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Summary: Background: Evidence is accumulating that elevated levels of particulate air pollution, including black carbon, have been linked to gastrointestinal disorders and a lower intestinal bacterial richness and diversity. One of the hypothesized underlying mechanisms is the absorption of air pollution-related particles from the gastrointestinal tract. Methods: We visualized and quantified black carbon particles via white light generation under femtosecond-pulsed laser illumination in ileum and colon biopsies of five human patients. The biodistribution was assessed in three different layers (i.e., mucosa, submucosa, and muscularis propria). Findings: Black carbon particles could be identified in all three tissue layers of the ileum and colon biopsies of five participants (two men and three women; mean ± standard deviation age, 76.40 ± 7.37 years), and their carbonaceous nature was confirmed via emission fingerprinting. The median (±SD) black carbon load was borderline statistically significantly higher in the ileum compared to the colon (1.21 × 105 ± 1.68 × 104 particles/mm3 versus 9.34 × 104 ± 1.33 × 104 particles/mm3; p = 0.07) and was driven by a difference in black carbon load in the submucosa layer (p = 0.01). Regarding the three tissue layers, loads were higher in the submucosa, compared with the mucosa (ileum: +76%, p

Abstract Background Mucoepidermoid carcinoma of the breast is a rare special type of salivary gland-like tumor of the breast, usually displaying triple-negative phenotype. To date, only 64 cases have been reported in the English literature. Herein, we report the first case of mucoepidermoid carcinoma of the breast with human epidermal growth factor receptor 2 gene amplification. Case presentation A 58-year-old Caucasian woman treated with breast-conserving surgery, radiotherapy, and chemotherapy for an invasive breast carcinoma of no special type, relapsed 20 years later in the ipsilateral left breast. Histological examination of the core needle biopsy of the relapse deferred to the surgical specimen for the definitive diagnosis, because of the broad differential diagnosis. On the resected specimen we observed the presence of a poorly differentiated carcinoma with mucoepidermoid carcinoma of the breast typical features consisting of epidermoid, intermediate and mucinous cells lacking true keratinization, in keeping with the latest World Health Organization diagnostic criteria. The mucoepidermoid carcinoma of the breast was weakly estrogen receptor and androgen receptor positive and progesterone receptor negative, but exceptionally showed human epidermal growth factor receptor 2 gene amplification. Mastermind-like transcriptional coactivator 2 gene translocations were not detected by fluorescent in situ hybridization. The patient received adjuvant chemotherapy with anti-human epidermal growth factor receptor 2 therapy but no endocrine therapy. After 61 months of follow-up, no signs of local or distant recurrence were observed. Conclusions Mucoepidermoid carcinoma of the breast is a very rare entity. Despite being most frequently triple negative, the standard evaluation of receptor status is mandatory, as well as strict application of World Health Organization diagnostic criteria for correct patient management.

With the advent of whole-slide imaging (WSI), a technology that can digitally scan whole slides in high resolution, pathology is undergoing a digital revolution. Detecting microsatellite instability (MSI) in colorectal cancer is crucial for proper treatment, as it identifies patients responsible for immunotherapy. Even though universal testing for MSI is recommended, particularly in patients affected by colorectal cancer (CRC), many patients remain untested, and they reside mainly in low-income countries. A critical need exists for accessible, low-cost tools to perform MSI pre-screening. Here, the potential predictive role of the most relevant artificial intelligence-driven models in predicting microsatellite instability directly from histology alone is discussed, focusing on CRC. The role of deep learning (DL) models in identifying the MSI status is here analyzed in the most relevant studies reporting the development of algorithms trained to this end. The most important performance and the most relevant deficiencies are discussed for every AI method. The models proposed for algorithm sharing among multiple research and clinical centers, including federal learning (FL) and swarm learning (SL), are reported. According to all the studies reported here, AI models are valuable tools for predicting MSI status on WSI alone in CRC. The use of digitized H&E-stained sections and a trained algorithm allow the extraction of relevant molecular information, such as MSI status, in a short time and at a low cost. The possible advantages related to introducing DL methods in routine surgical pathology are underlined here, and the acceleration of the digital transformation of pathology departments and services is recommended.

ABSTRACT Understanding the evolutionary dynamics of foodborne pathogens throughout our food production chain is of utmost importance. In this study, we reveal that Salmonella Typhimurium can readily and reproducibly acquire vastly increased heat shock resistance upon repeated exposure to heat shock. Counterintuitively, this boost in heat shock resistance was invariantly acquired through loss-of-function mutations in the dnaJ gene, encoding a heat shock protein that acts as a molecular co-chaperone of DnaK and enables its role in protein folding and disaggregation. As a trade-off, however, the acquisition of heat shock resistance inevitably led to attenuated growth at 37°C and higher temperatures. Interestingly, loss of DnaJ also downregulated the activity of the master virulence regulator HilD, thereby lowering the fraction of virulence-expressing cells within the population and attenuating virulence in mice. By connecting heat shock resistance evolution to attenuation of HilD activity, our results confirm the complex interplay between stress resistance and virulence in Salmonella Typhimurium.IMPORTANCEBacterial pathogens such as Salmonella Typhimurium are equipped with both stress response and virulence features in order to navigate across a variety of complex inhospitable environments that range from food-processing plants up to the gastrointestinal tract of its animal host. In this context, however, it remains obscure whether and how adaptation to one environment would obstruct fitness in another. In this study, we reveal that severe heat stress counterintuitively, but invariantly, led to the selection of S. Typhimurium mutants that are compromised in the activity of the DnaJ heat shock protein. While these mutants obtained massively increased heat resistance, their virulence became greatly attenuated. Our observations, therefore, reveal a delicate balance between optimal tuning of stress response and virulence features in bacterial pathogens.

In this study, the effect of various scanning electron microscope (SEM) imaging parameters, including voltage, beam current, and magnification, on the porosity analysis of U-Mo fuel was investigated by varying one parameter at a time during back-scattered electron (BSE) micrograph acquisition. Among the parameters assessed, porosity analysis is most sensitive to the SEM voltage. In the range from 5 kV to 30 kV, we reported relative differences as high as 30%, 10%, and 20% in the total porosity, average diameter, and pore density, respectively. Monte Carlo simulations were also performed to determine the influence of SEM voltage on the probing depths of back-scattered electrons. Increasing the voltage from 5 kV to 30 kV resulted in a change in probing depth from few tens of nanometers to several hundreds of nanometers. Portions of pores or entire pores residing below the polished plane that could not be seen at low voltages, and should not be counted for in the estimation of the open porosity, became visible at high voltages. Interestingly, in addition to allowing for a better estimation of the open porosity, the higher sensitivity to surface features at low voltages seems to reduce the number of pixels with intermediate gray levels in the final BSE image. This, in turn, could limit the ground for different interpretation by different analysts, and, as such, has the potential to facilitate a more consistent and uniform porosity analysis across different research laboratories.

