Efficacité de l'assainissement des eaux usées sur le bassin de la rivière Chaudière (Québec, Canada)

Le Québec a consacré des efforts techniques et financiers substantiels à l'assainissement des eaux usées municipales et à l'entreposage des déjections animales afin de satisfaire les demandes des citoyens en matière de restauration des usages des cours d'eau. L'assainissement de l'eau a, dans l'ensemble, par ses choix technologiques et administratifs, engendré des investissements publics dépassant 7,2 milliards de dollars et plus de 400 millions de dollars annuellement au chapitre de l'exploitation. Ces choix ont-ils permis d'atteindre un niveau de qualité de l'eau correspondant à un optimum social? À l'aide d'une étude de cas portant sur le bassin versant de la rivière Chaudière (Québec, Canada), cet article met en évidence les facteurs qui ont nuit à l'efficacité des politiques de contrôle de la pollution de l'eau au Québec. Sur ce bassin, 125 M$ont été consacrés entre 1981 et 1992 à l'érection d'usines d'épuration utilisant différents types de traitement, 8,6 M$ ont été alloués pour la construction de structures d'entreposage de fumiers et le service de la dette pour l'assainissement des eaux usées municipales atteindrait près de 527 M$selon une hypothèse de financement de 25 ans. La performance des usines d'épuration a permis de réduire significativement les apports au cours d'eau, notamment en DBO5 et en phosphore. Enfin, cette performance et le coût total de l'assainissement municipal sur le bassin de la Rivière Chaudière permettent d'évaluer, sur la base d'une relation coût-efficacité, qu'il y aurait un niveau optimal de qualité de l'eau pouvant résulté de l'établissement d'infrastructures d'assainissement des eaux usées municipales. Ainsi, dans l'optique d'une prise en charge sociale du problème collectif de la pollution de l'eau sur la base du bassin versant, il serait approprié que les gestionnaires et les usagers-contribuables de la ressource-eau, prennent en compte, non pas uniquement les objectifs de rejets, mais également les coûts et les performances de l'ensemble des usines d'épuration sur le bassin afin de retirer le maximum de charges polluantes là où les équipements sont les plus performants.Considerable technical and financial effort has been invested by Québec in the cleaning up of municipal wastewaters and storage of animal manure to meet demands by citizens to restore the province's rivers to their former state. Water pollution control has required technological and management choices that have resulted overall in public investments in excess of$7.2 billion, with over $400 million going to operation costs annually. Have these choices enabled Québec to attain a water quality level consistent with a social optimum?Based on a case study taken from the Chaudière river watershed, Québec, Canada, this article posits two conditions for achieving a social optimum and underscores the factors that have offset the efficiency of water pollution control policies in Québec. According to the data collected on this watershed, between 1981 and 1992,$125 M was invested in the construction of sewage water treatment plants using various treatment methods, while $8.6 M went towards manure storage facilities. On the whole,$527 M is expected to be spent over 25 years to service the debt for municipal wastewater treatment within the watershed.While inputs of pollutants, especially BOD5 and phosphorus, have dropped significantly with the construction of the wastewater treatment plants, levels of residual pollution in the watershed remain high. It is suspected that total residual loads of phosphorus from municipal and agricultural sources are still well above the loads eliminated through wastewater treatment. If they are to achieve an efficient watershed-based approach to water management, decision-makers are faced with two conditions: the first addresses intersectoral efficiency in controlling pollution in a watershed and the second involves minimizing intrasectoral costs of pollution control. The condition explains the administrative and technical choices made as well as the importance of the political market in allocating resources to water pollution control among the socioeconomic sectors responsible for water quality deterioration. The condition explains how to minimize the costs in a specific socioeconomic sector among the available water treatment solutions. Using performance data from wastewater treatment plants and the total cost of wastewater treatment in the Chaudière river watershed, it can be assumed, based on a cost efficiency ratio, that an optimal level of water quality should occur as a result of the establishment of municipal wastewater treatment infrastructures. However, it would appear from the results obtained that Québec's water treatment program has deviated from a social optimum, i.e., restoration costs have not been shared equitably among users/polluters within the watershed, and measures to ensure maximum removal of pollution at minimum cost have not been secured. The play of political forces is central to the allocation of resources among pollution sources. Without a proper hard core concept, a water pollution control policy will not be able to elaborate the best solutions oriented towards attaining a social optimum. In the context of the high residual pollution loads within the watershed, there remains the issue of what water quality level is desirable at what cost, particularly with respect to the community's contribution to date and the efficiency of the response strategies that have been implemented. Now that wastewater treatment infrastructures have been set up, and a watershed-based approach to water management becomes effective, water resource managers and users/taxpayers should turn their attention away from discharge objectives only to focus also on the costs and performance of the watershed's treatment plants as a whole, so that removal of pollutant loads at high-performance facilities may be maximized

