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Hutchinson‐Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene that provokes the synthesis of progerin, a mutant version of the nuclear protein lamin A that accelerates aging and precipitates death. The most clinically relevant feature of HGPS is the development of cardiac anomalies and severe vascular alterations, including massive loss of vascular smooth muscle cells, increased fibrosis, and generalized atherosclerosis. However, it is unclear if progerin expression in endothelial cells (ECs) causes the cardiovascular manifestations of HGPS. To tackle this question, we generated atherosclerosis‐free mice (LmnaLCS/LCSCdh5‐CreERT2) and atheroprone mice (Apoe−/−LmnaLCS/LCSCdh5‐CreERT2) with EC‐specific progerin expression. Like progerin‐free controls, LmnaLCS/LCSCdh5‐CreERT2 mice did not develop heart fibrosis or cardiac electrical and functional alterations, and had normal vascular structure, body weight, and lifespan. Similarly, atheroprone Apoe−/−LmnaLCS/LCSCdh5‐CreERT2 mice showed no alteration in body weight or lifespan versus Apoe−/−LmnaLCS/LCS controls and did not develop vascular alterations or aggravated atherosclerosis. Our results indicate that progerin expression in ECs is not sufficient to cause the cardiovascular phenotype and premature death associated with progeria. [ABSTRACT FROM AUTHOR]

Climate change poses a significant threat to endemic and endangered montane bird species with limited elevation and temperature ranges. Understanding their responses to changes in climate is essential for informing conservation actions. This study focused on the montane dwelling Yellow‐throated Apalis (Apalis flavigularis) in Malawi, aiming to identify key factors affecting its distribution and predicting its potential distribution under different climate change scenarios. Using an ensemble species distribution modeling approach, we found that the mean temperature of the driest quarter (Bio9), mean temperature of the wettest quarter (Bio8), and precipitation seasonality (Bio15) were the most important variables that influenced the distribution of this species. Across future climate scenarios, the species' geographic range declined where range losses varied from 57.74% (2050 RCP 6.0) to 82.88% (2070 RCP 6.0). We estimate its current range size to be 549 km2 which is lower than some previous estimates of its spatial distribution. Moreover, our projections indicate that under future climate scenarios, the species will shift to higher elevations with a large proportion of suitable areas located outside forests, posing challenges for adaptation. Our results suggest that the species may be under greater threat than previously thought; hence, urgent conservation actions are required. We recommend reinforcing the protection of areas predicted to remain suitable under future climate scenarios and the development of a species conservation action plan. [ABSTRACT FROM AUTHOR]

World forests face many threats, including wildfires, with tremendous ecological, social, and economic implications. Mediterranean ecosystems have evolved in the presence of fire, but changes to fire regimes associated with other global changes pose new challenges to postfire community regeneration. Forest regeneration largely depends on plant adaptations to survive wildfires or on the recolonization of burnt areas through seed dispersal. However, the value of the service provided by wild animals to postfire forest regeneration remains unevaluated. Here, we estimate the economic value of the biotic seed dispersal service in postfire restoration in Portugal. We combine budgeted costs of governmental Emergency Stabilisation Reports with network analysis that estimates the dependency of the Portuguese flora on biotic seed dispersal and on alternative fire regeneration strategies. Replacing the services provided by seed dispersers during postfire regeneration of Portuguese forests would cost 23,061,621€/year, highlighting the need for integrative policies that promote resilient forests. [ABSTRACT FROM AUTHOR]

This paper investigates a supply chain governed by a flat penalty service‐level contract in which missing the target fill rate can lead to costly operational disruption. We focus on near‐miss bias: (1) the preference for near‐miss events, that is, risky production quantities that reach the target but narrowly avoid disruption; and (2) riskier decision‐making due to such preferences. We propose a reference‐dependent behavioral model that explains the near‐miss bias. The findings of a laboratory experiment show that production quantities are evaluated based on realized profits and are below the optimal model prediction. Contracts associated with lower perceived severity, that is, the ratio of flat penalty to wholesale price, result in lower production quantities than those with higher perceived severity, even though the standard model does not predict any effect. A structural estimation analysis indicates that the behavioral model performs better than the standard model in terms of predictive accuracy and goodness of fit. Our analysis provides insights for managers who design supply chain contracts in settings with considerable risk of disruption due to a shortage of critical parts. [ABSTRACT FROM AUTHOR]

Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B‐cell lymphoma (BL). However, the current method of CAR T cell production is complicated and expensive, requiring collection of patient blood to enrich the T cell population, ex vivo engineering/activation, and quality assessment before the patient can receive the treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) to produce CAR T cells in situ and bypass the extensive and laborious process currently used. Optimized Spleen SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, and CD4+ T cells in wild‐type mice. Spleen SORT LNPs delivered Cre recombinase mRNA and CAR encoding mRNA to T cells in reporter mice and in a lymphoreplete B cell lymphoma model (respectively) after intravenous injection without the need for active targeting ligands. Moreover, in situ CAR T cells increased the overall survival of mice with a less aggressive form of B cell lymphoma. In addition, in situ transfected CAR T cells reduced tumor metastasis to the liver by increasing tumor infiltrating lymphocytes. Overall, these results offer a promising alternative method for CAR T cell production with pre‐clinical potential to treat hematological malignancies. [ABSTRACT FROM AUTHOR]

Purpose: To describe the construction and testing of a portable point‐of‐care low‐field MRI system on site in Africa. Methods: All of the components to assemble a 50 mT Halbach magnet‐based system, together with the necessary tools, were air‐freighted from the Netherlands to Uganda. The construction steps included individual magnet sorting, filling of each ring of the magnet assembly, fine‐tuning the inter‐ring separations of the 23‐ring magnet assembly, gradient coil construction, integration of gradient coils and magnet assembly, construction of the portable aluminum trolley and finally testing of the entire system with an open source MR spectrometer. Results: With four instructors and six untrained personnel, the complete project from delivery to first image took approximately 11 days. Conclusions: An important step in translating scientific developments in the western world from high‐income industrialized countries to low‐ and middle‐income countries (LMICs) is to produce technology that can be assembled and ultimately constructed locally. Local assembly and construction are associated with skill development, low costs and jobs. Point‐of‐care systems have a large potential to increase the accessibility and sustainability of MRI in LMICs, and this work demonstrates that technology and knowledge transfer can be performed relatively seamlessly. [ABSTRACT FROM AUTHOR]

