Para-Cycling: British Cycling has confirmed the 16-strong squad who will represent Great Britain at the forthcoming Newport Para-cycling International event, taking place from 30 January – 1 February.
The squad includes current track world champions Jody Cundy, Neil Fachie, Sophie Thornhill and Rachel James as well as Steve Bate, Adam Duggleby, Megan Giglia, Sally Hurst and Liz Saul who all make their debut for Great Britain.
The three-day event held at Wales National Velodrome in Newport is in its second year and counts as a qualifying event for track cycling at the Rio Paralympic Games in 2016.
See the British Cycling squad in full.
Short Track Speed Skating: The Great British Short Track Speed Skaters are making final preparations for the third ISU Star Class Cup competition, which will take place at Nottingham's National Ice Centre (NIC) for the first time this weekend (9-11 January).
The international competition will see the UK's best speed skaters compete against top athletes from the rest of Western Europe in the third round of this competition, which has already visited Belgium and Germany.
Amongst the skaters representing Great Britain will be Olympians Elise Christie, Jon Eley and Jack Whelbourne.
Find out more about the competition on the National Ice Skating Association website.
Skeleton: Olympic Champion, Lizzy Yarnold, returns to the fold for the opening World Cup of 2015 which is taking place in Altenberg, Germany, this week.
Yarnold rejoins the squad of Laura Deas, Rose McGrandle, Dominic Parsons and Ed Smith, after she was ruled out of the second world cup race of the season before Christmas which took place in Calgary, Canada.
The 26-year old from Kent was advised to take a break after experiencing dizziness during the penultimate World Cup of 2014 in Lake Placid, USA - an event which she won.
Yarnold though has made a full recovery and is seeking to continue the defence of her overall World Cup title from the 2013/14 season.
Read more on the British Skeleton website.
It was also announced this week that eight athletes have joined the British Skeleton talent squad after successfully coming through the UK Sport, English Institute of Sport and British Skeleton talent search Power2Podium.
Ski and Snowboard: British Ski and Snowboard have announced the team for the FIS Freestyle Ski and Snowboard World Championships, the biggest freestyle event on this year's calendar, taking place from 14 to 25 of January 2015 in Kreischberg, Austria.
National Lottery backed Sochi 2014 Olympians Aimee Fuller, Jamie Nicholls, Billy Morgan, Katie Summerhayes, Rowan Cheshrie, Murray Buchan and James Machon will all be competing, while James Woods will miss the event to compete in the X Games in Aspen.
See the British Ski and Snowboard squad in full.


ABSTRACT: Transcription and pre-mRNA alternative splicing was analyzed by in isogenic human HEK293 cell lines that inducibly express a-amanitin resistant mutants of the RNA polymerase II large subunit with slow and fast elongation rates. Alternative splicing was analyzed by, RNA-seq and RASL-seq of polyA+ RNA from a-amanitin treated cells; transcription elongation rate was analyzed by BrUTP-labelled GRO-seq of a-amanitin treated cells at time points after release from a DRB (5,6-dichloro-1-bold beta-D-ribofuranosylbenzimidazole) block.
Project description:Transcription termination was analyzed by anti RNA pol II ChIP-seq in isogenic human HEK293 cell lines that inducibly express a-amanitin resistant mutants of the RNA polymerase II large subunit with slow and fast elongation rates and in lines that inducbily over-express WT or an active site mutant of the RNA exonuclease "torpedo" Xrn2. Transcription termination zones were mapped by anti-pol II ChIP-seq under conditions where transcription elongation rate was increased or decreased by point mutations in the large subunit of the enzyme. Termination was also assayed under conditions where Xrn2 exonuclease activity was inhibited by over-expression of an active site mutant (D235A).
Project description:RBM10 is an RNA binding protein that was identified as a component of spliceosome complex, suggesting its potential role in splicing regulation. However, the direct experimental evidence for this function has been lacking. Here we characterized in vivo RBM10-RNA interactions and investigated the role of RBM10 in splicing regulation at the global level. We observed significant RBM10-RNA interactions in the vicinity of splice sites and identified hundreds of splicing changes following perturbation of cellular RBM10 abundance. A RNA splicing map integrating the binding pattern and splicing profiles revealed a significant correlation between RBM10-enhanced exon skipping events and its binding close to the splicing sites of both upstream and downstream introns. Furthermore, we demonstrated the splicing defects in a patient carrying a RBM10 mutation. Overall, our data provided insights into the mechanistic model of RBM10-mediated splicing regulation and established genomic resources for future studies on its function in different pathophysiological contexts. We sequenced the mRNA of HEK293 cells and LCL cells, and we determined the RBM10 binding sites using PARCLIP in HEK293 cells. In total we sequenced four mRNA-Seq libraries for KD and two for OE in HEK293 cells; for each of these libraries, we also sequenced one control library. We also sequenced the mRNA of one patient LCL and two normal LCL libraries. Two replicates of PARCLIP sequencing were perfomed.
Project description:The rate of RNA polymerase II (pol II) elongation can influence splice site selection in nascent transcripts, yet the extent and physiological relevance of this kinetic coupling between transcription and alternative splicing is not well understood. We performed experiments to perturb pol II elongation and then globally compared alternative splicing patterns with genome-wide pol II occupancy. RNA binding and RNA processing functions were significantly enriched among the genes with pol II elongation inhibition-dependent changes in alternative splicing. Under conditions that interfere with pol II elongation, including cell stress, increased pol II occupancy was detected in the intronic regions flanking the alternative exons in these genes, and these exons generally became more included. A disproportionately high fraction of these exons introduced premature termination codons that elicited nonsense-mediated mRNA decay (NMD), thereby further reducing transcript levels. Our results provide evidence that kinetic coupling between transcription, alternative splicing and NMD affords a rapid mechanism by which cells can respond to changes in growth conditions, including cell stress, to coordinate the levels of RNA processing factors with mRNA levels. To monitor pol II distributions, chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) was performed using an anti-pol II antibody (4H8) and cross-linked chromatin preparations from Jurkat cells, treated with or without pol II elongation inhibitor 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole (DRB) at 10 and 25 ug/ml respectively prior to phorbol 12-myristate 13-acetate (PMA) stimulation, for 5000+ alternative splicing events.
Project description:Transcription and pre-mRNA alternative splicing was analyzed by in isogenic human HEK293 cell lines that inducibly express a-amanitin resistant mutants of the RNA polymerase II large subunit with slow and fast elongation rates. Overall design: Alternative splicing was analyzed by, RNA-seq and RASL-seq of polyA+ RNA from a-amanitin treated cells; transcription elongation rate was analyzed by BrUTP-labelled GRO-seq of a-amanitin treated cells at time points after release from a DRB (5,6-dichloro-1-bold beta-D-ribofuranosylbenzimidazole) block.
Project description:HEK293T cells were transfected with the Rbp1-amr or slow (R729H-amr) α-amanitin resistant subunit of RNA Pol II and selected with α-amanitin 24 hours after transfection for additional 24 hours. Total RNA was extracted and global changes in gene expression were determined using microarray chips. MiRNAs are transcribed by RNA pol II but the transcriptional features influencing their synthesis are poorly defined. Here we report that a TATA-box in miRNA and a subset of protein-coding genes is associated with increased sensitivity to a slow rate of transcription elongation. We also show that promoters driven by TATA-box or NF-κB elicit high transcription re-initiation rate, but paradoxically lower levels of miRNA. Interestingly, miRNA synthesis was converted to a more productive mode by decreasing initiation rate, but less productive when the re-initiation rate increased. This phenomenon was found to be associated with a delay in miR-146a induction by NF-κB. We also demonstrate that miRNAs are remarkably strong pause sites. Our findings suggest that lower efficiency of miRNA synthesis directed by the TATA-box or NF-κB is a consequence of frequent transcription initiation that lead to Pol II crowding at pause sites, thereby increasing the chance of collision and premature termination. These findings highlight the importance of the transcription initiation mechanism for miRNA synthesis, and have implications for TATA-box promoters in general. HEK293T cells were transfected with plasmids directing the expression of α-amanitin-resistant variants of Pol II (Rpb1-amr and R749H-amr). α-amanitin was added and RNA was prepared 24 and 48 h later, respectively. The data provided is from 3 Rpb1-amr vs 3 R749H-amr (6 samples).
Project description:Xenopus laevis embryos were injected with alpha-amanitin to inhibit RNA polymerase II activity. Embryos were allowed to develop up to stage 10.5 (early gastrula, control and alpha-amanitin injected embryos) and subsequently collected for RNA isolation. The transcriptome profiles of alpha-amanitin injected and control embryos were compared.


