Phenotypic convergence is more frequent and stronger in herbivorous freshwater fishes.

Constraints on phenotypic evolution can lead to patterns of convergent evolution, by limiting the 'pool' of potential phenotypes in the face of endogenous (functional, developmental) or exogenous (competition, predation) selective pressures. Evaluation of convergence depends on integrating ecological and morphological data within a robust, comparative phylogenetic context. The staggering diversity of teleost fishes offers a multitude of lineages adapted for similar ecological roles, and therefore, offers numerous replicated evolutionary experiments for exploring phenotypic convergence. However, our understanding of fish feeding systems has been primarily shaped by marine species, with the monolithic exception of freshwater cichlids. Here we use piranhas and pacus (Serrasalmidae) to explore the evolution of different feeding ecologies and their morphological proxies in Neotropical freshwater environments. Specifically, we explore whether convergence is more widespread among plant-eating fishes, arising from strong constraints on phenotypic evolution in herbivores. Using osteological micro-computed tomographic imaging (µCT), we describe the major axes of morphological variation in pacus and piranhas, regarding their diet and feeding behaviors. Next, we evaluated whether herbivorous niches are less labile than other dietary guilds and whether herbivorous species' phenotypes evolve at a slower evolutionary rate than other taxa. We then assess how convergent herbivorous taxa are, using three different suites of morphological characters (dental, jaw, and abdominal morphometrics). Ecologically, herbivory is not a dead end, exhibiting similar observed transition rates as those between carnivores and omnivores. However, we documented widespread convergence in herbivores and that herbivores have slower rates of phenotypic evolution than carnivores. Most instances of convergence are found in herbivorous taxa, specifically in frugivores and folivores. Moreover, instances of 'complete' convergence, indicated by positive convergence metrics observed in more than one morphometric dataset, were only found in herbivores. Herbivores do appear to evolve under constrained circumstances, but this has not limited their ecological lability.

Genetic influences on central and peripheral nervous system activity during fear conditioning.

Fear conditioning is an evolutionarily conserved type of learning serving as a model for the acquisition of situationally induced anxiety. Brain function supporting fear conditioning may be genetically influenced, which in part could explain genetic susceptibility for anxiety following stress exposure. Using a classical twin design and functional magnetic resonance imaging, we evaluated genetic influences (h2) on brain activity and standard autonomic measures during fear conditioning. We found an additive genetic influence on mean brain activation (h2 = 0.34) and autonomic responses (h2 = 0.24) during fear learning. The experiment also allowed estimation of the genetic influence on brain activation during safety learning (h2 = 0.55). The mean safety, but not fear, related brain activation was genetically correlated with autonomic responses. We conclude that fear and safety learning processes, both involved in anxiety development, are moderately genetically influenced as expressed both in the brain and the body.

Efficacy and safety of mogamulizumab by patient baseline blood tumour burden: a post hoc analysis of the MAVORIC trial.

BACKGROUND: Mogamulizumab was compared with vorinostat in the phase 3 MAVORIC trial (NCT01728805) in 372 patients with relapsed/refractory mycosis fungoides (MF) or Sézary syndrome (SS) who had failed ≥1 prior systemic therapy. Mogamulizumab significantly prolonged progression-free survival (PFS), with a superior objective response rate (ORR) vs. vorinostat. OBJECTIVES: This post hoc analysis was performed to evaluate the effect of baseline blood tumour burden on patient response to mogamulizumab. METHODS: PFS, ORR, time to next treatment (TTNT), skin response (modified Severity-Weighted Assessment Tool [mSWAT]) and safety were assessed in patients stratified by blood classification (B0 [n = 126], B1 [n = 62], or B2 [n = 184], indicating increasing blood involvement). RESULTS: Investigator-assessed PFS was longer for mogamulizumab versus vorinostat across all blood classes, significantly so for B1 and B2 patients. ORR was higher with mogamulizumab than with vorinostat in all blood classification groups and more markedly so with escalating B class (B0: 15.6% vs. 6.5%, P = 0.0549; B1: 25.8% vs. 6.5%, P = 0.2758; B2: 37.4% vs. 3.2%, P < 0.0001). TTNT was significantly longer for patients treated with mogamulizumab versus vorinostat with B1 (12.63 vs. 3.07 months; HR 0.32 [95% CI 0.16-0.67]; P = 0.0018) and B2 (13.07 vs. 3.53 months; HR 0.30 [95% CI 0.21-0.43]; P < 0.0001) blood involvement. In the mogamulizumab arm, 81 patients (43.5%) had ≥50% change in the mSWAT vs. 41 patients (22.0%) with vorinostat; mSWAT improvements with mogamulizumab occurred most often in B1 and B2 patients. Rapid, sustained reductions were seen in CD4+ CD26- cell counts and CD4:CD8 ratios in mogamulizumab patients for all B classes. Treatment-emergent adverse events were less frequent overall with mogamulizumab and similar in frequency regardless of B class. CONCLUSIONS: This post hoc analysis indicates greater clinical benefit with mogamulizumab vs. vorinostat in patients with MF and SS classified as having B1 and B2 blood involvement.

