Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives.

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

Acrodermatitis continua of Hallopeau: clinical perspectives.

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

Emerging Methods to Objectively Assess Pruritus in Atopic Dermatitis.

INTRODUCTION:Atopic dermatitis (AD) is an inflammatory skin disease with a chronic, relapsing course. Clinical features of AD vary by age, duration, and severity but can include papules, vesicles, erythema, exudate, xerosis, scaling, and lichenification. However, the most defining and universal symptom of AD is pruritus. Pruritus or itch, defined as an unpleasant urge to scratch, is problematic for many reasons, particularly its negative impact on quality of life. Despite the profoundly negative impact of pruritus on patients with AD, clinicians and researchers lack standardized and validated methods to objectively measure pruritus. The purpose of this review is to discuss emerging methods to assess pruritus in AD by describing objective patient-centered tools developed or enhanced over the last decade that can be utilized by clinicians and researchers alike. METHODS:This review is based on a literature search in Medline, Embase, and Web of Science databases. The search was performed in February 2019. The keywords were used "pruritus," "itch," "atopic dermatitis," "eczema," "measurements," "tools," "instruments," "accelerometer," "wrist actigraphy," "smartwatch," "transducer," "vibration," "brain mapping," "magnetic resonance imaging," and "positron emission tomography." Only articles written in English were included, and no restrictions were set on study type. To focus on emerging methods, prioritization was given to results from the last decade (2009-2019). RESULTS:The search yielded 49 results in PubMed, 134 results in Embase, and 85 results in Web of Science. Each result was independently reviewed in a standardized manner by two of the authors (M.S., K.L.), and disagreements between reviewers were resolved by consensus. Relevant findings were categorized into the following sections: video surveillance, acoustic surveillance, wrist actigraphy, smart devices, vibration transducers, and neurological imaging. Examples are provided along with descriptions of how each technology works, instances of use in research or clinical practice, and as applicable, reports of validation studies and correlation with other methods. CONCLUSION:The variety of new and improved methods to evaluate pruritus in AD is welcomed by clinicians, researchers, and patients alike. Future directions include next-generation smart devices as well as exploring new territories, such as identifying biomarkers that correlate to itch and machine-learning programs to identify itch processing in the brain. As these efforts continue, it will be essential to remain patient-centered by developing techniques that minimize discomfort, respect privacy, and provide accurate data that can be used to better manage itch in AD

Gaming, Driving & Independence

The digital narratives were co-created with participants across a set of online, face-to-face workshops in addition to focus groups and follow-up one-to-one interviews. Each of the participants with the project team to examine, explore and create visual digital accessible books of their personal experiences with everyday technologies and share the impact upon their lives. The impact is positive and also, at times, negative with significant challenges due to the biases with AI technology design, especially for people with disabilities who are from minority diverse backgrounds and have access to few resources to fund comprehensive assistive technologies. Over a period of two years of working, research participants were able to critically engage with AI technologies and create these books to publicly disseminate their diverse experiences to enable others to learn from them

Autonomy, Freedom & Mobility

This book was created as part of the ADDEPT - Autonomy, Diversity & Disability: Everyday Practices of Technology funded by ARC Linkage Project LP190100099. The digital narratives were co-created with participants across a set of online, face-to-face workshops in addition to focus groups and follow-up one-to-one interviews. Each of the participants worked with the project team to examine, explore and create visual digital accessible books from their personal experiences with everyday technologies and share the impact upon their lives. The impact is mostly positive, particularly with appropriate support. But also, at times, negative with significant challenges due to the biases with technology design. This is especially so for people with disabilities who are from minority diverse backgrounds. Few have access to the necessary resources to fund comprehensive assistive technologies. Over a period of two years of working, research participants were able to critically engage with AI technologies and create these books to publicly disseminate their diverse experiences to enable others to learn from them. The stories are developed from the narratives of the participants, using AI technologies such as Mid Journey

Lifelong Learning & Remembering Sadie Daher

This book was created as part of the ADDEPT - Autonomy, Diversity & Disability: Everyday Practices of Technology funded by ARC Linkage Project LP190100099. The digital narratives were co-created with participants across a set of online, face-to-face workshops in addition to focus groups and follow-up one-to-one interviews. Each of the participants with the project team to examine, explore and create visual digital accessible books of their personal experiences with everyday technologies and share the impact upon their lives. For the alternative, text to voice, EPUB version please visit https://www.westernsydney.edu.au/ics/projects/autonomy,_diversity_and_disability_everyday_practices_of_technolog

Languages, Learning & Inclusion

This book was created as part of the ADDEPT - Autonomy, Diversity & Disability: Everyday Practices of Technology funded by ARC Linkage Project LP190100099. The digital narratives were co-created with participants across a set of online, face-to-face workshops in addition to focus groups and follow-up one-to-one interviews. Each of the participants with the project team to examine, explore and create visual digital accessible books of their personal experiences with everyday technologies and share the impact upon their lives. The impact is positive and also, at times, negative with significant challenges due to the biases with AI technology design, especially for people with disabilities who are from minority diverse backgrounds and have access to few resources to fund comprehensive assistive technologies. Over a period of two years of working, research participants were able to critically engage with AI technologies and create these books to publicly disseminate their diverse experiences to enable others to learn from them

[Ca2+]i in Human Heart Failure: A Review and Discussion of Current Areas of Controversy.

