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Mary Patricia Smith, Karen Ly, Quinn Thibodeaux, Tina Bhutani, Wilson Liao, Kristen M BeckDepartment of Dermatology, University of California, San Francisco, CA, USAAbstract: Acrodermatitis continua of Hallopeau (ACH) is a rare, sterile pustular eruption of one or more digits. The condition presents with tender pustules and underlying erythema on the tip of a digit, more frequently arising on a finger than a toe. As far as classification, ACH is considered a localized form of pustular psoriasis. The eruption typically occurs after local trauma or infection, but such a history is not always present and various other etiologies have been described including infectious, neural, inflammatory, and genetic causes. The natural progression of ACH is chronic and progressive, often resulting in irreversible complications such as onychodystrophy that can result in anonychia, as well as osteitis that can result in osteolysis of the distal phalanges. Because of the rarity of ACH, there have been no randomized controlled studies to evaluate therapies, resulting in an absence of standardized treatment guidelines. In clinical practice, a wide variety of treatments have been attempted, with outcomes ranging from recalcitrance to complete resolution. In recent years, the introduction of biologics has provided a new class of therapy that has revolutionized the treatment of ACH. Specifically, rapid and sustained responses have been reported with the use of anti-tumor necrosis factor agents like infliximab, adalimumab, and etanercept; IL-17 inhibitors like secukinumab; IL-12/23 inhibitors like ustekinumab; and IL-1 inhibitors like anakinra. Nevertheless, there remains a considerable need for more research into treatment for the benefit of individual patients with ACH as well as for the clinical knowledge gained by such efforts. The purpose of this review is to provide a comprehensive overview of the key features of ACH as well as a discussion of clinical management strategies for this unique and debilitating condition.Keywords: acrodermatitis continua of Hallopeau, psoriasis, pustular psoriasis, generalized pustular psoriasis, palmoplantar pustulosis

Karen Ly,1 Kristen M Beck,1 Mary P Smith,1 Ana-Maria Orbai,2 Wilson Liao11Department of Dermatology, University of California San Francisco, San Francisco, CA, USA; 2Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USACorrespondence: Kristen M BeckDepartment of Dermatology, University of California San Francisco, 515 Spruce Street, San Francisco, CA 94118, USATel +1 415 476 4701Fax +1 415 502 4126Email kristenbeckmd@gmail.comAbstract: Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of psoriatic arthritis (PsA). It provides an alternative option for patients who have had an inadequate response and tolerance to other disease modifying antirheumatic drugs (DMARDs). It has demonstrated comparable efficacy to biologics, is effective in the management of treatment resistant disease, and is reported to improve enthesitis, dactylitis, and radiographic progression. Tofacitinib is also associated with an increased risk of serious infections, malignancy, and laboratory abnormalities. There is currently a large armamentarium of therapies for psoriatic arthritis, and choosing among treatments can be challenging. Due to this wide selection, a thorough assessment of psoriatic disease phenotype, patient preference, disease presentation, and comorbidities is critical. This review addresses key considerations in patient selection for the treatment of PsA with tofacitinib.Keywords: tofacitinib, psoriatic arthritis, janus kinase, kinase inhibitors

Karen Ly,* Kristen M Beck*, Mary P Smith, Quinn Thibodeaux, Tina BhutaniDepartment of Dermatology, University of California, San Francisco, CA, USA*These authors contributed equally to this work Abstract: Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening variant of psoriasis that is characterized by recurrent, acute onset, widely distributed pustular eruptions on inflamed, erythematous skin. It is important to recognize acute GPP as a subtype of psoriasis associated with high morbidity and mortality so therapy can be initiated without delay. Since GPP was first described in 1910 by Leopold von Zumbusch, it has been inconsistently defined, stratified, and diagnosed in the literature. Multiple definitions and diagnostic criteria have been proposed over the years. Recently, formal consensus guidelines on GPP have been published by international groups. This article reviews the current evidence and understanding in the diagnosis and screening of GPP.Keywords: generalized pustular psoriasis, acute generalized pustular psoriasis of von Zumbusch, pustular psoriasis, diagnostic criteria