What is New in Fungal Pharmacotherapeutics?
Krazy Kodachromes Series updated regularly - Approach image questions on exams and practice with hours of discourse and differentials with GW School of Medicine faculty.
Watch the video at DermInReview.com.
Explore valuable career development resources for New Practitioners and Residents. Visit NextStepsinDerm.com.
Individuals with skin of color are a rapidly growing portion of the cosmetic procedures market. There are unique challenges to treating skin conditions in skin of color patients. This article and roundtable discussion focus on the use of energy-based modalities, particularly a 650-microsecond 1064nm laser that delivers energy in a collimated beam. Alone or in combination with other therapies, the 650-microsecond 1064nm laser has been used successfully to treat melasma, acne, postinflammatory hyperpigmentation, pseudofolliculitis barbae, hair removal, acne keloidalis nuchae, and aging skin in skin of color.
Topical delivery of therapeutic agents for skin diseases is a major advantage in dermatology. However, the efficacy and tolerability of topically applied therapies is dependent on several characteristics, including percutaneous penetration and permeation of active ingredient and lack of side effects, especially local tolerability reactions. Importantly, the ultimate performance of a topical product includes collectively the effects of the active ingredient and the impact that specific additives have on vehicle characteristics, such as penetration, permeation, epidermal barrier properties, relative irritancy, allergenicity potential, and patient acceptance/preference of the vehicle formulation used. Foam vehicles have evolved over time with the emergence of a menu of alcohol-based and aqueous-based variations that provide various advantages depending on clinical circumstances and the disease being treated. Aqueous-based foams have gained widespread acceptance and preference, especially due to favorable skin tolerability and the cosmetic elegance of the products. In this manuscript, data are presented supporting the efficacy, tolerability, and safety, of specific aqueous-based foam vehicles for calcipotriene used to treat plaque psoriasis, and for tazarotene used to treat acne vulgaris. Discussions include both vehicle-based properties that are relevant to clinical practice, and outcomes from the large-scale pivotal clinical trials that review efficacy and safety results and patient reported outcomes. The latter also discusses several practical subject assessments about use of the foam vehicle.
Atopic dermatitis affects up to 20% of children and continues to increase in prevalence. Effective disease control is aimed at decreasing symptoms and reducing the frequency of flares, which may be complicated by secondary bacterial infections. Although recent advances have produced a number of non-systemic treatment options, topical corticosteroids remain a fundamental component of treatment algorithms.
This supplement summarize recent advances in the scientific understanding of acne pathogenesis as it relates to effective treatment acne in patients of all skin types and describes the role of retinoids in the management of acne and effective treatment and prevention strategies for hypertrophic and atrophic acne scarring in all skin types.
Research into the immunopathological mechanisms of plaque psoriasis has produced increasingly targeted biologic therapies. The specificity of these agents allows for high rates of efficacy and decreased adverse events, most notably reduced immune system suppression. In recent years, the recognition of interleukin (IL)-17 as an important component in the pathogenesis of psoriasis has led to the development of a new class of biologics.
As specialists in the treatment of the skin, hair, and nails, we know what tools we need to accurately and efficiently diagnose and treat our patients. Therefore, we must take the time to understand the complexities of the new regulations for drug compounding, recognize the differences between legal and illegal compounding so that we can fight to preserve the appropriate and safe patient care and stop the illegal compounding. If we do not fight the fight ourselves then someone else will do it for us, which will not be the best outcome as we have seen in the past. As importantly, we must then respond to regulatory concerns with a reasonable argument to protect our practices. We must advocate for ourselves and for our patients to protect access. No one else has a vested interest in protecting our access to compounding.
Acne vulgaris (AV) is one of the most common diseases that we encounter in our clinics every day. Yet, despite the dermatology community's perceived familiarity with acne vulgaris, it is worthwhile to note that we continue to learn more and more about the epidemiology and the pathogenesis of AV as well as novel therapeutic options. Patients with acne desire clearance. Dermatology providers today have more options than ever to tailor treatment to each patient's needs, in light of current best evidence regarding the pathogenesis and treatment of the disease. While no new chemical entities for topical delivery have revolutionized our approach to acne management, ongoing evolution in topical vehicle formulation is optimizing therapeutic benefit and the patient experience, leading to better clinical outcomes.
As our understanding of the microenvironment of the hair follicle deepens, it is becoming increasingly clear that targeting a single pathway in this complex system is not ideal. Androgens, cortisol, and corticotropin-releasing hormone, all of which are not in balance in hair loss due to internal and external stress, and gene expression of pro-inflammatory mediators all affect the hair follicle to suppress "normal" function and negatively influence hair growth.
There is compelling evidence that Infrared A (IRA) from natural sunlight contributes to photoaging of human skin by inducing the expression of matrix metalloproteinase-1 (MMP-1) expression in human dermal fibroblasts. Corresponding mechanistic studies have shown that IRA does so by increasing the production of reactive oxygen species in irradiated cells. In the present study, we therefore asked if treatment of primary human skin fibroblasts with a blueberry-derived antioxidant matrix (BerrimatrixTM), which is employed as an active ingredient in commercially available skin care products that are topically applied, can prevent IRA-induced MMP-1 expression in these cells. In this in vitro study, we have found that this antioxidant containing matrix is well tolerated by fibroblast over a broad concentration range and that it efficiently prevents IRA-induced MMP-1 mRNA expression. It may thus be speculated that topical application of this antioxidant containing matrix may be efficient in protecting human skin against IRA-induced wrinkle formation.
At the Annual Meeting of the American Academy of Dermatology in 2016, I directed the symposium entitled 'Aging Gracefully' for the second time. The symposium's primary learning objective was to give the audience a framework for managing aesthetic patients. In the last decade, there has been a significant increase in the options for and availability of noninvasive and minimally invasive rejuvenation. With that has been an associated surge in interest by physicians and patients. And, as the number of procedures across the globe increases, so too do the number of aesthetically poor outcomes. Most come from practitioners doing paint-by-numbers treatment. As experts in skin biology and treatment, dermatologists should practice the highest-level cosmetic as well as general dermatology. The faculty presented information to aid practitioners how best to approach patients and formulate a cosmetic plan. The faculty discussed important considerations based on patient gender, age, and skin type. Updated information on the science of cosmeceuticals and the benefits of early noninvasive intervention was presented as were next generation devices and alternatives to standard therapies. The faculty have kindly condensed their AAD presentations for this supplement. I thank L'Oréal and the Journal of Drugs in Dermatology for giving us the opportunity to present this information to a wider audience in this e-supplement.
The limitations of photoprotection modalities have been the inability to arrest the progression of photodamage. Chemoprevention strategies involving a sunscreen has been incomplete because of the need to induce sustained repair of mutations and slow carcinogenesis. Photolyases, or photoreactivation enzymes, serve the role of repairing mutations and damage to DNA induced by ultraviolet (UV) radiation and therefore influence the initiation phases of carcinogenesis. As these enzymes are absent in humans, exogenous forms have been manufactured and are now utilized in topical agents to supplement and augment the innate repair mechanisms that are mostly inefficient.
J Drugs Dermatol. 2017;16(5 Suppl):61-66.
Herpes labialis remains a common worldwide affliction. Recent advances in understanding the basic pathogenesis have led to new therapeutic intervention, both on-label and off-label. Aside from reducing the duration and symptomatology of acute outbreaks, another goal of treatment is to decrease the frequency of future episodes. Oral and topical acyclovir and its analogues are the mainstay of both chronic suppressive and episodic therapy. A new muco-adhesive formulation of acyclovir provides a decrease in outbreaks, probably due to a diminution of herpesvirus load in all reservoir sites. Acyclovir-resistant strains are rare in immunocompetent hosts; parenteral foscarnet and cidofovir are administered in this situation. Parenteral acyclovir is the drug of choice for eczema herpeticum, which may begin as herpes labialis in an atopic dermatitis patient. Thermotherapy may be beneficial, and a certified device to deliver heat is available outside the United States.
J Drugs Dermatol. 2017;16(3 Suppl):s49-53.
Nitric oxide (NO) is a diatomic gas that is synthesized within and released by multiple host cell types functioning to provide a variety of physiologic and homeostatic effects. Nitric oxide exhibits a variety of effects that relate significantly with outcomes that can provide therapeutic benefit if properly formulated and released. These include anti-inflammatory, immunomodulatory, antimicrobial, vasodilatory properties, and effects that are beneficial to wound healing. Lack of antibiotic resistance appears to be one major advantage of topically delivered NO. A specific topical formulation of NO has been developed that has been shown thus far in clinical studies to exhibit favorable efficacy and safety. This article provides a thorough review of the biologic effects of NO, discusses modes of action and potential pharmacologic benefits, and reviews currently available clinical data for acne.
