Cosmology and fundamental physics with the ELT-ANDES spectrograph.

State-of-the-art 19th century spectroscopy led to the discovery of quantum mechanics, and 20th century spectroscopy led to the confirmation of quantum electrodynamics. State-of-the-art 21st century astrophysical spectrographs, especially ANDES at ESO's ELT, have another opportunity to play a key role in the search for, and characterization of, the new physics which is known to be out there, waiting to be discovered. We rely on detailed simulations and forecast techniques to discuss four important examples of this point: big bang nucleosynthesis, the evolution of the cosmic microwave background temperature, tests of the universality of physical laws, and a real-time model-independent mapping of the expansion history of the universe (also known as the redshift drift). The last two are among the flagship science drivers for the ELT. We also highlight what is required for the ESO community to be able to play a meaningful role in 2030s fundamental cosmology and show that, even if ANDES only provides null results, such 'minimum guaranteed science' will be in the form of constraints on key cosmological paradigms: these are independent from, and can be competitive with, those obtained from traditional cosmological probes.

Star formation inside a galactic outflow.

Recent observations have revealed massive galactic molecular outflows that may have the physical conditions (high gas densities) required to form stars. Indeed, several recent models predict that such massive outflows may ignite star formation within the outflow itself. This star-formation mode, in which stars form with high radial velocities, could contribute to the morphological evolution of galaxies, to the evolution in size and velocity dispersion of the spheroidal component of galaxies, and would contribute to the population of high-velocity stars, which could even escape the galaxy. Such star formation could provide in situ chemical enrichment of the circumgalactic and intergalactic medium (through supernova explosions of young stars on large orbits), and some models also predict it to contribute substantially to the star-formation rate observed in distant galaxies. Although there exists observational evidence for star formation triggered by outflows or jets into their host galaxy, as a consequence of gas compression, evidence for star formation occurring within galactic outflows is still missing. Here we report spectroscopic observations that unambiguously reveal star formation occurring in a galactic outflow at a redshift of 0.0448. The inferred star-formation rate in the outflow is larger than 15 solar masses per year. Star formation may also be occurring in other galactic outflows, but may have been missed by previous observations owing to the lack of adequate diagnostics.

[The use of RCGO triggers in the obstetric - gynecological procedures: the impact on the reduction of adeverse events. The experience of the Lombardia Region]. / L'utilizzo dei RCOG trigger in area ostetrica - ginecologica e la riduzione degli eventi avversi. L'esperienza della regione Lombardia.

The last few weeks of pregnancy are critical to a baby's health because important organs, including the brain and lungs, are not completely developed until the end of pregnancy. The adverse events during labor and childbirth can have very serious physical, psychological and financial consequences for the child, the family, health professionals and the whole community. These events can be reduced through interventions aimed at improving the safety and quality of care, based on evidence-based knowledge, guidelines and practices that must be widely and effectively applied. This work reports the experience of the Lombardy Region on improvement actions in the obstetric and gynecological procedures for the reduction of adverse events and sentinel events through the monitoring and management of the RCGS trigger tool.

Meditation training for people with amyotrophic lateral sclerosis: a randomized clinical trial.

BACKGROUND AND PURPOSE: Studies investigating psychological interventions for the promotion of well-being in people with amyotrophic lateral sclerosis (ALS) are lacking. The purpose of the current study was to examine the use of an ALS-specific mindfulness-based intervention for improving quality of life in this population. METHODS: A randomized, open-label and controlled clinical trial was conducted on the efficacy of an ALS-specific meditation programme in promoting quality of life. Adults who received a diagnosis of ALS within 18 months were randomly assigned either to usual care or to an 8-week meditation training based on the original mindfulness-based stress reduction programme and tailored for people with ALS. Quality of life, assessed with the ALS-Specific Quality of Life Revised scale, represented the primary outcome, whilst secondary outcomes included anxiety and depression, assessed with the Hospital Anxiety and Depression Scale, and specific quality of life domains. Participants were assessed at recruitment and after 2, 6 and 12 months. The efficacy of the treatment was assessed on an intention-to-treat basis of a linear mixed model. RESULTS: A hundred participants were recruited between November 2012 and December 2014. Over time, there was a significant difference between the two groups in terms of quality of life (ß = 0.24, P = 0.015, d = 0.89). Significant differences between groups over time were also found for anxiety, depression, negative emotions, and interaction with people and the environment. CONCLUSIONS: An ALS-specific meditation programme is beneficial for the quality of life and psychological well-being of people with ALS.