Eric J Yang,1,2 Kristen M Beck,1 Wilson Liao1 1Department of Dermatology, University of California San Francisco, San Francisco, CA, USA; 2Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA Abstract: Secukinumab is a human monoclonal antibody targeting IL-17A that has been approved for three indications: moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In Phase III clinical trials for each of these three indications, secukinumab has proven to be both highly efficacious and well-tolerated. However, several biologic medications are currently approved for the treatment of moderate-to-severe plaque psoriasis, and many demonstrate excellent efficacy and safety. Due to this wide selection, it is often unclear how to choose biologics for specific patients. Important considerations in biologic selection include clinical efficacy, safety, cost, convenience, onset of action, and management of comorbid disease. This article aims to outline the key considerations in patient selection for the treatment of plaque psoriasis with secukinumab. Keywords: secukinumab, IL-17 inhibitor, IL-17A, biologics, psoriasis, patient selection

Eric J Yang,1,2,* Kristen M Beck,1,* Isabelle M Sanchez,1,3 John Koo,1 Wilson Liao1 1Department of Dermatology, University of California San Francisco, San Francisco, CA, USA; 2Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA; 3University of Illinois at Chicago College of Medicine, Chicago, IL, USA *These authors contributed equally to this work Abstract: Psoriasis is a chronic immune-mediated inflammatory disease with significant medical and psychological comorbidities. In addition to having increased cardiovascular risk and mortality, psoriasis patients are more likely to be depressed, anxious, and endorse suicidal ideation than the general population. These patients often have low self-esteem and feel stigmatized due to their skin disease, which can prevent them from pursuing relationships, dating, and attending social activities. Up to 63% of adult psoriasis patients experience psoriatic lesions on their genital area during their lifetime, but often do not discuss these issues with their physicians due to embarrassment, stigmatization, or shyness about this sensitive location. However, psoriasis in sensitive areas, such as the genitals, may result in quality of life impairment greater than that of patients with psoriasis elsewhere on their body, particularly in respect to romantic relationships, intimacy, and sexual function. This article evaluates the current literature regarding the impact of genital psoriasis on the quality of life of affected patients. Keywords: genital psoriasis, quality of life, sexual function, sexual distress, impact

Kristen M Beck, Isabelle M Sanchez, Eric J Yang, Wilson Liao Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Abstract: Plaque psoriasis is an immune-mediated skin disease that affects roughly 3% of adults in the United States. Advances over the past 20 years in understanding the immune-mediated pathophysiology of psoriasis have led to the development of targeted biologic therapies for this condition. Currently, biologic medications approved for the treatment of plaque psoriasis include tumor necrosis factor α inhibitors, interleukin (IL)-17 or IL-17 receptor inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors. Tildrakizumab-asmn is a monoclonal antibody that targets the p19 subunit of IL-23 and is approved for use in adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This article reviews the current pharmacologic, efficacy, and safety data on tildrakizumab-asmn. Keywords: tildrakizumab, IL-23, IL-23p19, biologics, psoriasis

Incorporating a steric barrier between the two stations in a bistable [2]rotaxane based on monopyrrolotetrathiafulvalene and cyclobis(paraquat- p -phenylene) allows the high-energy metastable-state co-conformation to be physically isolated following a single redox cycle, thus making it possible to store energy (4.4 J L -1 ) and to follow its interconversion back to the ground-state co-conformation.

The recent advent of quantum computing has the potential to overhaul security, communications, and scientific modeling. Superconducting qubits are a leading platform that is advancing noise-tolerant intermediate-scale quantum processors. The implementation requires scaling to large numbers of superconducting qubits, circuit depths, and gate speeds, wherein high-purity RF signal generation and effective cabling transport are desirable. Fiber photonic-enhanced RF signal generation has demonstrated the principle of addressing both signal generation and transport requirements, supporting intermediate qubit numbers and robust packaging efforts; however, fiber-based approaches to RF signal distribution are often bounded by their phase instability. Here, we present a silicon photonic integrated circuit-based version of a photonic-enhanced RF signal generator that demonstrates the requisite stability, as well as a path towards the necessary signal fidelity.

Through the use of modified nucleotides, synthetic nucleic acids have found several fields of application within biotechnology and in the pharmaceutical industry. We have previously introduced nucleotides with an additional functional nucleobase linked to C2' of arabinonucleotides ( B X ). These double-headed nucleotides fit neatly into DNA·DNA duplexes, where they can replace the corresponding natural dinucleotides and thus condense the molecular information. Here, we introduce a 2'-deoxy version of the B X design with inversion of the C2' stereochemistry ( d S B X ) with the aim of obtaining improved RNA recognition. Specifically, d S B X analogues with cytosine or isocytosine attached to C2' of 2'-deoxyuridine ( d S U C and d S U iC ) were synthesized and evaluated in duplexes. Whereas the d S B X design did not outperform the B X design in terms of mimicking dinucleotides in nucleic acid duplexes, it was able to engage in reverse Watson-Crick pairing using its 2'-base. This was evident from the ability of the d S U C cytosine to form stable mis-matching base pairs with opposite cytosines identified as hemiprotonated C·C + pairs. Furthermore, specific base-pairing with guanine was only observed for the isocytosine-bearing d S U iC monomer. Very stable duplexes were obtained with d S U C/iC monomers in each strand indicating that fully modified double-headed nucleic acid sequences could be based on the d S B X design.