As the rst point of contact with a potentially drying external environment, the primary function of the stratum corneum (SC) is to limit evaporative water loss from the aqueous interior. Yet this is just one of many functionalities conferred by this unique barrier, also protecting against mechanical insults, the assault of foreign chemicals, and microorganisms, and even serving as the rst inherent defense against ultraviolet radiation. Beyond barrier function, the stratum corneum acts as a biosensor, reacting to and mobilizing as a result of both external and internal changes in order to maintain homeostasis and ultimately wear its multiple aforementioned hats. Since the stratum corneum is so profoundly responsible for maintaining healthy skin, there has been signi cant motivation to bet- ter understand the mechanisms through which it protects the viable epidermis from offending agents, as well as elucidate the way in which the SC ensures adequate hydration in order to enable proper epidermal enzyme function and tactile perception. Much of our understanding of the stratum corneum's functional structure is derived from various disease states in which key SC elements are dysfunctional or absent, thereby providing the impetus for utilizing said components or derivations thereof in a wide range of products. In the article by Lee and Friedman, the biology of the stratum is reviewed to provide the framework for translational thera- peutic indications.To better appreciate the impact of primary skin disease on barrier stability and functionalities and what strategies to consider, Jordan and Baldwin identify speci c alterations in the stratum corneum in the setting of Acne Vulgaris, both inherent and iatrogenic resulting from use of therapeutics targeting said skin disease. Lastly, Schwartz and Friedman breakdown the various categories and ingredients used in moisturizers and barrier repair devices with the epidermal biology in mind to help the reader identify which elements are important for maximum impact. Targeted and personalized therapies don't just have to be small molecule inhibitors and biologics – selecting even over the counter products based on their biologically relevant ingredients ts this popular and modern approach. Herein this supplement, we provide the tools to join the club.
The purpose of this supplement is to provide both the biological basis and clinical impact of several targeted products aimed at specific physiologic and pathologic states including aging skin, diaper dermatitis, occupational irritant dermatitis, and atopic dermatitis.
Similar to how the chronic wound healing process requires wound bed preparation before therapeutic intervention, treatment of chronic aging of the skin would likely benefit from a "skin bed preparation" to optimize the outcome of rejuvenation procedures and skin maintenance programs. This involves introducing agents that can combat stress-induced oxidation, proteasome dysfunction, and non-enzymatic cross linkages involved in glycation end products, to collectively modulate the damaged extracellular matrix, and upregulate neocollagenesis and elastin production.
This supplement explores the microbiology of topical antifungal drugs, the science behind vehicle formulations and delivery systems, and the data on topical treatment efficacy. Armed with this knowledge, clinicians can more effectively target superficial cutaneous fungal infections and ultimately increasing their patients' quality of life.
Acne vulgaris is a chronic inflammatory cutaneous disease and is the most common skin disease in the United States, affecting 80% of the population at some point in their lifespan. Because the pathogenesis of acne is not fully understood, it is imperative that the dermatology healthcare practitioner expand their medical knowledge on the current understanding of the development of this condition so that effective treatment strategies may be explored and initiated with confidence. There is need for dermatologists to expand their knowledge of the rationale for combination therapy for the treatment of inflammatory acne, and to understand the efficacy of fixed dose combinations in the reduction of inflammatory and non-inflammatory acne lesions and acne severity and the reduction in skin irritation and dryness.
Skin aging is a combination of multifactorial mechanisms that are not fully understood. Intrinsic and extrinsic factors modulate skin aging, activating distinctive processes that share similar molecular pathways. One of the main characteristics of youthful skin is its large capacity to retain water, and this decreases significantly as we age. A key molecule involved in maintaining skin hydration is hyaluronic acid (HA). Concentration of HA in the skin is determined by the complex balance between its synthesis, deposition, association with cellular structures, and degradation. HA bio-equivalency and bio-compatibility have been fundamental in keeping this macromolecule as the favorite of the skincare industry for decades. Scientific evidence now shows that topically applied HA is unable to penetrate the skin and is rapidly degraded on the skin surface.
Dermatophyte infections of the skin and nails are increasing, with up to 25% of the worldwide population affected; and they account for approximately 10% to 20% of all visits to the dermatology office in the United States. Increased awareness of the clinical impact of these infections is essential because, if left untreated, they can predispose patients to superinfections and potentially serious medical complications. Onychomycosis in particular constitutes an important public health problem because of its high prevalence and associated morbidity.
New antifungal medicines on the market include topical drugs such as luliconazole, naftifine, efinaconazole, and tavaborole. This CME supplement translates a plethora of recent data on efficacy, ease of use, and safety data for each drug into dermatologists' real world practices to help them optimize clinical outcomes in the treatment of onychomycosis, tinea corporis, tinea cruris, and tinea pedis.
However, proper drug selection is only one part of achieving a successful clinical outcome. This supplement also explains the patient education needed to avoid primary treatment failure, recurrence, or spread to other body parts or close contacts.
In the United States alone, 50% of women suffer from hair loss at some point in their lives and 50% of men experience hair loss before the age of 50. In addition to aesthetic concerns, alopecia and thinning hair have adverse psychological effects, such as low self-esteem and poor self-confidence.
Identifying the causes of alopecia and thinning hair has proven especially complex in women. Current treatment options include topical formulations, prescription medications, oral supplements, and costly hair transplants; but they all have drawbacks, such that a novel therapy is needed.
This supplement presents a summary of clinical studies that have demonstrated the welcome safety and efficacy of the nutraceutical Viviscal® (Lifes2good, Inc., Chicago, IL), which contains a proprietary blend of proteins, lipids, and glycosaminoglycans of marine origin that provide essential nutrients for stimulating existing hair growth and reducing hair shedding. The summary is followed by a lively panel discussion on hair loss and current therapies amongst experts in dermatology and plastic surgery: Vivian Bucay MD (San Antonio, TX), Wendy Roberts MD (Palm Springs, CA), Heidi Waldorf MD (New York, NY), and Steven Dayan MD (Chicago, IL).
A recent and growing body of evidence now indicates that, along with ultraviolet (UV) light, both infrared (IR) and visible light from solar radiation may also contribute to extrinsic skin aging.
Currently, sunscreens play an important role in maintaining the health of the skin by providing "broad spectrum" protection against the harmful effects of UV radiation. However, this does not protect human skin from 94.2% of solar radiation (comprised of visible and IR lights), and nor does it prevent heat accumulation damage. Thus, none of the commercially-available sunscreens is able to block 100% of UV radiation.
Inspired by the need to provide patients with a more comprehensive solar protection, SkinMedica® has created Total Defense + Repair (TD+R), which combines broad spectrum UV protection with a unique blend of antioxidants (SOL-IR Advanced Antioxidant ComplexTM) that provide protection from IR radiation while promoting skin repair. These antioxidants are the product of scientific research and breakthrough technology, providing the next generation of multifunctional skin care products.
Ninety percent of people with rosacea say it lowers their self-esteem and can be accompanied by burning, itching, and stinging; but tolerable, effective therapies are increasingly available due to improved understanding of rosacea's inflammatory mediators and molecular basis.
Since being approved by the FDA over a decade ago, azelaic acid (AzA) 15% gel has boasted a long track-record in efficacy and safety in the topical treatment of papulopustular rosacea (PPR), both as monotherapy and in combination with oral therapy. AzA 15% gel markedly reduced both papulopustular lesions and overall facial erythema in pivotal Phase 3 studies.
This supplement gives the latest information on the pharmacologic properties of AzA that correlate with therapeutic action in rosacea; and explores new horizons related to formulation development, such as an oil-in-water emulsion foam of micronized AzA 15% that is proving to be well-tolerated and effective for patients with moderate to severe PPR.
Impaired epidermal barrier function plays a role in causing inflammatory dermatoses, so skin care regimens are recognized by dermatologists to be critical for efficient barrier function and healthy skin. Acne vulgaris, however, has always presented a challenge when it comes to skin care products, as a delicate balance needs to be struck between maintaining the skin barrier whilst controlling oil and shine.
Cetaphil® DermaControl™ Moisturizer SPF 30 (Galderma Laboratories, L.P., Fort Worth, Texas) is a new widely available and affordable skin care therapy specifically designed for use by patients with acne-prone skin and acne-affected skin. Its state-of-the-art psuedoceramide technology helps maintain barrier function without adding excessive surface greasiness, which leads to better compliance and fewer side effects; and it also provides protection against ultraviolet radiation.
Topical corticosteroids are used to treat a wide variety of eczematous and inflammatory skin disorders, such as atopic dermatitis. However, as topical products become available as generic formulations, patients often experience problems of increased allergies and irritancy, impairment of the epidermal barrier, and loss of efficacy. This is because although the active ingredient and its potency are the same, the vehicle excipients may differ. Dermatologists therefore report concerns in prescribing these generics to their patients.
Fortunately, Promius Pharma, one of the leaders in this field, has now brought to market a generic formulation of clocortolone pivalate 0.1% that is exactly the same as their original branded product. This has been shown to be effective and well tolerated in the management of several corticosteroid-responsive dermatoses, and is a welcome addition to the treatment armamentarium.
Acne is perhaps the most prevalent skin disease in Western societies, yet dermatologists are now learning that simply "dubbing the medicine on the pimples" is not the way to manage it successfully. Acne is primarily an inflammatory disease, so treatment needs to be aimed not only at eradicating existing lesions but also at preventing long-term scarring and hyperpigmentation by rapidly reducing inflammation.
Moreover, the old-fashioned way of using antibiotics long-term as monotherapy is contributing to the global public health challenge of antibiotic resistance, which requires a new treatment paradigm emphasizing antibiotic stewardship. Antibiotic limiting regimens, including a combination of topic retinoids and benzoyl peroxide, are shown to be effective; and topical probiotics can also play a useful role.
These new understandings of acne pathogenesis, treatment targets (including those in skin of color), and antibiotic stewardship are all discussed in this supplement.
Soft tissue augmentation is an important option in aesthetic enhancement and continues to grow in popularity for a number of reasons, including its minimally invasive nature and ability to directly nullify volume loss associated with facial ageing. Cosmetic agents that replace collagen are effective tools for addressing volume loss, and among these poly-L-lactic acid (PLLA) carries great potential, acting to volumize soft tissue in a gradual, progressive, and predictable manner, and providing natural-looking restoration of lost facial volume.