The capture of tumour-derived extracellular vesicles (TEVs) by cells in the tumour microenvironment (TME) contributes to metastasis and notably to the formation of the pre-metastatic niche (PMN). However, due to the challenges associated with modelling release of small EVs in vivo, the kinetics of PMN formation in response to endogenously released TEVs have not been examined. Here, we have studied the endogenous release of TEVs in mice orthotopically implanted with metastatic human melanoma (MEL) and neuroblastoma (NB) cells releasing GFP-tagged EVs (GFTEVs) and their capture by host cells to demonstrate the active contribution of TEVs to metastasis. Human GFTEVs captured by mouse macrophages in vitro resulted in transfer of GFP vesicles and the human exosomal miR-1246. Mice orthotopically implanted with MEL or NB cells showed the presence of TEVs in the blood between 5 and 28 days after implantation. Moreover, kinetic analysis of TEV capture by resident cells relative to the arrival and outgrowth of TEV-producing tumour cells in metastatic organs demonstrated that the capture of TEVs by lung and liver cells precedes the homing of metastatic tumour cells, consistent with the critical roles of TEVs in PMN formation. Importantly, TEV capture at future sites of metastasis was associated with the transfer of miR-1246 to lungmacrophages, liver macrophages, and stellate cells. This is the first demonstration that the capture of endogenously released TEVs is organotropic as demonstrated by the presence of TEV-capturing cells only in metastatic organs and their absence in non-metastatic organs. The capture of TEVs in the PMN induced dynamic changes in inflammatory gene expression which evolved to a pro-tumorigenic reaction as the niche progressed to the metastatic state. Thus, our work describes a novel approach to TEV tracking in vivo that provides additional insights into their role in the earliest stages of metastatic progression. [ABSTRACT FROM AUTHOR]

Dissociation is a complex phenomenon which is present in a wide variety of psychiatric disorders and also in the general population. The objective of this study was to examine the relationship between childhood and adolescent traumas and development of dissociative phenomena in a nonclinical population, emphasizing the potentially mediating role of rumination, intrusive thoughts and negative affect in a population with no psychiatric pathology in adulthood. The sample was comprised of 337 participants from the general population (58.8% women) with a mean age of 33.10 years (SD: 14.08). They completed the Juvenile Victimization Questionnaire (JVQ), the Ruminative Response Scale (RRS), the White Bear Suppression Scale (WBSI), the Dissociative Experience Scale, 2d ver. Rev. (DES‐II) and the Depression, Anxiety and Stress Scale (DASS‐21). The results supported the starting hypotheses showing a positive correlation between childhood and adolescent trauma and dissociation, and between childhood and adolescent trauma and rumination, intrusive thoughts and negative affect, and mediation of these variables between childhood and adolescent trauma and dissociative states. The relationship between trauma in early ages and dissociation in adulthood is complex. Although the design used in this study was cross‐sectional, the results are compatible with the starting hypothesis that rumination, intrusive thoughts and negative affect mediate this relationship. [ABSTRACT FROM AUTHOR]

Aims: Transthyretin amyloid cardiomyopathy (ATTR‐CM) is increasingly recognized as a cause of heart failure in the elderly. Although wild‐type transthyretin amyloidosis is the most frequent form of ATTR‐CM found in the elderly, hereditary transthyretin amyloidosis (ATTRv) can also occur. We sought to determine the prevalence of ATTRv among elderly ATTR‐CM patients, identify predictors of ATTRv and evaluate the clinical consequences of positive genetic testing in this population. Methods and results: Prevalence of ATTRv in elderly ATTR‐CM patients (≥70 years) was assessed in a cohort of 300 consecutive ATTR‐CM patients (median age 78 years at diagnosis, 82% ≥70 years, 16% female, 99% Caucasian). ATTRv was diagnosed in 35 (12%; 95% confidence interval [CI] 3.1–8.8) and 13 (5.3%; 95% CI 5.6–26.7) patients in the overall cohort and in those ≥70 years, respectively. Prevalence of ATTRv among elderly female patients with ATTR‐CM was 13% (95% CI 2.1–23.5). Univariate analysis identified female sex (odds ratio [OR] 3.66; 95% CI 1.13–11.85; p = 0.03), black ancestry (OR 46.31; 95% CI 3.52–Inf; p = 0.005), eye symptoms (OR 6.64; 95% CI 1.20–36.73; p = 0.03) and polyneuropathy (OR 10.05; 95% CI 3.09–32.64; p < 0.001) as the only factors associated with ATTRv in this population. Diagnosis of ATTRv in elderly ATTR‐CM patients allowed initiation of transthyretin‐specific drug treatment in 5 individuals, genetic screening in 33 relatives from 13 families, and identification of 9 ATTRv asymptomatic carriers. Conclusions: Hereditary transthyretin amyloidosis is present in a substantial number of ATTR‐CM patients aged ≥70 years. Identification of ATTRv in elderly patients with ATTR‐CM has clinical meaningful therapeutic and diagnostic implications. These results support routine genetic testing in patients with ATTR‐CM regardless of age. [ABSTRACT FROM AUTHOR]

Allergic diseases are allergen‐induced immunological disorders characterized by the development of type 2 immunity and IgE responses. The prevalence of allergic diseases has been on the rise alike cardiovascular disease (CVD), which affects arteries of different organs such as the heart, the kidney and the brain. The underlying cause of CVD is often atherosclerosis, a disease distinguished by endothelial dysfunction, fibrofatty material accumulation in the intima of the artery wall, smooth muscle cell proliferation, and Th1 inflammation. The opposed T‐cell identity of allergy and atherosclerosis implies an atheroprotective role for Th2 cells by counteracting Th1 responses. Yet, the clinical association between allergic disease and CVD argues against it. Within, we review different phases of allergic pathology, basic immunological mechanisms of atherosclerosis and the clinical association between allergic diseases (particularly asthma, atopic dermatitis, allergic rhinitis and food allergy) and CVD. Then, we discuss putative atherogenic mechanisms of type 2 immunity and allergic inflammation including acute allergic reactions (IgE, IgG1, mast cells, macrophages and allergic mediators such as vasoactive components, growth factors and those derived from the complement, contact and coagulation systems) and late phase inflammation (Th2 cells, eosinophils, type 2 innate‐like lymphoid cells, alarmins, IL‐4, IL‐5, IL‐9, IL‐13 and IL‐17). [ABSTRACT FROM AUTHOR]

Objective: Obesity and metabolic diseases such as metabolic syndrome (MetS) are more prevalent in people with type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). MetS components might be associated with neurocognitive and functional impairments in these individuals. The predictive and discriminatory validity of MetS and its components regarding those outcomes were assessed from prospective and transdiagnostic perspectives. Methods: Metabolic syndrome components and neurocognitive and social functioning were assessed in 165 subjects, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HCs). A posteriori, individuals were classified into two groups. The MetS group consisted of those who met at least three of the following criteria: abdominal obesity (AO), elevated triglycerides (TG), reduced high‐density lipoprotein cholesterol (HDL), elevated blood pressure (BP), and elevated fasting glucose (FPG); the remaining participants comprised the No‐MetS group. Mixed one‐way analysis of covariance and linear and binary logistic regression analyses were performed. Results: Cognitive impairment was significantly greater in the MetS group (n = 82) than in the No‐MetS group (n = 83), with small effect sizes (p < 0.05; η²p = 0.02 – 0.03). In both groups, the most robust associations between MetS components and neurocognitive and social functioning were observed with TG and FPG (p < 0.05). There was also evidence for a significant relationship between cognition and BP in the MetS group (p < 0.05). The combination of TG, FPG, elevated systolic BP and HDL best classified individuals with greater cognitive impairment (p < 0.001), and TG was the most accurate (p < 0.0001). Conclusions: Specific MetS components are significantly associated with cognitive impairment across somatic and psychiatric disorders. Our findings provide further evidence on the summative effect of MetS components to predict cognition and social functioning and allow the identification of individuals with worse outcomes. Transdiagnostic, lifestyle‐based therapeutic interventions targeted at that group hold the potential to improve health outcomes. [ABSTRACT FROM AUTHOR]