Introdução: Os aspectos individuais de cada criança, as tarefas que ela realiza e o ambiente no qual ela vive são determinantes para o desenvolvimento motor. Objetivo: Conhecer as oportunidades para o desenvolvimento motor presentes nas residências de crianças entre dezoito e trinta e seis meses de idade do bairro mais populoso de uma capital da região sudeste do Brasil. Material e Métodos: Estudo transversal, observacional e analítico, realizado com responsáveis legais de crianças da educação infantil pública, que responderam ao questionário Affordances in the Home Environment for Motor Development - Self Report (AHEMD – SR) na versão em português. As residências foram classificadas e a análise estatística descritiva e o teste de correlação de Pearson realizados. Resultados: A média de idade das crianças foi de 21,9 meses (DP= 3,6). Das 37 residências avaliadas, 22% tiveram uma classificação baixa para as oportunidades oferecidas, e 78,5% uma classificação média. Os espaços interno e externo das residências, na maioria, foram classificados como bons promotores e muito bons promotores de oportunidades, respectivamente. Em relação aos materiais e brinquedos para o desenvolvimento das motricidades fina e grossa, a maioria das residências não oferecia oportunidades suficientes ou oferecia poucas oportunidades. As correlações do escore total do AHEMD com as variáveis escolaridade do pai, rendimento mensal da família, número de crianças e de quartos no domicílio foram fracas e positivas e com a escolaridade da mãe e a idade das crianças, fracas e negativas. Conclusão: Os espaços internos e externos das residências são adequados, mas os brinquedos não são suficientes para o desenvolvimento das motricidades fina e grossa. O nível socioeconômico das famílias interfere nas oportunidades para o desenvolvimento motor das residências.

ABSTRACT Despite our extensive knowledge of the genetic regulation of heat shock proteins (HSPs), the evolutionary routes that allow bacteria to adaptively tune their HSP levels and corresponding proteostatic robustness have been explored less. In this report, directed evolution experiments using the Escherichia coli model system unexpectedly revealed that seemingly random single mutations in its tnaA gene can confer significant heat resistance. Closer examination, however, indicated that these mutations create folding-deficient and aggregation-prone TnaA variants that in turn can endogenously and preemptively trigger HSP expression to cause heat resistance. These findings, importantly, demonstrate that even erosive mutations with disruptive effects on protein structure and functionality can still yield true gain-of-function alleles with a selective advantage in adaptive evolution.

Exposure to air pollution during pregnancy has been associated with impaired birth outcomes. Here, Bové et al. report evidence of black carbon particle deposition on the fetal side of human placentae, including at early stages of pregnancy, suggesting air pollution could affect birth outcome through direct effects on the fetus.

BACKGROUND: An increasing number of coronavirus disease 2019 (COVID-19) related autoimmune hepatitis (AIH) and autoimmune liver disease (AILD) has been already described so far in the last three years. This rise has set up some diagnostic and therapeutic concerns, although steroid therapy has mostly been efficient, avoiding main significant side effects. CASE PRESENTATION: We report the case of a 52-year-old subject displaying liver function impairment at the laboratory tests while positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab. Needle liver biopsy showed severe portal inflammation, interface hepatitis, lobular inflammation, abundant plasma cells, bridging necrosis, endothelialitis, bile duct vanishing disease, and ductular reaction. The diagnosis of autoimmune liver disease (AILD) was performed. After a month of steroid and ursodeoxycholic acid medications, liver function fully recovered. Azathioprine was introduced, and steroids were gradually reduced. CONCLUSIONS: Probably triggered by the SARS-CoV-2-induced cytokine storm, the association between COVID-19 and autoimmune-related inflammatory injury may display a particular paradigm of AILD pathogenesis. [ABSTRACT FROM AUTHOR]

Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson’s disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson’s disease. On the basis of the similarities, at histological level, between Wilson’s disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.

In recent years, the spectrum of possible applications of gold in diagnostics and therapeutic approaches in clinical practice has changed significantly, becoming surprisingly broad. Nowadays, gold-based therapeutic agents are used in the therapy of multiple human diseases, ranging from degenerative to infectious diseases and, in particular, to cancer. At the basis of these performances of gold, there is the development of new gold-based nanoparticles, characterized by a promising risk/benefit ratio that favors their introduction in clinical trials. Gold nanoparticles appear as attractive elements in nanomedicine, a branch of modern clinical medicine, which combines high selectivity in targeting tumor cells and low toxicity. Thanks to these peculiar characteristics, gold nanoparticles appear as the starting point for the development of new gold-based therapeutic strategies in oncology. Here, the new gold-based therapeutic agents developed in recent years are described, with particular emphasis on the possible applications in clinical practice as anticancer agents, with the aim that their application will give rise to a new golden age in oncology and a breakthrough in the fight against cancer.

Prof. Peter Van Eyken, a renowned Belgian pathologist, answers to the following 10 questions: 1. You are a pupil of Valeer Desmet, one of the leading liver pathologists in the world. What was it like spending so many years with him? 2. Your first research project focused on cytokeratins: how has your research changed liver biopsy interpretation in clinical practice? 3. What are the most important innovations in pathology of the last years? What is changing in your approach to histology and to cytology? 4. What is the role of pathologists in pediatric pathology? How is their relationship with pediatricians is changing? 5. How is the role of the pathologist changing in neonatal and in perinatal medicine? 6. As a young researcher, you published many articles on liver development and on bile duct atresia: did your studies change the way you approach liver biopsy interpretation in a newborn? 7. After years of involvement in kidney biopsy interpretation in adults, recently, you became involved in studies on nephrogenesis. Which is the relationship between renal development and adult kidney pathology? 8. What is your opinion on networks in medicine? Should pathology be integrated with “omic” sciences and informatics ? 9. What about the future of pathology? New techniques or new eyes in the interpretation of H&E-stained sections? What is the role of immunohistochemistry? And of of molecular pathology? 10. Could you advise young medical doctors to become pathologists? What are your suggestions?

