Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

New oral and topical approaches for the treatment of melasma.

Melasma is a common, therapeutically challenging, and universally relapsing disorder of hyperpigmentation that is most often observed in women and individuals with Fitzpatrick Skin Types III through VI. The pathogenesis of melasma is complex and protean. Contributing factors that are often implicated in the etiopathogenesis of this condition include a genetic predisposition, intense ultraviolet radiation exposure, and hormonal influences. Therapeutic interventions for melasma include a multimodality approach incorporating photoprotection agents, topical and oral skin lighteners, and resurfacing procedures. Given our expanding knowledge of the pathogenesis of melasma, new and effective treatments are expanding our therapeutic armamentarium. This article reviews new and emerging oral and topical treatments for melasma.

International Initiative for Outcomes (INFO) for vitiligo: workshops with patients with vitiligo on repigmentation.

BACKGROUND: There is no cure or firm clinical recommendations for the treatment of vitiligo. One of the main issues is the heterogeneity of outcome measures used in randomized controlled trials for vitiligo. OBJECTIVES: To define successful repigmentation from the patients' point of view and to propose how and when repigmentation should be evaluated in clinical trials in vitiligo. METHODS: We conducted three workshops with patients with vitiligo and their parents or caregivers. Workshop 1 was held at World Vitiligo Day (Detroit, MI), workshop 2 at the University of Texas Southwestern Medical Center and workshop 3 at the Vitiligo and Pigmentation Institute of Southern California, University of California. RESULTS: Seventy-three participants were recruited. Consensus on the following questions was achieved unanimously: (i) the definition of 'successful repigmentation' was 80-100% of repigmentation of a target lesion and (ii) both an objective and a subjective scale to measure repigmentation should be used. CONCLUSIONS: This was the largest patients' outcomes workshop. We followed the guidance from the CSG-COUSIN and the Vitiligo Global Issues Consensus Group. Our recommendations to use percentage of repigmentation quartiles (0-25%, 26-50%, 51-79%, 80-100%) and the Vitiligo Noticeability Scale are based on the best available current evidence. A limitation of the research is that the workshops were conducted only in the U.S.A., due to pre-existing organisational support and the availability of funding.

Vitiligo: Patient stories, self-esteem, and the psychological burden of disease.

Vitiligo is a relatively common disorder that is characterized by depigmented patches of skin. Multiple studies characterize the overwhelming psychological burden that is experienced by many patients around the globe. This review examines personal patient stories and the impacts of age, culture, sex, race, and ethnicity in relationship to altered self-esteem and quality of life in patients who live with vitiligo.

A closer look at the role of the dermatologist in championing total women's health through the dermatology gateway.

New data collected by the Women's Dermatologic Society (WDS) through a membership survey conducted in August 2018 reflect the key role of the dermatologist in championing the overall health of the total woman through the dermatology gateway. These meaningful results provide a first-ever metric glimpse into the myriad systemic/internal diseases, disorders, and conditions that WDS dermatologists detect and diagnose in female dermatology patients and the wide scope of our collaborations with other physician specialists to manage complex, underlying medical conditions. Insightful perspectives from medical and health experts outside of dermatology address the importance of teamwork, reaffirm the unique role that dermatologists play on the medical team, and underscore the vital importance of our proclivity toward collaboration, the latter of which is shown to be significant according to the WDS data. Given an apparent general lack of awareness about the role of the dermatologist in the health journey of the total woman, we have an important opportunity to advance this broadened perspective among our colleagues in and outside of dermatology, our patients, the media, and the public at-large. By raising awareness, we can elevate our specialty in the medical profession and in the public eye, increase the likelihood that people will consult a dermatologist (proactively and reactively), inspire mutual referrals and greater cross-specialty teamwork and communications to benefit patients, and positively affect public health.

A randomized, controlled comparative study of the wrinkle reduction benefits of a cosmetic niacinamide/peptide/retinyl propionate product regimen vs. a prescription 0.02% tretinoin product regimen.