Microscopic evidence for Mn-induced long range magnetic ordering in MAX phase compounds.

Zero and low field nuclear magnetic resonance measurements have been performed on MAX phase samples (Cr1-x Mn x )2AC with A = Ge and Ga in order to obtain local microscopic information on the nature of magnetism in this system. Our results unambiguously provide evidence for the existence of long-range magnetic order in (Cr0.96Mn0.04)2GeC and for (Cr0.93Mn0.07)2GaC, but not for (Cr0.97Mn0.03)2GaC. We point to a possible dependence of long range magnetic order in these MAX phase compounds on the A atom.

Dermatology consultation service at a large metropolitan hospital system serving minority populations.

BACKGROUND: Dermatology consultations in the inpatient hospital setting can improve diagnostic accuracy and management. OBJECTIVE: Characterize dermatologic diagnostic and treatment trends in the hospital setting and identify variables that may affect patient care. METHODS: Retrospective chart review from 1 January 2012 to 31 December 2017 at Jackson Memorial Hospital (JMH) (Miami, Florida, USA), an academic non-profit tertiary care centre affiliated with University of Miami Miller School of Medicine, was performed. Patients who received dermatology consultations in the emergency department (ED) or inpatient settings were included. Patient demographics, admission information, provisional diagnosis and management plans by primary teams, final diagnosis, management plans and testing recommendations by the dermatology consults team, and follow-up information were collected. Analysis using Microsoft Excel of how time to consultation, admission length, inpatient versus ED setting and primary team affected diagnostic accuracy was also performed. RESULTS: The 1004 consultations for 812 patients (n = 812) were reviewed (359 women, 453 men). Most patients were Hispanic (n = 359; 44.2%) or African American (n = 273; 33.6%). Mean admission length was 20.6 days (range 0-439; median 6). The most common consulting service was internal medicine (n = 452). In 387 cases (47.6%), primary teams did not give a provisional diagnosis. The most common provisional diagnoses were bacterial infection (n = 93), viral infection (n = 49) and drug reaction (n = 44). The most common diagnoses by dermatology were viral infection (n = 93), bacterial infection (n = 90) and drug reaction (n = 80). Dermatology consultation changed the provisional diagnosis in 55.7% of cases, more often in cases where consultation took place ≥2 days after admission (P < 0.05). Primary teams followed dermatology treatment recommendations in 85.2% of cases. CONCLUSION: Dermatology consultation improves diagnostic accuracy in skin disorders in the hospital setting and serves as a valuable resource for inpatient care. A notable aspect of data from this study is the unique patient population, predominantly comprised of underrepresented racial and ethnic minorities including Hispanics and African Americans.

Correction: Alterations in Wnt- and/or STAT3 signaling pathways and the immune microenvironment during metastatic progression.

The original version of this Article incorrectly matched the supplementary files with their titles. This has been corrected. The following information has also been added to the Methods section.