In the considerable time that has passed since the introduction of PLLA for soft tissue augmentation, methodology and patient selection has improved, leading to far fewer adverse events such as nodules or papules and better patient outcomes. An international group of experts was convened in 2013 to discuss the optimum use of PLLA, and this collective experience and requisite knowledge is described in this supplement.
As one of the most powerful and versatile features of the human face, the eyebrow informs the perception of beauty and plays a critical role in sexual dimorphism, facial recognition, and non-verbal communication. Eyebrow hair also serves many important biologic functions, including sensory transmission and protection from the elements, as well as playing an important role in cosmesis and expression.
New technologies to tighten and resurface the skin, to grow the hair of the eyelashes and eyebrows, to smooth-en and lighten the skin, and to replace volume lost from this area have created opportunities for rejuvenation that were not possible until recently. These include prostaglandin analogues that not only increase the length and width of the eyelashes but also improve the length and girth of eyebrow hair. Use of topical bimatoprost daily resulted in an improvement of eyelashes in 78.1% of subjects after 16 weeks. Using it in conjunction with botulinum toxins, light sources, topical cosmeceuticals, and fillers such as hyaluronic acid has vastly improved physicians' ability to treat the periorbital region.
Dermatophyte infections account for over 4 million physician visits each year in the United States. Moreover, recent analysis of data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for the period from 1995 to 2004 have found that improper treatment of tinea pedis, tinea corporis, and tinea cruris is common and expensive. However, the selection of inappropriate agents is just one impediment to effective care. Therapeutic non-adherence by patients, and especially failure to continue therapy until the infectious organisms are completely eradicated, are additional challenges. Naftifine cream 2% is a topical allylamine antifungal agent for the treatment of superficial dermatomycoses, and this novel topical formulation is a welcome new option. A study of naftifine cream 2% for the treatment of tinea pedis found that 2 weeks of treatment was significantly more effective than vehicle and equivalent to 4 weeks of treatment with naftifine 1% gel. Naftifine 2% cream offers a cosmetically elegant, once-daily topical treatment option for dermatomycoses that may lead to better compliance and better treatment outcome in patients.
Approximately 2.8 million basal cell carcinomas (BCCs) occur in the United States each year, accounting for 80% of all non-melanoma skin cancers. Historically, BCCs that are not surgically resectable or candidates for radiation therapy have had few treatment options. However, the development of vismodegib and its approval by the United States Food and Drug Administration (FDA) for use in patients with locally advanced or metastatic BCC carries with it a renewed sense of hope. Vismodegib is the first oral medication approved by the FDA for adults with metastatic or locally advanced BCCs who are not candidates for surgery or radiation or for BCCs that have recurred after surgery. The overwhelming majority of BCCs are the result of hedgehog pathway activation, and vismodegib inhibits a key regulatory protein in the hedgehog pathway, resulting in response rates of between 30% to 60% for locally advanced and metastatic BCCs.
Natural supplements are currently experiencing a renaissance in dermatology. Although they have been used for centuries, many have been recently validated for various skin conditions by scientific studies. Natural supplements, such as mushroom extracts, are capable of accelerating the skin turnover rate and repairing dermal molecular components that provide structure and elasticity to the skin. Moreover, teas and feverfew have anti-inflammatory, anti-irritant, and antioxidant properties, and their applications include the treatment of sensitive skin, shaving-induced irritation or redness, and photoprotection. Dyschromia is one of the most common dermatological concerns in patients with darker skin, and blinded controlled studies have found that hyperpigmentation can be assuaged by the skin lightening effects of soy, niacinamide, n-acetylglucosamine, licorice extract, arbutin, vitamin c, kojic acid, emblica extract, lignin peroxidase, and glutathione. Blinded controlled studies have also demonstrated that atopic dermatitis can be mitigated by oatmeal, feverfew, chamomile, aloe vera, licorice, and dexpanthenol.
The understanding of acne vulgaris (AV) has evolved with a greater recognition of the sequence of inflammation, especially prelesional inflammation. An important facet of the new paradigm is that a specific follicular pattern of innate inflammation occurs before and during follicular hyperkeratinization. Moreover, this inflammation persists during the resolution of the macular phase after inflammatory lesions flatten toward the end of their life cycle. The current understanding of AV pathogenesis presents novel therapeutic options for patients because the use of benzoyl peroxide and a topical retinoid suppresses several components of acne pathogenesis, including reduced follicular hyperkeratinization, decreased innate inflammation, and dermal matrix degradation.
Onychomycosis is a fungal infection of the nail unit that is caused by a variety of fungi including dermatophytes, nondermatophyte molds, and Candida. Efinaconazole 10% solution is a new topical treatment for onychomycosis that has a broad spectrum of activity against dermatophyte, nondermatophyte, and numerous yeast species. In clinical trials of mild to moderate onychomycosis, mycologic and complete cure rates for efinaconazole are comparable to those seen with oral itraconazole. Efinaconazole may be an important primary medication for those patients for whom effective topical treatment would be ideal, and could also be used in combination with an oral agent, or with adjunct therapies such as lasers and debridement.
The efficacy of Galderma's Cetaphil® and Restoraderm® support the emerging and available data that epidermal barrier function and its repair are a crucial element in treating patients with atopic dermatitis and several other common dermatoses. The Galderma Restoraderm products are novel formulations that support the epidermal barrier by enhancing filaggrin expression, which restores natural moisturizing factors in the skin and helps to rebuild a healthy skin barrier. The Restoraderm products are over-the-counter, widely available, and competitively priced, making them accessible to a large majority of the patient population.
The understanding of acne vulgaris (AV) has evolved with a greater recognition of the sequence of inflammation, especially prelesional inflammation. Propionibacterium acnes is not the primary inducer of acne pathogenesis, but it promotes multiple mechanisms of inflammation that correlate mostly with inflammatory lesions. An important facet of the new paradigm is that a specific follicular pattern of innate inflammation occurs before and during follicular hyperkeratinization. Moreover, this inflammation persists during the resolution of the macular phase after inflammatory lesions flatten toward the end of their life cycle. The current understanding of AV pathogenesis presents novel therapeutic options for patients because the use of benzoyl peroxide and a topical retinoid suppresses several components of acne pathogenesis, including reduced follicular hyperkeratinization, decreased innate inflammation, and dermal matrix degradation.
This is a CME supplement; visit the JDD Medical Education Library to participate in this activity and earn 1 AMA PRA Category 1 Credit.
Over the last 4 decades, topical retinoids have become standard therapy for the treatment of acne vulgaris. Although the market currently encompasses multiple formulations of next-generation topical retinoids, Tazorac is unique among them due to its dual role as a treatment option for both acne vulgaris and psoriasis vulgaris. Tazorac has also demonstrated that it is highly effective for the treatment of acne vulgaris as a monotherapy or in combination with other agents. Recent studies show that Tazorac can be combined effectively with dapsone 5% gel or with a benzoyl-peroxide - containing formulation to augment efficacy. Additionally, Tazorac does not have a generic substitution, so physicians can be assured that their patients will receive exactly what they have been prescribed.
The gold standard for the treatment of abnormal melanin accumulation has long been 4% hydroquinone, but, given the proliferating safety concerns posed by hydroquinone, the search for novel skin brighteners has been ongoing. Several studies have demonstrated that the future for skin brighteners is now, because of the skin brightening efficacy of SkinMedica's Lytera™, a hydroquinone-free skin-brightening complex. Lytera includes a series of formulations that utilize a multi-modal treatment approach, and it is as effective as hydroquinone over the course of 24 weeks for the treatment of facial hyperpigmentation without the concomitant toxicities of the latter.
Clinicians treating corticosteroid-responsive dermatoses, such as eczema and atopic dermatitis, contact dermatitis, seborrheic dermatitis, and psoriasis, have numerous treatment options. The decision to choose a topical corticosteroid depends on several different factors, such as potency, formulation, dosage, cosmetic elegance, cost, etc. Among these, Promius Pharma's Cloderm (clocortolone pivalate cream 0.1%) was introduced into the market more than 3 decades ago, and it remains a versatile treatment option for dermatoses. Phase 3 clinical trial data have demonstrated the efficacy and tolerability of Cloderm in several steroid responsive dermatoses. In studies for eczema and atopic dermatitis, statistically significant improvement relative to placebo was seen at day 4 with Cloderm. In psoriasis trials, Cloderm cream demonstrated superiority to placebo by day 7, continuing at days 14, 21, and 28. Thus, Cloderm's early onset of action will contribute to increased compliance for patients.
FDA regulations require that generic topical steroids match the active ingredients, concentration, and dosage of brand topical steroids, but the generic formulations do not have to match the bioequivalence of branded formulations. Vasoconstrictor assays have found large differences in bioequivalence between generic and trade name topical steroid formulations containing the same steroid in the same concentration in both cream and ointment vehicles. However, Taro Pharmaceuticals desoximetasone 0.05% and desoximetasone 0.25% ointments are a notable exception. Both branded and generic desoximetasone 0.05% and desoximetasone 0.25% ointments are produced by Taro Pharmaceuticals and contain the same excipients in the vehicle. Consequently, physicians do not have to be concerned about differences in therapeutic effectiveness between Taro's generic and brand desoximetasone ointments.
This CME supplement reviews the science behind a select group of natural ingredients in the context of treating cosmetic and medical conditions. Dr. Magdalene A. Dohil discusses the data supporting certain natural ingredients in the treatment of atopic dermatitis and a defective skin barrier. Drs. Whitney P. Bowe and Alan C. Logan address the role of antioxidants in acne vulgaris and aging and discuss biologically active ingredients as they relate to the skin. Finally, Dr. Andrew F. Alexis focuses on skin of color and the use of natural ingredients to aid in the management of hyperpigmentation. After reviewing this publication, practitioners should be in a better position to help their patients discriminate potentially effective over-the-counter products from those that lack any scientific basis for their claims. This is a CME supplement; visit the JDD Medical Education Library to participate in this activity and earn 1 AMA PRA Category 1 Credits.