Modern subsurface imaging techniques allow obtaining high‐quality images but with high computational costs. Nonetheless, depending on the amount of data, their execution is limited by memory in the current generation's hardware. However, with the advancement of new hardware and cloud‐based solutions, these problems are mitigated but still with the risk of work loss and instability. To mitigate the execution problems in memory‐limited and fail‐prone environments, we propose two high‐performance computing techniques. The first is based on independent checkpointing alongside a fault‐tolerant framework to store an execution state and recover from that state in case of failures. Besides, for memory‐limited graphics processing units, we present a technique to reduce the amount of memory requirement that we call the hybrid strategy. The experiments showed that the independent checkpointing alongside the fault‐tolerant framework is able to mitigate the performance penalty of node failures, with the independent checkpointing technique being more relevant when multiple nodes are terminated. Furthermore, the hybrid strategy technique has shown the possibility of execution of larger models that could make the graphics processing unit run out of memory otherwise. Finally, our implementation is scalable, allowing a significant improvement in performance when adding new nodes. In conclusion, our techniques can be used to deliver fast, high‐fidelity subsurface imaging in unstable and memory‐limited environments, such as the cloud. [ABSTRACT FROM AUTHOR]

Fluid systems in inverted rifted margins are challenging to interpret because fractures formed before compression were often reactivated acting as fluid pathways as new ones formed. Deciphering the fracture and fluid flow history in such complex settings has key implications for the prediction of the distribution of mineral resources. As an example, we reconstruct the fluid flow evolution of a portion of the inverted Pyrenean rift, the Upper Pedraforca thrust sheet, from the Mesozoic extension to the Alpine orogeny. We combine structural analysis and petrographic, geochemical and geochronological data obtained from 87 samples of fracture‐filling carbonate cements. During the Late Jurassic‐Early Cretaceous, low‐temperature seawater produced dolomitization of Jurassic and Lower Cretaceous limestones in an extensional setting. During the Early Cretaceous salt‐related extension, formation waters, probably evolved seawater or fluids that interacted with Triassic evaporites, at temperatures from 125 to 149°C migrated through fractures. The formation of breccias within post‐salt rocks in primary weld zones facilitated the upward migration of formation waters that interacted with pre‐salt rocks with high 87Sr/86Sr ratios. Formation waters at temperatures of 80°C migrated during the emplacement of the Upper Pedraforca thrust sheet in the Late Cretaceous‐Palaeocene. These fluids interacted with Upper Cretaceous Carbonates and/or Triassic evaporites. In contrast, the influence of meteoric fluids increased in shallower positions due to the exhumation of the SE Pyrenees during the Eocene‐Oligocene. Coevally, hot dolomitizing fluids migrated along diapir walls during the formation of secondary welds. Supergene ores documented in diapiric areas worldwide related to meteoric fluids, and the similar meteoric percolation occurred in the Upper Pedraforca thrust sheet, suggest that supergene mineralization could be found in the Pyrenees. Brecciation of rocks in primary weld zones and evaporite detachments, where mineralization accumulate in fractures from basement‐derived fluids, also suggests that similar ores could be found in the Pyrenees. [ABSTRACT FROM AUTHOR]

Absolute dating helps to define the age and duration of orogen building. Here we present new U–Pb ages of syn‐faulting calcites collected in the northern foreland basin of the Pyrenees. The studied area underwent deformation during the Eocene growth of the belt. This orogenic growth is considered to have persisted until the Late Oligocene, after which post‐orogenic processes prevailed. Microstructural analysis coupled with U–Pb dating of syn‐faulting calcite confirms the well‐known NW‐SE to N–S main shortening stage of the Pyrenean orogen during the Eocene (from 48.7 ± 2.2 to 43.2 ± 5.3 Ma). But our data further reveal NE‐SW shortening during the Miocene, ca. 16 Ma ago, that has never been seen in the northern Pyrenean foreland. We propose that this tectonic phase, now identified on both sides of the Pyrenean Belt, is a consequence of a stronger coupling between Africa, Iberia and Europe at this time. [ABSTRACT FROM AUTHOR]

Introduction: Brief psychotic disorder (BPD) is a relatively uncommon and underexplored psychotic condition. Even though BPD has been related to a more favorable outcome than other schizophrenia spectrum disorders (SSD), current knowledge of its predictive factors remains scant. This study aimed to examine its prevalence and find early predictors of BPD diagnostic stability. Methods: SSD diagnosis following Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) criteria was explored in a large epidemiological cohort (n = 569) of non‐affective first‐episode psychosis (FEP) patients enrolled in a three‐year longitudinal intervention program (PAFIP). Premorbid, sociodemographic, and clinical information was collected to characterize BPD patients and determine factors predictive of diagnostic stability. Multivariate analysis included predictors selected from clinical knowledge and also those that had achieved marginal significance (p ≤ 0.1) in univariate analysis. Results: A total of 59 patients enrolled in the PAFIP program (10.4% of the whole cohort) met DSM‐IV criteria for BPD, of whom 40 completed the three‐year follow‐up. The temporal stability of BPD in our sample was as high as 40% (n = 16). Transition from BPD to schizophrenia occurred in 37% (n = 15) of patients. Fewer hallucinations at baseline and better insight independently significantly predicted BPD diagnostic stability over time. Conclusion: Our findings confirm that BPD is a clinical condition with moderate‐to‐low temporal stability and demonstrate that approximately two‐thirds of FEP individuals experiencing BPD will develop a long‐lasting psychotic disorder during follow‐up, mainly schizophrenia. [ABSTRACT FROM AUTHOR]