The IL-17A inhibitor secukinumab is efficacious for the treatment of psoriasis. To better understand its mechanism of action, we investigated its impact on psoriatic lesions from 15 patients with moderate-to-severe plaque psoriasis undergoing secukinumab treatment. We characterized the longitudinal transcriptomic changes of whole lesional skin tissue as well as cutaneous CD4 + and CD8 + T effector cells and CD4 + T regulatory cells across 12 weeks of treatment. Secukinumab was clinically effective and reduced disease-associated overexpression of IL17A , IL17F, IL23A, IL23R , and IFNG in whole tissue as soon as 2 weeks after initiation of treatment. IL17A overexpression in T-cell subsets, primarily CD8 + T cells, was also reduced. Although secukinumab treatment resolved 89‒97% of psoriasis-associated expression differences in bulk tissue and T-cell subsets by week 12 of treatment, we observed expression differences involved in IFN signaling and metallothionein synthesis that remained unresolved at this time point as well as potential treatment-associated expression differences involved in IL-15 signaling. These changes were accompanied by shifts in broader immune cell composition on the basis of deconvolution of RNA-sequencing data. In conclusion, our study reveals several phenotypic and cellular changes within the lesion that underlie clinical improvement from secukinumab., (© 2021 The Authors.)

Nucleotide monomers that hold two nucleobases each, i.e. double-headed nucleotides, have been shown to form two sets of functional Watson-Crick base pairs when incorporated into dsDNA, and they hereby behave as dinucleotides. To form the basis for fully modified double-headed nucleic acids (DhNA), we have prepared three new DhNA monomers and can now demonstrate that the molecular information of 10 Watson-Crick base pairs can be condensed to highly stable 5-mer DhNA duplexes.

Background: Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8 + T cells have been identified as pathogenic drivers., Objective: Our study focused on comprehensively characterizing the phenotypic variation of CD8 + T cells in psoriatic lesions., Methods: We used single-cell RNA sequencing to compare CD8 + T-cell transcriptomic heterogeneity between psoriatic and healthy skin., Results: We identified 11 transcriptionally diverse CD8 + T-cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed 2 Tc17 cell subsets that were metabolically divergent, were developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity and which achieved comparable or greater accuracy than IL17A in a support vector machine classifier of psoriasis and healthy transcriptomes. Despite high coinhibitory receptor expression in the Tc17 cell clusters, a comparison of these cells with melanoma-infiltrating CD8 + T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program., Conclusion: Using high-resolution single-cell profiling in tissue, we have uncovered the diverse landscape of CD8 + T cells in psoriatic and healthy skin, including 2 nonexhausted Tc17 cell subsets associated with disease severity., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Xeno nucleic acids (XNAs) are artificial genetic systems based on sugar-modified nucleotides. Herein, we investigate double-headed nucleotides as a new XNA. A new monomer, AT, is presented, and together with previous double-headed nucleotide monomers, new nucleic acid motifs consisting of up to five consecutive A·T base pairs have been obtained. Sections composed entirely of double-headed nucleotides are well-tolerated within a DNA duplex and can condense the genetic information. For instance, a 13-mer duplex is condensed to an 11-mer modified duplex containing four double-headed nucleotides while simultaneously improving duplex thermal stability with +14.0 °C. Also, the transfer of information from double-headed to natural nucleotides by DNA polymerases has been examined. The first double-headed nucleoside triphosphate was prepared but could not be recognized and incorporated by the tested DNA polymerases. On the other hand, it proved possible for Therminator DNA polymerase to transfer the information of a double-headed nucleotide in a template sequence to natural DNA under controlled conditions.