OBJECTIVE: The atherosclerotic plaque is a complex dynamic pathological lesion of the arterial wall, characterized by multiple elementary lesions of different diagnostic and prognostic significance. Fibrous cap thickness, lipid necrotic core dimension, inflammation, intra-plaque hemorrhage (IPH), plaque neovascularization and endothelial dysfunction (erosions) are generally considered the most relevant morphological details of plaque morphology. In this review, the most relevant features able to discriminate between stable and vulnerable plaques at histological level are discussed. SUBJECTS AND METHODS: Retrospectively, we have evaluated the laboratory results from one hundred old histological samples from patients treated with carotid endarterectomy. These results were analyzed to assess elementary lesions that characterize stable and unstable plaques. RESULTS: A thin fibrous cap (<65 micron), loss of smooth muscle cells, collagen depletion, a large lipid-rich necrotic core, infiltrating macrophages, IPH and intra-plaque vascularization are identified as the most important risk factors associated with plaque rupture. CONCLUSIONS: Immunohistochemistry for smooth muscle actin (smooth muscle cell marker) and for CD68 (marker of monocytes/macrophages) and glycophorin (marker of red blood cells) are suggested as useful tools for an in deep characterization of any carotid plaque and for distinguishing plaque phenotypes at histology. Since patients with a carotid vulnerable plaque are at higher risk of developing vulnerable plaques in other arteries as well, the definition of the vulnerability index is underlined, in order to stratify patients at higher risk for undergoing cardiovascular events. [ABSTRACT FROM AUTHOR]

Stem/progenitor cells in the adult liver are able to differentiate both into hepatocyte and cholangiocyte lineage. The identification and the role of human liver stem/progenitor cells has been a challenge topic in the recent scientific literature. The existence of stem/progenitor cells in the liver was first claimed in experimental animal models. CD34, c-kit, cytokeratin 7, cytokeratin 19, α-fetoprotein, OV6 and CD90 were the first markers shown. The major support for the existence of hepatic stem/progenitor cells has come from studies on liver carcinogenesis, human liver disease and cirrhosis. Where exactly the putative stem/progenitor cells reside in the normal liver is still controversial and their specific anatomical location is still unclear. Preliminary data from our lab indicate the portal tracts as the preferential site of the stem cell niches thanks to the expression of biliary-type cytokeratin 19, SOX9 and c-kit. Small undifferentiated cells were easily identified in H&E as well. Like in other organs, hepatic stem/progenitor cell niche was hypothesized and described as composed of numerous cell types that interact and cross-talk with hepatic stem/progenitor cells. Hepatic stem/progenitor cells represent a heterogeneous population with a spectrum of morphological and immunohistochemical features ranging from bile duct cells to hepatocytes, including the multipotent hepatic stem/progenitor cells, the hepatoblasts, the committed progenitors and the diploid adult cells. Inside this complex and articulate spectrum, cells without hepatobiliary markers and hematopoietic stem/progenitor cells can be identified. The hepatic stem/progenitor cells exhibit specific population functions and can be identified by specific population immunohistochemical markers, including CD133, CXCR4, SOX9, SOX17, cytokeratins, Hedgehog proteins, MDR1 and many others. In conclusion, this study represents the basis for further studies, aimed at better characterizing these stem/progenitor cells and at identifying possible subtypes of hepatic stem progenitor cells. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015) · Cagliari (Italy) · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

In the first part of this review a brief summary of the embryology and histology of the gastrointestinal tract is provided. In the second part intestinal stem cells (ISCs) are discussed. Several signaling pathways play a crucial role in the crypt base in the regulation of ISC proliferation and self-renewal; Wnt, Notch, BMP, Ephrin, JAK/STAT1, PTEN, AKT, PI3K and many more. Numerous investigators are involved in studying the location, number, and behavior of ISCs within the base of the intestinal crypts. Several markers are espressed by ISCs. Among these, Leucine-rich-repeat-containing G-protein-coupled receptor-5 (Lgr5), Sox9, Prominin-1, DCAMKL-1, EphB2, p-PTEN, p-AKT, Fgfr3, m-TER, and CD44. Stem cell therapy has shown promise for the treatment of some diseases characterized by tissue damage with ischemic and inflammatory lesions like inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015) · Cagliari (Italy) · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

The renal stem cell niche represents the most important structure of the developing kidney, responsible for nephrogenesis. Recently, some Authors have reported, at ultrastructural level, a previously unknown complexity of the architecture of renal stem cell niche in experimental models. This study was aimed at studying, at histological level, the anatomy of renal stem cell niches in the human fetal kidney. To this end, ten fetal kidneys, whose gestational ages ranged from 11 up to 24 weeks, were studied. H&E-stained sections were observed at high power. The study of the anatomy of renal stem cell niches in the human kidney revealed a previously unreported complexity: some niches appeared as a roundish arrangement of mesenchymal cells; others showed the initial phases of induction by ureteric buds; in other niches the process of mesenchymal epithelial transition was more evident; finally, in other stem cell niches the first signs of nephron origin were detectable. These findings suggest the existence of niches with different anatomy in the same kidney, indicating different stages of evolution even in adjacent niches. All stem cell niches were in strict contact with the capsular cells, suggesting a major role of the renal capsule in nephrogenesis. Finally, our study confirms the existence of a strict contact between the bud tip cells and the surrounding mesenchyme in the human developing kidney, giving a morphological support to the theory of intercellular channels allowing the passage of transcription factors from the epithelial to the mesenchymal stem/progenitors cells. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015) · Cagliari (Italy) · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

A case of horseshoe kidney is reported in a 11 week-old fetus affected by trisomy 18. Macroscopic examination did not show any other pathological change. The histological picture of the fused-kidney was characterized by architectural and glomerular changes. At x 100 magnification, large areas of metanephric mesenchyme, characterized by spindle cells surrounded by a loose oedematous stroma, were detected in the deep cortex and in the medulla. At higher power, multiple glomerular changes were observed. Maldeveloped glomeruli showed enlarged capsular spaces, adhesions between vascular tuft and capsular cells, podocytes in multiple layers, and large glomerular bodies formed by two vascular tufts. Our data confirm previous reports on glomerular changes in horseshoe kidney, and reinforce the hypothesis that horseshoe kidney should not be considered a simple fusion problem, but a complex developmental abnormality, possibly involving glomerular development.