Differences in cannabis-related experiences between patients with a first episode of psychosis and controls.

BACKGROUND: Many studies have reported that cannabis use increases the risk of a first episode of psychosis (FEP). However, only a few studies have investigated the nature of cannabis-related experiences in FEP patients, and none has examined whether these experiences are similar in FEP and general populations. The aim of this study was to explore differences in self-reported cannabis experiences between FEP and non-psychotic populations. METHOD: A total of 252 subjects, who met International Classification of Diseases (ICD)-10 criteria for FEP, and 217 controls who reported cannabis use were selected from the Genetics and Psychosis (GAP) study. The Medical Research Council Social Schedule and the Cannabis Experience Questionnaire were used to collect sociodemographic data and cannabis use information, respectively. RESULTS: Both 'bad' and 'enjoyable' experiences were more commonly reported by FEP subjects than controls. Principal components factor analysis identified four components which explained 62.3% of the variance. Linear regression analysis on the whole sample showed that the type of cannabis used and beliefs about the effect of cannabis on health all contributed to determining the intensity and frequency of experiences. Linear regression analysis on FEP subjects showed that the duration of cannabis use and amount of money spent on cannabis were strongly related to the intensity and frequency of enjoyable experiences in this population. CONCLUSIONS: These results suggest a higher sensitivity to cannabis effects among people who have suffered their first psychotic episode; this hypersensitivity results in them reporting both more 'bad' and 'enjoyable' experiences. The greater enjoyment experienced may provide an explanation of why FEP patients are more likely to use cannabis and to continue to use it despite experiencing an exacerbation of their psychotic symptoms.

Gas accretion as the origin of chemical abundance gradients in distant galaxies.

It has recently been suggested that galaxies in the early Universe could have grown through the accretion of cold gas, and that this may have been the main driver of star formation and stellar mass growth. Because the cold gas is essentially primordial, it has a very low abundance of elements heavier than helium (referred to as metallicity). If funnelled to the centre of a galaxy, it will result in the central gas having an overall lower metallicity than gas further from the centre, because the gas further out has been enriched by supernovae and stellar winds, and not diluted by the primordial gas. Here we report chemical abundances across three rotationally supported star-forming galaxies at redshift z ≈ 3, only 2 Gyr after the Big Bang. We find 'inverse' gradients, with the central, star-forming regions having lower metallicities than less active ones, which is opposite to what is seen in local galaxies. We conclude that the central gas has been diluted by the accretion of primordial gas, as predicted by 'cold flow' models.

Expression of nuclear survivin in normal skin and squamous cell carcinoma: a possible role in tumour invasion.

BACKGROUND: Survivin is detected in few adult normal cells and it is highly expressed in cancer. Nuclear survivin facilitates cell cycle entry, whereas the mitochondrial pool protects cells from apoptosis. Survivin is overexpressed in keratinocyte stem cells (KSCs) and protects them from apoptosis. METHODS: As KSCs are at the origin of squamous cell carcinoma (SCC), we evaluated survivin expression in normal and cancerous skin in vivo by immunohistochemistry and western blotting. HaCaT cells overexpressing survivin and wound-healing assay are used. Analysis of variance and Student's T-tests are used for statistical analysis. RESULTS: Survivin is localised in both the cytoplasm and nucleus of normal adult and young keratinocytes. Nuclear survivin is detected in one every 10 of 11 basal keratinocytes. When present in suprabasal cells, nuclear survivin is coexpressed with K10 but not with K15 or p75-neurotrophin receptor (p75NTR), a transit amplifying cell marker. Nuclear, but not cytoplasmic, survivin expression markedly increases in actinic keratosis and in SCC in situ, as compared with normal epidermis, and it is highest in poorly differentiated SCC. In SCC tumours, nuclear survivin-positive cells are mainly K10/p75NTR-negative and K15-positive. In poorly differentiated tumours, survivin mostly localises in the deep infiltrating areas. When overexpressed in keratinocytes, survivin increases cell migration. CONCLUSION: High survivin expression and the subcellular localisation of survivin correlate with keratinocyte differentiation and are associated with undifferentiated and more invasive SCC phenotype.