Efficiently entangling pairs of qubits is essential to fully harness the power of quantum computing. Here, we devise an exact protocol that simultaneously entangles arbitrary pairs of qubits on a trapped-ion quantum computer. The protocol requires classical computational resources polynomial in the system size, and very little overhead in the quantum control compared to a single-pair case. We demonstrate an exponential improvement in both classical and quantum resources over the current state of the art. We implement the protocol on a software-defined trapped-ion quantum computer, where we reconfigure the quantum computer architecture on demand. Our protocol may also be extended to a wide variety of other quantum computing platforms.

Quantum mechanical expectation values for subsets can differ substantially from those for the whole ensemble. This implies that the effect of interactions between two systems can be altered substantially by conditioning. Here, we experimentally demonstrate that, for two light fields ψ_{S} (signal) and ψ_{A} (ancilla) that have only weakly interacted with one another, subsequent measurements on the ancilla can produce substantial conditional amplification, attenuation, or phase shift of ψ_{S}. We observe conditional signal power changes over a large range of 30, and phase shift up to π/2, induced by measurements in ancilla bases that differ only slightly from one another. The method is generically applicable to a variety of systems, and allows one to modify or boost a given interaction by trading in success probability for interaction strength.

The excimer laser has emerged as an efficacious treatment modality for many dermatologic diseases. The excimer laser is an alternative to standard narrowband ultraviolet B (NBUVB) phototherapy treatment in patients with limited disease. In comparison to standard NBUVB, the excimer laser requires fewer treatment sessions, has reduced treatment duration, requires a lower cumulative UVB dose, and limits UVB exposure to lesional skin. This review addresses the mechanism, safety, application, and efficacy of the excimer laser for the treatment of these conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Treatments used for managing atopic dermatitis (AD) may have adverse ocular effects that permanently affect vision. The objective of this review is to raise awareness among dermatologists regarding the potential ocular adverse effects of various AD therapies, including corticosteroids, calcineurin inhibitors, an interleukin-4 receptor α (IL-4Rα) antagonist, and phototherapy. Pertinent potential short- and long-term risks of these therapies include elevations in intraocular pressure from use of topical corticosteroids and conjunctivitis from use of dupilumab. Since some of these adverse effects may not exhibit symptomatology until permanent vision impairment occurs, it is important for dermatologists to understand these risks and proactively ensure their patients are receiving appropriate measures to prevent them.

Ocular diseases associated with atopic dermatitis (AD) may be sight-threatening. A general understanding of the pathophysiology, diagnosis, and treatment of atopic eye disease may assist dermatologists in knowing when to refer to ophthalmology and in co-managing these diseases with ophthalmologists. Ocular diseases associated with AD include eyelid dermatitis, keratoconjunctivitis, keratoconus, cataract, and retinal detachment. AD patients are also at higher risk for bacterial and viral ocular infections. The objective of this article is to provide a current review of ocular diseases that commonly affect AD patients. The pathogenesis, clinical manifestations, diagnosis, and treatment of ocular co-morbidities of AD will be discussed.

The field of quantum computing has grown from concept to demonstration devices over the past 20 years. Universal quantum computing offers efficiency in approaching problems of scientific and commercial interest, such as factoring large numbers, searching databases, simulating intractable models from quantum physics, and optimizing complex cost functions. Here, we present an 11-qubit fully-connected, programmable quantum computer in a trapped ion system composed of 13 171 Yb + ions. We demonstrate average single-qubit gate fidelities of 99.5[Formula: see text], average two-qubit-gate fidelities of 97.5[Formula: see text], and SPAM errors of 0.7[Formula: see text]. To illustrate the capabilities of this universal platform and provide a basis for comparison with similarly-sized devices, we compile the Bernstein-Vazirani and Hidden Shift algorithms into our native gates and execute them on the hardware with average success rates of 78[Formula: see text] and 35[Formula: see text], respectively. These algorithms serve as excellent benchmarks for any type of quantum hardware, and show that our system outperforms all other currently available hardware.

Moisturization is the pillar of daily skin care and has significant benefit in improving hydration, strengthening the skin barrier, and ameliorating inflammatory dermatoses. Bioactive ingredients such as endocannabinoids, bioactive lipids, growth factors, microbiome modulators, and antioxidant enzymes are increasingly being incorporated into moisturizer formulations. These novel ingredients have been shown to improve skin barrier function, upregulate barrier lipid synthesis, decrease itch and inflammation, and have antioxidative properties. In this article, we highlight evidence supporting their mechanisms of action and efficacy in atopic dermatitis, uremic pruritus, asteatotic eczema, acne vulgaris, and vitiligo., (© 2019 Wiley Periodicals, Inc.)