The differential diagnosis between hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and metastatic colorectal adenocarcinoma (MCA) may be difficult when only based on morphology. For this purpose immunohistochemical analyses are often required, utilizing antibodies directed against CK8- 18, Hep-Par1, glypican 3, CK7, CK19, CK20. Here we report a case of a 65-year-old man who presented with a clinical picture of decompensated cirrhosis. Ultrasonography revealed two nodular areas in the right liver lobe. Liver needle biopsy revealed micro-macronodular cirrhosis associated with HCC with trabecular and pseudoglandular patterns. Immunohistochemically, tumour cells were diffusely positive for CK8- 18 and also diffusely immunostained by glypican 3 and Hep- Par1. Interestingly, a diffuse and strong staining for CK20 was detected in the vast majority of tumor cells, particularly in the areas showing a pseudo-glandular pattern. No immunostaining for CK7 and CK19 was found in the tumor cells. The tumor behaved aggressively, with a rapid diffusion to the whole liver. The patient died from the disease few months after presentation. These findings underline that the interpretation of the expression of CK20 alone in the differential diagnosis among HCC, CC and MCA should be done with caution because a diffuse immunoreactivity for CK20 alone may not rule out the diagnosis of HCC.

O monitoramento dos fatores de risco para as doenças cardiovasculares vem sendo indicado em todo o mundo. Nesse sentido, o objetivo do estudo foi estimar a prevalência de tabagismo, sobrepeso/obesidade, atividade física insuficiente, hipertensão arterial e pressão arterial limítrofe entre homens adscritos à Estratégia Saúde da Família em área urbana de Juiz de Fora, Minas Gerais, Região Sudeste do Brasil. Foi realizado um inquérito domiciliar com 217 homens, entre 20 e 49 anos, selecionados por meio de amostragem sistemática baseada em listagem de moradores desta faixa etária. O sobrepeso/obesidade foi o fator de risco de maior freqüência (43,3%; IC95%: 36,6-50,2). Os sedentários e irregularmente ativos fisicamente totalizaram 28% (IC95%: 22,2-34,6). O consumo de cigarros era hábito de 25,3% (IC95%: 19,7-31,7) da população. Foram classificados como hipertensos 24% (IC95%: 18,4-30,2) dos entrevistados e 19,4% (IC95%: 14,3-25,2) com pressão arterial limítrofe. A simultaneidade de dois ou mais fatores de risco foi encontrada em 45,2% da população. A magnitude das prevalências sugere que é preciso intensificar as estratégias de promoção de saúde voltadas para a população masculina.Surveillance of cardiovascular risk factors has been recommended worldwide. The current study aimed to estimate the prevalence of smoking, overweight/obesity, insufficient physical activity, arterial hypertension, and pre-hypertension among men covered by the Family Health Program in urban Juiz de Fora, Minas Gerais State, in Southeast Brazil. A household survey was performed with a systematic sample of 217 men 20 to 49 years of age, from a list of residents within this age range. Prevalence of risk factors was high, with overweight/obesity the most frequent (43.3%; 95%CI: 36.6-50.2). Men classified as sedentary or with irregular physical activity totaled 28% (95%CI: 22.2-34.6). Smoking was reported by 25.3% (95%CI: 19.7-31.7). Overt hypertension was present in 24% (95%CI: 18.4-30.2) and borderline hypertension in 19.4% (95%CI: 14.3-25.2). Two or more simultaneous risk factors were found in 45.2% of the sample. The high prevalence rates suggest that health promotion strategies need to be intensified in the male population.

Results are presented from the first two active experimental campaigns undertaken by the new SPEAR (Space Plasma Exploration by Active Radar) high-power system that has recently become operational on Spitzbergen, in the Svalbard archipelago. SPEAR's high-power beam was used to excite artificial enhancements in the backscatter detected by the ESR (EISCAT Svalbard Radar) parallel to the geomagnetic field, as well as coherent backscatter detected by both of the CUTLASS (Co-operative UK Twin Located Auroral Sounding System) coherent radars, in directions orthogonal to the geomagnetic field. The ESR detected both enhanced ion-lines as well as enhanced plasma-lines, that were sustained for the whole period when SPEAR was transmitting ordinary mode radio waves, at frequencies below the maximum F-region plasma frequency. On a number of occasions, coherent backscatter was also observed in one or in both of the CUTLASS radars, in beams that intersected the heated volume. Although the levels of enhanced backscatter varied considerably in time, it appeared that ion-line, plasma-line and coherent backscatter were all excited simultaneously, in contrast to what has typically been reported at Tromsø, during EISCAT heater operations. A description of the technical and operational aspects of the new SPEAR system is also included.

Using data from the EISCAT (European Incoherent Scatter) VHF radar and DMSP (Defense Meteorological Satellite Program) spacecraft passes, we study the motion of the dayside open-closed field line boundary during two substorm cycles. The satellite data show that the motions of ion and electron temperature boundaries in EISCAT data, as reported by Moen et al. (2004), are not localised around the radar; rather, they reflect motions of the open-closed field line boundary at all MLT throughout the dayside auroral ionosphere. The boundary is shown to erode equatorward when the IMF points southward, consistent with the effect of magnetopause reconnection. During the substorm expansion and recovery phases, the dayside boundary returns poleward, whether the IMF points northward or southward. However, the poleward retreat was much faster during the substorm for which the IMF had returned to northward than for the substorm for which the IMF remained southward - even though the former substorm is much the weaker of the two. These poleward retreats are consistent with the destruction of open flux at the tail current sheet. Application of a new analysis of the peak ion energies at the equatorward edge of the cleft/cusp/mantle dispersion seen by the DMSP satellites identifies the dayside reconnection merging gap to extend in MLT from about 9.5 to 15.5 h for most of the interval. Analysis of the boundary motion, and of the convection velocities seen near the boundary by EISCAT, allows calculation of the reconnection rate (mapped down to the ionosphere) from the flow component normal to the boundary in its own rest frame. This reconnection rate is not, in general, significantly different from zero before 06:45 UT (MLT

Using data from the EISCAT (European Incoherent Scatter) VHF and CUTLASS (Co-operative UK Twin-Located Auroral Sounding System) HF radars, we study the formation of ionospheric polar cap patches and their relationship to the magnetopause reconnection pulses identified in the companion paper by Lockwood et al. (2005). It is shown that the poleward-moving, high-concentration plasma patches observed in the ionosphere by EISCAT on 23 November 1999, as reported by Davies et al. (2002), were often associated with corresponding reconnection rate pulses. However, not all such pulses generated a patch and only within a limited MLT range (11:00-12:00 MLT) did a patch result from a reconnection pulse. Three proposed mechanisms for the production of patches, and of the concentration minima that separate them, are analysed and evaluated: (1) concentration enhancement within the patches by cusp/cleft precipitation; (2) plasma depletion in the minima between the patches by fast plasma flows; and (3) intermittent injection of photoionisation-enhanced plasma into the polar cap. We devise a test to distinguish between the effects of these mechanisms. Some of the events repeat too frequently to apply the test. Others have sufficiently long repeat periods and mechanism (3) is shown to be the only explanation of three of the longer-lived patches seen on this day. However, effect (2) also appears to contribute to some events. We conclude that plasma concentration gradients on the edges of the larger patches arise mainly from local time variations in the subauroral plasma, via the mechanism proposed by Lockwood et al. (2000).

