration (IC50) in the millimolar range, and kojic acid showed a weak efficacy (IC50 > 500 μmol/L). The most potent inhibitors of human tyrosinase identified in this screen were resorcinyl-thiazole derivatives, especially the newly identified Thiamidol (Beiersdorf AG, Hamburg, Germany) (isobutylamido thiazolyl resorcinol), which had an IC50 of 1.1 μmol/L. In contrast, Thiamidol only weakly inhibited mushroom tyrosinase (IC50 = 108 μmol/L). In melanocyte cultures, Thiamidol strongly but reversibly inhibited melanin production (IC50 = 0.9 μmol/L), whereas hydroquinone irreversibly inhibited melanogenesis (IC50 = 16.3 μmol/L). Clinically, Thiamidol visibly reduced the appearance of age spots within 4 weeks, and after 12 weeks some age spots were indistinguishable from the normal adjacent skin. The full potential of Thiamidol to reduce hyperpigmentation of human skin needs to be explored in future studies.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and is caused by an expansion of cytosine-guanine-guanine (CGG) repeats in the FMR1 gene. Female premutation allele carriers (55-200 CGG repeats) are at risk to have an affected child. Currently, specific population-based carrier screening for FXS is not recommended. Previous studies exploring female premutation carrier frequency have been limited by size or ethnicity. This retrospective study provides a pan-ethnic estimate of the Fragile X premutation carrier frequency in a large, ethnically diverse population of women referred for routine carrier screening during a specified time period at Progenity, Inc. Patient ethnicity was self-reported and categorized as: African American, Ashkenazi Jewish, Asian, Caucasian, Hispanic, Native American, Other/Mixed/Unknown, or Sephardic Jewish. FXS test results were stratified by ethnicity and repeat allele category. Total premutation carrier frequency was calculated and compared against each ethnic group. A total of 134,933 samples were included. The pan-ethnic premutation carrier frequency was 1 in 201. Only the Asian group differed significantly from this frequency. Using the carrier frequency of 1 in 201, a conservative pan-ethnic risk estimate for a male fetus to have FXS can be calculated as 1 in 2,412. This risk is similar to the highest ethnic-based fetal risks for cystic fibrosis and spinal muscular atrophy, for which population-wide screening is currently recommended. This study adds to the literature and supports further evaluation into specific population-wide screening recommendations for FXS.

The most polymorphic part of the human genome, the MHC, encodes over 160 proteins of diverse function. Half of them, including the HLA class I and II genes, are directly involved in immune responses. Consequently, the MHC region strongly associates with numerous diseases and clinical therapies. Notoriously, the MHC region has been intractable to high-throughput analysis at complete sequence resolution, and current reference haplotypes are inadequate for large-scale studies. To address these challenges, we developed a method that specifically captures and sequences the 4.8-Mbp MHC region from genomic DNA. For 95 MHC homozygous cell lines we assembled, de novo, a set of high-fidelity contigs and a sequence scaffold, representing a mean 98% of the target region. Included are six alternative MHC reference sequences of the human genome that we completed and refined. Characterization of the sequence and structural diversity of the MHC region shows the approach accurately determines the sequences of the highly polymorphic HLA class I and HLA class II genes and the complex structural diversity of complement factor C4A/C4B. It has also uncovered extensive and unexpected diversity in other MHC genes; an example is MUC22, which encodes a lung mucin and exhibits more coding sequence alleles than any HLA class I or II gene studied here. More than 60% of the coding sequence alleles analyzed were previously uncharacterized. We have created a substantial database of robust reference MHC haplotype sequences that will enable future population scale studies of this complicated and clinically important region of the human genome.