BACKGROUND: Tretinoin is considered the benchmark prescription topical therapy for improving fine facial wrinkles, but skin tolerance issues can affect patient compliance. In contrast, cosmetic antiwrinkle products are well tolerated but are generally presumed to be less efficacious than tretinoin. OBJECTIVES: To compare the efficacy of a cosmetic moisturizer regimen vs. a prescription regimen with 0.02% tretinoin for improving the appearance of facial wrinkles. METHODS: An 8-week, randomized, parallel-group study was conducted in 196 women with moderate to moderately severe periorbital wrinkles. Following 2 weeks washout, subjects on the cosmetic regimen (n = 99) used a sun protection factor (SPF) 30 moisturizing lotion containing 5% niacinamide, peptides and antioxidants, a moisturizing cream containing niacinamide and peptides, and a targeted wrinkle product containing niacinamide, peptides and 0.3% retinyl propionate. Subjects on the prescription regimen (n = 97) used 0.02% tretinoin plus moisturizing SPF 30 sunscreen. Subject cohorts (n = 25) continued treatment for an additional 16 weeks. Changes in facial wrinkling were assessed by both expert grading and image analysis of digital images of subjects' faces and by self-assessment questionnaire. Product tolerance was assessed via clinical erythema and dryness grading, subject self-assessment, and determinations of skin barrier integrity (transepidermal water loss) and stratum corneum protein changes. RESULTS: The cosmetic regimen significantly improved wrinkle appearance after 8 weeks relative to tretinoin, with comparable benefits after 24 weeks. The cosmetic regimen was significantly better tolerated than tretinoin through 8 weeks by all measures. CONCLUSIONS: An appropriately designed cosmetic regimen can improve facial wrinkle appearance comparably with the benchmark prescription treatment, with improved tolerability.

A global survey of the role of ultraviolet radiation and hormonal influences in the development of melasma.

BACKGROUND: It has been generally believed that the four main causes of melasma are pregnancy, hormonal contraception, family history and sun exposure; however, there are few published comprehensive studies that confirm these assertions. The Pigmentary Disorders Academy - an international group of experts in pigmentary disorders - designed and conducted a global survey of women to investigate the effect of these factors on onset and chronicity of melasma and the course of the disease in order to gain a better understanding of the causative factors associated with this disorder, with a particular focus on hormonal factors and UV exposure in females. METHODS: A 40-item largely self-administered questionnaire was completed by 324 women being treated for melasma in nine clinics worldwide. RESULTS: The mean age at onset of melasma was 34 years, and 48% of subjects questioned had a family history of melasma (97% in a first-degree relative). Subjects with family history of melasma tended to have darker skin (90% types III-VI) compared to those without (77% types III-VI). The most common time of onset was after pregnancy (42%), often years after the last pregnancy, with 29% appearing pre-pregnancy and 26% during pregnancy. Onset was related to darker skin type post-pregnancy (P = 0.002). Risk of onset during pregnancy was associated with having spent more time outdoors (an extra 10 h per week spent working outside increases the odds of onset of melasma during pregnancy by approximately 27%) and an increased maternal age at pregnancy (increased by approximately 8% for each year of age at first pregnancy; P = 0.02). The odds of melasma occurring for the first time during a pregnancy were also increased with multiple pregnancies (twice the odds if 2 vs. 1 pregnancies, three times higher if 3 or more vs. 1 pregnancy). Of the women, 25% who had used hormonal contraception claimed that melasma appeared for the first time after its use, the rate being higher for those without vs. with a family history. CONCLUSIONS: The results suggest that, whilst accepted causes do affect onset of melasma, a combination of these factors often triggers this disorder. These factors may provide further insights into how physicians can manage individual melasma cases, support recommendation of preventative measures and even anticipate treatment results and recurrence.

The safety of hydroquinone.

Hydroquinone is one of the most effective molecules for the treatment of hyperpigmentary disorders, with over 40 years of efficacy and safety data. Concerns over its safety have been raised because of the fact that it is a derivative of benzene and because of the long-term side-effects observed with cosmetic products containing high concentrations of hydroquinone. However, despite 40-50 years use of hydroquinone for medical conditions, there has not been a single documented case of either a cutaneous or internal malignancy associated with this drug. This article reviews the evidence for the safety of hydroquinone in the treatment of hyperpigmentation conditions.

Laser resurfacing-induced hypopigmentation: histologic alterations and repigmentation with topical photochemotherapy.