Part II of this two-part supplement brings together experts from the U.S., France, Germany, and Italy to discuss state-of-the-art soft tissue fillers in a fair-balanced, CME-accredited format. It includes two roundtable discussions: the first, on new and emerging concepts in fillers, provides an overview of commonly used alloplastic filler products and examines how new strategies for soft tissue augmentation are developing as filler options continue to expand; the second discusses the physicochemical properties and potential clinical applications of two new ranges of hyaluronic acid fillers that display enhanced tissue integration after implantation. International case vignettes highlight our current understanding of facial fat compartments, special considerations for skin of color, and the Tower Technique for filler implantation. Finally, consensus recommendations for the use of blunt-tipped microcannulas in injecting soft tissue fillers are presented, as well as quick poll surveys on current hot topics.
This is a CME supplement; visit the JDD Medical Education Library to participate in this activity and earn 2 AMA PRA Category 1 Credits.
This supplement covers practical, real world strategies for customizing acne regimens to the patients' specific needs. Dr. Linda Stein Gold presents information on topical retinoids and antibiotics and discusses the role of benzoyl peroxide. Dr. Joshua Zeichner describes the issues of acne treatment in specific populations, mainly pre-pubertal patients. Dr. Feldman describes the typical ways patients use their treatments and then concrete approaches dermatologists can undertake to enhance patients' adherence behavior.
This supplement to the Journal of Drugs in Dermatology help address various components of psoriasis and comorbidities, as well as hidradenitis suppurativa and biologic treatments. Dr. Kircik and Onumah's article covers psoriasis and its identified comorbidities or chronic proinflammatory disorders driven by similar immunopathologic expression of immune response mechanisms. Dr. Zeichner covers immunologic therapies for treatment of psoriasis-tumor necrosis factor (TNF) inhibitors and interleukin (IL)-12 and IL-23 inhibitors: etanercept, adalimumab, infliximab, golimumab, and ustekinumab. Dr. Zeichner also considers therapeutic management prior to initiating biologic therapy. Lastly, Drs. Elena Sotiriou MD PhD et al from Aristotle University in Thessaloniki, Greece provides perspectives on a prospective clinical trial of efficacy of adalimumab in the treatment of hidradenitis suppurativa. The study demonstrates the significant efficacy of the once weekly regimen, as well as its benefit regarding time to recurrence.
Part I of this two-part supplement brings together experts from the U.S., Europe, Canada, and Israel to discuss the state-of-the-art in soft tissue fillers in a fair-balanced, CME-accredited format. It includes a roundtable discussion on hyaluronic acid (HA) fillers that charts the clinical and scientific path that has led dermatologists from wrinkle-chasing to true volumetry. International case vignettes with commentary highlight a variety of applications for fillers'some currently available in the U.S., and some available elsewhere and on the American horizon. Topics covered include single-product and multi-product volumetry, anatomic and safety considerations, and the use of blunt injection microcannulas. Quick poll surveys provide an engaging snapshot of the faculty's personal approaches, with the first three surveys focusing on the palette of HA fillers.
Emervel: Full-Face Rejuvenation With a Range of Customized Hyaluronic Acid Fillers This supplement to the Journal of Drugs in Dermatology discusses a new range of hyaluronic acid fillers suited for various indications. The authors highlight the key physical properties of this new range of fillers and present results of a multi-center, comprehensive trial in which up to eight indications could be treated simultaneously (including nasolabial folds, marionette lines, periorbital lines, upper lip lines, cheek folds, tear-troughs, lips and cheeks) using this filler range.
As the population of the world shifts to include more patients of skin of color than ever before, learning how to appropriately treat this patient population has become increasingly more important to practicing clinicians. Patients of skin of color face unique challenges when it comes to procedures such as laser hair removal and treatment of conditions such as Pseudofolliculitis Barbae. This body of work seeks to provide dermatologists with unique clinical pearls discussing the use of safe treatment modalities in the skin of color population. From the use of lasers to the effective use of fillers and injectables, this body of work is filled with expert advice for optimizing treatment outcomes and increasing patient satisfaction. Via these clinical pearls, dermatologists can better meet the needs of a changing patient population as well as expand their knowledge base.
This supplement to the Journal of Drugs in Dermatology seeks to advance our knowledge of the structure and function of the stratum corneum. Previously considered a "static" or unremarkable barrier, it has now attained new clinical importance in regards to its role in conditions such as atopic dermatitis and other cutaneous abnormalities. Dr. Brian Berman provides an insightful introduction to articles by Dr. James Q. Del Rosso and Dr. Jacquelyn Levin, as well as by Dr. Paul C. Contard, that discuss the role and relevance of the stratum corneum in today's dermatologic world.
The dermatologic application of natural ingredients in skin care has evolved significantly in the past two decades. Research into the mechanisms and biochemistry of natural ingredients has lead to the development of new technologies and formulations that provide a therapeutic benefit in the treatment of dermatologic conditions and the aging process.
Providing optimal patient outcomes continues to be a challenge in the treatment and management of dermatologic conditions. Most physicians and patients are interested in doing everything possible to optimize the treatment of their skin disease. This is especially important in treating patients with chronic disorders such as eczema, acne, psoriasis, rosacea, photodamage and the negative effects of aging. Physicians and patients often explore the therapeutic benefits of natural ingredients as alternative or complementary treatments to conventional methods. It is important that dermatologists remain up-to-date on the research and new advances in skin care products with natural ingredients.
This is a CME supplement; visit the JDD Medical Education Library to participate in this activity and earn 1 category 1 CME Credit.
Despite the fact that acne is among the most common conditions treated by dermatologists, challenges in managing acne patients are encountered on a daily basis. The articles in this supplement help to address some of those challenges, namely choice of appropriate topical formulations, management of acne in patients with skin of color and appropriate use of oral antibiotics in an age of emerging antibiotic-resistant bacteria.
Acne vulgaris can cause both physical and emotional scarring. Effective treatment requires an understanding of acne pathogenesis and the key elements of keratinocyte differentiation and comedone formation, sebum production, colonization with Propionibacterium acnes (P. acnes) and subsequent inflammation. Addressing issues of compliance is critical for good outcomes, and newer combination therapies help improve adherence to daily therapy.
Natural ingredients have been used traditionally for millennia and their application in topical creams, lotions and preparations within the traditional medicines and healing traditions of many cultures has been observed. Over the last 20 years, clinical and laboratory studies have identified the benefits of an array of natural ingredients for skin care. Consequently, a number of these ingredients and compounds are today being developed, used or considered not only for anti-aging effects, but also for use in dermatologic disorders. Certain ingredients, such as colloidal oatmeal and aloe vera, have been identified as beneficial in the treatment of psoriasis and atopic dermatitis, respectively, due to their anti-inflammatory properties. For combating acne and rosacea, green tea, niacinamide and feverfew are considered efficacious. As to hyperpigmentation and antioxidative capabilities, licorice, green tea, arbutin, soy, acai berry, turmeric and pomegranate are among those plants and compounds found to be most beneficial. Additional research is needed to determine to confirm and elucidate the benefits of these ingredients in the prevention and management of skin disease.
This supplement to the Journal of Drugs in Dermatology is supported by an educational grant from Medicis Pharmaceutical Corporation.
This supplement to the Journal of Drugs in Dermatology is jointly sponsored by the Annenberg Center for Health Sciences at Eisenhower and Signature Business Solution, LLC.This activity is supported by an independent educational grant from Medicis Pharmaceutical Corporation.
This supplement to the Journal of Drugs in Dermatology is supported by Alma Lasers, Candela Corporation, Cynosure, and Syneron.
This activity is supported by an educational donation provided by Astellas Pharma US Inc. and Amgen and Wyeth Pharmaceuticals.
Funding for the supplement provided by Galderma Laboratories, L.P..
This supplement to the Journal of Drugs in Dermatology is sponsored by P&G Beauty & Grooming.
This supplement to the Journal of Drugs in Dermatology was supported by a medical education grant from Johnson & Johnson.
This supplement to the Journal of Drugs in Dermatology was made possible through an educational grant provided by SkinMedica.
This supplement to the Journal of Drugs in Dermatology was made possible through an educational grant provided by Genentech, Inc.
This supplement to the Journal of Drugs in Dermatology was supported by a medical education grant from Cosmetic Bootcamp.
Cosmetic Bootcamp would like to thank the sponsors of the JDD April 2009 supplement issue, "Update on Injectable Facial Rejuvenation," for their dedication and ongoing commitment to core physician education and optimal patient outcomes.
This supplement to the Journal of Drugs in Dermatology was supported by an independent educational grant from Ortho Dermatologics.
This supplement to the Journal of Drugs in Dermatology was supported by an independent educational grant from Galderma.
This supplement to the Journal of Drugs in Dermatology was supported by a medical educational grant from OrthoNeutrogena.
This supplement to the Journal of Drugs in Dermatology was supported by an independent educational grant from Obagi Medical.
This supplement to the Journal of Drugs in Dermatology was supported by a medical education grant from Graceway Pharmaceauticals.
This supplement to the Journal of Drugs in Dermatology was supported by Dermik.
This supplement to the Journal of Drugs in Dermatology was supported by Dusa Pharmacueticals.
This supplement to the Journal of Drugs in Dermatology was supported by Medicis Pharmaceutical Corp..
This supplement to the Journal of Drugs in Dermatology was supported by Dermik Laboratories.
Copyright © 2002-2019 Journal of Drugs in Dermatology. All Rights Reserved.
JDD, a peer-reviewed, MEDLINE®/PubMed® indexed journal, offers the dermatology community strong content of utmost quality and relevance on drugs, devices, and methods.