Melasma is a pigmentary disorder characterized by hyperpigmented patchy skin in sun-exposed areas, especially the face. Treatment of melasma can be challenging because long-term therapy is required, reoccurrence is common, and existing therapies are insufficient and unsatisfactory. To investigate new treatment options, we performed an exploratory double-blinded, randomized split-face study to assess the efficacy of the tyrosinase inhibitor Thiamidol compared to hydroquinone in women with mild to moderate melasma. After 12 weeks, modified Melasma Area and Severity Index scores significantly improved on both the Thiamidol-treated and the hydroquinone-treated sides of the face. Additionally, Thiamidol treatment improved modified Melasma Area and Severity Index scores significantly better than hydroquinone, and more subjects improved following treatment with Thiamidol (79%) compared with hydroquinone (61%). During treatment, no subjects displayed worsening of modified Melasma Area and Severity Index scores on the Thiamidol-treated side, while approximately 10% of the subjects showed a worsening of modified Melasma Area and Severity Index scores on the hydroquinone-treated side. All subjects routinely used sunscreens and consistent results were obtained in low and in high UV ambient conditions. Subjects rated the efficacy of the Thiamidol formulation significantly better with regard to overall decreased intensity of dark spots and their overall appearance throughout the study. Thiamidol was well-tolerated and well-perceived and represents an effective agent to reduce hyperpigmentation.

Studies on patients with degenerative joint disease of the hip show that femoral periprosthetic bone mineral decreases following total hip arthroplasty. Scarcely any osteodensitometric data exist on femoral neck fracture (FNF) patients and periprosthetic bone remodelling. In two parallel cohorts we enrolled 87 patients (mean age, 72 ± 12 years; male:female ratio, 30:57) undergoing total hip arthroplasty for either primary osteoarthritis (OA) of the hip (n = 37) or for an acute FNF (n = 50) and followed them for a mean of 5.4 years. Outcomes were bone mineral density (BMD) changes in the periprosthetic Gruen zones 1–7, the incidence of periprosthetic fractures and clinical outcome. The bone mineral loss in the fracture group was more than twice that of the osteoarthritis group, −16.9% versus −6.8% (p = 0.004). The incidence of periprosthetic fractures was 12% (6/50) in the fracture cohort compared with none (0%) in the OA cohort (p = 0.03). Periprosthetic bone mineral loss following total hip arthroplasty is significantly greater in patients who are treated for acute FNF than in OA patients. This decrease of BMD follows a different pattern with the FNF patients losing larger proportions of bone in Gruen zones 1, 2, 6, and 7 while the OA patients tend to have larger losses only in zones 1 and 7. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:504–512, 2015.

This study compared the use of reverse and hemishoulder arthroplasty for the treatment of proximal humeral fractures among orthopedic surgeons taking part II of the American Board of Orthopaedic Surgery board examination. We hypothesized that the use of reverse shoulder arthroplasty for fractures in the elderly is increasing amongst newly trained orthopedic surgeons.We queried the American Board of Orthopaedic Surgery database for the cases of proximal humeral fractures treated with arthroplasty submitted between 2005 and 2012. We evaluated the prosthesis used, patient-specific factors, complications, and the difference in use by shoulder fellowship-trained surgeons.From 2005 to 2012, 5395 board-eligible orthopedic surgeons submitted cases to the database. Of these, 435 (mean, 54 per year) were proximal humeral fractures treated with arthroplasty. The overall incidence of reverse shoulder arthroplasty for fracture increased from 2% to 4% during 2005 to 2007 to 38% in 2012. Shoulder surgeons treated 5 times more proximal humeral fractures with shoulder arthroplasty and were also more than 20 times more likely to use a reverse implant (P .0001). The difference in complication rates between reverse and hemishoulder arthroplasty was not significant (P = .49). Patients who received a hemiarthroplasty tended to be younger (mean age, 70.8 vs 75.7 years; P = .0015).Overall, the use of a hemiarthroplasty for fracture is still more common (62% in 2012), although the relative proportion of reverse implants is rising. Among shoulder surgeons, more than 50% of the arthroplasties performed for fractures during the past 3 years (2010-2012) have been reverse arthroplasties.