The existence of a month-long continuous database of incoherent scatter radar observations of the ionosphere from the EISCAT Savlbard Radar (ESR) at Longyearbyen, Norway, provides an unprecedented opportunity for model/data comparisons. Physics-based ionospheric models, such as the Utah State University Time Dependent Ionospheric Model (TDIM), are usually only compared with observations over restricted one or two day events or against climatological averages. In this study, using the ESR observations, the daily weather, day-to-day variability, and month-long climatology can be simultaneously addressed to identify modeling shortcomings and successes. Since for this study the TDIM is driven by climatological representations of the magnetospheric convection, auroral oval, neutral atmosphere, and neutral winds, whose inputs are solar and geomagnetic indices, it is not surprising that the daily weather cannot be reproduced. What is unexpected is that the horizontal neutral wind has come to the forefront as a decisive model input parameter in matching the diurnal morphology of density structuring seen in the observations.

This paper describes the ionospheric response to a geomagnetic storm beginning on 17 April 2002. We present the measurements of ionospheric parameters in the F-region obtained by the network of eight incoherent scatter radars. The main effects of this storm include a deep decrease in the electron density observed at high and middle latitudes in the pre-noon sector, and a minor enhancement in the density observed in the daytime sector at middle latitudes. Extreme plasma heating (>1000-3000 K) is observed at high latitudes, subsiding to 200-300K at subauroral latitudes. The western hemisphere radar chain observed the prompt penetration of the electric field from auroral to equatorial latitudes, as well as the daytime enhancement of plasma drift parallel to the magnetic field line, which is related to the enhancement in the equatorward winds. We suggest that in the first several hours after the storm onset, a negative phase above Millstone Hill (pre-noon sector) results from counteracting processes - penetration electric field, meridional wind, and electrodynamic heating, with electrodynamic heating being the dominant mechanism. At the lower latitude in the pre-noon sector (Arecibo and Jicamarca), the penetration electric field becomes more important, leading to a negative storm phase over Arecibo. In contrast, in the afternoon sector at mid-latitudes (Kharkov, Irkutsk), effects of penetration electric field and meridional wind do not counteract, but add up, leading to a small (~15%), positive storm phase over these locations. As the storm develops, Millstone Hill and Irkutsk mid-latitude radars observe further depletion of electron density due to the changes in the neutral composition.

Idiopathic infantile arterial calcification (IIAC) is a rare disease characterized by abnormal calcification of the arterial vessels, resulting in calcium deposits in the wall of medium-sized and large arteries. IIAC is caused by mutations in the ENPP1 gene, localized on chromosome 6q22, resulting in deficiency of the enzyme PC-1 nucleoside triphosphate pyrophosphohydrolase (NPP). Clinical presentation may occur during the intrauterine life, with fetal hydrop, aorto-pulmonary calcification, or as fatal hypertensive cardiomyopathy. In other patients, the clinical presentation is in the postnatal period with hypertrophic cardiomyopathy, with a fatal outcome within 6 months due to intractable heart failure. Here we report the clinico-pathological findings of a preterm affected with IIAC, with particular emphasis on renal glomerular pathological lesion not previously described in this disease.

A continuous band of high ion temperature, which persisted for about 8h and zigzagged north-south across more than five degrees in latitude in the dayside (07:00-15:00MLT) auroral ionosphere, was observed by the EISCAT VHF radar on 23 November 1999. Latitudinal gradients in the temperature of the F-region electron and ion gases (Te and Ti, respectively) have been compared with concurrent observations of particle precipitation and field-perpendicular convection by DMSP satellites, in order to reveal a physical explanation for the persistent band of high Ti, and to test the potential role of Ti and Te gradients as possible markers for the open-closed field line boundary. The north/south movement of the equatorward Ti boundary was found to be consistent with the contraction/expansion of the polar cap due to an unbalanced dayside and nightside reconnection. Sporadic intensifications in Ti, recurring on ~10-min time scales, indicate that frictional heating was modulated by time-varying reconnection, and the band of high Ti was located on open flux. However, the equatorward Ti boundary was not found to be a close proxy of the open-closed boundary. The closest definable proxy of the open-closed boundary is the magnetosheath electron edge observed by DMSP. Although Te appears to be sensitive to magnetosheath electron fluxes, it is not found to be a suitable parameter for routine tracking of the open-closed boundary, as it involves case dependent analysis of the thermal balance. Finally, we have documented a region of newly-opened sunward convecting flux. This region is situated between the convection reversal boundary and the magnetosheath electron edge defining the open-closed boundary. This is consistent with a delay of several minutes between the arrival of the first (super-Alfvénic) magnetosheath electrons and the response in the ionospheric convection, conveyed to the ionosphere by the interior Alfvén wave. It represents a candidate footprint of the low-latitude boundary mixing layer on sunward convecting open flux.

