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This post hoc analysis evaluated efficacy and safety of roflumilast cream in patients with psoriasis involving the face/neck or intertriginous areas from a phase IIb trial. Of 331 patients enrolled in the phase IIb trial, 160 had psoriasis involving the face/neck and/or intertriginous areas. Once-daily roflumilast cream was well tolerated with efficacy across multiple endpoints in these patients.

IBAPA is the culmination of a decades-long journey in which there has been much progress in the development of Native American economies, but still rather modest progress in the development of Native American academic theory in the fields of business and public administration. There are multiple reasons why academic progress has been sluggish. One of the primary reasons is the lack of business professors who publish research about our community. This journal seeks to address this problem straight on. The editorial provides background on our purpose.

Characterizing the spatial distribution of ruptures from historical and recent earthquakes is key to understanding the seismic cycle of large earthquakes in subduction zones, and thus to assessing the potential risks associated with future earthquakes. Central Chile (35$^{\circ}$S-38$^{\circ}$S) has been continuously affected by large earthquakes, such as the 2010 Maule (Mw 8.8) and the 1835 earthquakes witnessed by Robert Fitzroy (HMS Beagle captain). Here, we identify the rupture pattern and tsunami propagation of the 1751, 1835, and 2010 mega-earthquakes, events that overlapped in central Chile, by compiling historical records and applying robust statistical tools. We used an adaptation of a logic tree methodology to generate random sources of slip distribution for each event, constrained by tsunami and deformation data. We find that the three events studied have different slip peaks. The 1751 earthquake has the largest slip with a maximum patch of $\sim$ 26 m, while the 2010 and 1835 earthquakes reach slips of $\sim$ 16 m and $\sim$ 10 m, respectively. Our results show that a part of the segment between 36$^{\circ}$S and 37$^{\circ}$S was consistently affected by large earthquakes, but with different slip and depth. The northern part of the segment accumulated energy for at least 300 years and was released by the 2010 earthquake. This work provides important information for identifying rupture patterns between historical and recent earthquakes, and highlights the importance of extending the time scale of earthquake slip distribution analyses to multiple cycles to describe both earthquake characteristics and their spatial relationship, and thus gain a better understanding of seismic hazard.

Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and in silico experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer. We demonstrate that Col3-deficient, human fibroblasts produce tumor-permissive collagen matrices that drive cell proliferation and suppress apoptosis in noninvasive and invasive breast cancer cell lines. In human TNBC biopsy samples, we demonstrate elevated deposition of Col3 relative to type I collagen (Col1) in noninvasive compared to invasive regions. Similarly, in silico analyses of over 1000 breast cancer patient biopsies from The Cancer Genome Atlas BRCA cohort revealed that patients with higher Col3:Col1 bulk tumor expression had improved overall, disease-free and progression-free survival relative to those with higher Col1:Col3 expression. Using an established 3D culture model, we show that Col3 increases spheroid formation and induces formation of lumen-like structures that resemble non-neoplastic mammary acini. Finally, our in vivo study shows co-injection of murine breast cancer cells (4T1) with rhCol3-supplemented hydrogels limits tumor growth and decreases pulmonary metastatic burden compared to controls. Taken together, these data collectively support a tumor-suppressive role for Col3 in human breast cancer and suggest that strategies that increase Col3 may provide a safe and effective modality to limit recurrence in breast cancer patients.