The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10−5 cm/h, licorice: 4.68·10−6 cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10−5 cm/h, licorice: 24.0·10−6 cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1142–1148, 2014

Fracture-dislocations of the proximal interphalangeal joint encompass a spectrum of injury severity, ranging from injuries that require little intervention to those that require advanced reconstructive surgery for optimal outcome. Three fracture-dislocation patterns are recognized: dorsal, volar, and pilon. Acceptable outcome is dependent on achieving and maintaining a well-aligned and well-reduced joint, re-establishing normal joint kinematics, and restoring motion. Anatomic articular surface reduction is desirable but not absolutely necessary for a good outcome. Treatment depends on both the type of injury and patient-dependent factors. Optimal outcome for a specific injury is predicated on expedient diagnosis and recognition of injury severity, which enables initiation of appropriate management.

Background Hyperpigmentary disorders like melasma, actinic and senile lentigines are a major cosmetic concern. Therefore, many topical products are available, containing various active ingredients aiming to reduce melanin production and distribution. The most prominent target for inhibitors of hyperpigmentation is tyrosinase, the key regulator of melanin production. Many inhibitors of tyrosinase are described in the literature; however, most of them lack clinical efficacy. Methods We were interested in evaluating the inhibition of skin pigmentation by well-known compounds with skin-whitening activity like hydroquinone, arbutin, kojic acid and 4-n-butylresorcinol. We compared the inhibition of human tyrosinase activity in a biochemical assay as well as inhibition of melanin production in MelanoDerm™ skin model culture. For some compounds, the in vivo efficacy was tested in clinical studies. Results Arbutin and hydroquinone only weakly inhibit human tyrosinase with a half maximal inhibitory concentration (IC50) in the millimolar range. Kojic acid is 10 times more potent with an IC50 of approximately 500 μmol/L. However, by far the most potent inhibitor of human tyrosinase is 4-n-butylresorcinol with an IC50 of 21 μmol/L. In artificial skin models, arbutin was least active with an IC50 for inhibition of melanin production > 5000 μmol/L. Kojic acid inhibited with an IC50 > 400 μmol/L. Interestingly, hydroquinone inhibited melanin production in MelanoDerms with an IC50 below 40 μmol/L, probably due to a mechanism different from tyrosinase inhibition. Again, 4-n-butylresorcinol was the most potent inhibitor with an IC50 of 13.5 μmol/L. In vivo efficacy of 4-n-butyl-resorcinol was confirmed in clinical studies. Subjects with age spots on the forearm treated twice daily two age spots with a formula containing 4-n-butylresorcinol and two control age spots with the corresponding vehicle. Within 8 weeks, 4-n-butylresorcinol reduced visibly the appearance of age spots, while the control spots showed no improvement. A second study showed that 4-butylresorcinol was more effective than 4-hexylresorcinol and 4-phenylethylresorcinol. Conclusion The present in vitro and in vivo data prove the high inhibitory capacity of 4-n-butylresorcinol on human tyrosinase activity, exceeding by far the potency of hydroquinone, arbutin and kojic acid. The resulting clinical improvement of skin hyperpigmentations reveals 4-n-butylresorcinol as a very valuable active compound for the management of pigmentation disorders.

We investigate whether applying an internal radiocarpal-spanning plate with the wrist in slight extension affects the biomechanical stability of the construct. An unstable distal radius fracture was simulated in 10 cadaveric specimens and immobilized with a radiocarpal-spanning plate holding the wrist in a neutral position. This construct was then physiologically loaded through the wrist flexor and extensor tendons. The resulting motion at the fracture was captured with a displacement sensor. The plate was then extended using an in situ bending technique, placing the wrist in extension, and the experiment was repeated. No statistically significant difference in the biomechanical stability afforded by the radiocarpal-spanning plate was detected with the wrist in extension compared to that in the traditional neutral position. The radiocarpal-spanning plate fixation was more stable when loaded through the extensor tendons. We conclude that immobilizing a distal radius fracture with an internal radiocarpal-spanning plate that holds the wrist in extension does not compromise biomechanical stability.