Birth defects in a national cohort of pregnant women with HIV infection in Italy, 2001-2011.

OBJECTIVE: We used data from a national study of pregnant women with HIV to evaluate the prevalence of congenital abnormalities in newborns from women with HIV infection. DESIGN: Observational study. SETTING: University and hospital clinics. POPULATION: Pregnant women with HIV exposed to antiretroviral treatment at any time during pregnancy. METHODS: The total prevalence of birth defects was assessed on live births, stillbirths, and elective terminations for fetal anomaly. The associations between potentially predictive variables and the occurrence of birth defects were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs) for exposed versus unexposed cases, calculated in univariate and multivariate logistic regression analyses. MAIN OUTCOME MEASURES: Birth defects, defined according to the Antiretroviral Pregnancy Registry criteria. RESULTS: A total of 1257 pregnancies with exposure at any time to antiretroviral therapy were evaluated. Forty-two cases with major defects were observed. The total prevalence was 3.2% (95% CI 1.9-4.5) for exposure to any antiretroviral drug during the first trimester (23 cases with defects) and 3.4% (95% CI 1.9-4.9) for no antiretroviral exposure during the first trimester (19 cases). No associations were found between major birth defects and first-trimester exposure to any antiretroviral treatment (OR 0.94, 95% CI 0.51-1.75), main drug classes (nucleoside reverse transcriptase inhibitors, OR 0.95, 95% CI 0.51-1.76; non-nucleoside reverse transcriptase inhibitors, OR 1.20, 95% CI 0.56-2.55; protease inhibitors, OR 0.92, 95% CI 0.43-1.95), and individual drugs, including efavirenz (prevalence for efavirenz, 2.5%). CONCLUSIONS: This study adds further support to the assumption that first-trimester exposure to antiretroviral treatment does not increase the risk of congenital abnormalities.

Erbium emission in MOS light emitting devices: from energy transfer to direct impact excitation.

The electroluminescence (EL) at 1.54 µm of metal­oxide­semiconductor (MOS) devices withEr3C ions embedded in the silicon-rich silicon oxide (SRSO) layer has been investigated under different polarization conditions and compared with that of erbium doped SiO2 layers. EL time-resolved measurements allowed us to distinguish between two different excitation mechanisms responsible for the Er3C emission under an alternate pulsed voltage signal (APV). Energy transfer from silicon nanoclusters (Si-ncs) to Er3C is clearly observed at low-field APV excitation. We demonstrate that sequential electron and hole injection at the edges of the pulses creates excited states in Si-ncs which upon recombination transfer their energy to Er3C ions. On the contrary, direct impact excitation of Er3C by hot injected carriers starts at the Fowler­Nordheim injection threshold (above 5 MV cm(-1)) and dominates for high-field APV excitation.

Upper urinary tract biopsy: an old device for a new approach.

PURPOSE: The authors sought to evaluate the feasibility, diagnostic accuracy and safety of urological biopsy performed using a flexible alligator forceps. MATERIALS AND METHODS: Twenty-seven patients with suspected urothelial malignancy underwent retrograde biopsy using a 7-F biopsy forceps (Cordis, Miami, FL, USA). Mild sedation was guaranteed by an anaesthesiologist. The final diagnosis was confirmed by cytohistological data and subsequently by pathology findings at surgery. Lesions with benign histopathology were closely monitored for at least 12 months. RESULTS: The technical success rate was 92.6%. The high diagnostic accuracy was related to the positive correspondence between histological outcomes and surgical results or follow-up observations. As regards sample site, the procedure was less successful in calyceal lesions than in lesions located in the upper urinary tract, with a technical success of 71.43%. Twenty patients had asymptomatic haematuria in the early hours after the procedure; ten of them had mild dysuria. No one require medication, and no major complications occurred. CONCLUSIONS: Urological forceps biopsy is a safe and easy procedure. It provides a relatively high level of accuracy in the diagnosis of lesions of the upper urinary tract.

How many roads lead to stillbirth rate reduction? A 30-year analysis of risk factors in a Northern Italy University care center.