Janet DuBois,1 Suzanne Bruce,2 Daniel Stewart,3 Steven Kempers,4 Christy Harutunian,5 Terry Boodhoo,5 Amy Weitzenfeld,6 Joan-En Chang-Lin5 1DermResearch, Inc., Austin, TX, USA; 2Suzanne Bruce and Associates, PA, Houston, TX, USA; 3Midwest Center for Dermatology & Cosmetic Surgery, Clinton Township, MI, USA; 4Associated Skin Care Specialists, Fridley, MN, USA; 5Allergan Aesthetics, an AbbVie Company, Irvine, CA, USA; 6Allergan Aesthetics, an AbbVie Company, Madison, NJ, USACorrespondence: Joan-En Chang-LinClinical Development, Allergan Aesthetics, an AbbVie Company, 2525 Dupont Dr, Irvine, CA, 92612, USATel +1 714-246-4680Email joanen.lin@abbvie.comPurpose: To evaluate oral setipiprant versus placebo for scalp hair growth in men with androgenetic alopecia (AGA).Patients and Methods: Males aged 18 to 49 years with AGA were enrolled in a double-blind, multicenter, 32-week, phase 2a trial; randomized to twice-daily (BID) 1000-mg (2× 500 mg for a total daily dose of 2000 mg) setipiprant tablets or placebo for 24 weeks; and assessed at weeks 4, 8, 16, and 24, with a week 32 follow-up. The study initially included a finasteride 1-mg once-daily group, removed by protocol amendment. Changes from baseline to week 24 in target area hair count (TAHC) and blinded Subject Self-Assessment (SSA) of target area photographs were coprimary efficacy endpoints. Hair growth was also evaluated using blinded Investigator Global Assessment (IGA). Safety assessments included adverse events (AEs) and clinical laboratory tests. Analysis of covariance models were used to test statistical significance for TAHC, SSA, and IGA. Data were summarized without statistical analysis for finasteride.Results: Randomized subjects (N=169) included 74 placebo, 83 setipiprant, and 12 finasteride subjects; 117 (69.2%) and 113 (66.9%) subjects completed week 24 and 32 visits, respectively. Treatment groups had similar baseline characteristics. Neither coprimary efficacy endpoint was met. At week 24, TAHC and SSA findings indicated no hair growth improvements with setipiprant versus placebo. Setipiprant also did not improve hair growth versus placebo per the IGA. Treatment-related AEs, all mild or moderate in severity, occurred in 12.3%, 25.9%, and 25.0% of the placebo, setipiprant, and finasteride groups, respectively. Two treatment-emergent serious AEs (TESAEs), cellulitis and multiple sclerosis, were reported in the placebo group, both unrelated to treatment. No TESAEs were reported with setipiprant or finasteride.Conclusion: Setipiprant 1000 mg BID was safe and well tolerated but did not demonstrate efficacy versus placebo for scalp hair growth in men with AGA.Keywords: scalp, hair loss, hair growth and development, prostaglandin receptors

PurposeMeasuring the efficacy of workplace culture-shift efforts presented a substantial challenge in the author's research exploring how culture shifts during deliberate change initiatives. In response to this challenge this conceptual article proposes that the relative value participants attribute to desired culture outcomes can function as a proxy for measuring culture shift over time, providing applied researchers and practitioners with a simple way to measure efficacy of change initiatives.Design/methodology/approachThis conceptual article reviews the difficulties of defining and measuring workplace culture using widely known, contemporary models and instruments. It then builds an argument for using differential measurement of the relative value attributed to culture shift outcomes (valuing) as a proxy for workplace culture shift, followed by discussion of how to conduct measurement.FindingsThis article deductively demonstrates that parsimonious measurement of culture shift is not only simple and feasible, but that practitioners and researchers alike can use a valuing approach to determine the efficacy of efforts to shift workplace culture.Originality/valueUsed to complement existing methods and instruments, or on its own, this approach to measurement can build deeper insights into what is going on during deliberate change initiatives, while answering the reflexive questions “are we doing the right things,” and “are we doing those things the right way?”

Chronotype can be defined as an overt expression of circadian rhythmicity in an individual that dictates tendencies towards being a morning or evening person - also referred to as 'morningness' or 'eveningness.' Chronotypes generally impact preferred bed and wake times, in addition to a range of personal and social factors. This study examined how matching/mismatching chronotypes within relationships impact sexual satisfaction and sleep quality. A sample of 32 couples (52% females, 38.3 ± 11.7 years) each completed an online survey that assessed chronotype (reduced Morningness Eveningness Questionnaire), sleep (Pittsburgh Sleep Quality Index), and sexual satisfaction (Index of Sexual Satisfaction). Partner surveys were matched to identify whether chronotypes were matching or mismatching. Couples with matched chronotypes reported greater sexual satisfaction than those with mismatched chronotypes, F(1, 58) = 19.57, p .001. Matched couples also reported better sleep quality than couples whose chronotypes were mismatched, F(1,62) = 48.02, p .001. The individual chronotype did not seem to impact on sleep quality or sexual satisfaction. To improve sleep quality and sexual satisfaction, strategies (e.g., circadian phase advance or delay) could be used to increase circadian alignment between members of a couple.