Purpose This study was conducted to examine the comparative effectiveness of 2 different approaches, 1 domain-specific and the other domain-general, to language and attention rehabilitation in participants with stroke-induced aphasia. The domain-specific treatment consisted of language-specific attention treatment (L-SAT), and the domain-general treatment consisted of direct attention training (DAT) using the computerized exercises included in Attention Process Training-3 (Sohlberg & Mateer, 2010). Method Four individuals with mild-moderate aphasia participated in this study. A randomized controlled cross-over single-subject design was used to assess the effectiveness of the 2 treatments administered in this study. Treatment outcomes were evaluated in terms of participants' task performance for each program, standardized language and attention measures, tests of functional abilities, and patient-reported outcomes. Results Visual comparisons demonstrated linear improvements following L-SAT and variable patterns following DAT. Omnibus effect sizes were statistically significant for 9 of the 13 L-SAT tasks. The weighted standardized effect sizes for posttreatment changes following L-SAT ranged from small to large, with the exception of 1 task. The average group gain following DAT was 5%. The Western Aphasia Battery-Revised Aphasia Quotients (Kertesz, 2007) demonstrated reliable improvements for 3 of the 4 participants following L-SAT, whereas only 1 of the participants improved reliably following DAT. The margins of improvements in functional language were substantially larger following L-SAT than DAT. Performance on the Test of Everyday Attention improved significantly for 2 participants following L-SAT and for 1 participant following DAT on selected Test of Everyday Attention (Robertson, Ward, Ridgeway, & Nimmo-Smith, 1994) subtests. Patient-reported outcomes for communication and attention following treatment favored L-SAT compared to DAT. Conclusions The results support the view that attention is allocated in ways that are particular to specific tasks rather than as a general resource that is allocated equivalently to all processing tasks. Domain-specific treatment for language deficits due to attentional impairment appears to be a suitable, if not preferable, approach for aphasia rehabilitation. Supplemental Material https://doi.org/10.23641/asha.8986427.

Introduction: Brodalumab is one of the most efficacious biologic agents available for psoriasis. It also has a unique mechanism; it is the only agent that blocks the entire interleukin 17 receptors instead of blocking individual cytokines. However, the main drawback is that brodalumab has an FDA mandated black box warning regarding suicide. This is an up-to-date article reviews the scientific validity of this issue with brodalumab and suicide. Areas covered: A worldwide literature search was conducted on the above issue regarding suicide risk and brodalumab. All relevant articles on this topic searchable in public domain were utilized. Expert opinion: The FDA black box warning is based on three completed suicides that happened in one research location out of 390 research sites worldwide. All three completed suicides have alternative explanations unrelated to brodalumab. The overall data from phase III clinical trials shows that psoriasis patients recorded significant improvement in depression after treatment with brodalumab. The overall impression is that the suicide issue is far from being scientifically validated and this is why the FDA itself stated in the package insert that "the cause and effect relationship these suicides and brodalumab has not been established."

Background: Atopic dermatitis (AD) is an extremely common childhood disease, with considerable impact on the quality of life of affected children and their families. While pruritus is the hallmark symptom of this disease, AD has been well-documented to impact patients beyond physical symptoms, resulting in behavior problems, mood disorders, and sleep disturbance., Objective: This literature review outlines how atopic dermatitis impacts the quality of life of families of children affected by AD., Methods: A total of 3436 articles were identified via an online search of the MEDLINE health literature database and were screened for relevance to quality of life impacts on families with children affected by AD., Results: Caring for children affected by AD can be an extremely time-consuming task that can impair personal relationships, decrease psychosocial functioning, and cause sleep loss among family members of affected patients. Additionally, AD may result in work absence or decreased work productivity for caregivers. Special diets, irritant and allergen avoidance strategies, and alternative therapies are commonly used by patients to manage their disease and require large amounts of family involvement., Conclusions: Atopic dermatitis can greatly decrease quality of life of families of affected children in various domains, including sleep, finances, and relationships. Early intervention and psychotherapy may be needed in some patients to address these quality of life impairments., (© 2018 Wiley Periodicals, Inc.)