Purpose The management of distal radius fractures differs based on the nature of the fracture and the experience of the surgeon. We hypothesized that patients requiring surgical intervention would undergo different procedures when in the care of a surgeon with subspecialty training in hand surgery as compared with surgeons with no subspecialty training in hand surgery. Methods We queried the ABOS database for case log information submitted for part II of the ABOS examination. Queries for all codes involved with distal radius fracture management were combined with associated codes for the management of median nerve neuropathy, triangular fibrocartilage complex tears, ulnar shaft, and styloid fractures. Hand fellowship trained orthopedic surgeons were compared with those completing other fellowships and non–fellowship trained orthopedic surgeons during their board collection period. Results During the study period, 2,317 orthopedic surgeons reported treatment of 15,433 distal radius fractures. Of these surgeons, 411 had hand fellowship training. On a per surgeon basis, fellowship trained hand surgeons operatively treated more multifragment intra-articular distal radius fractures than their non-hand fellowship trained counterparts (5.3 vs 1.2). Additional procedures associated with the management of distal radius fractures were also associated with the fellowship training of the treating surgeon. Conclusions Among orthopedic surgeons taking part II of the ABOS certifying examination, differences exist in the type, management, and reporting of distal radius fractures among surgeons with different areas of fellowship training. Clinical relevance This study describes the association of hand surgery fellowship training on the choice of intervention for distal radius fractures and associated conditions.

Interactions between melanocytes and neighboring cells in the skin are important in regulating skin color in humans. We recently demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates Wnt signaling. In this study, we tested the hypothesis that dermal fibroblasts regulate the constitutive skin color of individuals ranging from very light to very dark. We used microarray analysis to compare gene expression patterns in fibroblasts derived from lighter skin types compared to darker skin types, with a focus on secreted proteins. We identified a number of genes that differ dramatically in expression and, among the expressed proteins, neuregulin-1, which is secreted by fibroblasts derived from dark skin, effectively increases the pigmentation of melanocytes in tissue culture and in an artificial skin model and regulates their growth, suggesting that it is one of the major factors determining human skin color.

Substantivity of sunscreen formulations is affected by the wash-out rate of ultraviolet-absorber and -reflector compounds in water. Water-resistance of sunscreen formulations is currently determined according to a standardized European Cosmetic Toiletry and Perfumery Association (COLIPA) protocol, encompassing the determination of a minimal erythemal dose before and after a defined immersion step in water. It can be supposed that the higher the wettability of a treated skin area, the higher is the wash-out rate of sunscreen compounds. This present report addresses the validity of determining the wettability of treated skin alone as a measure for the water-resistance of sunscreen products. The report addresses the robustness, accuracy and congruence of a recently developed wettability test, based on the measurement of the contact angle (CA) of a sessile water drop on treated skin areas. Contact angle data of 66 sunscreen formulations are compared with the corresponding results of 81 water-resistance tests, using the sun protection factor (SPF)/immersion/SPF method. Sunscreen products tested by the CA method were applied to the skin of the volar forearm of test subjects at a defined dose and drying-time, using a standardized application and recording device. Contact angles between a sessile water drop and skin were recorded by a Charge-Coupled Device (CCD) camera and subjected to automatic contour analysis. Taking the SPF/immersion/SPF method as gold standard, accuracy parameters of the CA method were determined. By using an appropriate cut-off level of CAs, the CA method has a specificity and positive-predictive value of 100%, and turns out to be a reliable screening method to identify water-resistant formulations. Based on our findings, those formulations that give CAs above 30 degrees may be categorized water-proof without further testing by the COLIPA water-resistance method.