Alterations in Wnt- and/or STAT3 signaling pathways and the immune microenvironment during metastatic progression.

Metastatic breast cancer is an extremely complex disease with limited treatment options due to the lack of information about the major characteristics of metastatic disease. There is an urgent need, therefore, to understand the changes in cellular complexity and dynamics that occur during metastatic progression. In the current study, we analyzed the cellular and molecular differences between primary tumors and paired lung metastases using a syngeneic p53-null mammary tumor model of basal-like breast cancer. Distinct subpopulations driven by the Wnt- and/or STAT3 signaling pathways were detected in vivo using a lentiviral Wnt- and STAT3 signaling reporter system. A significant increase in the overlapping populations driven by both the Wnt- and STAT3 signaling pathways was observed in the lung metastases as compared to the primary tumors. Furthermore, the overlapping populations showed a higher metastatic potential relative to the other populations and pharmacological inhibition of both signaling pathways was shown to markedly reduce the metastatic lesions in established lung metastases. An analysis of the unique molecular features of the lung metastases revealed a significant association with immune response signatures. Specifically, Foxp3 gene expression was markedly increased and elevated levels of Foxp3 + Treg cells were detected in close proximity to lung metastases. Collectively, these studies illustrate the importance of analyzing intratumoral heterogeneity, changes in population dynamics, and the immune microenvironment during metastatic progression.

A review of the evidence and cost of therapies for cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE)-a common presentation of lupus erythematosus-may exist independently or as a part of the systemic manifestations of systemic lupus erythematosus. The effects of living with and treating a chronic condition such as CLE can be debilitating to a patient's health and finances. The management of patients with CLE is made particularly challenging by poor compliance, limited therapeutic options, scarcity of evidence supporting their use, and significant differences in costs of medications. Effective management of CLE should center on prevention, individualized treatment regimens, and a mutual understanding of the challenges that patients with CLE face. This article seeks to provide an overview of the efficacy, safety, and cost of therapeutic options for CLE.

Generation of structured light by multilevel orbital angular momentum holograms.

Structured light has been created by a myriad of near-and far-field techniques and has found both classical and quantum applications. In the case of orbital angular momentum (OAM), continuous spiral phase patterns in dynamic or geometric phase are often employed with the phase patterns existing across the entire transverse plane. Here, we exploit the uncertain relationship between OAM and angle in order to create structured OAM fields by using multilevel OAM holograms. We show theoretically and experimentally that only a multilevel angular phase contour in the near-field is needed to create structured OAM light in the far-field, exploiting the reciprocal nature of angular momentum and angle. We use this approach to demonstrate exotic 3D structured light control to show the Poynting vector's evolution in such fields and to highlight the physics underlying this phenomenon.

Validation of 'ItchApp©' in Poland and in the USA: multicentre validation study of an electronical diary for the assessment of pruritus.

BACKGROUND: Although chronic pruritus affects a large part of the population, its reliable assessment remains difficult. Electronical diaries (eDiaries) are often used in multicentre clinical trials. The ItchApp© for Android was developed to assess itch intensity and course and was validated for the German language in 2017. OBJECTIVE: To validate ItchApp© for the use in the Polish and US English languages. METHODS: Fifty-three subjects in Poland and thirty subjects in the USA with chronic pruritus completed the paper-based and app-based questionnaires. These questionnaires contained items for measuring the itch intensity, including a numerical rating scale (NRS) and verbal rating scale (VRS), and for detecting the change of pruritus since the beginning of treatment. RESULTS: The ItchApp© showed a high level of test-retest reliability [Intraclass correlation, Kappa and Kendall-Tau B coefficients: 0.915-1.000 (Poland) and 0.863-1.000 (USA)]. The convergent validity showed strong correlation between the itch intensity scales on the ItchApp© (Items II-IV = VRS mean, NRS mean and NRS worst) and the paper-based itch intensity scales (mean and worst: VRS, NRS, VAS) [Spearman-Rho and Pearson correlation coefficients: 0.710-0.987 (Poland) and 0.646-0.954 (USA)]. The ItchApp© items moderately correlated with the ItchyQol scores [Spearman-Rho and Pearson correlation coefficients: 0.303-0.554 (Poland) and 0.275-0.447 (USA)]. After completing the ItchApp© questionnaire, a feasibility questionnaire was completed and showed that subjects feel the app is well suited for assessing pruritus. CONCLUSION: We provide evidence for the ItchApp© as a validated eDiary for the assessment of pruritus in Polish and US English languages, enabling its use in multicentre international clinical trials.