Too splendid to remain hidden away in Lucca, Italy, this stunning angel is an heirloom investment for generations to come. Peace emanates from the tranquil face and sloping shoulders, while prayerful hands offer a graceful shell. Every detail, from feathered wings to the soft folds of its gown, is skillfully captured in high-quality fiberglass resin and hand-painted in an antique stone finish. Due to an unprecedented agreement with an Italian company that specializes in antique religious statues, this monumental work of art was rescued from obscurity, perfect for any church, serene garden or home gallery 17"Wx17"Dx61"H.


text:
+ NASA Homepage
+ NASA en Español
+ Marte en Español
+ Mars Home
Mars Atlas
Global Views of Mars
Mars Artwork
Craters
Martian Terrain
Return to Martian Terrain index.
(a) E09-00029
High Res GIF (1.0 MB)
(b) E12-02319
(c) M11-01795
Southern Hemisphere Polygonal Patterned Ground
On Earth, periglacial is a term that refers to regions and processes where cold climate contributes to the evolution of landforms and landscapes. Common in periglacial environments on Earth, such as the arctic of northern Canada, Siberia, and Alaska, is a phenomenon called patterned ground. The "patterns" in patterned ground often take the form of large polygons, each bounded by either troughs or ridges made up of rock particles different in size from those seen in the interior of the polygon. On Earth, many polygons in periglacial environments are directly linked to water: they typically form from stresses induced by repeated freezing and thawing of water, contraction from stress induced by changing temperatures, and sorting of rocks brought to the surface along polygon boundaries by the freeze-thaw processes. Although not exclusively formed by freezing and thawing of water, that is often the dominant mechanism on Earth.
Polygons similar to those found in Earth's arctic and antarctic regions are also found in the polar regions of Mars. Typically, they occur on crater floors, or on intercrater plains, between about 60° and 80° latitude. The polygons are best seen when bright frost or dark sand has been trapped in the troughs that form the polygon boundaries. Three examples of martian polygons seen by the Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) are shown here. Each is located in the southern hemisphere:
(a) Polygon troughs highlighted by frost as the south polar cap retreats during spring. The circular features are the locations of buried craters that were originally formed by meteor impact. This image, E09-00029, is located at 75.1°S, 331.3°W, and was acquired on 1 October 2001.
(b) Summertime view of polygons, highlighted by dark, windblown sand, on the floor of a crater at 71.2°S, 282.6°W. The image, E12-02319, was obtained on 21 January 2002.
(c) Polygon troughs highlighted by the retreating south polar frost cap during southern summer near 80.7°S, 70.4°W. This picture, M11-01795, was taken by MOC on 13 January 2000.
Some Mars researchers assume that polygons on the Red Planet are key indictors that ground ice is present or was present in the recent past. However, whether these polygons actually required water ice to form is, in fact, unknown, since dry processes are also known on Earth for form similar polygons.
Photo Credit: NASA/JPL/Malin Space Science Systems
JPL Image Use Policy
+ Freedom of Information Act
+ The President's Management Agenda
+ FY 2002 Agency Performance and
accountability report
+ NASA Privacy Statement, Disclaimer, and
Accessiblity Certification
+ Freedom to Manage
+ Comments and Questions