BACKGROUND: Stillbirths affect more than 2.5 million pregnancies worldwide every year and the progress in reducing stillbirth rates is slower than that required by World Health Organization. The aim of the present study was to investigate which factors were associated with stillbirths in a University Hospital in the North of Italy, over a time span of 30 years. The goal was to identify which factors are potentially modifiable to reduce stillbirth rate. METHODS: Retrospective case-control study (358 stillbirths, 716 livebirths) subdivided into two study periods (1987-2006 and 2007-2017). RESULTS: The prevalence of conception obtained by assisted reproductive technologies, pregnancy at advanced maternal age, and complications of pregnancy such as preeclampsia, fetal growth restriction (FGR), and other fetal diseases (abnormal fetal conditions including fetal anemia, fetal hydrops, TORCH infections) increased through the years of the study. Despite a rising prevalence, the last 10 years showed a significant reduction in stillbirths associated with preeclampsia and FGR. Similarly, the risk of stillbirth related to abnormal fetal conditions decreased in the second study period and a history of previous stillbirth becomes a nonsignificant risk factor. CONCLUSIONS: Altogether these results suggest that in pregnancies perceived as "high risk" (i.e. previous stillbirth, preeclampsia, FGR, abnormal fetal conditions) appropriate care and follow-up can indeed lower stillbirth rates. In conclusion, the road to stillbirth prevention passes inevitably through awareness and recognition of risk factors.

Changing patterns in HIV-1 non-B clade prevalence and diversity in Italy over three decades.

BACKGROUND: HIV-1 non-B subtypes have recently entered Western Europe following immigration from other regions. The distribution of non-B clades and their association with demographic factors, over the entire course of the HIV-1 epidemic, have not been fully investigated in Italy. METHODS: We carried out a phylogenetic analysis of HIV-1 pol sequences derived from 3670 patients followed at 50 Italian clinical centres over nearly three decades. RESULTS: Overall, 417 patients (11.4%) carried non-B subtypes. The prevalence of non-B strains increased from 2.6% in 1980-1992 to 18.9% in 1993-2008 (P<0.0001) in a subset of 2479 subjects with a known year of diagnosis. A multivariate analysis on a subset of 1364 patients for whom relevant demographic data were available indicated that African ethnicity, heterosexual route of infection and year of diagnosis were independently associated with non-B HIV-1 infection (P ≤ 0.0001). All pure subtypes, except for clade K, and seven circulating recombinant forms were detected, accounting for 56.6 and 34.1% of the non-B infections, respectively. The F1 subtype was the most prevalent non-B clade among Europeans and was acquired heterosexually in half of this patient population. Unique recombinant forms accounted for 9.4% of the non-B sequences and showed a B/F1 recombination pattern in one-third of cases. CONCLUSIONS: The circulation of non-B clades has significantly increased in Italy in association with demographic changes. Spread of the F1 subtype and B/F recombinants appears to predominate, which may result in a redistribution of the relative proportions of the different strains, and this could lead to overlapping epidemics. Thus, the HIV-1 landscape in Italy may in future be distinct from that of the rest of Europe.

Transforming growth factor-beta 1 modulates beta 1 and beta 5 integrin receptors and induces the de novo expression of the alpha v beta 6 heterodimer in normal human keratinocytes: implications for wound healing.

The molecular mechanism underlying the promotion of wound healing by TGF-beta 1 is incompletely understood. We report that TGF-beta 1 regulates the regenerative/migratory phenotype of normal human keratinocytes by modulating their integrin receptor repertoire. In growing keratinocyte colonies but not in fully stratified cultured epidermis, TGF-beta 1: (a) strongly upregulates the expression of the fibronectin receptor alpha 5 beta 1, the vitronectin receptor alpha v beta 5, and the collagen receptor alpha 2 beta 1 by differentially modulating the synthesis of their alpha and beta subunits; (b) downregulates the multifunctional alpha 3 beta 1 heterodimer; (c) induces the de novo expression and surface exposure of the alpha v beta 6 fibronectin receptor; (d) stimulates keratinocyte migration toward fibronectin and vitronectin; (e) induces a marked perturbation of the general mechanism of polarized domain sorting of both beta 1 and beta 4 dimers; and (f) causes a pericellular redistribution of alpha v beta 5. These data suggest that alpha 5 beta 1, alpha v beta 6, and alpha v beta 5, not routinely used by keratinocytes resting on an intact basement membrane, act as "emergency" receptors, and uncover at least one of the molecular mechanisms responsible for the peculiar integrin expression in healing human wounds. Indeed, TGF-beta 1 reproduces the integrin expression pattern of keratinocytes located at the injury site, particularly of cells in the migrating epithelial tongue at the leading edge of the wound. Since these keratinocytes are inhibited in their proliferative capacity, these data might account for the apparent paradox of a TGF-beta 1-dependent stimulation of epidermal wound healing associated with a growth inhibitory effect on epithelial cells.