Ti n+1C n MXenes with fully saturated and thermally stable Cl terminations.

MXenes are a rapidly growing family of 2D materials that exhibit a highly versatile structure and composition, allowing for significant tuning of the materials properties. These properties are, however, ultimately limited by the surface terminations, which are typically a mixture of species, including F and O that are inherent to the MXene processing. Other and robust terminations are lacking. Here, we apply high-resolution scanning transmission electron microscopy (STEM), corresponding image simulations and first-principles calculations to investigate the surface terminations on MXenes synthesized from MAX phases through Lewis acidic melts. The results show that atomic Cl terminates the synthesized MXenes, with mere residual presence of other termination species. Furthermore, in situ STEM-electron energy loss spectroscopy (EELS) heating experiments show that the Cl terminations are stable up to 750 °C. Thus, we present an attractive new termination that widely expands the MXenes' functionalization space and enables new applications.

Overlap between functional abdominal pain disorders and organic diseases in children. / Sobreposición entre los trastornos funcionales de dolor abdominal y enfermedades orgánicas en niños.

Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults.

Curriculum for neurogastroenterology and motility training: A report from the joint ANMS-ESNM task force.

Although neurogastroenterology and motility (NGM) disorders are some of the most frequent disorders encountered by practicing gastroenterologists, a structured competency-based training curriculum developed by NGM experts is lacking. The American Neurogastroenterology and Motility Society (ANMS) and the European Society of Neurogastroenterology and Motility (ESNM) jointly evaluated the components of NGM training in North America and Europe. Eleven training domains were identified within NGM, consisting of functional gastrointestinal disorders, visceral hypersensitivity and pain pathways, motor disorders within anatomic areas (esophagus, stomach, small bowel and colon, anorectum), mucosal disorders (gastro-esophageal reflux disease, other mucosal disorders), consequences of systemic disease, consequences of therapy (surgery, endoscopic intervention, medications, other therapy), and transition of pediatric patients into adult practice. A 3-tiered training curriculum covering these domains is proposed here and endorsed by all NGM societies. Tier 1 NGM knowledge and training is expected of all gastroenterology trainees and practicing gastroenterologists. Tier 2 knowledge and training is appropriate for trainees who anticipate NGM disorder management and NGM function test interpretation being an important part of their careers, which may require competency assessment and credentialing of test interpretation skills. Tier 3 knowledge and training is undertaken by trainees interested in a dedicated NGM career and may be restricted to specific domains within the broad NGM field. The joint ANMS and ESNM task force anticipates that the NGM curriculum will streamline NGM training in North America and Europe and will lead to better identification of centers of excellence where Tier 2 and Tier 3 training can be accomplished.

Age and experience dependent changes in Egr-1 expression during the ontogeny of the context preexposure facilitation effect (CPFE).