A portable surface plasmon resonance (SPR) biosensor system was designed for deployment in a surrogate unmanned aerial vehicle (UAV). The nose of the aircraft was fitted with two nozzles for release of analytes during flight. Ovalbumin and horseradish peroxidase were chosen as simulants for airborne toxic proteins. The two protein analytes were released sequentially from the nozzles as aerosols with low concentrations of analytes during the ground test and each of three flights. A two-stage collector accumulated the sample prior to de-aeration and monitoring by the SPR system. An automated liquid handling unit directed buffer, sample, amplification and regeneration solutions to the sensor and metered the flow rate. Following detection of analyte, secondary antibodies were pumped through the sensor to both amplify and verify analyte detection, thus avoiding false positive detection and at the same time achieving higher sensitivity with the system. Analyte concentrations varied from 1 to 10 nM and the altitude at which the detection was performed varied from 1800 to 10,000 feet. All analyte releases during the three flights were successfully detected and verified. Flight parameters, such as airspeed, altitude, position and meteorological conditions, data necessary for UAV applications, were automatically recorded. The aircraft flight path obtained by GPS was temporally aligned with the SPR detection signal, allowing mapping of the geographical distribution of analyte release. The results reported here illustrate the usefulness of the portable aircraft-mounted SPR system for detection of airborne analytes.

Epigenomic changes are commonly observed in cancer. We developed a next-generation sequencing (NGS) assay which can identify subtle changes in global methylation as well as copy number alterations (CNAs). The assay measures the methylation level of some repeat elements, covering over 25% of all CpG in the genome. Genomic DNA extracted from 18 pairs of matched colorectal tumor to normal tissue was tested (four adenocarcinomas, including one associated with inflammatory bowel disease, and fourteen adenomas, including one adenoma from a Lynch syndrome patient, one familial adenomatous polyposis (FAP) and two sessile serrated adenomas (SSA)). We also assayed organoids established from these tissues at early (2 month) and late (more than 6 months) timepoints in culture. Briefly, bisulfite conversion and enrichment of the repeats was performed. The Illumina compatible products were sequenced on a HiSEQ 2500. Analysis was performed using Bismark (Krueger F., Babraham institute) and Nexus copy number (BioDiscovery) to determine the global methylation and the CNAs, respectively. Finally, somatic and germline variants were determined by targeted sequencing of 71 genes using the QIAseq colorectal cancer panel (QIAGEN). Our data showed that all adenocarcinoma presented hypomethylation and CNAs as well as multiple somatic variants in APC, KRAS, TP53, SMAD4 and PIK3CA. Six out of the fourteen adenomas presented CNAs and nine showed hypomethylation. The most frequently observed copy number gain affected the chromosomes 8q and 13. Eight adenomas presenting somatic mutations in APC also exhibited distinct global hypomethylation. Previous publications have reported that mutations in APC precede global hypomethylation. Interestingly, one adenoma showed significant hypomethylation but no detectable CNAs or APC mutations. The two SSA samples showed the characteristic BRAF V600E mutations and the FAP sample presented germline mutation in APC. The FAP and the SSA samples did not show hypomethylation or CNAs. Most organoids presented CNAs and somatic mutations similar to their matched tissue even after 2 years in culture. However, few organoids developed new CNAs and somatic variants. Monitoring the changes in organoid may provide important information on tumor progression. This assay measured CNAs and methylation in colorectal cancer samples, findings which may assist in determining the status of the disease and provide guidance to the appropriate action. Our NGS assay interrogates a significant portion of the genome leading to a more accurate and sensitive evaluation of the state of these cancer cells. Note: This abstract was not presented at the meeting. Citation Format: Julie C. Laliberte, Michael K. Dame, Durga Attili, Bodrul Islam, Kevin Kim, Jessica Zhang, Erica L. Katz, Gina M. Newsome, Priya H. Dedhia, Adele Kruger, Tobias Mann, Tom Goodman, Jeffrey Buis, Dean E. Brenner, James Varani, Jason R. Spence, Justin A. Colacino, Jay Stoerker. Simultaneous measurement of global methylation and copy number alterations in human colorectal cancer samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-093. doi:10.1158/1538-7445.AM2017-LB-093