Aim: To explore if the entire duration of active psychosis (DAP) is related to neurocognitive performance at baseline and at 3‐year follow‐up in patients with first episode psychosis (FEP). Methods: DAP was estimated for 481 FEP patients. A neuropsychological battery was administered to measure neurocognitive specific domains, and a global indicator of neurocognitive impairment (global deficits score, GDS) was calculated. According to the DAP quartiles, four subgroups were formed, and these were compared. In addition, a logistic regression analysis was carried out to predict neurocognitive impairment at 3‐year follow‐up. Results: FEP patients with the longest DAP (more than 18.36 months) presented a more severe global neurocognitive impairment evidenced in their GDS, both at baseline (F = 5.53; p˂.01) and at 3‐year follow‐up (F = 4.16; p˂.01). Moreover, a subgroup of participants with DAP between 7.40 and 18.36 months showed a specific attentional decline over the 3‐year follow‐up (F = 3.089; p˂.05).The logistic regression model showed that sex (Wald = 7.29, p <.010), premorbid adjustment (Wald = 7.24, p <.010), attention (Wald = 12.10, p <.001), verbal memory (Wald = 16.29, p <.001) and visual memory (Wald = 9.41, p <.010) were significant predictors of neurocognitive impairment 3 years after the FEP. The variables composing the DAP were not significant predictors in this model. Conclusions: DAP seems to be related to global neurocognitive impairment in FEP patients. These findings contribute in several ways to our understanding of the effects of active psychosis on the brain, and provide the basis for future research. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the 10‐year stability of schizophrenia diagnosis in a cohort of first‐episode psychosis (FEP) patients and the factors associated with it. Methods: Changes in diagnosis of 209 FEP patients were described during 10 years of follow‐up. Related factors with maintenance or change of schizophrenia diagnosis were evaluated in prospective and retrospective approaches through binary logistic regressions, ROC and survival curves. Results: Out of the 209 patients, 126 were diagnosed of schizophrenia 6 months after their inclusion in the clinical program. Prospective analyses showed that eight of those 126 schizophrenia patients had changed to a different diagnosis after 10 years, and predictors of change were better childhood premorbid adjustment, less severity of clinical global impression at baseline, and diagnosis of comorbid personality disorder during follow‐up. Retrospectively, out of the 154 patients with schizophrenia in the 10‐year assessment, 36 had a different diagnosis at baseline, and those factors related to a different prior diagnosis than schizophrenia were better socioeconomic status and shorter duration of untreated psychosis (DUP). A survival analysis on the timing of schizophrenia diagnosis showed that male gender and longer DUP were predictors of earlier definite diagnosis. Conclusions: Diagnostic stability of schizophrenia in our FEP sample is high, especially prospective stability, and the group of patients with diagnostic change corresponded to a milder psychopathological profile before and at the onset of disease. Moreover, we observed a cautious attitude in the diagnosis of schizophrenia in patients with shorter DUP who had schizophrenia diagnosis after 10 years. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing incidence of anaphylaxis, its underlying molecular mechanisms and biomarkers for appropriate diagnosis remain undetermined. The rapid onset and potentially fatal outcome in the absence of managed treatment prevent its study. Up today, there are still no known biomarkers that allow an unequivocal diagnosis. Therefore, the aim of this study was to explore metabolic changes in patients suffering anaphylactic reactions depending on the trigger (food and/or drug) and severity (moderate and severe) in a real‐life set‐up. Methods: Eighteen episodes of anaphylaxis, one per patient, were analysed. Sera were collected during the acute phase (T1), the recovery phase (T2) and around 2–3 months after the anaphylactic reaction (T0: basal state). Reactions were classified following an exhaustive allergological evaluation for severity and trigger. Sera samples were analysed using untargeted metabolomics combining liquid chromatography coupled to mass spectrometry (LC‐MS) and proton nuclear magnetic resonance spectroscopy (1H‐NMR). Results: 'Food T1 vs T2' and 'moderate T1 vs T2' anaphylaxis comparisons showed clear metabolic patterns during the onset of an anaphylactic reaction, which differed from those induced by drugs, food + drug or severe anaphylaxis. Moreover, the model of food anaphylaxis was able to distinguish the well‐characterized IgE (antibiotics) from non‐IgE‐mediated anaphylaxis (nonsteroidal anti‐inflammatory drugs), suggesting a differential metabolic pathway associated with the mechanism of action. Metabolic differences between 'moderate vs severe' at the acute phase T1 and at basal state T0 were studied. Among the altered metabolites, glucose, lipids, cortisol, betaine and oleamide were observed altered. Conclusions: The results of this exploratory study provide the first evidence that different anaphylactic triggers or severity induce differential metabolic changes along time or at specific time‐point, respectively. Besides, the basal status T0 might identify high‐risk patients, thus opening new ways to understand, diagnose and treat anaphylaxis. [ABSTRACT FROM AUTHOR]

The laboratories of control theory are often limited to simulations and a few or none experimental tests. As in other technical subjects, practical experiments really help to understand the theory but need much time and the experimental platforms are usually expensive. This paper describes a platform that implements a universal third‐order discrete controller based on field programmable gate array (FPGA). The controller is implemented using fixed‐point arithmetic, with 17‐bit coefficients, but students can reduce the number of bits to find the resolution problems that may arise. This low‐cost platform, based on a Xilinx Spartan FPGA, allows students to try controllers just by configuring the coefficients of the controller through a computer application and a USB port. It drastically reduces the implementation time, allowing more time for design and testing. Therefore, students can try many controllers in the same laboratory session so that they can check experimentally their behavior in real prototypes and see the differences between simulations and physical systems. This platform has been applied in a real course over two academic years. The student opinion survey shows that the survey respondents consider the platform useful for more deeply understanding the subject, with an average score of 4.47/5.00 on a Likert scale (with a margin of error of 15.56% with a 95% confidence level). Besides this, the platform records the usage statistics showing that there is a relationship between the application usage and the marks in both the theory and laboratory parts. [ABSTRACT FROM AUTHOR]

Background: Disability encompasses impairments, activity limitations, and restrictions on participation. Improvement in functioning has therefore become a crucial outcome of treatment in psychosis.Objective: The main aim of this study was to analyze the potential relationship between suicidal behavior after first episode of psychosis (FEP) and family disability. The second aim was to find out whether personality traits are associated with disability dimensions.Method: The study sample was composed of 65 FEP patients. The personal care, occupational, family, and social dimensions of disability were evaluated at 12 months after FEP. Bivariate and multivariate analyses were performed to explore any putative outcome factors associated with dimensions of disability.Results: Personal care during the 1-year follow-up was significantly impaired in suicide attempters and significantly associated with sociopathic personality traits. A decline in occupational functioning was significantly associated with schizotypy traits. On the other hand, deterioration in family, social, and global functioning at 1 year after FEP was related to poor premorbid adjustment during late adolescence.Conclusions: Suicidal behavior prevention could improve psychosocial functioning, particularly personal care, in FEP. In addition, sociopathic and schizotypy personality traits as well as poor premorbid adjustment during late adolescence appear to be useful early markers of future disability. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 39-year-old man with the evaluation of dyspnea on exertion. Topics include patient developing symptoms of heart failure, documenting complete AVB, and severe left ventricular systolic dysfunction; and atrial and biventricular paced rhythm being observed after the effective shock therapy.