redpajama_set_name: RedPajamaCommonCrawl


We're great at giving advice to others. We're terrible at making decisions for ourselves.
So the authors of Decisive recommend that, when you're facing a tough decision, you ask yourself, "What would I tell my best friend to do?" It's amazing how quickly this clears away any haze around the issue.
Humans are kinda weird. In theory, it shouldn't matter whether the decision is facing me, or my best friend, if I'm trying to analyze it logically. But for some reason, just giving ourselves that little extra bit of breathing room yields better results.


text:
Ematurga ophthalmaria är en fjärilsart som beskrevs av Otto Staudinger 1920. Ematurga ophthalmaria ingår i släktet Ematurga och familjen mätare. Inga underarter finns listade i Catalogue of Life.

Källor

Mätare
ophthalmaria

redpajama_set_name: RedPajamaWikipedia


text:
Site Shop > Otherland, Volume 1: City of Golden Shadow
The first book in the Otherland Saga, City of Golden Shadow serves as an introduction and ground setting book that enriches and deepens the later works. Among the many aspects of life in this near-future world it depicts in detail, is an advanced virtual reality technology.
City of Golden Shadow introduces the basics of total immersion VR technologies, slightly further ahead than those of William Gibson?s Neuromancer. It delves into all the possible uses for such technology in stunning depth and detail, yet it does so in such a way that the pace of the plot never slackens.
It showcases many different applications from gaming to shopping, to relaxation, social nooks and crannies. The darker, legal side of things, and the sinister aspects that flow as an undercurrent, giving meat to the scientific, absorbing saga begin here, as the political and socio-economic climate of the parent world is defined.
A place of glittering towers, of crowded cyber-shopping malls, and of role playing landscapes true to the tabletop vision. Deep within the recesses of this playground of the masses, cyberspace so intertwined with reality that it is a part of normal life, there lurks the next great evolution in VR, Otherland.
Many lesser VR situations, still decades ahead of our current tech, are explored in detail, in the build-up to finding Otherland, that ultimate alternative reality. Otherland, the pinnacle of what VR can be, that is birthed by the best minds of two generations. Otherland, shrouded in secrecy. Otherland, that appears to be eating children.
Reviews by our members. Become a member today, and submit a review!
By Tad Williams
Produced By DAW Books


Trick kids into practicing mental math.
Because each time children have their turn, or the other person has a turn, they are analysing and processing the math equation. In one game of 'Find King Ten' each child will complete over 50 short quick math equations in their head. Genius!
Keep dice games in your purse and use them when you are out and about. Indirectly you could be getting your kids doing over 100 math equations a day without them knowing!
Number Ten is a constant reference point in mental math. Knowing to look for King Ten is a great habit for kids to learn. This one skill will speed up mental addition and subtraction onwards from 2nd grade.
100 has so many different combinations. Learning to see the common ones instantly helps math recall.
'Oh Fishily' reached kids to find 15. Knowing double fish is thirty and parts of Fishteen act as a scaffold for the tricky thirty something numbers.
Times tables are made fun when you get to visit the candy store 24. Roll and first to make 24 wins. Repeat game and first to ten is the winner!


The Bed Upreti Trust is a non-profit organisation that has already set up an Aviation Museum in an abandoned Fokker 100 in Dhangadi. The revenue from that project goes to assist cancer patients. This Museum is a sequel to the Dhangadi venture for which the Trust has partnered with CAAN. The Aviation Museum was funded by the savings of Capt Bed Upreti, and a loan from Everest Bank. It does not get any other financial help from the government or other charities.


We help marketing technology (adtech) firms and start-ups scale their businesses through new sales by connecting them with the right decision makers at national brands and their respective agencies. Whether you're looking for marketing, branding, digital, mobile or e-commerce decision-makers, The List can bridge the gap and put you in front of the right contacts the first time.
To start connecting with titles such as CIO, CTO, VP of Digital Marketing, CMO, CRM Manager and Director of eCommerce, start your free trial of The List today.


text:
An Ode to the Community Shield
FeatureRecent | 4 August, 2018
This is the first part of a new series that looks at some of the unsung aspects of football that don't necessarily get the shout outs and the column inches among the glitz and glamour of the modern game.
Whether it's lesser-valued trophies, unheralded officials and rules, unfancied formations and tactics, or simply half-time pies, this series will be about recognising all the things, big and small, that make football the beautiful game.
One such thing is the Community Shield.
Is it really a trophy? No, not really. Does it matter whether you win or lose? Again, no.
But the Community Shield serves one purpose and one purpose only: it's the opening gong, the firing pistol for the start of a new season.
And we should all bloody love it.
We've been lucky this year, in that we've only had to put up with about three football-less weeks in the summer thanks to the World Cup.
The odd-numbered years, any football fan will know, are absolute hell.
Sometimes as much as 10 weeks without "proper" football.
At first you think you can cope without it, you can finally act like a normal person for a while. Your family and partner organise activities on a Saturday and you actually go, and don't spend the day checking BBC Sport on your phone.
You go to overpriced festivals and rooftop bars and get away for a few weeks to the Costa del wherever.
You've almost not thought about football, this whole time. Well, you're still constantly checking Twitter ITK accounts in case a Brazillian wonderkid has been spotted at the airport nearest your team… but maybe this no football thing is alright, you think.
And then it's gets to the end of July and beginning of August, and suddenly the urge starts to creep back in.
Down the pub when your mates are discussing Brexit negotiations you feel the sudden desire to describe it as "unbelievable, Jeff".
Scottish football starts and you almost think it would be worth watching.
You find yourself tempted by things like the MLS, or fancy-titled pre-season tournaments, just to give yourself that taster of the real thing.
But it doesn't satisfy you.
You begin to yearn for Martin Tyler's bellows of "and it's liiiive". You're getting desperate for that first glimpse of Gary Lineker's cheeky mug on a Saturday night, twinkle in his eye, ready to say "we've got a great lineup of games for you tonight". You start checking your FPL team on a daily basis even though no games have been played.
And then, in that first or second week of August, out from the ashes of whatever distractions you can muster; cricket, sunstroke, days out to Ikea with the other half — you spot it.
Like a pal who's been off travelling through South East Asia for months, only to turn up at your flat with a dodgy tan, some beads and exactly £4.55 in their bank account, the Premier League strolls back into your life.
And just like that traveller pal, you need to do something to celebrate the occasion.
So you get your mates together and go down to the pub, and have a good old catchup.
That's the Community Shield. It's the catchup, it's the celebration of the return of the prodigal son.
Imagine, for a moment, if we didn't have this ritual.
Imagine if it was just, out of nowhere, a Friday night in August and Man Utd are suddenly playing Leicester and you're like "oh, I guess we're back into it then?".
Like if your traveller mate just one day strolled into the pub, sat down and started mouthing off about whatever the last topic was you'd been chatting to him about before he left.
It would feel weird. Out of place. A jolt.
The Community Shield gives us an opportunity to reconfigure ourselves.
We sit down, watch the game, remember who does what and how things work, maybe there'll be a new player or two, something a bit different. It gives us a chance to get to grips with how the new season is going to be.
It's a game of pure promise, even for the teams not involved.
You watch the Community Shield, not yet sure of your fate. Maybe you'll win the league, maybe you'll get relegated. But you don't know yet. Anything could happen in the next nine months.
A lot of people don't like the Community Shield, they say it's a meaningless game.
In pure footballing terms, yes it's meaningless. But it's role is far more important than that.
It gives us just the required taste we need to remember what it's all about. The hope, the joy, the anguish — just a little twinge of it. In one ultimately sanitised, meaningless football match, we're reminded of why we do this to ourselves every year and what delights and disasters we have to come.
The Community Shield is not an important football match.
The Community Shield is football…
…and it's liiive!


text:
China Looms Large For New Indian Air Force Chief
The Indian air force (IAF) has long had big ambitions, and the pending arrival of a new leader with a broad agenda indicates there will be no easing up in efforts to strengthen the service's capabilities….
The foreign hardware inflow into India will be substantial during Browne's time in office. His tenure as IAF chief will also likely see the signing of contracts worth tens of billions of dollars….
One key program that Browne will have to oversee is the $12-billion Medium Multi-Role Combat Aircraft (MMRCA). This is a befitting turn of events, since Browne played a central role in navigating the MMRCA teams through the competitive process during his 2007-09 tenure as deputy chief of the IAF.
During his time in office, the government will likely sign deals for 10 or more Boeing C-17 heavy transports, six new-generation tanker transports (the Airbus Military A330 and Ilyushin Il-78 are in the running), 22 attack helicopters, 12 heavy-lift helicopters and nearly 200 basic trainer aircraft. Browne will also be under pressure to ensure the smooth introduction of several large network-centric systems…..
Aviation Week and Space Technology, June 06, 2011. p. 56
Asia-Pacific Staff, New Delhi


Energy Crystal Soap sold individually. This soap is made with an organic clear glycerin base, organic tea tree essential oil, and contains a large genuine raw green aventurine crystal inside. My crystals are hand picked, solar, lunar, and earth charged. Prior to use in soap the crystal is buried in the earth for 3 months, it is then cleaned three times with a water bath and placed on a grid to solar and lunar charge so it is ready for use. You will receive one carefully crafted crystal soap.
The rockhound in me couldn't resist this lovely soap! A beautiful gem incased in crystal shaped soap that has a wonderful fragrance, wonderful item!