We report on observations of a diverging ion flow along the geomagnetic field that is often seen at the EISCAT Svalbard radar. The flow is upward above the peak of the electron density in the F-region and downward below the peak. We estimate that in such events mass transport along the field line is important for the ionization balance, and that the shape of the F-layer and its ion composition should be strongly influenced by it. Diverging flow typically occurs when there are signatures of direct entry of sheath plasma to the ionosphere in the form of intense soft particle precipitation, and we suggest that it is caused by the ionization and ionospheric electron heating associated with this precipitation. On average, 30% of all events with ion upflow also show significant ion downflow below. Key words.Ionosphere (polar ionosphere; ionization mechanism; plasma temperature and density)

Extrahepatic biliary atresia (EHBA) refers to stenosis or atresia of the extrahepatic biliary tree. It accounts for 25-30% of cases of neonatal cholestasis. If left untreated, EHBA progresses to biliary cirrhosis and is universally fatal within the first 2 years of life. Early diagnosis is crucial since surgical treatment (Kasai procedure) is the only treatment option. Histopathologic examination of liver biopsy specimens is a key element in the diagnostic work-up of infants with suspected EHBA. Pathologic diagnosis aims at excluding non-surgically correctable causes of neonatal cholestasis thereby leading to surgical exploration for confirmation of the diagnosis. All published data indicate that pathologists can diagnose EHBA with high sensitivity, high specificity and reasonable interobserver agreement. The most useful histologic features in the diagnosis of EHBA are portal tract changes including ductular proliferation and bile plugs in ducts and ductules. These lesions are not pathognomonic but can be seen in extrahepatic obstruction of any cause. Total parenteral nutrition (TPN)-associated cholestasis and alpha1-antitrypsin (A1AT) deficiency cannot be differentiated from EHBA without access to clinical data and may lead to false-positive diagnosis. False-negative interpretation may be caused by early age at diagnosis or by small/indequate specimens. The pathologist also plays a role in the examination of the resected fibrotic segment and of explant specimens. Histopathology can yield prognostic information, being also an indispensable tool in research for the possible pathogenesis of this disease. A well-coordinated, multidisciplinary approach is required in the assessment of suspected cases of EHBA. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014) · Cagliari (Italy) · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

Neonatal acute kidney injury (AKI), that becomes acute renal failure (when renal replacement is needed), represents a common clinical problem in critically ill infants admitted to neonatal intensive care unit (NICU) centers. This article is aimed at reviewing the most important histological renal changes generally considered typical of AKI, useful to confirm, at morphological level, the structural and cell lesions responsible for the clinical picture. In the first part a simple schematic approach to the elementary lesions of the developing kidney will be proposed, aimed to decipher the renal lesions. In the second part, the typical lesions of AKI in the neonate will be presented and discussed. In the final part, we’ll prospect the necessity for a more accurate microscopic analysis of the kidney in every neonate undergoing asphyxia or sepsis, in order to reveal subtle renal changes that might allow a pathological diagnosis of AKI even in newborns in which the clinical and laboratory pictures were not representative of a severe kidney damage. Finally, the role of the clinical-pathological discussion between the pathologist and the neonatologist will be underlined, in order to reach a final diagnosis, based on the clinical history, the laboratory findings, and the histological lesions. In this article, the role of the pathologist in the evaluation of a neonatal kidney in a newborn with the clinical diagnosis of AKI is described, with particular attention to the differences existing between the preterm and the at term kidney, focusing on the differentiation between developmental changes occurring in the kidney in the perinatal period and the histological lesions induced by pathological events occurring around birth. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014) · Cagliari (Italy) · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

Pathologists and clinicians come together and exchange views, they instil in one another doubts, they break down barriers. Asphyxia, respiratory distress, sepsis, multi-organ failure (MOF), cerebral ischemia and neuroprotection, necrotizing enteritis, renal and biliary pathology (including congenital nephrotic syndrome), injury caused by drugs, cardiac decompensation, placental pathology, neonatal issues in mothers with tumor: these are the topics debated, in the true sense of the word, by perinatologists and pathologists. In some pathologies (e.g. MOF) the pathophysiology is surprisingly the same in the neonate and the adult. Different disciplines deal for example with immunohistochemistry and metabolomics with the processing of thousands of data in search of something that cannot be found with the classic criteria of anamnesis, objective examination, laboratory tests and imaging. Big data and information science promise to change the world. To come to grips with the extreme biological complexity of our organism and each of our organs, the completeness of enormous amounts of data is of extraordinary value if assessed holistically with the “omic” disciplines. Thus we have the possibility of understanding our extraordinary interindividual variability. The new technologies and their application do not diminish the role of physicians: on the contrary, they represent a formidable instrument for extending their diagnostic potential and make possible 5-P medicine: personalized, prospective, predictive, preventive, participatory. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014) · Cagliari (Italy) · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

We have extensively studied the ultrastructural picture of the liver by scanning electron microscopy (SEM) but these studies were not used, up to now, in clinical practice because they were considered to be mainly a means of research in the 3D structure of liver specimens. Our new technique allows us to introduce ourselves to the 3D structure of intracellular organelles, making it possible to study them in normal and pathologic conditions. We used a very small part of the liver biopsies from 5 children aged 3 to 8 years old, who underwent a liver biopsy for diagnostic purposes. The specimens were fixed and processed according to our modification of the OsO4 maceration method of Tanaka and Mitsushima. Liver biopsies fixed for 20’ in a mixture of glutaraldehyde and paraformaldehyde, postfixed in 1% OsO4 for 2 h, cut with a tissue sectioner and then macerated in 0.1% OsO4 for 60 h at room temperature. Specimens were dehydrated in graded acetone, critical point dried and coated with gold palladium. To selectively remove cell components, some specimens were subjected to ultrasound treatment (25 Hz for 1’) prior to dehydration. To demonstrate the hepatic stroma, some aldehyde-fixed specimens were submitted to maceration with NaOH 1N according to Ohtani method. With this method, all cells were removed, allowing the visualization of collagen fibers. Observation was carried out by an Hitachi S4000 Field Emission SEM (Hitachi High-Technologies Co., Tokyo, Japan) operated at 20 kV. We are showing the results of our new technique applied to the liver tissue. These data open, in our opinion, a new field in the research of nuclear pathology, with possible intriguing data on pathological nuclear pore changes in the setting of different liver diseases.