Background: Obesity may represent a chronic low-grade inflammation, but there is a lack of long-term longitudinal studies. The aim of this longitudinal study was to evaluate the recurrence of periodontal disease in obese and normal weight patients submitted to scaling and root planing.Methods: The study included 22 patients who had received periodontal treatment 2 years previously, 13 obese and nine non-obese. The patients were evaluated for anthropometric measurements of body mass index, waist circumference, waist-to-hip ratio, and fat percentage through bioimpedance. The following periodontal parameters were recorded: visible plaque index (VPI), gingival bleeding index (GBI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP). The immunological evaluation analyzed the proinflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in the gingival crevicular fluid (GCF).Results: Obese and normal weight patients did not differ in relation to the periodontal parameters of VPI, GBI, PD, CAL, or BOP 2 years after completion of the periodontal therapy. Sites with periodontitis in obese individuals showed higher levels of IL-6 and TNF-α in the gingival fluid (P <0.05).Conclusion: Obese and normal weight individuals had similar periodontal behaviors, with low recurrence of the periodontal disease; however, obesity was related to increased inflammatory activity in gingival fluid, which may become a risk indicator for future greater recurrence of the disease in the presence of inadequate plaque control. [ABSTRACT FROM AUTHOR]

Aim: Early intervention psychiatric services for patients with psychosis aim to limit the most damaging outcomes and reduce the patient's risk of social drift, decreasing illness severity and thus containing healthcare costs. There is a scarcity of studies that focus on first‐episode psychosis (FEP), and those few that have been published only looked at direct health costs, but not at indirect costs, which make up the bulk of the budget. Our study aims to explore the short‐term (1‐year follow‐up) economic cost of a FEP Program, including both direct and indirect costs. Methods: Data were collected retrospectively from the clinical records of 157 patients included in the Programa Atención Fases Iniciales de Psicosis, from Marqués de Valdecilla University Hospital, Santander. Our data collection sheet collated data from direct and indirect costs associated with the illness. Data were also extracted from the Cantabria Health Service Records. STATA 15.0 was used for statistical analysis. Results: On average, the total costs during the first year were €48 353.51 per patient, with direct healthcare costs being €13 729.47 (28.39%), direct non‐medical costs €108.6 (0.22%), and indirect costs €34 515.44 (71.39%). We found that hospitalization costs were higher in males (p = 0.081) and in cannabis users (p = 0.032). The number of relapses increased both, hospitalization and treatment costs (r = 0.40 p = 0.000; r = 0.24 p = 0.067, respectively). Conclusions: Intensive Early Intervention in Psychosis Services may result in cost savings by decreasing hospitalization, premature mortality, disability, unemployment, and legal problems; however, the first year after diagnosis would represent the one with the highest costs. [ABSTRACT FROM AUTHOR]

The nesting phenology and productivity of hole‐nesting woodland passerines, such as tit species (Paridae), has been the subject of many studies and played a central role in advancing our understanding of the causes and consequences of trophic mismatch. However, as most studies have been conducted in mature, oak‐rich (Quercus sp.) woodlands, it is unknown whether insights from such studies generalise to other habitats used by woodland generalist species. Here we applied spatial mixed models to data collected over three years (2014–2016) from 238 nestboxes across 40 sites – that vary in woodland habitat and elevation – along a 220 km transect in Scotland. We evaluate the importance of habitat, biogeography and food availability as predictors of mesoscale among‐site variation in blue tit Cyanistes caeruleus nestbox occupancy and two components of productivity (clutch size and fledging success). We found that habitat was not a significant predictor of occupancy or clutch size but that occupancy exhibited pronounced biogeographic trends, declining with increasing latitude and elevation. However, fledging success, defined as the proportion of a clutch that fledged, was positively correlated with site level availability of birch, oak and sycamore, and tree diversity. The lack of correspondence between the effects of habitat on fledging success versus occupancy and clutch size may indicate that blue tits do not accurately predict the future quality of their breeding sites when selecting territories and laying clutches. We found little evidence of spatial autocorrelation in occupancy or clutch size, whereas spatial autocorrelation in fledging success extends over multiple sites, albeit non‐significantly. Taken together, our findings suggest that the relationship between breeding decisions and breeding outcomes varies among habitats, and we urge caution when extrapolating inferences from one habitat to others. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to evaluate the use of flaxseed in animals subjected to ethanol‐induced hepatotoxicity. Twenty‐four male rats were divided into four groups (n = 6): control group (CG) which received a control diet and water ad libitum; flaxseed group (FG) which received control diet with an addition of 25% flaxseed flour and water ad libitum; ethanol control group (ECG) which received control diet and a solution of 10% ethanol (v/v) as the only liquid source; and ethanol flaxseed group (EFG) which received control diet with an addition of 25% flaxseed flour and a solution of 10% ethanol (v/v) as the only liquid source. The animals were euthanized at 60 days, when blood was collected for biochemical analysis and liver was collected for histomorphometric analysis. Rats fed with diets containing flaxseed showed lower values of alkaline phosphatase (P = 0.020) and lower concentration of total bilirubin (P = 0.006), direct bilirubin (P = 0.013) and indirect bilirubin (P = 0.018) compared to ECG and EFG. The groups receiving flaxseed diets demonstrated higher expression of superoxide dismutase (SOD) enzyme (P < 0.001) than CG and ECG but did not affect thiobarbituric acid (TBARS) expression (P = 0.055). Regarding liver analysis, the ECG and EFG showed larger hepatocyte nuclei and paler cytoplasm than the groups who had not received ethanol, and less in fluid accumulation (oedema) in the cytoplasm than was seen in the FG and EFG livers. These latter two groups showed fewer fatty cells than was seen in the groups that had not been given flaxseed, so that the diagnosis of hepatic steatosis was not justified. In conclusion, therefore, this study showed that the indicators of ethanol chronic consumption can be reduced by the introduction of continuous flaxseed dietary intake. [ABSTRACT FROM AUTHOR]

