Long-term exposure to ambient air pollutant concentrations is known to cause chronic lung inflammation, a condition that may promote increased severity of COVID-19 syndrome caused by the novel coronavirus (SARS-CoV-2). In this paper, we empirically investigate the ecologic association between long-term concentrations of area-level fine particulate matter (PM 2.5) and excess deaths in the first quarter of 2020 in municipalities of Northern Italy. The study accounts for potentially spatial confounding factors related to urbanization that may have influenced the spreading of SARS-CoV-2 and related COVID-19 mortality. Our epidemiological analysis uses geographical information (e.g., municipalities) and negative binomial regression to assess whether both ambient PM 2.5 concentration and excess mortality have a similar spatial distribution. Our analysis suggests a positive association of ambient PM 2.5 concentration on excess mortality in Northern Italy related to the COVID-19 epidemic. Our estimates suggest that a one-unit increase in PM 2.5 concentration (µg/m 3) is associated with a 9% (95% confidence interval: 6-12%) increase in COVID-19 related mortality.

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pro-B cells from healthy donors (Zwollo et al, 1997; Sekine et al, 2007).In conclusion, our data show an association between PAX5 aberrant splicing and BCP-ALL. We also provide, for the first time, evidence of imbalance between the full-length and PAX5D2 isoforms as a common event in BCP-ALL. Given the well-documented role of this gene in the development of BCP, the cumulative effect of point mutations and post-transcriptional regulation of alternative splicing of PAX5 pre-mRNA may suggest its primary pathogenic role in BCP-ALL of both children and adults.

Although there is widespread agreement about the importance of men in reproductive decisionmaking (Ryder 1973), most research on fertility intentions has been directed only at women. A number of authors have adopted a couple-oriented approach (Fried and Some of these studies have shown that models based on both partners' fertility intentions are superior to those based on only one partner's intentions (Fried and Udry 1979;Fried, Hofferth, and Udry 1980;Morgan 1985) and that models based solely on women's intentions are likely to be misspecified (Corijn, Liefbroer, and Gierveld 1996). The continuing emphasis on the woman's perspective is usually justified by the high degree of homogamy within couples and the fact that women are the main actors and the most reliable reporters of childbearing events.Couple-level research requires high-quality survey data that include information on both partners, possibly in repeated waves. These data are indispensable for ascertaining the differences between partners' reproductive goals and identifying the contribution of each partner to the childbearing outcome. In European countries, longitudinal household surveys have only rarely been conducted in recent decades.We address the topic of fertility decisionmaking in Italy using longitudinal data on couples over a three-year period from the end of 2003 to the beginning of 2007. We address two questions. In a context of high fertility control, is one partner's intention not to have a child sufficient to prevent a birth? Does gender equality in bargaining power and in access to economic resources correspond to gender equality in fertility decisionmaking?

gamma-Secretase inhibitors (GSIs) have been proposed for combined therapies of malignancies with a dysregulated Notch signaling. GSI I (Z-Leu-Leu-Nle-CHO) induces apoptosis of some tumor cells by inhibiting proteasome and Notch activity. Alterations in these two cell survival regulators contribute to apoptosis resistance of chronic lymphocytic leukemia (CLL) cells. Here, we investigated the mechanisms whereby GSI I increases apoptosis of primary CLL cells. Time-course studies indicate that initial apoptotic events are inhibition of proteasome activity, concomitant with an increased endoplasmic reticulum (ER) stress apoptotic signaling, and a consistent Noxa protein up-regulation. These events precede, and some of them contribute to, mitochondrial alterations, which occur notwithstanding Mcl-1 accumulation induced by GSI I. In CLL cells, GSI I inhibits Notch1 and Notch2 activation only in the late apoptotic phases, suggesting that this event does not initiate CLL cell apoptosis. However, Notch inhibition may contribute to amplify GSI I-induced CLL cell apoptosis, given that Notch activation sustains the survival of these cells, as demonstrated by the evidence that both Notch1 and Notch2 down-regulation by small-interfering RNA accelerates spontaneous CLL cell apoptosis. Overall, our results show that GSI I triggers CLL cell apoptosis by inhibiting proteasome activity and enhancing ER stress, and amplifies it by blocking Notch activation. These findings suggest the potential relevance of simultaneously targeting these three important apoptosis regulators as a novel therapeutic strategy for CLL