BACKGROUND: Hypopigmentation is a relatively common side effect of CO2 laser resurfacing. Little is known regarding the histologic features of the areas of pigmentation loss. To date, hypopigmentation is considered a permanent complication of this procedure. OBJECTIVE: To assess the histologic features of hypopigmentation caused by laser resurfacing and to evaluate the efficacy and safety of topical psoralen photochemotherapy. METHODS: Ten patients were included in this pilot study. Four had baseline biopsies performed. Histologic parameters assessed included epidermal melanin, dermal melanophages, perivascular inflammation, Mel-5 immunostaining for melanocytes, and dermal fibrosis. Seven patients were treated twice a week with topical photochemotherapy utilizing 0.001% 8-methoxypsoralen. RESULTS: All of the biopsy specimens demonstrated varying quantities of epidermal melanin and residual epidermal melanocytes. Mild perivascular inflammation was evident in two specimens. Superficial dermal fibrosis was noted in all biopsy specimens. Topical photochemotherapy induced moderate to excellent repigmentation in 71% of the treated patients. Adverse effects were minimal. CONCLUSION: The results of this investigation suggest that hypopigmentation induced by laser resurfacing may result from a suppression of melanogenesis rather than destruction of area melanocytes. The preliminary data further suggest that hypopigmentation caused by laser resurfacing can be effectively treated by topical photochemotherapy.

A 76-bp deletion in the Mip gene causes autosomal dominant cataract in Hfi mice.

Hfi is a dominant cataract mutation where heterozygotes show hydropic lens fibers and homozygotes show total lens opacity. The Hfi locus was mapped to the distal part of mouse chromosome 10 close to the major intrinsic protein (Mip), which is expressed only in cell membranes of lens fibers. Molecular analysis of Mip revealed a 76-bp deletion that resulted in exon 2 skipping in Mip mRNA. In Hfi/Hfi this deletion resulted in a complete absence of the wildtype Mip. In contrast, Hfi/+ animals had the same amount of wildtype Mip as +/+. Results from pulse-chase expression studies excluded hetero-oligomerization of wildtype and mutant Mip as a possible mechanism for cataract formation in the Hfi/+. We propose that the cataract phenotype in the Hfi heterozygote mutant is due to a detrimental gain of function by the mutant Mip resulting in either cytotoxicity or disruption in processing of other proteins important for the lens. Cataract formation in the Hfi/Hfi mouse is probably a combined result of both the complete loss of wildtype Mip and a gain of function of the mutant Mip.

Skin and hair cosmetic issues in women of color.

Women of color comprise many phenotypically heterogeneous groups. Despite the general heterogeneity, however, there are unique skin and hair care issues and needs. These issues often present therapeutically challenging problems for the dermatologist and the skin and hair care industry.

Anatomic and biomechanical analysis of the lower lumbar foraminal ligaments.

STUDY DESIGN: An anatomic cadaveric study to characterize the lumbar intraforaminal nerve root attachments. OBJECTIVES: To characterize the intraforaminal nerve root attachments and describe their anatomic relationships and biomechanical properties. SUMMARY OF BACKGROUND DATA: Observations during foraminotomies for lateral recess stenosis as well as lateral approaches for far lateral disc herniation have shown dense attachments between the nerve root and adjacent structures. Little or no information has appeared in the literature describing intraforaminal nerve root attachments. METHODS: Twelve fresh-frozen human cadaveric lumbar spines were used to study intraforaminal ligamentous structures. Four cadavers were cut into sagittal sections for qualitative description, and eight were used for biomechanical testing. Histologic analyses were performed on samples of the foraminal attachments to assure that they were not vascular or neural structures. Biomechanical testing of the nerve roots with ligamentous attachments was performed measuring load to failure along the anatomic axis of the root. RESULTS: The dissections showed four distinct bands extending radially from the nerve root sleeve. The most prominent nerve root attachment was to the facet capsule posteriorly. Other ligaments fanned out with attachments inferiorly and superiorly to the adjacent pedicles and anteriorly to the intervertebral disc. Biomechanical study of the L3, L4, and L5 nerve roots showed a significant increase in strength at failure with axial traction, progressing from L3 to L5. CONCLUSIONS: The results demonstrate that these foraminal ligaments are normal anatomic structures within the intervertebral foramen of the lumbar spine. In addition, they may play a role in limiting motion along the nerve root.