Studies on patients with degenerative joint disease of the hip show that femoral periprosthetic bone mineral decreases following total hip arthroplasty. Scarcely any osteodensitometric data exist on femoral neck fracture (FNF) patients and periprosthetic bone remodelling. In two parallel cohorts we enrolled 87 patients (mean age, 72 ± 12 years; male:female ratio, 30:57) undergoing total hip arthroplasty for either primary osteoarthritis (OA) of the hip (n = 37) or for an acute FNF (n = 50) and followed them for a mean of 5.4 years. Outcomes were bone mineral density (BMD) changes in the periprosthetic Gruen zones 1-7, the incidence of periprosthetic fractures and clinical outcome. The bone mineral loss in the fracture group was more than twice that of the osteoarthritis group, -16.9% versus -6.8% (p = 0.004). The incidence of periprosthetic fractures was 12% (6/50) in the fracture cohort compared with none (0%) in the OA cohort (p = 0.03). Periprosthetic bone mineral loss following total hip arthroplasty is significantly greater in patients who are treated for acute FNF than in OA patients. This decrease of BMD follows a different pattern with the FNF patients losing larger proportions of bone in Gruen zones 1, 2, 6, and 7 while the OA patients tend to have larger losses only in zones 1 and 7.

The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10(-5) cm/h, licorice: 4.68·10(-6) cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10(-5) cm/h, licorice: 24.0·10(-6) cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered.

Primary glenohumeral osteoarthritis is a common indication for shoulder arthroplasty. Historically, both total shoulder arthroplasty (TSA) and hemi-shoulder arthroplasty (HSA) have been used to treat primary glenohumeral osteoarthritis. The choice between procedures is a topic of debate, with HSA proponents arguing that it is less invasive, faster, less expensive, and technically less demanding, with quality of life outcomes equivalent to those of TSA. More recent evidence suggests TSA is superior in terms of pain relief, function, ROM, strength, and patient satisfaction. We therefore investigated the practice of recently graduated orthopaedic surgeons pertaining to the surgical treatment of this disease.We hypothesized that (1) recently graduated, board eligible, orthopaedic surgeons with fellowship training in shoulder surgery are more likely to perform TSA than surgeons without this training; (2) younger patients are more likely to receive HSA than TSA; (3) patient sex affects the choice of surgery; (4) US geographic region affects practice patterns; and (5) complication rates for HSA and TSA are not different.We queried the American Board of Orthopaedic Surgery's database to identify practice patterns of orthopaedic surgeons taking their board examination. We identified 771 patients with primary glenohumeral osteoarthritis treated with TSA or HSA from 2006 to 2011. The rates of TSA and HSA were compared based on the treating surgeon's fellowship training, patient age and sex, US geographic region, and reported surgical complications.Surgeons with fellowship training in shoulder surgery were more likely (86% versus 72%; OR 2.32; 95% CI, 1.56-3.45, p0.001) than surgeons without this training to perform TSA rather than HSA. The mean age for patients receiving HSA was not different from that for patients receiving TSA (66 versus 68, years, p=0.057). Men were more likely to receive HSA than TSA when compared to women (RR 1.54; 95% CI, 1.19-2.00, p=0.0012). The proportions of TSA and HSA were similar regardless of US geographic region (Midwest HSA 21%, TSA 79%; Northeast HSA 25%, TSA 75%; Northwest HSA 16%, TSA 84%; South HSA 27%, TSA 73%; Southeast HSA 24%, TSA 76%; Southwest HSA 23%, TSA 77%; overall p=0.708). The overall complication rates were not different with the numbers available: 8.4% (15/179) for HSA and 8.1% (48/592) for TSA (p=0.7555).The findings of this study are at odds with the recommendations in the current clinical practice guidelines for the treatment of glenohumeral osteoarthritis published by the American Academy of Orthopaedic Surgeons. These guidelines favor using TSA over HSA in the treatment of shoulder arthritis. Further investigation is needed to clarify if these practice patterns are isolated to recently graduated board eligible orthopaedic surgeons or if the use of HSA continues with orthopaedic surgeons applying for recertification.Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