[Validation of a screening method for occupational bladder cancer]. / Neoplasie transizionali della vescica di origine professionale: valutazione della accuratezza di un metodo di screening basato su intervista strutturata.

BACKGROUND: Transitional bladder cancer is the most frequent malignant urinary neoplasm. Occupational exposure to aromatic amines and to polycyclic aromatic hydrocarbons are the main risk factors, in addition to cigarette smoking, recurrent inflammatory diseases of the urinary tract, consumption of certain drugs and a positive family history. Nevertheless cases of work-related bladder cancer are poorly identified in Italy. OBJECTIVE: The aim of this study is to assess the screening accuracy of a short structured interview to detect suspected cases of occupational bladder cancer, which may be confirmed in a second step assessment by an occupational physician. METHODS: The study sample consisted of 94 transitional bladder cancer patients, first hospitalised in 2004 and 2005 at the Department of Urology of the Ospedale di Circolo - Fondazione Macchi, in Varese, Italy. Based on data collected through a simple structured interview, it was possible to estimate two occupational exposure indices: one taking into account only the length of employment in industrial settings (DS Index) and the other considering job title in addition (DSM Index). For all cases a second-step assessment by an occupational physician (gold standard) made it possible to establish the occupational origin of cancer and to assess accuracy. RESULTS: Satisfactory values of the area under the ROC curve were found for both indices (AUC 0,81 for DS and 0,87 for DSM). In particular at the same level of sensitivity (90%), the DSM Index showed a better specificity (72%) in comparison to the DS Index (64%). CONCLUSIONS: The short structured interview proposed here proved to be a valuable tool for general practitioners and urologists to detect cases of bladder cancer of suspected occupational aetiology, which can be referred to an occupational physician for further investigations.

Promoting the well-being of mothers with multidisciplinary psychosocial interventions in the perinatal period.

BACKGROUND: Antenatal depressive and anxiety symptoms are common and may persist over time after delivery, with negative consequences on the mothers and their children. Evidence on the efficacy of psychological and pharmacological interventions during pregnancy aimed at preventing post-partum depression is controversial. METHODS: A consecutive sample of 318 women presenting for scheduled obstetric visits during pregnancy was screened for risk factors and anxiety or depressive symptoms. Based on the screening results, women were classified into three groups at increasing risk of post-partum depression (PPD) and were offered different interventions. RESULTS: Depressive or anxiety symptoms were found in 91 (28.6%) women, 89 (28.0%) had low risk of PPD and 138 (43.4%) had no risk of PPD. The multidisciplinary psychosocial interventions offered to women with clinical symptoms were well accepted, with an uptake of 76/91 (83.5%). Thirty-three women who did not improve with psychotherapy were offered sertraline or paroxetine as a second-line treatment: 7 accepted and 26 (78.8%) refused. Eleven women already on medication at baseline continued their treatment along with the MPI. The MPI interventions had some positive effects in terms of post-partum recovery, symptom reduction, and in preventing a new onset of depression. Among the 227 non-symptomatic during pregnancy, only 5 (2.2%) developed symptoms in the post-partum period. At 12 months post-partum, 84.6% of women who were symptomatic at 2 months post-partum recovered. LIMITATIONS: Our results should be interpreted in light of important limitations, including the lack of a control group that was not offered the MPI, the lack of information on the reasons for refusal and discontinuation and on the number of psychotherapy sessions attended. CONCLUSIONS: Our findings underscore the potential usefulness of MPI in recognizing early signs or symptoms during pregnancy and the advantage of building specific interventions for preventing post-natal depression. The MPI has positive effects on women with depressive or anxiety symptoms during pregnancy, that however did not exceed significantly those observed in women who refused the intervention. Thus, in the absence of a control group, our results are preliminary and warrant confirmation and testing in future randomized clinical trials.