Genital psoriasis affects approximately 63% of psoriasis patients at least once in their lifetime. More than any other area on the body, genital lesions significantly impair patients' psychologic well-being and quality of life. We aimed to systematically review the published evidence on the safety, efficacy, and tolerability of treatments of genital psoriasis and synthesize the available clinical data. A total of 1 randomized controlled trial, 11 open-label studies, and 26 case reports were included in our analysis, representing a total of 458 patients, of which 332 were adults and 126 were children. Topical corticosteroids were commonly used first-line for genital psoriasis and were well tolerated. Nonsteroidal agents, such as topical calcineurin inhibitors or vitamin D analogs, were also efficacious, but were often irritating. One systemic agent, ixekizumab, demonstrated efficacy in reducing genital psoriasis symptoms in a large, randomized, placebo-controlled trial. Various systemic and topical medications may improve genital psoriasis lesions, but there is a lack of high-quality evidence to guide clinical decision-making. Specific reporting of efficacy for genital psoriasis in larger controlled studies of psoriasis treatments are necessary to improve the available evidence regarding the optimal treatment regimen for genital psoriasis.

The American Academy of Dermatology (AAD) has prioritized skin cancer prevention efforts in 2018, as photoprotection measures adopted by the general public remain suboptimal. A large proportion of patients lack understanding of primary prevention methods for skin cancer, and mistruths in advertising may contribute significantly to this deficit. Sunscreen labels are often stacked with multiple claims of seemingly high significance, making it difficult for patients to differentiate their validity when selecting a sunscreen. The United States Food and Drug Administration (FDA) published its monograph in 2011 to address these controversies in sunscreen labeling, but the reliability of several other claims remain unclear. In this article, we discuss several claims commonly made on sunscreen labels, and address the truths and mistruths surrounding them., (© 2018 Wiley Periodicals, Inc.)

Atopic dermatitis (AD) is a bothersome and common skin disease affecting ∼10.7% of children in the United States. This skin condition significantly decreases quality of life in not only patients, but in their families as well. Pediatricians are often the first physicians to diagnose and manage these patients and thus are relied on by families to answer questions about this disease. AD is complex, multifactorial, and has historically had limited therapeutic options, but the landscape of this disease is now rapidly changing. Pathways contributing to the pathogenesis of this disease are continually being discovered, and new therapies for AD are being developed at an unprecedented rate. With this article, we will review the current guidelines regarding the management of AD, outline updates in the current understanding of its pathophysiology, and highlight novel developments available for the treatment of this burdensome disease., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Bhutani is an investigator for AbbVie, Janssen, Merck, Eli Lilly, and Strata Skin Sciences; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Introduction: We describe a novel device for rapid and economical minimal erythema dose testing in patients undergoing ultraviolet (UV) light phototherapy for treatment of skin diseases., Methods: A minimal erythema testing device was designed and created using transparent plastic sheeting and printed patterns with increasing ink density, allowing for graded UV transmission of 100%, 80%, 60%, 40%, 20%, and 10% energy through six 10-mm square apertures. The plastic sheet was placed in a UV-impenetrable and Velcro-fitted adjustable sleeve, designed to fit easily onto a patient's arm. A pilot validation study was performed, comparing this device with a commercially available windowed device in which the dose is controlled by varying the UV exposure time through sequential opening of each window. The pilot was conducted on healthy skin of two human subjects with different Fitzpatrick skin types., Results: In our subjects, tested with one device on each forearm, the minimal erythema dose (MED), judged visually, was identical. However, the test device allowed MED testing in 3 min compared with 15 min for the traditional device. The test device is equally effective for use with ultraviolet-A (UVA), narrowband ultraviolet-B (NB-UVB) and broadband ultraviolet-B (BB-UVB) wavelengths. The test device is economical, with manufacturing cost of less than US $2., Conclusion: We designed an MED testing device that is quick, accurate, cost-effective, and easy to use in the setting of a busy phototherapy practice. This device therefore has many advantages over existing MED testing approaches.

Inflammatory skin diseases are difficult to treat because of a lack of available treatment options for severe disease. However, recent advances have shown that vagus nerve stimulation can be used to decrease inflammation and reduce disease severity in rheumatoid arthritis and inflammatory bowel disease. Changes in cytokine profiles observed in these studies are similar to those seen with use of biologics in inflammatory skin disease, suggesting that they act along similar pathways to disrupt chronic inflammation and treat inflammatory disease. This commentary explores the existing evidence demonstrating the efficacy of neuromodulation in inflammatory disease, and outlines reasons why these findings could translate to the dermatology setting to treat inflammatory skin disease.