The science return from future robotic exploration of the Martian surface can be enhanced by performing routine processing using onboard computers. This can be accomplished by using software that recognizes scientifically relevant surface features from imaging and other data and prioritizes the data for return transmission to Earth. Two algorithms have been designed and evaluated with field data to identify the properties of the environment that can be reliably detected with onboard imaging and multispectral observation. One algorithm identifies variations in surface textures in images and successfully distinguishes between rocks and soil and between differences in grain size in a rock of a single composition. A second algorithm utilizes a neural net to recognize selected carbonate minerals from spectral reflectance data and successfully identifies carbonates from a set of spectra collected in the field. These types of algorithms will contribute to the efficiency of a landed instrument suite given the limited resources of time, data storage, and available communications opportunities.

URRENT OPINION atients are often advised to avoid blood pressure meaurements or blood draws after axillary lymph node issection or axillary radiation treatment for breast caner. The idea is that even patients who do not develop ymphedema during the immediate post-treatment peiod are at risk for developing so-called “late onset” ymphedema years and even decades after treatment. here is essentially a taboo against even minor proceures on the arm, and this can be an emotional issue for ome patients. Among hand surgeons, it is generally elieved that elective hand surgery—including tourniuet use—is safe in patients who have had a lymph ode dissection but do not have lymphedema. This is an ntriguing divide that merits examination.

Synopsis The sun protection factor (SPF) of two products, one with an expected SPF of 4 and another with an expected SPF of 15 were determined, using two solar simulators: Multiport Solar UV Simulator (xenon, Solar Light, Philadelphia, PA, USA), and Supersun 5000 (metal halide, Mutzhas, Munich, Germany). The mean SPFs using the Multiport were: 4.8 for the low SPF product and 19.4 for the high SPF one. The results using the Supersun were lower: 2.6 for the low SPF product and 7.2 for the high SPF one. Relative emission spectra of the two sources were recorded using a fluorescence spectrophotometer in bioluminescence mode. Efficacy spectra were calculated and compared with the corresponding spectrum of natural sunlight. It was evident that the spectral power of the xenon source is too high in the UVB, leading to overestimation of SPFs, whereas the Supersun irradiator emits too much in the UVA, resulting in too low SPFs. Heat effects and photodegradation of UV filters are discussed as further possible reasons for the discrepancies between the experimentally determined SPFs. Our results confirm a recent publication about theoretical SPFs, calculated with emission spectra of a xenon source and spectra of the sun at different elevation angles, where the authors provide evidence that in natural sunlight the contribution of UVA to total UV radiation is twice as high as in a xenon source. This may contribute to an understanding of why sunscreens tested according to the FDA method (xenon sources) often yield higher SPFs than those obtained from European testing procedures. Resume L'indice de protection solaire (IPS) de deux produits, l'un ayant un indice attendu de 4 et l'autre de 15, a eteetudie a l'aide de deux simulateurs: Simulateur Multiport Solar UV (xenon, Solar Light, Pennsylvania. USA) et Supersun 5000 (halogenure metallique, Mutzhas, Munich, Allemagne). Pour le Multiport, la moyenne des indices obtenus est: IPS 4.8 pour le produit de moindre protection et IPS 19.4 pour le produit hautement protecteur. Les resultats obtenus avec le Supersun son plus bas: IPS 2.6 pour le produit de moindre protection et IPS 7.2 pour le produit hautement protecteur. Les spectres d'emission relatifs des deux sources ont ete mesures par un spectrophotometre a fluorescence, en mode bioluminescence. Les spectres d'efficacite ont ete calcules et compares avec le spectre correspondant de la lumiere solaire naturelle. Il est apparu evident que la puissance spectrale de la source au xenon est trop forte dans les UVB, entrainant une sur-estimation de l'IPS, alors que le simulateur Supersun emet trop dans les UVA. entrainant une sous-estimation de l'IPS. Les effets de la chaleur et de la photodegradation des filtres UV sont commentes comme explications possibles de la divergence entre les IPS mesures experimentalement. Nos resultats confirment une publication recente sur les IPS theoriques, calcules avec le spectre emis par une source au xenon et le spectre solaire sous differents angles d'elevation, ou les auteurs prouvent que dans la lumiere solaire la part des UVA dans les UV totaux est deux fois plus elevee qu'avec une source au xenon. Ceci pourrait expliquer pourquoi les ecrans solaires testes selon le protocole de la FDA (source au xenon) ont souvent des IPS plus eleves que ceux testes selon les normes Europeennes.