In 2021, during a drug-related death crisis in the UK, the Government published its ten-year drugs strategy. This article, written in collaboration with the Faculty of Public Health and the Association of Directors of Public Health, assesses whether this Strategy is evidence-based and consistent with international calls to promote public health approaches to drugs, which put ‘people, health and human rights at the centre’. Elements of the Strategy are welcome, including the promise of significant funding for drug treatment services, the effects of which will depend on how it is utilized by services and local commissioners and whether it is sustained. However, unevidenced and harmful measures to deter drug use by means of punishment continue to be promoted, which will have deleterious impacts on people who use drugs. An effective public health approach to drugs should tackle population-level risk factors, which may predispose to harmful patterns of drug use, including adverse childhood experiences and socioeconomic deprivation, and institute evidence-based measures to mitigate drug-related harm. This would likely be more effective, and just, than the continuation of policies rooted in enforcement. A more dramatic re-orientation of UK drug policy than that offered by the Strategy is overdue.

Colonial Chile is known in part for its continual military conflicts that forced the Spanish Crown to station there a permeant standing army. This paper looks at a unique aspect of this conflict, in that it focuses on the administrative details of a specially created system by which common soldiers could purchase officer´s titles and form part of a newly created semi-retired officer corps. Many of these officers on paper were then able to enter the civilian society with an acquired level of nobility that permitted them to receive specific economic benefits reserved for those of noble birth

Electronic medical records have made great advances in the provision of quality health care but have increased physician workload and often limit face-to-face time with patients. These effects are particularly felt in the academic dermatology clinic, a critical time of practice development. Time constraints from implementation of electronic medical records have resulted in low patient volume and reduced educational opportunities. A review of the literature suggests that utilizing scribes as physician aides in the academic dermatology setting may increase patient access, clinic volume, educational experience, and hospital revenue.

The role and function of a professional clinical counselor require a breadth of knowledge and skill. But it is more than just knowing a theory or how to implement an intervention; clinical counselors need to develop a counselor identity that is centered on cultural sensitivity, cultural humility, and social justice. Regardless of the types of services clinical counselors are offering, whether it’s individual counseling, group counseling, art therapy, or psychosocial evaluations, who we are as a profession needs to be expressed in every aspect of our work. The guiding principle of ethical practice should be the platform on which our identity as counselors is built upon. I had the opportunity to interview Courtnee Reis, a Licensed Professional Clinical Counselor in California who provides services to clients from diverse backgrounds drawing upon post-modern narrative therapy and strengths-based practices. Her work demonstrates the ever-growing need to provide competent and ethical services while holding space for each of our clients to live a meaningful, productive, and beneficial life. The following is an account of our interview.

Confidence in vaccination presents a global challenge, and innovative interventions are needed to address this reluctance. This thesis presents the findings from a pragmatic randomised controlled trial (RCT) designed to ascertain whether an educational card game provided to high school students as an incentive within the context of a local government school-based vaccination programme was associated with an increase in the return of consent to vaccinate forms, vaccine hesitancy or increased confidence in vaccination.