Abstract: Livestock production has been highly relevant in the Azores, boosted by European agricultural policies, increasing the demand for pasture and competing for space with other land uses. Therefore, it is important to understand the spatial evolution of pasture and related land use/land cover (LULC) trade‐offs. This study describes a geographical information systems‐based LULC change detection approach to identify, map and assess pasture‐related land use changes and respective trade‐offs in Pico Island in the period between 1998 and 2013 (15 years). Pasture in 1998 occupied a total area of 17,131 ha (about 39% of Pico Island surface), while in 2013, this same area was of 17,621 ha (about 40% of Pico Island surface). During this period, about 16,316 ha of pasture remained unchanged, while 2,110 ha (about 5% of Pico Island surface) of land use have changed from pasture to another land use (810 ha), or from a previous land use to pasture (1,300 ha). The whole pasture spatial dynamics and its net increase of 3% from 1998 to 2013 (490 ha, about 1% of Pico Island surface) were analysed through the identification, mapping and assessment of LULC trade‐offs and interpreted according to several physical (elevation) and socio‐economic/policy drivers. Pasture and livestock grazing activity with adequate management may not constitute per se threats to nature conservation and biodiversity protection in Pico Island, as the identified issues have been shown to be mostly related to the pasture dynamics (changes and respective trade‐offs). Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Core Ideas: We propose a Hydrophysical Database for Brazilian Soils (HYBRAS).Data in HYBRAS comprise 445 soil profiles, with 1075 samples of Brazilian soils.We compared the accuracy of water retention estimates based on climate‐based PTFs.In general, the Brazilian PTFs performed better than the temperate models for HYBRAS.Model performance differed due to clay content and mineralogical properties. Soil water retention data are fundamental in soil modeling studies. Temperate pedotransfer functions (PTFs) have been commonly used to estimate water retention of Brazilian soils, mainly because of the lack of soil data for Brazil. However, these PTFs may not be suitable for tropical or subtropical conditions such as those found in Brazil. The objective of this study was to establish a dedicated Hydrophysical Database for Brazilian Soils (HYBRAS) suitable for PTF development. Data present in HYBRAS comprise 445 soil profiles with 1075 samples and are representative of a wide range of Brazilian soils. The data are organized in a relational structure of tables that cover general site descriptions, land cover, and hydrophysical and chemical measurement methods. Raw data (e.g., water retention points covering the 0–15,000‐cm suction range) and derived data are included in the tables. Another objective of this study was to use the database to compare the accuracy of water retention estimates based on PTFs developed for Brazilian and temperate regions. In general, the Brazilian PTFs performed better than the temperate models, especially for weathered (Ferralsols, Acrisols, and Nitisols) fine‐textured (clay, sandy clay, clay loam, silty clay loam, and silty clay) soils. Silt content was not a successful criterion for distinguishing performance of Brazilian and temperate PTFs for Brazilian weathered soils. The water retention of weathered soils was shown to differ from that of temperate soils due to differences in pore structure resulting from their clay content and mineralogical nature, thus confirming results reported in the literature. [ABSTRACT FROM AUTHOR]

Background: dementia can be defined as a clinical syndrome developed by pathological processes that affect cognitive functioning, which influences the individual's way of perceiving and understanding the meaning of facts and feelings. Stigma is also a very broad concept, but it can be understood as negative attitudes and prejudices towards individuals who are perceived as different, whether because of a diagnosis, condition, or disease. Method: an integrative systematic literature review was developed to analyze the relationship between stigma and dementia in order to give support to the research question. Drawing upon the Database of Descriptors in Health Sciences (Decs/Mesh), the following descriptors were applied: Estigma e demência (Port.), stigma and dementia (Eng.) estigma y demencia (Spa.). No result on the relationship between these descriptors were found at the Cochrane Library, which may confirm the originality of this review. As for the Open Access Documents, no date limit was applied. The databases used were BVS, PsycInfo, Pubmed, Scopus and Web of Science, following the PRISMA methodology. Result: The initial search resulted in 8,127 titles; after the screening and exclusion criteria process, 42 articles were found for reading and categorization: 25 qualitative papers, 12 quantitative, 1 mixed quantitative and qualitative; 4 articles aimed at the validation and analysis of scales and intervention protocols. The articles mainly analyzed people with dementia, their caregivers, and families. All articles, empirical or theoretical, supported the correlation between stigma and dementia Conclusion: the research outcome points out to the possible of analyze stigma in relation to dementia in different cultures, by applying different approach and methods, such as interviews, scales, questionnaires, and observation, among others. Stigma involves beliefs, attitudes, and behaviors which are susceptible to interventions that may improve public awareness of dementia. Further studies and intervention approach are needed to diminish stigma related to dementia. [ABSTRACT FROM AUTHOR]

Background and Aims Research suggests that tobacco smokers may develop psychosis at an earlier age than non-smokers, with effects on psychotic symptoms. We aimed to test the difference in age of onset of psychosis between smokers and non-smokers. Design Self-report data were collected from smokers and non-smokers in a population of first-episode psychosis patients. Setting Out-patient first-episode psychosis programme in Santander (Cantabria), Spain. Participants Three hundred and ninety-seven patients (226 male, 171 female) who agreed to take part between 2001 and 2011. Measurements Age of onset of psychosis, age of smoking initiation, demographics, family history of psychosis and cannabis use were collected by self-report. Findings Kaplan-Meier analysis showed that smokers had a significantly lower mean age of psychosis onset [smokers = 27.4 (± 8.1) years, non-smokers = 30.5 (± 9.9) years] than non-smokers (χ2(1) = 11.72, P = 0.001). The Cox proportional hazard model showed no significant difference in the age of psychosis onset between smokers and non-smokers adjusted for covariates [hazard ratio (HR) = 1.034, 95% confidence interval (CI) = 0.828-1.291]. Age of psychosis onset was predicted significantly by cannabis use (HR = 2.073, 95% CI = 1.633-2.633) and gender (HR = 1.706, 95% CI = 1.363-2.135). Conclusions Smokers do not appear to have a significantly earlier age of psychosis onset than non-smokers after taking into account cannabis use and gender. [ABSTRACT FROM AUTHOR]

The balanced counseling strategy developed in Peru improved family planning care and clients' knowledge of their contraceptive method choice, but few providers adopted it. To expand its use, an algorithm was introduced and training, job aids, and reinforcement were supplied to Ministry of Health providers, most of whom were paraprofessionals, from two areas (40 clinics) in Guatemala. Mystery clients made pretest and post-test visits to these clinics and to providers from a nonequivalent control group (40 clinics). The results showed that the strategy was used in 85 percent of the controlled consultations at the experimental clinics. Use of the strategy improved quality of care regardless of the provider's performance at baseline and regardless of ethnic or regional differences. Counseling session length increased by nine minutes, but real-client load did not change. Guatemalan clients can be expected to benefit from the strategy. The increased session length has not yet caused problems, but it may pose policy dilemmas in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND Over the last two decades, the attractive colours and shapes of pigmented tubers and the increasing concern about the relationship between nutrition and health have contributed to the expansion of their consumption and a specialty market. Thus, we have quantified the concentration of health promoting compounds such as soluble phenolics, monomeric anthocyanins, carotenoids, vitamin C, and hydrophilic antioxidant capacity, in a collection of 18 purple- and red-fleshed potato accessions. RESULTS Cultivars and breeding lines high in vitamin C, such as Blue Congo, Morada and Kasta, have been identified. Deep purple cultivars Violet Queen, Purple Peruvian and Vitelotte showed high levels of soluble phenolics, monomeric anthocyanins, and hydrophilic antioxidant capacity, whereas relatively high carotenoid concentrations were found in partially yellow coloured tubers, such as Morada, Highland Burgundy Red, and Violet Queen. CONCLUSION The present characterisation of cultivars and breeding lines with high concentrations of phytochemicals is an important step both to support the consideration of specialty potatoes as a source of healthy compounds, and to obtain new cultivars with positive nutritional characteristics. Moreover, by using near infrared spectroscopy a non-destructive identification and classification of samples with different levels of phytochemicals is achieved, offering an unquestionable contribution to the potato industry for future automatic discrimination of varieties. © 2015 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Dystonia is a neurological disorder that can cause constant muscle contractions and motor limitations. This work reports a clinical case of periodontal treatment in a patient with generalized idiopathic dystonia. The intraoral clinical examination was focused on the presence of caries and periodontal diseases. The plaque index (PI), probing depth (PD), and bleeding on probing (BOP) were measured. Initially, oral hygiene instruction was provided using a soft conventional toothbrush and dental floss, but the clinical results achieved using these methods were inadequate. Alternative methods of plaque removal were offered, such as the use of a power toothbrush and a dental floss fork, which resulted in improvement in the PI, PD, and BOP and allowed the patient to undergo periodontal surgery for the restoration of subgingival caries. Our results suggested that generalized idiopathic dystonia leads to motor limitations that may cause difficulty with regard to plaque control, but adaptations of the methods used for oral hygiene may improve the oral health conditions in these patients. [ABSTRACT FROM AUTHOR]