Background: Infant feeding in the first postnatal year of life has an important role in an infant's risk of developing food allergy. Consumer infant feeding advice is diverse and lacks consistency., Aim: The Australian Infant Feeding Summit was held with the aim of achieving national consensus on the wording of guidelines for infant feeding and allergy prevention., Methods: Two meetings were hosted by the Centre for Food and Allergy Research, the Australasian Society of Clinical Immunology and Allergy, and the Australian National Allergy Strategy. The first meeting of 30 allergy researchers, clinicians, and consumers assessed the evidence. The second consensus meeting involved 46 expert stakeholders including state and federal health care agencies, consumers, and experts in allergy, infant feeding, and population health., Results: Partner stakeholders agreed on consensus wording for infant feeding advice: CONCLUSIONS: Consensus was achieved in a context in which there is a high prevalence of food allergy. Guidelines for other countries are being updated. Provision of consistent wording related to infant feeding to reduce food allergy risk will ensure clear consumer advice., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

We demonstrate cavity cooling of all motional degrees of freedom of an atomic ensemble using light that is far detuned from the atomic transitions by several gigahertz. The cooling is achieved by cavity-induced frequency-dependent asymmetric enhancement of the atomic emission spectrum, thereby extracting thermal kinetic energy from the atomic system. Within 100 ms, the atomic temperature is reduced from 200 to 10  μK, where the final temperature is mainly limited by the linewidth of the cavity. In principle, the technique can be applied to molecules and atoms with complex internal energy structure.

The need for a specific, language-based treatment approach to aphasic impairments associated with attentional deficits is well documented. We describe language-specific attention treatment, a specific skill-based approach for aphasia that exploits increasingly complex linguistic tasks that focus attention. The program consists of eight tasks, some with multiple phases, to assess and treat lexical and sentence processing. Validation results demonstrate that these tasks load on six attentional domains: (1) executive attention; (2) attentional switching; (3) visual selective attention/processing speed; (4) sustained attention; (5) auditory-verbal working memory; and (6) auditory processing speed. The program demonstrates excellent inter- and intrarater reliability and adequate test-retest reliability. Two of four people with aphasia exposed to this program demonstrated good language recovery whereas three of the four participants showed improvements in auditory-verbal working memory. The results provide support for this treatment program in patients with aphasia having no greater than a moderate degree of attentional impairment., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Deterministic optical quantum logic requires a nonlinear quantum process that alters the phase of a quantum optical state by π through interaction with only one photon. Here, we demonstrate a large conditional cross-phase modulation between a signal field, stored inside an atomic quantum memory, and a control photon that traverses a high-finesse optical cavity containing the atomic memory. This approach avoids fundamental limitations associated with multimode effects for traveling optical photons. We measure a conditional cross-phase shift of [Formula: see text] (and up to [Formula: see text] by postselection on photons that remain in the system longer than average) between the retrieved signal and control photons, and confirm deterministic entanglement between the signal and control modes by extracting a positive concurrence. By upgrading to a state-of-the-art cavity, our system can reach a coherent phase shift of π at low loss, enabling deterministic and universal photonic quantum logic., Competing Interests: The authors declare no conflict of interest.

Asymmetric cell division (ACD) in a perpendicular orientation promotes cell differentiation and organizes the stratified epithelium. However, the upstream cues regulating ACD have not been identified. Here, we report that phosphoinositide-dependent kinase 1 (PDK1) plays a critical role in establishing ACD in the epithelium. Production of phosphatidyl inositol triphosphate (PIP3) is localized to the apical side of basal cells. Asymmetric recruitment of atypical protein kinase C (aPKC) and partitioning defective (PAR) 3 is impaired in PDK1 conditional knockout (CKO) epidermis. PDK1(CKO) keratinocytes do not undergo calcium-induced activation of aPKC or IGF1-induced activation of AKT and fail to differentiate. PDK1(CKO) epidermis shows decreased expression of Notch, a downstream effector of ACD, and restoration of Notch rescues defective expression of differentiation-induced Notch targets in vitro. We therefore propose that PDK1 signaling regulates the basal-to-suprabasal switch in developing epidermis by acting as both an activator and organizer of ACD and the Notch-dependent differentiation program., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To date, patients with pre-existing autoimmune conditions have been excluded from immunotherapy trials out of concern for severe autoimmune exacerbations., Case Presentation: We describe the first case of a patient with metastatic cKIT mutated acral melanoma, brain metastasis, and pre-existing severe autoimmune bullous pemphigoid (BP) with stable and asymptomatic disease 10 months after treatment with pembrolizumab. The patient experienced severe BP exacerbation after therapy with ipilimumab requiring systemic immune suppression, but nonetheless pembrolizumab was administered on further disease progression., Conclusions: This case suggests that pembrolizumab may confer more benefit than risk even in patients with known severe autoimmune conditions who require intermittent systemic immunosuppression.