Biodiversity conservation decisions are difficult, especially when they involve differing values, complex multidimensional objectives, scarce resources, urgency, and considerable uncertainty. Decision science embodies a theory about how to make difficult decisions and an extensive array of frameworks and tools that make that theory practical. We sought to improve conceptual clarity and practical application of decision science to help decision makers apply decision science to conservation problems. We addressed barriers to the uptake of decision science, including a lack of training and awareness of decision science; confusion over common terminology and which tools and frameworks to apply; and the mistaken impression that applying decision science must be time consuming, expensive, and complex. To aid in navigating the extensive and disparate decision science literature, we clarify meaning of common terms: decision science, decision theory, decision analysis, structured decision-making, and decision-support tools. Applying decision science does not have to be complex or time consuming; rather, it begins with knowing how to think through the components of a decision utilizing decision analysis (i.e., define the problem, elicit objectives, develop alternatives, estimate consequences, and perform trade-offs). This is best achieved by applying a rapid-prototyping approach. At each step, decision-support tools can provide additional insight and clarity, whereas decision-support frameworks (e.g., priority threat management and systematic conservation planning) can aid navigation of multiple steps of a decision analysis for particular contexts. We summarize key decision-support frameworks and tools and describe to which step of a decision analysis, and to which contexts, each is most useful to apply. Our introduction to decision science will aid in contextualizing current approaches and new developments, and help decision makers begin to apply decision science to conservation problems.Las decisiones sobre la conservación de la biodiversidad son difíciles de tomar, especialmente cuando involucran diferentes valores, objetivos multidimensionales complejos, recursos limitados, urgencia y una incertidumbre considerable. Las ciencias de la decisión incorporan una teoría sobre cómo tomar decisiones difíciles y una variedad extensa de marcos de trabajo y herramientas que transforman esa teoría en práctica. Buscamos mejorar la claridad conceptual y la aplicación práctica de las ciencias de la decisión para ayudar al órgano decisorio a aplicar estas ciencias a los problemas de conservación. Nos enfocamos en las barreras para la aceptación de las ciencias de la decisión, incluyendo la falta de capacitación y de conciencia por estas ciencias; la confusión por la terminología común y cuáles herramientas y marcos de trabajo aplicar; y la impresión errónea de que la aplicación de estas ciencias consume tiempo y debe ser costosa y compleja. Para asistir en la navegación de la literatura extensa y dispar de las ciencias de la decisión, aclaramos el significado de varios términos comunes: ciencias de la decisión, teoría de la decisión, análisis de decisiones, toma estructurada de decisiones y herramientas de apoyo para las decisiones. La aplicación de las ciencias de la decisión no tiene que ser compleja ni debe llevar mucho tiempo; de hecho, todo comienza con saber cómo pensar detenidamente en los componentes de una decisión mediante el análisis de decisiones (es decir, definir el problema, producir objetivos, desarrollar alternativas, estimar consecuencias y realizar compensaciones). Lo anterior se logra de mejor manera mediante la aplicación de una estrategia prototipos rápidos. En cada paso, las herramientas de apoyo para las decisiones pueden proporcionar visión y claridad adicionales, mientras que los marcos de apoyo para las decisiones (p.ej.: gestión de amenazas prioritarias y planeación sistemática de la conservación) pueden asistir en la navegación de los diferentes pasos de un análisis de decisiones para contextos particulares. Resumimos los marcos de trabajo y las herramientas más importantes de apoyo para las decisiones y describimos el paso, y el contexto, del análisis de decisiones para el que es más útil aplicarlos. Nuestra introducción a las ciencias de la decisión apoyará en la contextualización de las estrategias actuales y los nuevos desarrollos, y ayudarán al órgano decisorio a comenzar a aplicar estas ciencias en los problemas de conservación.

Early detection of invasive species is an important predictor of management success. Non-native narrow-leaved cattail (Typha angustifolia) has been detected in the Fraser River Estuary (FRE) in recent decades, but questions around their degree of establishment, and the potential emergence of hybrid cattail (Typha x glauca), remain unanswered. This study models the current and potential future distribution of non-native cattails in the FRE using a unique combination of spectral imagery analysis and species distribution modelling. Contrary to our expectation, we find that non-native cattails are already widespread, currently occupying approximately 4% of FRE tidal marshes. Though never formally recorded in the FRE, hybrid cattail is the more abundant of the two taxa, suggesting that heterosis may be facilitating this invasion. In our species distribution model, we distinguish between site suitability (ability to establish and persist) and site susceptibility (risk of being colonized when suitable). Our model predicts that 28% of the estuary has > 50% probability of suitability, and 21% has > 50% probability of susceptibility to non-native Typha, indicating the scale of this invasion may increase over time. Restoration projects had proportionally more cattail, susceptible habitat, and suitable habitat than the overall estuary, casting doubt on their effectiveness at mitigating wetland destruction. Due to their resemblance to native Typha latifolia, these cattails qualify as cryptic invaders, which explains how they were able to establish and remain undetected for decades. Regional eradication is unlikely given the extent of invasion, therefore management should prioritize areas of high conservation and cultural values.