This paper examines how queer practices of transformation enable the preservation and perversion of the logics, aspirations, and violences that animated Imelda Marcos's 'war of urban beautification'. It traces conceptual overlaps between the notions of truth and beauty that underpinned Imelda's faith in architectural modernism and which operate in the sex/gender tradition of kabaklaan. Using the case study of the Manila Film Center, a formerly abandoned and famously haunted Marcos-era building that has been transformed into the host site of a 'transgender' revue, the paper demonstrates how queerness, necropower, architecture, and dreams of urban and global modernity come together through the spatial effects of authoritarian power. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives To analyse anthropometric parameters, clinical pain and experimental pain in women with chronic pelvic pain ( CPP). Methods Ninety-one women with a clinical diagnosis of CPP, mean age of 40.03 ± 9.97 years, submitted to anthropometric evaluation based on body mass index ( BMI) and percent body fat (% BF) using bioimpedance body composition monitor; pain intensity was determined by visual analogue scale ( VAS), numerical categorical scale ( NCS) and Mc Gill Pain Questionnaire; experimental pain was determined by transcutaneous electrical nerve stimulation ( TENS), and anxiety and depression symptoms were determined by the Hospital Anxiety and Depression scale. Results A total of 54.8% of the women showed % BF >32 risk of disease associated with obesity. Regarding the anthropometric data, a statistically significant difference was observed between groups for both BMI and % BF ( P < 0.0001). In the analysis of pain intensity by the VAS, NCS and total Mc Gill, there was no significant difference between the groups, and experimental pain by TENS revealed significant difference only between the normal weight and overweight groups ( P = 0.0154). The results of anxiety symptoms were above the cut-off point in all groups, with no significant difference between them ( P = 0.3710). The depression symptoms were below the cut-off point in the normal weight group and above the cut-off point in the overweight and obese groups, 9.469(4.501) and 9.741(4.848), respectively, with no significant difference between them ( P = 0.6476). Conclusion Evaluation of anthropometric parameters and pain measurements can be applied in clinical practice, making a contribution to the diagnosis and influencing the choice of a more effective treatment for women with CPP. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis ( PD) is a form of renal replacement therapy whose repeated use can alter dialytic function through induction of epithelial-mesenchymal transition ( EMT) and fibrosis, eventually leading to PD discontinuation. The peritoneum from Cav1−/− mice showed increased EMT, thickness, and fibrosis. Exposure of Cav1−/− mice to PD fluids further increased peritoneal membrane thickness, altered permeability, and increased the number of FSP-1/cytokeratin-positive cells invading the sub-mesothelial stroma. High-throughput quantitative proteomics revealed increased abundance of collagens, FN, and laminin, as well as proteins related to TGF-β activity in matrices derived from Cav1−/− cells. Lack of Cav1 was associated with hyperactivation of a MEK- ERK1/2-Snail-1 pathway that regulated the Smad2-3/Smad1-5-8 balance. Pharmacological blockade of MEK rescued E-cadherin and ZO-1 inter-cellular junction localization, reduced fibrosis, and restored peritoneal function in Cav1−/− mice. Moreover, treatment of human PD-patient-derived MCs with drugs increasing Cav1 levels, as well as ectopic Cav1 expression, induced re-acquisition of epithelial features. This study demonstrates a pivotal role of Cav1 in the balance of epithelial versus mesenchymal state and suggests targets for the prevention of fibrosis during PD. [ABSTRACT FROM AUTHOR]

ABSTRACT Although several treatments for tendon lesions have been proposed, successful tendon repair remains a great challenge for orthopedics, especially considering the high incidence of re-rupture of injured tendons. Our aim was to evaluate the pharmacological potential of Aloe vera on the content and arrangement of glycosaminoglycans (GAGs) during tendon healing, which was based on the effectiveness of A. vera on collagen organization previously observed by our group. In rats, a partial calcaneal tendon transection was performed with subsequent topical A. vera application at the injury site. The tendons were treated with A. vera ointment for 7 days and excised on the 7th, 14th, or 21st day post-surgery. Control rats received ointment without A. vera. A higher content of GAGs and a lower amount of dermatan sulfate were detected in the A. vera-treated group on the 14th day compared with the control. Also at 14 days post-surgery, a lower dichroic ratio in toluidine blue stained sections was observed in A. vera-treated tendons compared with the control. No differences were observed in the chondroitin-6-sulfate and TGF-β1 levels between the groups, and higher amount of non-collagenous proteins was detected in the A. vera-treated group on the 21st day, compared with the control group. No differences were observed in the number of fibroblasts, inflammatory cells and blood vessels between the groups. The application of A. vera during tendon healing modified the arrangement of GAGs and increased the content of GAGs and non-collagenous proteins. Microsc. Res. Tech. 77:964-973, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The goal of this paper is to examine the impact of commodity market reforms on producer price volatility using evidence from the East African coffee market. The results, based on time‐varying volatility models and key summary statistics, show that coffee market reforms in the East African Community (EAC) are associated with changes in producer price volatility and volatility persistence at both country and regional levels. However, reforms were not the only cause of changes in price volatility. The study further shows that reforms had different effects on prices volatilities of Arabica and Robusta varieties of coffee grown in individual EAC countries. These findings have wider implication for commodity market reforms and producer price stabilisation policies in the EAC and coffee producing countries in sub‐Sahara Africa. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives To analyse anthropometric parameters, clinical pain and experimental pain in women with chronic pelvic pain (CPP). Methods Ninety-one women with a clinical diagnosis of CPP, mean age of 40.03 ± 9.97 years, submitted to anthropometric evaluation based on body mass index (BMI) and percent body fat (%BF) using bioimpedance body composition monitor; pain intensity was determined by visual analogue scale (VAS), numerical categorical scale (NCS) and McGill Pain Questionnaire; experimental pain was determined by transcutaneous electrical nerve stimulation (TENS), and anxiety and depression symptoms were determined by the Hospital Anxiety and Depression scale. Results A total of 54.8% of the women showed %BF >32 risk of disease associated with obesity. Regarding the anthropometric data, a statistically significant difference was observed between groups for both BMI and %BF (P < 0.0001). In the analysis of pain intensity by the VAS, NCS and total McGill, there was no significant difference between the groups, and experimental pain by TENS revealed significant difference only between the normal weight and overweight groups (P = 0.0154). The results of anxiety symptoms were above the cut-off point in all groups, with no significant difference between them (P = 0.3710). The depression symptoms were below the cut-off point in the normal weight group and above the cut-off point in the overweight and obese groups, 9.469(4.501) and 9.741(4.848), respectively, with no significant difference between them (P = 0.6476). Conclusion Evaluation of anthropometric parameters and pain measurements can be applied in clinical practice, making a contribution to the diagnosis and influencing the choice of a more effective treatment for women with CPP. [ABSTRACT FROM AUTHOR]