We report the continuous and partially nondestructive measurement of optical photons. For a weak light pulse traveling through a slow-light optical medium (signal), the associated atomic-excitation component is detected by another light beam (probe) with the aid of an optical cavity. We observe strong correlations of g_{sp}^{(2)}=4.4(5) between the transmitted signal and probe photons. The observed (intrinsic) conditional nondestructive quantum efficiency ranges between 13% and 1% (65% and 5%) for a signal transmission range of 2% to 35%, at a typical time resolution of 2.5  μs. The maximal observed (intrinsic) device nondestructive quantum efficiency, defined as the product of the conditional nondestructive quantum efficiency and the signal transmission, is 0.5% (2.4%). The normalized cross-correlation function violates the Cauchy-Schwarz inequality, confirming the nonclassical character of the correlations.

The globally warm climate of the early Pliocene gradually cooled from 4 million years ago, synchronous with decreasing atmospheric CO2 concentrations. In contrast, palaeoceanographic records indicate that the Nordic Seas cooled during the earliest Pliocene, before global cooling. However, a lack of knowledge regarding the precise timing of Nordic Seas cooling has limited our understanding of the governing mechanisms. Here, using marine palynology, we show that cooling in the Nordic Seas was coincident with the first trans-Arctic migration of cool-water Pacific mollusks around 4.5 million years ago, and followed by the development of a modern-like Nordic Seas surface circulation. Nordic Seas cooling precedes global cooling by 500,000 years; as such, we propose that reconfiguration of the Bering Strait and Central American Seaway triggered the development of a modern circulation in the Nordic Seas, which is essential for North Atlantic Deep Water formation and a precursor for more widespread Greenland glaciation in the late Pliocene.

Deterministic photon-photon interactions are a long-standing goal in optical science. Using an atomic ensemble inside a cavity, we demonstrate the mutual cross modulation of two continuous light beams at the level of individual photons. The originally uncorrelated beams derived from independent lasers become anticorrelated, as evidenced by an equal-time cross-correlation function g^{(2)}=0.89(1), showing that one photon in one beam extinguishes a photon in the other beam with a probability of 11(1)%. With further technical improvements, our approach should enable the nondestructive continuous detection of traveling optical photons.

The realization of an all-optical transistor, in which one "gate" photon controls a "source" light beam, is a long-standing goal in optics. By stopping a light pulse in an atomic ensemble contained inside an optical resonator, we realized a device in which one stored gate photon controls the resonator transmission of subsequently applied source photons. A weak gate pulse induces bimodal transmission distribution, corresponding to zero and one gate photons. One stored gate photon produces fivefold source attenuation and can be retrieved from the atomic ensemble after switching more than one source photon. Without retrieval, one stored gate photon can switch several hundred source photons. With improved storage and retrieval efficiency, our work may enable various new applications, including photonic quantum gates and deterministic multiphoton entanglement.

Quantum fluctuations of the electromagnetic vacuum are responsible for physical effects such as the Casimir force and the radiative decay of atoms, and set fundamental limits on the sensitivity of measurements. Entanglement between photons can produce correlations that result in a reduction of these fluctuations below the ordinary vacuum level, allowing measurements that surpass the standard quantum limit in sensitivity. The effects of such 'squeezed states' of light on matter were first considered in a prediction of the radiative decay rates of atoms in squeezed vacuum. Despite efforts to demonstrate such effects in experiments with natural atoms, a direct quantitative observation of this prediction has remained elusive. Here we report a twofold reduction of the transverse radiative decay rate of a superconducting artificial atom coupled to continuum squeezed vacuum. The artificial atom is effectively a two-level system formed by the strong interaction between a superconducting circuit and a microwave-frequency cavity. A Josephson parametric amplifier is used to generate quadrature-squeezed electromagnetic vacuum. The observed twofold reduction in the decay rate of the atom allows the transverse coherence time, T2, to exceed the ordinary vacuum decay limit, 2T1. We demonstrate that the measured radiative decay dynamics can be used to reconstruct the Wigner distribution of the itinerant squeezed state. Our results confirm a canonical prediction of quantum optics and should enable new studies of the quantum light-matter interaction.