Thymosin beta 4 (Tβ4) and thymosin beta 10 (Tβ10) are two members of the beta-thymosin family involved in many cellular processes such as cellular motility, angiogenesis, inflammation, cell survival and wound healing. Recently, a role for beta-thymosins has been proposed in the process of carcinogenesis as both peptides were detected in several types of cancer. The aim of the present study was to investigate the expression pattern of Tβ4 and Tβ10 in hepatocellular carcinoma (HCC). To this end, the expression pattern of both peptides was analyzed in liver samples obtained from 23 subjects diagnosed with HCC. Routinely formalin-fixed and paraffin-embedded liver samples were immunostained by indirect immunohistochemistry with polyclonal antibodies to Tβ4 and Tβ10. Immunoreactivity for Tβ4 and Tβ10 was detected in the liver parenchyma of the surrounding tumor area. Both peptides showed an increase in granular reactivity from the periportal to the periterminal hepatocytes. Regarding HCC, Tβ4 reactivity was detected in 7/23 cases (30%) and Tβ10 reactivity in 22/23 (97%) cases analyzed, adding HCC to human cancers that express these beta-thymosins. Intriguing finding was seen looking at the reactivity of both peptides in tumor cells infiltrating the surrounding liver. Where Tβ10 showed a strong homogeneous expression, was Tβ4 completely absent in cells undergoing stromal invasion. The current study shows expression of both beta-thymosins in HCC with marked differences in their degree of expression and frequency of immunoreactivity. The higher incidence of Tβ10 expression and its higher reactivity in tumor cells involved in stromal invasion indicate a possible major role for Tβ10 in HCC progression.

During the interval between 8:00–9:30 on 14 January 2001, the four Cluster spacecraft were moving from the central magnetospheric lobe, through the dusk sector mantle, on their way towards intersecting the magnetopause near 15:00 MLT and 15:00 UT. Throughout this interval, the EISCAT Svalbard Radar (ESR) at Longyearbyen observed a series of poleward-moving transient events of enhanced F-region plasma concentration ("polar cap patches"), with a repetition period of the order of 10 min. Allowing for the estimated solar wind propagation delay of 75 ( ± 5) min, the interplanetary magnetic field (IMF) had a southward component during most of the interval. The magnetic footprint of the Cluster spacecraft, mapped to the ionosphere using the Tsyganenko T96 model (with input conditions prevailing during this event), was to the east of the ESR beams. Around 09:05 UT, the DMSP-F12 satellite flew over the ESR and showed a sawtooth cusp ion dispersion signature that also extended into the electrons on the equatorward edge of the cusp, revealing a pulsed magnetopause reconnection. The consequent enhanced ionospheric flow events were imaged by the SuperDARN HF backscatter radars. The average convection patterns (derived using the AMIE technique on data from the magnetometers, the EISCAT and SuperDARN radars, and the DMSP satellites) show that the associated poleward-moving events also convected over the predicted footprint of the Cluster spacecraft. Cluster observed enhancements in the fluxes of both electrons and ions. These events were found to be essentially identical at all four spacecraft, indicating that they had a much larger spatial scale than the satellite separation of the order of 600 km. Some of the events show a correspondence between the lowest energy magnetosheath electrons detected by the PEACE instrument on Cluster (10–20 eV) and the topside ionospheric enhancements seen by the ESR (at 400–700 km). We suggest that a potential barrier at the magnetopause, which prevents the lowest energy electrons from entering the magnetosphere, is reduced when and where the boundary-normal magnetic field is enhanced and that the observed polar cap patches are produced by the consequent enhanced precipitation of the lowest energy electrons, making them and the low energy electron precipitation fossil remnants of the magnetopause reconnection rate pulses.Key words. Magnetospheric physics (polar cap phenomena; solar wind – magnetosphere interactions; magnetosphere – ionosphere interactions)

We study a series of transient entries into the low-latitude boundary layer (LLBL) of all four Cluster spacecraft during an outbound pass through the mid-afternoon magnetopause ( [ XGSM, YGSM, ZGSM ] ≈ [ 2, 7, 9 ] RE). The events take place during an interval of northward IMF, as seen in the data from the ACE satellite and lagged by a propagation delay of 75 min that is welldefined by two separate studies: (1) the magnetospheric variations prior to the northward turning (Lockwood et al., 2001, this issue) and (2) the field clock angle seen by Cluster after it had emerged into the magnetosheath (Opgenoorth et al., 2001, this issue). With an additional lag of 16.5 min, the transient LLBL events correlate well with swings of the IMF clock angle (in GSM) to near 90°. Most of this additional lag is explained by ground-based observations, which reveal signatures of transient reconnection in the pre-noon sector that then take 10–15 min to propagate eastward to 15 MLT, where they are observed by Cluster. The eastward phase speed of these signatures agrees very well with the motion deduced by the cross-correlation of the signatures seen on the four Cluster spacecraft. The evidence that these events are reconnection pulses includes: transient erosion of the noon 630 nm (cusp/cleft) aurora to lower latitudes; transient and travelling enhancements of the flow into the polar cap, imaged by the AMIE technique; and poleward-moving events moving into the polar cap, seen by the EISCAT Svalbard Radar (ESR). A pass of the DMSP-F15 satellite reveals that the open field lines near noon have been opened for some time: the more recently opened field lines were found closer to dusk where the flow transient and the poleward-moving event intersected the satellite pass. The events at Cluster have ion and electron characteristics predicted and observed by Lockwood and Hapgood (1998) for a Flux Transfer Event (FTE), with allowance for magnetospheric ion reflection at Alfvénic disturbances in the magnetopause reconnection layer. Like FTEs, the events are about 1 RE in their direction of motion and show a rise in the magnetic field strength, but unlike FTEs, in general, they show no pressure excess in their core and hence, no characteristic bipolar signature in the boundary-normal component. However, most of the events were observed when the magnetic field was southward, i.e. on the edge of the interior magnetic cusp, or when the field was parallel to the magnetic equatorial plane. Only when the satellite begins to emerge from the exterior boundary (when the field was northward), do the events start to show a pressure excess in their core and the consequent bipolar signature. We identify the events as the first observations of FTEs at middle altitudes.Key words. Magnetospheric physics (magnetopause, cusp and boundary layers; magnetosphere-ionosphere interactions; solar wind-magnetosphere interactions)

On 14 January 2001, the four Cluster spacecraft passed through the northern magnetospheric mantle in close conjunction to the EISCAT Svalbard Radar (ESR) and approached the post-noon dayside magnetopause over Green-land between 13:00 and 14:00 UT. During that interval, a sudden reorganisation of the high-latitude dayside convection pattern occurred after 13:20 UT, most likely caused by a direction change of the Solar wind magnetic field. The result was an eastward and poleward directed flow-channel, as monitored by the SuperDARN radar network and also by arrays of ground-based magnetometers in Canada, Greenland and Scandinavia. After an initial eastward and later poleward expansion of the flow-channel between 13:20 and 13:40 UT, the four Cluster spacecraft, and the field line footprints covered by the eastward looking scan cycle of the Söndre Strömfjord incoherent scatter radar were engulfed by cusp-like precipitation with transient magnetic and electric field signatures. In addition, the EISCAT Svalbard Radar detected strong transient effects of the convection reorganisation, a poleward moving precipitation, and a fast ion flow-channel in association with the auroral structures that suddenly formed to the west and north of the radar. From a detailed analysis of the coordinated Cluster and ground-based data, it was found that this extraordinary transient convection pattern, indeed, had moved the cusp precipitation from its former pre-noon position into the late post-noon sector, allowing for the first and quite unexpected encounter of the cusp by the Cluster spacecraft. Our findings illustrate the large amplitude of cusp dynamics even in response to moderate solar wind forcing. The global ground-based data proves to be an invaluable tool to monitor the dynamics and width of the affected magnetospheric regions.Key words. Magnetospheric cusp, ionosphere, reconnection, convection flow-channel, Cluster, ground-based observations