Multiple abnormalities have been reported in the setting of human heart failure. It is unclear whether detected changes reflect adaptive alterations in myocardium subjected to increased and sustained hemodynamic overload or are pathogenic to the disease process. As a result of the observation that the primary defect in heart failure is decreased pump function, investigators have concentrated their efforts on determining systolic [Ca2+]i as a logical corollary and a causative mechanism for contractile dysfunction. A simple cause and effect relationship has therefore been proposed with regard to contractile dysfunction and [Ca2+]i. Yet some investigators have found no difference in peak systolic [Ca2+]i between failing and non-failing human myocardium, whereas others have found peak [Ca2+]i to be significantly reduced in failing hearts. Resting calcium concentrations have been reported either to be elevated in failing human myocardium or not different from non-failing human myocardium. Investigators should now appreciate that the force-calcium relationship is not a simple relationship. One must take into account the prolonged time course and slowed mobilization of [Ca2+]i as opposed to simply peak [Ca2+]i. When put in perspective of mechanisms and determinants of the Ca(2+)-force relationship, we begin to realize that failing human myocardium has the "potential" to generate normal levels of force. Only when stressed by [Ca2+]i overload and/or frequency perturbation does myocardium from patients with end-stage heart disease demonstrate contractile failure. Although [Ca2+]i availability and mobilization are likely to play a role in the systolic as well as diastolic dysfunction reported in human heart failure, it is likely that other mechanisms are involved as well (e.g., myocardial energetics). Myocardial energetics is directly related to [Ca2+]i and mobilization in failing human myocardium, because metabolites, e.g., ADP, inhibit pumps, such as sarcoplasmic reticulum Ca2+ ATPase activity. We therefore conclude that there is a role for intracellular calcium mobilization and myocardial energetics for systolic and diastolic dysfunction seen in human heart failure

A Co-Citation Analysis of Cross-Disciplinarity in the Empirically-Informed Philosophy of Mind

Empirically-informed philosophy of mind (EIPM) has become a dominant research style in the 21st century. EIPM relies on empirical results in various ways. However, the extant literature lacks an empirical description of how EIPM philosophers rely on empirical results. Moreover, though EIPM is essentially a form of cross-disciplinary research, it has not been analyzed as cross-disciplinary research so far. We aim to fill the above two gaps in the literature by producing quantitative and qualitative descriptions of EIPM as a kind of cross-disciplinary research. Our descriptions aim to enable metaphilosophers to evaluate EIPM methodologically and epistemically. Our analyses use co-citation and categorization analyses informed by the literature on interdisciplinarity. We present five sets of descriptions and identify the three most common types of cross-disciplinary interactions in EIPM. The resulting descriptions enable us to locate two metaphilosophical challenges for EIPM philosophers. One concerns how they should incorporate empirical results in different disciplinary contexts, and the other concerns which theoretical virtue(s) they should aim for when tinkering with scientific theories

In Situ TEM Study of the Degradation of PbSe Nanocrystals in Air

PbSe nanocrystals have attracted widespread attention due to a variety of potential applications. However, the practical utility of these nanocrystals has been hindered by their poor air stability, which induces undesired changes in the optical and electronic properties. An understanding of the degradation of PbSe nanocrystals when they are exposed to air is critical for improving the stability and enhancing their applications. Here, we use in situ transmission electron microscopy (TEM) with an environmental cell connected to air to study PbSe nanocrystal degradation triggered by air exposure. We have also conducted a series of complementary studies, including in situ environmental TEM study of PbSe nanocrystals exposed to pure oxygen and PbSe nanocrystals in H2O using a liquid cell, and ex situ experiments, such as O2 plasma treatment and thermal heating of PbSe nanocrystals under different air exposure. Our in situ observations reveal that when PbSe nanocrystals are exposed to air (or oxygen) under electron beam irradiation, they experience a series of changes, including shape evolution of individual nanocrystals with the cuboid intermediates, coalescence between nanocrystals, and formation of PbSe thin films through drastic solid-state fusion. Further studies show that the PbSe thin films transform into an amorphous Pb rich phase or eventually pure Pb, which suggest that Se reacts with oxygen and can be evaporated under electron beam illumination. These various in situ and ex situ experimental results indicate that PbSe nanocrystal degradation in air is initiated by the dissociation and removal of ligands from the PbSe nanocrystal surface