Throughout history, humans have settled in areas of high biodiversity. Today these areas are home to our biggest urban centers with biodiversity at increasing risk from escalating cumulative threats. Identifying the management strategies to conserve species within such regions, and ensuring effective governance to oversee their implementation, presents enormous challenges. Using a novel Priority Threat Management (PTM) approach that calculates the cost‐effectiveness of conservation action and co‐governance, we discover that the 102 species at risk of local extinction within Canada's most diverse, heavily urbanized coastal region, the Fraser River estuary, require urgent investment in management strategies costing an estimated CAD$381 M over 25 years. Our study also suggests that co‐governance underpins conservation success in urban areas, by increasing the feasibility of management strategies. This study underscores that biodiversity conservation in heavily urbanized areas is not a lost cause but does require strategic planning, attention to governance, and large‐scale investment.

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Tribally owned American Indian enterprises provide a unique cross-cultural setting for emerging Native American business leaders. This article examines the manner in which American Indian leaders negotiate the boundaries between their indigenous organizations and the nonindigenous communities in which they do business. Through a series of qualitative interviews, we find that American Indian business leaders fall back on a strong sense of “self,” which allows them to maintain effective leadership across boundaries. This is highly consistent with theories of authentic leadership. Furthermore, we find that leaders define self through their collective identity, which is heavily influenced by tribal affiliation and tribal culture. We add to the literature on authentic leadership by showing the role that culture and collective identity have in creating leader authenticity within the indigenous community.

Background Canine rabies is endemic in Ethiopia and presents a significant burden for both animal and human health. We investigate barriers to dog vaccination in Addis Ababa, Ethiopia. These results can be utilized to improve and target future rabies control efforts. Methodology/Principle findings During May of 2017, dog owners were surveyed during a free canine rabies vaccination programs that utilized both door-to-door (DtD) and central point (CP) vaccination methods. Surveys collected information on preferences for rabies vaccine delivery and were administered in Amharic. A total of 1057 surveys were completed. Of those surveyed, 62.4 % indicated that their dogs had been vaccinated against rabies within the last year. Commonly reported barriers to vaccination were a lack of awareness that dogs required rabies vaccines (18.1 %) and lack of knowledge about where to find vaccine (15.0 %). The median price owners were willing to pay for vaccination was 25 birr ($0.91 USD) and the median distance willing to travel was 1.0 km; however, 48.9 % of those surveyed during DtD were unwilling to travel at all. We identified 3 classes of respondents who were grouped due to their responses by latent class analysis: ‘the Unaware’, ‘the Vaccinators’, and ‘the Multiple Barriers’. Conclusions/Significance Although many respondents were willing to pay for rabies vaccine (94.0 %); the preferred cost (median) was less than the actual cost of providing the vaccine. This supports the need for reduced-cost or free vaccine to achieve and sustain the 70 % vaccine coverage target threshold for canine rabies elimination. Additionally, a significant portion (41.5 %) of those surveyed indicated that they were unwilling to travel in order to have their dog vaccinated. The latent class analysis provides useful guidance on how to reach target vaccination. Owners from ‘the Unaware’ group made up 18.1 % of respondents and their high rate of allowing their dogs to roam identifies them as a prime target for canine health and behavior education. ‘The Multiple Barriers’ owners reported lower degrees of dog roaming and were substantially more likely to be found by DtD campaigns, possibly because they have limited ability/interest in handling their dogs. These results demonstrate the importance of incorporating DtD vaccination as well as subsidies to maximize vaccine coverage in Addis Ababa.