The recent availability of substantial data sets taken by the EISCAT Svalbard Radar allows several important tests to be made on the determination of convection patterns from incoherent scatter radar results. During one 30-h period, the Svalbard Radar made 15 min scans combining local field aligned observations with two, low elevation positions selected to intersect the two beams of the Common Programme Four experiment being simultaneously conducted by the EISCAT VHF radar at Tromsø. The common volume results from the two radars are compared. The plasma convection velocities determined independently by the two radars are shown to agree very closely and the combined three-dimensional velocity data used to test the common assumption of negligible field-aligned flow in this regime.Key words: Ionosphere (auroral ionosphere; polar ionosphere) - Magnetospheric physics (plasma convection)

Incoherent scatter radars measure ionosphere parameters using modified Thomson scatter from free electrons in the target (see e.g. Hagfors, 1997). The integrated cross section of the ionospheric scatterers is extremely small and the measurements can easily be disturbed by signals returned by unwanted targets. Ground clutter signals, entering via the antenna side lobes, can render measurements at the nearest target ranges totally impossible. The EISCAT Svalbard Radar (ESR), which started measurements in 1996, suffers from severe ground clutter and the ionosphere cannot be measured in any simple manner at ranges less than about 120–150 km, depending on the modulation employed. If the target and clutter signals have different, and clearly identifiable, properties then, in principle, there are always ways to eliminate the clutter. In incoherent scatter measurements, differences in the coherence times of the wanted and unwanted signals can be used for clutter cancellation. The clutter cancellation must be applied to all modulations, usually alternating codes in modern experiments, used for shorter ranges. Excellent results have been obtained at the ESR using a simple pulse-to-pulse clutter subtraction method, but there are also other possibilities.Key words: Radio science (ionospheric physics; signal processing; instruments and techniques)

In 1997, reliable operation of the EISCAT Svalbard Radar (ESR) was achieved and a rocket launching facility at Ny Ålesund on Svalbard (79°N, 12°E) (SVALRAK) was established. On 20 November, 1977, the first instrumented payload was launched from SVALRAK. Although the payload configuration had been flown many times previously from Andøya Rocket Range on the Norwegian mainland, this presented an unprecedented in situ determination of positive ion density over Svalbard. Simultaneously, ESR measured similar density profiles but in a higher altitude regime. We have combined the ESR measurements with ionosonde data to establish a calibration and subsequently combined the ground-based and in situ determined profiles to give a composite positive ion density profile from the mesosphere to the thermosphere.Key words: Ionosphere (polar ionosphere; instruments and techniques)

We report important results of the first campaign specially designed to observe the formation and the initial convection of polar cap patches. The principal instrumentation used in the experiments comprised the EISCAT, the Sondrestrom, and the Super DARN network of radars. The experiment was conducted on February 18, 1996 and was complemented with additional sensors such as the Greenland chain of magnetometers and the WIND and IMP-8 satellites. Two different types of events were seen on this day, and in both events the Sondrestrom radar registered the formation and evolution of large-scale density structures. The first event consisted of the passage of traveling convection vortices (TCV). The other event occurred in association with the development of large plasma jets (LPJ) embedded in the sunward convection part of the dusk cell. TCVs were measured, principally, with the magnetometers located in Greenland, but were also confirmed by the line-of-sight velocities from the Sondrestrom and SuperDARN radars. We found that when the magnetic perturbations associated with the TCVs were larger than 100 nT, then a section of the high-latitude plasma density was eroded by a factor of 2. We suggest that the number density reduction was caused by an enhancement in the O+ recombination due to an elevated Ti, which was produced by the much higher frictional heating inside the vortex. The large plasma jets had a considerable (>1000 km) longitudinal extension and were 200-300 km in width. They were seen principally with the Sondrestrom, and SuperDARN radars. Enhanced ion temperature (Ti) was also observed by the Sondrestrom and EISCAT radars. These channels of high Ti were exactly collocated with the LPJs and some of them with regions of eroded plasma number density. We suggest that the LPJs bring less dense plasma from later local times. However, the recent time history of the plasma flow is important to define the depth of the density depletion. Systematic changes in the latitudinal location and in the intensity of the LPJs were observed in the 2 min time resolution data of the SuperDARN radars. The effect of the abrupt changes in the LPJs location is to create regions containing dayside plasma almost detached from the rest of the oval density. One of these density features was seen by the Sondrestrom radar at 1542 UT. The data presented here suggest that two plasma structuring mechanisms (TCVs and LPJs) can act tens of minutes apart to produce higher levels of density structures in the near noon F-region ionosphere.Key words. Ionosphere (ionospheric irregularities) · Magnetospheric physics (electric fields; polar cap phenomena)

Galectin-3 (Gal-3) is a member of the lectin family, including 14 mammalian galectins, and has been shown to be involved in the many biological processes. In fact it has been reported to be expressed during human nephrogenesis, in the ureteric bud tips and in the medullary regions. In 11 developing human kidney the immunoexpression of Gal-3 was studied. Previously observations on Gal-3 expression in collecting ducts were confirmed and a wild variable reactivity was detected among the range from 20 to 36 weeks of gestational age considered. Between the early and late phases of gestation two phases have been identified: the first, from 20 up to 26 weeks of gestation, with a strong reactivity and the second, from 30 to 36 weeks, with a decrease in Gal-3 expression. This finding clearly indicates a major role for Gal-3 in early human nephrogenesis ending around the 30th week of gestation. In conclusion, Gal-3 apparently plays a role in kidney development at different check points, participating both to ureteric bud proliferation and to differentiation of structures originating from the metanephric mesenchyme. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy) · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research