The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups.

BACKGROUND: There is a dearth of published data regarding chemical peels in darker racial-ethnic groups. OBJECTIVE: The purpose of the present investigation was to assess the clinical efficacy and safety of a new superficial salicylic acid peel in individuals of skin types V and VI. METHODS: Twenty-five patients were included in this pilot investigation. Nine had acne vulgaris, 5 had post-inflammatory hyperpigmentation, 6 had melasma, and 5 had rough, oily skin with enlarged pores. The patients were pre-treated for 2 weeks with hydroquinone 4% prior to undergoing a series of five salicylic acid chemical peels. The concentrations of salicylic acid were 20% and 30%. The peels were performed at 2 week intervals. RESULTS. Moderate to significant improvement was observed in 88% of the patients. Minimal to mild side effects occurred in 16%. CONCLUSION: The results of this study suggest that superficial salicylic acid peels are both safe and efficacious for treatment of acne vulgaris, oily skin, textural changes, melasma, and post-inflammatory hyperpigmentation in patients with skin types V and VI.

Azelaic acid 20% cream in the treatment of facial hyperpigmentation in darker-skinned patients.

This multicenter, randomized, double-masked, parallel-group study assessed the efficacy, safety, and tolerability of azelaic acid 20% cream compared with those of its vehicle for the treatment of facial hyperpigmentation in darker-skinned patients (phototypes IV to VI). Following a 24-week treatment period, azelaic acid produced significantly greater decreases in pigmentary intensity than did vehicle as measured by both an investigator's subjective scale (P = 0.021) and a chromometer analysis (P = 0.039). There was a significantly greater global improvement with azelaic acid than with vehicle at week 24 (P = 0.008). Azelaic acid produced a slightly but significantly greater amount of burning (weeks 4 and 12, P < or = 0.046) and stinging (week 4, P = 0.002) than did vehicle. At the end of the study, more patients treated with azelaic acid than with vehicle reported having much smoother skin and being very satisfied or satisfied with their treatment. Also, more patients treated with azelaic acid than with vehicle rated their medication as being more effective or the same as past treatments. Thus azelaic acid is an effective and well-tolerated treatment for hyperpigmentation in darker-skinned patients.

Abnormal eye development associated with Cat4a, a dominant mouse cataract mutation on chromosome 8.

PURPOSE: Cat4a, one of four mutant alleles at the mouse Cat4 locus, causes central corneal opacity and anterior polar cataract in heterozygotes and microphthalmia in homozygotes. The Cat4 locus has been mapped to chromosome 8, 31 cM from the centromere. In this study ocular development of Cat4a mutant mice was investigated to characterize the defects in eye morphogenesis. METHODS: Serial sections from eyes of wild-type, heterozygous, and homozygous littermates were examined by means of light microscopy at selected intervals from embryonic day 11 to postnatal day 1. Eyes of adult heterozygous and homozygous mice also were evaluated histologically. RESULTS: Failure of separation of the lens vesicle from the surface ectoderm was the earliest structural defect observed. In heterozygous embryos, the abnormality was limited to persistent connection of the anterior pole of the lens to the cornea. Adult heterozygotes had defects in the central corneal stroma and endothelium and anterior polar cataracts with or without keratolenticular adhesion. In homozygous embryos, the persistent connection of lens to surface ectoderm was associated with aborted lens development, failure of closure of the optic fissure, and impairment of growth of the eyecup. Microphthalmic eyes of adult homozygous mice had a poorly developed cornea, and the anterior chamber and vitreous compartment were absent. An extensively folded retina and remnants of a degenerated lens filled the interior of the globe. CONCLUSIONS: A developmental defect inhibits separation of the lens vesicle from surface ectoderm in mice heterozygous or homozygous for the Cat4a mutation. In homozygotes subsequent lens and eye morphogenesis are also severely affected. Cat4a shows phenotypical similarity to several other independent mouse mutations including Small eye, a mutation of the Pax6 gene. Cat4 may be one of several genes involved in a common developmental path and may be part of the Pax6-regulated gene cascade governing eye morphogenesis.