Fate and characterization of circulating tumor cells in a NOD/SCID mouse model of human hepatocellular carcinoma.

There is much debate about the way in which epithelial tumors metastasize. It has been proposed that the bone marrow (BM) acts as a tumor cell reservoir. We injected human hepatocellular carcinoma (HCC) cells (Mahlavu cell line) into the livers, circulation or BM of NOD/SCID mice and circulating tumor cells were quantified. When injected under the Glisson capsule, a primary tumor developed and continuously yielded circulating tumor cells. Liver tumor removal led to a very low level of Mahlavu cells both in blood and BM 30 days later. When Mahlavu cells (cultured or from BM of primary mice femurs) were intravenously injected into mice, the number of cells in the bloodstream (BS) steadily decreased, whereas the BM was not significantly colonized. When Mahlavu cells were directly injected into one femur, the controlateral femur was not colonized. Microscopic analysis and a sensitive PCR assay (<1 Mahlavu cell/nuclear cells) both failed to detect human tumor cells in other organs regardless of injection route. In conclusion, our model strongly supports the hypothesis that HCCs continuously release cells into the BS. However, in sharp contrast with the current hypothesis, the BM is not specifically colonized by tumor cells but could store them at a very low level.

[Duration of mechanical ventilation and development of bronchopulmonary dysplasia]. / Tempo de ventilação mecânica e desenvolvimento de displasia broncopulmonar.

OBJECTIVE: Verify the association between duration of mechanical ventilation and development of bronchopulmonary dysplasia in neonates weighting at birth less than 1500 g. METHODS: Retrospective study conducted with neonates weighting less than 1500 g at birth submitted to mechanical ventilation. Neonates presenting major birth defects, transferred to other services or died before the 28th day of life were excluded from the study. Three groups were analyzed according to duration of mechanical ventilation: 1 to 7 days, 8 to 14 days and more than 15 days. The chance ratio of developing bronchopulmonary dysplasia was calculated for each group. RESULTS: From the 216 clinical histories assessed, 121 met the criteria for inclusion in the study. Mean birth weight and gestational age were 1199.8 g and 31.8 weeks. Of all neonates submitted to mechanical ventilation from 1 to 7 days, 15.5% developed bronchopulmonary dysplasia; from 8 to 14 days 60% and from more than 15 days, 88.2%; chance ratios were equal to 0.16; 11.25 and 16.36, respectively. CONCLUSION: The chance of a neonate weighting less than 1500 g developing bronchopulmonary dysplasia was 11 times higher in those submitted to mechanical ventilation for up to 14 days. This chance was even higher in those ventilated for more than 15 days. That is why the nursing staff assisting high risk patients should consider the possibility of extubating neonates during their first week of life.

Expression and function of neurotrophins and their receptors in human melanocytes.

Melanocytes and cells of the nervous system are of common ectodermal origin and neurotrophins (NT) have been shown to be released by human keratinocytes. We investigated the expression and function of NT [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, NT-4/-5] and their receptors in human melanocytes. Human melanocytes produce all NT in different amounts, whereas they only release NT-4. NT-4 release is downregulated, whereas NT-3 is upregulated by ultraviolet (UVB) irradiation. Melanocytes treated with phorbol 12-myristate 13-acetate (PMA) express TrkA and TrkB, but not TrkC. NT fail to stimulate melanocyte proliferation, whereas they stimulate the synthesis of tyrosinase and tyrosinase-related protein-1 (TRP-1). Finally, NT-3, NT-4 and NGF increase melanin production. Taken together, these results demonstrate an intriguing interaction between melanocytes and the nervous system. We speculate that NT could be considered the target of therapy for disorders of skin pigmentation.

[Airborne contact dermatitis]. / Airborne contact dermatitis.

A comprehensive bibliographical retrieval of case reports on "airborne contact dermatitis" (ACD) was performed. The present review deals with the first cases published in 1986, 1991, 2001 by Huygens as well as by Dooms-Goossens, and continues with the other pertaining clinical presentations until to day. Solid particles, rather than gases or droplets, are the most frequently reported causes of ACD.