The context preexposure facilitation effect (CPFE) is a variant of contextual fear conditioning in which acquisition of the contextual representation and association of the retrieved contextual memory with an immediate foot-shock are separated by 24 h. During the CPFE, learning- related expression patterns of the early growth response-1 gene (Egr-1) vary based on training phase and brain sub-region in adult and adolescent rats (Asok, Schreiber, Jablonski, Rosen, & Stanton, 2013; Schreiber, Asok, Jablonski, Rosen, & Stanton, 2014; Chakraborty, Asok, Stanton, & Rosen, 2016). The current experiments extended our previous findings by examining Egr-1 expression in infant (PD17) and juvenile (PD24) rats during the CPFE using preexposure protocols involving single-exposure (SE) or multiple-exposure (ME) to context. Following a 5 min preexposure to the training context (i.e. the SE protocol), Egr-1 expression in the medial prefrontal cortex (mPFC), dorsal hippocampus (dHPC) and lateral nucleus of the amygdala (LA) was differentially increased in PD24 rats relative to PD17 rats. In contrast, increased Egr-1 expression following an immediate foot-shock (2s, 1.5 mA) did not differ between PD17 and PD24 rats, and was not learning-related. Interestingly, increasing the number of exposures to the training chamber on the preexposure day (i.e. ME protocol) altered training-day expression such that a learning-related increase in expression was observed in the mPFC in PD24 but not PD17 rats. Together, these results illustrate a clear maturation of Egr-1 expression that is both age- and experience-dependent. In addition, the data suggest that regional activity and plasticity within the mPFC on the preexposure but not the training day may contribute to the ontogenetic profile of the effect. Further studies are necessary to elucidate the causal role of sub-region-specific neuroplasticity in the ontogeny of the CPFE.

Optogenetic silencing of a corticotropin-releasing factor pathway from the central amygdala to the bed nucleus of the stria terminalis disrupts sustained fear.

The lateral central nucleus of the amygdala (CeAL) and the dorsolateral bed nucleus of the stria terminalis (BNSTDL) coordinate the expression of shorter- and longer-lasting fears, respectively. Less is known about how these structures communicate with each other during fear acquisition. One pathway, from the CeAL to the BNSTDL, is thought to communicate via corticotropin-releasing factor (CRF), but studies have yet to examine its function in fear learning and memory. Thus, we developed an adeno-associated viral-based strategy to selectively target CRF neurons with the optogenetic silencer archaerhodopsin tp009 (CRF-ArchT) to examine the role of CeAL CRF neurons and projections to the BNSTDL during the acquisition of contextual fear. Expression of our CRF-ArchT vector injected into the amygdala was restricted to CeAL CRF neurons. Furthermore, CRF axonal projections from the CeAL clustered around BNSTDL CRF cells. Optogenetic silencing of CeAL CRF neurons during contextual fear acquisition disrupted retention test freezing 24 h later, but only at later time points (>6 min) during testing. Silencing CeAL CRF projections in the BNSTDL during contextual fear acquisition produced a similar effect. Baseline contextual freezing, the rate of fear acquisition, freezing in an alternate context after conditioning and responsivity to foot shock were unaffected by optogenetic silencing. Our results highlight how CeAL CRF neurons and projections to the BNSTDL consolidate longer-lasting components of a fear memory. Our findings have implications for understanding how discrete amygdalar CRF pathways modulate longer-lasting fear in anxiety- and trauma-related disorders.

An investigation of the in-plane chemically ordered atomic laminates (Mo2/3Sc1/3)2AlC and (Mo2/3Y1/3)2AlC from first principles.

We have calculated electronic, vibrational, and elastic properties of (Mo2/3Sc1/3)2AlC and (Mo2/3Y1/3)2AlC, two recently discovered nanolaminated materials in the family of so-called i-MAX phases. A comparison is made to the properties of the related hypothetical MAX phases Sc2AlC, Y2AlC, and Mo2AlC. From an analysis of the electronic band structures and projected crystal orbital Hamilton populations (pCOHP), we show that the i-MAX phases have more isotropic band structures than the MAX phases, but that their bonding characteristics are very similar, despite belonging to different space groups. However, the similar bonding notwithstanding, qualitative as well as significant quantitative differences are seen in the phonon density of states (PDOS). We also compare the Voigt-Reuss-Hill (VRH) bulk, shear, and Young's moduli. For (Mo2/3Sc1/3)2AlC, BVRH = 132 GPa, GVRH = 89 GPa, and EVRH = 218 GPa, all of which are higher values than for Sc2AlC, but lower than for Mo2AlC. For (Mo2/3Y1/3)2AlC, BVRH = 117 GPa, GVRH = 85 GPa, and EVRH = 205 GPa, which are higher than for Y2AlC, but lower than for Mo2AlC.