Aim The following paper describes the Autism Spectrum Assessment Clinic which operates at Melton Health, a publically funded health service in Melbourne's west. Methods A retrospective audit of 234 children assessed between 2007 and 2012 in the Autism Spectrum Assessment Clinic was undertaken. Characteristics of the children assessed (age, sex, locality, referral source) were examined along with characteristics of the clinic (clinicians, assessment outcome). Results A detailed description of the model is provided, including evident changes since the clinic began. Data were split between the 2007 to 2009 and 2010 to 2012 time periods to reflect changes in the operation of the clinic. Overall, 48 girls and 186 boys were assessed with a mean age of 71 months; the average waiting time between referral and assessment was 136.6 days. Across the two time periods, the proportion of children receiving a diagnosis of autism spectrum disorder increased from 43.1% to 66.3%. Changes are evident in the referral sources between the two time periods, and in the disciplines of clinicians involved in the assessment. Conclusions The research illustrates an assessment model, within the Victorian public health context, which currently operates effectively according to best-practice guidelines. This research begins to fill a gap between localised clinical practice and the dissemination of this information to a wider audience, allowing for comparison for other assessment providers. It is hoped that we can contribute more broadly to future assessment processes becoming more consistent, reproducible and equitable for children suspected of having autism spectrum disorders. [ABSTRACT FROM AUTHOR]

Background: APOEε4 is the strongest genetic risk factor for AD[1]. Although plasma apoE does not cross the blood‐brain‐barrier[2], altered plasma apoE levels have been linked to increased risk of AD[3] and to unfavorable CSF Aβ42 and tau levels[4]. Translation of results from studies of apoE in rodents to the human situation is difficult due species‐specific difference for instance in lipid metabolism[5]. Here we have studied the effects of a humanized APOEε4 liver[6] on synaptic integrity, insulin signaling and gliosis in a mouse model that reproduces the human plasma profile and that retains its endogenous apoE expression in the brain. Method: Tissue samples from the cortex, hippocampus, cerebellum and thalamus were obtained from FRGN mice with humanized APOEε2/ε3 (n=4) versus APOEε4/ε4 (n=8) livers, and from APOEε3/ε3 (n=3) and APOEε4/ε4 (n=3) TR mice. Using established protocols[7], nuclei‐ and synaptosome‐enriched, and synaptosome‐depleted fractions were generated and analyzed for contents of markers relating to synapse integrity, gliosis and insulin signaling using western blotting. Levels of apoE4 were assessed in plasma from FRGN mice with humanized APOEε4/ε4 livers. Result: Cortical and hippocampal levels of endogenous apoE, cortical levels of tubulin‐βIII, AMPAR, NMDAR, bassoon, mTOR, pAkt and a‐synuclein as well as hippocampal levels of synaptophysin, EAAT2, GFAP, NMDAR, pmTORS2448 and pIRS616 were reduced in FRGN mice with humanized APOEε4/ε4 versus APOEε2/ε3 livers (p≤0.05). Several of these findings were recapitulated in brain tissues from APOEε4/ε4 versus APOEε3/ε3 TR mice (p≤0.05). In both mouse models we observed a shift of a‐synuclein content from the synaptosomal (reduction) to the extra‐synaptosomal (increase) compartment (p<0.05). Altered expression levels of synaptic markers were also found in the thalamus and to a lesser extent in the cerebellum. Plasma levels of apoE appeared lower in the humanized APOEε4/ε4 liver mice and correlated positively to cortical levels of endogenous apoE but negatively to various markers of synaptic integrity and insulin signaling mainly in the hippocampus. Conclusion: We here provide the first evidence of a profound and negative effect of a liver APOEε4 phenotype in a human‐like setting, on key markers related to brain synaptic integrity, insulin signaling and glial cells involved in neuroinflammation. [ABSTRACT FROM AUTHOR]

Early pregnancy and multiparity are known to reduce the risk of women to develop breast cancer at menopause. Based on the knowledge that the differentiation of the breast induced by the hormones of pregnancy plays a major role in this protection, this work was performed with the purpose of identifying what differentiation-associated molecular changes persist in the breast until menopause. Core needle biopsies (CNB) obtained from the breast of 42 nulliparous (NP) and 71 parous (P) postmenopausal women were analyzed in morphology, immunocytochemistry and gene expression. Whereas in the NP breast, nuclei of epithelial cells were large and euchromatic, in the P breast they were small and hyperchromatic, showing strong methylation of histone 3 at lysine 9 and 27. Transcriptomic analysis performed using Affymetrix HG_U133 oligonucleotide arrays revealed that in CNB of the P breast, there were 267 upregulated probesets that comprised genes controlling chromatin organization, transcription regulation, splicing machinery, mRNA processing and noncoding elements including XIST. We concluded that the differentiation process induced by pregnancy is centered in chromatin remodeling and in the mRNA processing reactome, both of which emerge as important regulatory pathways. These are indicative of a safeguard step that maintains the fidelity of the transcription process, becoming the ultimate mechanism mediating the protection of the breast conferred by full-term pregnancy. [ABSTRACT FROM AUTHOR]

In this work, a study of the mirror symmetries appearing in multiple diffraction patterns of face-centred cubic crystals is carried out. Several different X-ray and neutron multiple diffraction patterns have been simulated for different face-centred cubic structures. The patterns were plotted in circular plots which showed that two types of symmetry mirrors coexist in the patterns: isomorphic and anamorphic mirrors. The number and types of mirrors depend on the n-fold symmetry of the scattering vector associated with the primary reflection. For n even, only n isomorphic mirrors appear in the patterns. For n odd, n isomorphic mirrors are formed intercalated between n anamorphic mirrors. [ABSTRACT FROM AUTHOR]