Purpose: To explore whether the characteristics of vacuum delivery are associated with the occurrence of head injury and neonatal complications. Methods: Retrospectively cohort study of vacuum-assisted attempted vaginal deliveries of singletons. We studied the association of total duration of vacuum application and number of pulls and cup dislodgement with (1) primary outcome: the occurrence of major (subgaleal hemorrhage, skull fracture, and intracranial hemorrhage) or minor (cephalohematoma, scalp laceration more extensive than simple abrasions) neonatal head injuries and (2) secondary outcome: the occurrence of neonatal complications, including 5-min Apgar score

Gitelman syndrome is caused by inactivating mutations of the gene that encodes the renal sodium/chloride cotransporter (NCC; encoded by SLC12A3), resulting in hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Renal salt wasting commonly provokes mild hypotension. The paucity of previous kidney transplants from donors with known tubulopathies suggests that such conditions may be considered contraindications to donation. A 76-year-old man received a live unrelated kidney transplant from a donor with known Gitelman syndrome secondary to a pathogenic mutation of SLC12A3. Immediate graft function preceded the emergence of the Gitelman syndrome biochemical phenotype and blood pressure subsequently improved. The recipient developed unexpected hyponatremia. Potential causes are discussed, including the possibility that it paralleled the physiologic changes seen in the high-volume state of thiazide-induced hyponatremia. Transplanted kidneys are subject to nephrotoxicity from the use of calcineurin inhibitors. Acquired Gitelman syndrome may confer a potential long-term advantage to the recipient through both improved blood pressure control and protection against the calcineurin inhibitor–induced side-effect profile caused by NCC overactivation. Both the donor and recipient remain well. In conclusion, Gitelman syndrome need not preclude kidney donation and transference of the phenotype may have benefits for the recipient.

This article explores the contingent role that social ties play in the emergence of status hierarchies. We argue that, while status is formed based on actors’ perception and understanding of social cues, network structure, and position influence this process by influencing the attention and legitimacy given to the focal actor in accordance with social cues that signal an actor’s identity. Using a large data set from an open-source software development community, we find that a broker linking diverse network members is less likely to receive status ratings from others and that the rating is more likely to be low when a broker receives a rating. Furthermore, we find evidence that the effects of brokerage are contingent upon certain factors that may affect the attention and legitimacy given to actors in the process of status evaluation, such as the actor’s prior status. An actor’s prior status was found to weaken the negative effect of brokerage. The importance of this study for theories of status, social networks, and attention is discussed.

This study presents a roadmap for converting California's all-purpose (electricity, transportation, heating/ cooling, and industry) energy infrastructure to one derived entirely from wind, water, and sunlight (WWS) generating electricity and electrolytic hydrogen. California's available WWS resources are first evaluated. A mix of WWS generators is then proposed to match projected 2050 electric power demand after all sectors have been electrified. The plan contemplates all new energy from WWS by 2020, 80e85% of existing energy converted by 2030, and 100% by 2050. Electrification plus modest efficiency measures may reduce California's end-use power demand ~44% and stabilize energy prices since WWS fuel costs are zero. Several methods discussed should help generation to match demand. A complete conversion in California by 2050 is estimated to create ~220,000 more 40-year jobs than lost, eliminate ~12,500 (3800 e23,200) state air-pollution premature mortalities/yr, avoid $103 (31e232) billion/yr in health costs, representing 4.9 (1.5e11.2)% of California's 2012 gross domestic product, and reduce California's 2050 global climate cost contribution by $48 billion/yr. The California air-pollution health plus global climate cost benefits from eliminating California emissions could equal the $1.1 trillion installation cost of 603 GW of new power needed for a 100% all-purpose WWS system within ~7 (4e14) years.

This commentary examines the use of American Indian culture in the strategic marketing of goods and services produced from within the American Indian community. Building on concepts from multiple academic disciplines, we introduce a new construct for this practice: the "culture-of-origin" effect. Specifically, the culture-of-origin effect is the strategic use of one's cultural identity as a resource that increases the value of one's products. Moreover, we explore the ethical ramifications of exploiting one's cultural identity for capital gain by highlighting the quandary that emerges when individuals seek to profit from a resource (cultural capital) that belongs collectively to the tribe.