A key determinant of overall morphogenesis in flowering plants such as Arabidopsis thaliana is the shoot apical meristem (growing tip of a shoot). Gene regulation networks can be used to model this system. We exhibit a very preliminary two-dimensional model including gene regulation and intercellular signaling, but omitting cell division and dynamical geometry. The model can be trained to have three stable regions of gene expression corresponding to the central zone, peripheral zone, and rib meristem. We also discuss a space-engineering motivation for studying and controlling the morphogenesis of plants using such computational models.

Aim The dominant and varied influences of HLA polymorphism on the incidence of disease and its treatment necessitate determination of complete, accurate sequences of entire HLA haplotypes, encompassing all HLA class I and II genes and representing human populations worldwide. Methods To this end we developed a high-throughput and versatile method to sequence complete 4.8Mb HLA haplotypes from genomic DNA. Oligonucleotide probes were designed to capture genomic DNA fragments originating from the targeted HLA region. The fragments obtained by this selection were sequenced to high depth (>500x) and haplotype coverage (>99%) using Illumina paired-end technology. Results In the process of validating this new method on the HLA haplotypes studied with conventional techniques by the MHC Haplotype Consortium, the sequences of all eight haplotypes were completed. The method was then applied to the haplotypes of 96 additional HLA-homozygous IHWC cells, which defined the location and structure of the genomic block containing the enigmatic HLA-Y pseudogene. Informing this work were the coordinates of homozygous tracts defined by high-resolution genome-wide SNP array (Omni1Quad). This analysis, which examined 13,000 SNPs in the HLA region, also estimated the size and location of further structural variants that track with particular HLA class I and II alleles. Haplotype assembly, phasing and annotation all required new methods that were tailored specifically to the data-collection methods and the unusual properties of the HLA genomic region. New statistical methods are being developed to incorporate the scale and complexity of the haplotype sequence data to the analysis of disease-associations. Currently under study is a panel of family trios representing West-African HLA diversity. Conclusions In summary, these data mark significant progress towards understanding the evolution of HLA haplotypes, their co-evolution with infectious diseases, and their contribution to autoimmune disease and disordered pregnancy.

The problem addressed in this paper is that of clustering image pixels into regions of homogenous geological texture. Future rovers on Mars will need to be able to intelligently select data collection targets. One goal of intelligent data selection for maximizing scientific return is to sample all distinct types of rocks that may be encountered. Different rock types often have a characteristic visual texture, thus visual texture is rich source of information for separating rocks into different types. Recent work on using texture to segment images has been very successful on images with homogenous textures such as mosaics of Brodatz textures and some natural scenes. The geologic history of a rock leads to irregular shapes and surface textures. As a result, the textures in our images are not as homogeneous as those in Brodatz mosaics. Our approach is to extract textural information by applying a bank of Gabor filters to the image. The resulting texture vectors are then clustered. Banks of filters constrain the relationships of the filter parameters both within a single filter and between filters. Often researchers have used parameter values that are thought to correspond to the human visual system, however the effects of adjusting these parameters have not been thoroughly studied. We systematically explore tradeoffs in the parameter space of the filter bank and quantify the effects of the takeoffs on the quality of the resulting clusters.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

This paper describes the DATA-CHASER Automated Planner/Scheduler (DCAPS) system for automatically generating low-level command sequences from high-level user goals. DCAPS uses Artificial Intelligence (AI)-based search techniques and an iterative repair framework in which the system selectively resolves conflicts with the resource and temporal constraints of the DATA-CHASER Shuttle payload activities.