Suddenly scroll bar vanished in the Survey Gizmo build page and final landing page. Please help.
What you're describing sounds like an HTML issue. It sounds like you might have some broken HTML code in your survey build somewhere that's causing conflicts with the way the survey displays.
I would recommend making a copy of your survey (so that you don't mess up the original), then in the copy, go into Tools > Find & Replace, then click on "Show all text with HTML tags". Remove the HTML from the survey bit by bit. After you remove each bit of HTML, view the survey in Build to see if the problem is fixed. Keep deleting HTML bit by bit until you the scroll bar is available again in Build, and you'll know you found the culprit bad HTML. Once you find it, you can go back into your original survey and fix it in there.


Park in the small car park just before the hamlet of Tinette (D).
Continue down the road to Tinette; this is the GRP footpath (Grande Randonnée de Pays – Long Regional Hike) that goes around the Lure mountains. In Tinette (1) the road becomes a track and then a path.
Keep following the path until you reach the restored sheepfold of Jas des Terres de Roux (2).
Keep following the GRP path due north for about 1km until you reach a crossing at right-angles that is not on the IGN map. Take the wide track to the right (3) (no waymarks) and keep going along the plateau towards the ruins of the Fraches sheepfold (4).
Turn left and head due north. The path will take you past another sheepfold that is also in ruins and then reaches the Jas des Agneaux sheepfold (5), which is 5 minutes from the GRP footpath.
Join the GRP footpath and stay on it until you reach the high point marked by a large cairn (6).
Head due south down the path to the right with the yellow waymarks. Keep going until you reach a large junction where you can make a detour to the left to see the last sheepfold (7).
Come back to the crossroads, turn left down the path, and then turn right at the next crossing. Walk down the edge of the forest until you reach the crossing with the DFCI (forest fire prevention) water tank (8). Turn left onto the path which leads back to the car park.
There are many shelters in the area, all in the form of sheepfolds.
The sheepfold of Terre de Roux has been restored and is now classified as a historic monument. It is well worth the visit, being careful to respect the site, to admire the remarkable stack of stones forming the roof. A pure masterpiece.
The highest sheepfold, that of Jas des Agneaux, has a special history: it was here that Jean Giono shot them film Crésus, with Fernandel in the lead role.
We advise taking IGN maps with you on this walk. Click here to buy : 3341OT.


The Burmilla, as the name might suggest, is half Burmese and half Chinchilla. Its existence was the result of an accident, a beautiful one that is. This unplanned mating happened in England in 1981. The Burmese cat responsible was said to belong to Baroness Mirnda von Kirchberg. It escaped the house one day and bred with the Chinchilla Persian cat next door. This led to the unexpected production of a litter of four female kittens with black shaded silver coat and a considerably breathtaking appearance.
A breeder soon took notice of this stunning breed and decided to develop it to recognition. Together with other breeders, a campaign was organized, leading to the successful recognition of the cat by the Governing Council of the Cat Fancy (GCCF) in 1989. The name Burmilla was given to reflect it as the beautiful combination of its parent breed.
By breeding the cat back to the pure Burmese cat every alternating generation in the early days has helped to establish the Burmese type of the breed in its coat texture and temperament. Even so, the Burmilla also has a beautiful coat on the side of the Chinchilla. As it has two standard looks, the Burmilla cats do not always look alike. It took a few years, from 1981 to 1987, for the Burmilla to be recognized internationally as its own breed. On a side note, it is possible for longhair kittens to be born to a Shorthair Burmilla.
Head of the Burmilla is gently rounded and taper into a blunt wedge. Atop the head is a pair of medium - large ears that are widely set. They are broad at the base and taper into a vaguely rounded tip. Viewed in profile, a slight forward tilt is evident. The muzzle also appears relatively short and blunt with a gentle nose break. The tip of the nose should be aligned to the tip of the firm chin. Burmilla has large eyes that are about an eye width apart with the outer corners slanted slightly towards the ears. What makes this breed unmistakably Burmilla is that the lips, nose and eyes are outlined with a dark smoky color. It appears as if it has undergone a quick makeover. However, such feature has given it an exceptionally charming appearance and has helped to accentuate its beautiful eye color, which comes in any shade of green. Gold or yellow tinge in kittens or young adults is acceptable.
The coat of Burmilla can come in two different lengths, namely the shorthair and semi-longhair. The Shorthair variety is more popular. The hair lies close to the body and it feels slightly padded like the Burmese cat due to an extra layer of undercoat. It is soft and silky to the touch. The Longhair variety will appear when two Longhair Burmillas are mated together. It is the result of a recessive longhair gene inherited from the Chinchilla. Thus, shorthair Burmilla can also produce a Longhair Burmilla if it carries the longhair gene. The hair texture of longhair variety is also soft and silky. The hair length runs longer towards the hind legs and along the tail, which extends into a full gorgeous plume. Ear tufts may also furnish the inner side of the ears.
The coat stands out with a silver white base color that is either tipped or shaded with another contrasting color. In the tipped pattern, the color runs about 1/8 of the entire hair shaft and is well distributed across the entire body, giving the coat a lustring effect. The tipped pattern usually appears lighter than the shaded pattern. In the shaded pattern coat, the color runs about 1/3 of the hair shaft, which explains why it appears darker than the tipped pattern. The colors for both patterns include tortoiseshell, red, cream, chocolate, lilac, blue, brown and black.
The Burmilla has a personality that reflects the qualities found in both its parent breeds. It has an extroverted, friendly and sociable side like the Burmese; as well as an easy-going and relaxed side like the Chinchilla. Its mischievousness is more evident when it is a kitten, but the Burmilla grows to become a remarkably intelligent and affectionate breed. It is not as noisy as the Burmese and is more fearless and inquisitive than the Chinchilla.
This is a sociable and friendly breed that bonds well with children and enjoys being part of the family. Even though it is playful, it is not overly active and a preference over resting in your arms or cuddling on your laps would even be made over long hours of play. While it does not shy away from showing its affections to its favorite people, it does become wary towards strangers. Attributing to the build of its body, the Burmilla is also an avid climber, but it is might not be as careful as other cat breeds. Thus, caution would have to be taken over breakables.
The Burmilla is a generally healthy breed with an average lifespan of 15 years. However, it is prone to kidney diseases and allergies. Thus, it is necessary to visit the vet yearly to maintain the overall good health of the cat. It is also important to obtain a written health guarantee from qualified breeders when purchasing the cat. This will help to ensure that the cat is not contracted with any common feline diseases.
Grooming the Burmilla is relatively easy. The Shorthair variety will require only a weekly brushing to help distribute skin oil evenly. Brushing will be more frequent for the Longhair variety to help remove tangles and prevent matting. Brush the teeth frequently with vet-approved toothpaste to prevent periodontal diseases. The nails will need to be trimmed whenever necessary. Also, check the ears for redness or odors that might indicate infections and clean them with a damp cloth if needed.
This inquisitive and playful breed would appreciate an outdoor space where it can explore and run. However, the outdoor space would need to be safe and escape-proof. Burmilla can adapt well to indoor living, provided that an adventure zone, equipped with interactive toys, cat trees and cat gym sets, are available to encourage a hearty and active growth. The even temper, sociable personality and adaptability have made Burmilla a suitable breed for most homes. Coupled with is charming appearance and affectionate nature, the Burmilla is sure to be a winsome pet to have in the home.