Differences in Maternal and Infant Cord Blood Vitamin D Between Racial/Ethnic Groups

Background: Vitamin D deficiency associated with lower 25-hydroxyvitamin D (25(OH)D) concentration is common among individuals with more melanin pigmentation. Low 25(OH)D levels in pregnant women may be related to increased risk of low birth weight and preterm delivery. Still, few studies have assessed how serum levels of 25(OH)D vary between maternal and infant race/ethnicity. Objective: This study aimed to investigate the relationship between 25(OH)D levels in maternal blood and infant cord blood within certain ethnic groups, prematurity status, and low birth weight. Experimental Design:An IRB-approved study enrolled 86 mother-infant pairs. Maternal blood samples and infant cord blood samples were analyzed for 25(OH)D serum levels. Descriptive statistics and Kruskal-Willis tests comparisons were conducted with the use of IBM SPSS Statistics 28 software to assess the relationship between maternal and cord blood 25(OH)D levels in other race/ethnicity groups, birthweight, and preterm birth. Prematurity was categorized into two groups: premature (weeks) and term (≥37 weeks). Birth weight was categorized into two groups: low birth weight (\u3c 2500 g weeks) and not low birth weight (≥2500 g weeks). A p-value of Results:Median levels of 25(OH)D serum were lower in infant’s cord blood (22.52 ng/mL) than maternal blood (38.06 ng/mL). White participants had significantly higher 25(OH)D levels than African American participants in both maternal blood (40.76 ng/mL vs 27.79, p = Conclusion: Our findings suggest a possible association with lower serum 25-hydroxyvitamin D concentration in darker skin pigmentation, even in a small sample size. These results suggest that prematurity and birth weight should be replicated in larger sample sizes of different Race/Ethnic groups, limiting this finding. Further studies should focus on examining differences with larger and more diverse sample sizes. Such research should include measuring Vitamin D intake in pregnancy and clinical outcomes.https://digitalcommons.unmc.edu/surp2021/1008/thumbnail.jp

Impact of COVID-19 Infection During Pregnancy on Neonatal Birth Outcomes

Approximately 116 million births have been reported worldwide in the nine months following the start of the COVID-19 pandemic. Currently, the effects of COVID-19 infection during pregnancy on birth outcomes are not fully understood. An IRB-approved study enrolled 115 mothers since March 2020, 5 of whom had a confirmed history of COVID-19 infection during pregnancy. For each COVID-19-infected mother, two mothers of similar age, gestation period, and race who were not infected with COVID-19 during pregnancy were matched 2-to-1 for a case-control analysis. Descriptive statistics were generated, and the Mann-Whitney U test was used to compare continuous variables between the two groups. Fisher’s Exact test was used to evaluate categorical outcomes between the groups. Phttps://digitalcommons.unmc.edu/surp2021/1007/thumbnail.jp

Integrated safety analysis of umbralisib, a dual PI3Kd/CK1« inhibitor, in relapsed/refractory lymphoid malignancies

Phosphoinositide 3-kinase-d (PI3Kd) inhibitors are active in lymphoid malignancies, although associated toxicities can limit their use. Umbralisib is a dual inhibitor of PI3Kd and casein kinase-1« (CK1«). This study analyzed integrated comprehensive toxicity data from 4 open-label, phase 1 and 2 studies that included 371 adult patients (median age, 67 years) with relapsed/refractory non-Hodgkin lymphoma (follicular lymphoma [n 5 147]; marginal zone lymphoma [n 5 82]; diffuse large B-cell lymphoma/mantle cell lymphoma [n 5 74]; chronic lymphocytic leukemia [n 5 43]; and other tumor types [n 5 25]) who were treated with the recommended phase 2 dose of umbralisib 800 mg or higher once daily. At data cutoff, median duration of umbralisib treatment was 5.9 months (range, 0.1-75.1 months), and 107 patients (28.8%) received umbralisib for $12 months. Any-grade treatment-emergent adverse events (AEs) occurred in 366 (98.7%) of 371 patients, with the most frequent being diarrhea (52.3%), nausea (41.5%), and fatigue (31.8%). Grade 3 or higher treatment-emergent AEs occurred in 189 (50.9%) of 371 patients and included neutropenia (11.3%), diarrhea (7.3%), and increased aminotransferase levels (5.7%). Treatment-emergent serious AEs occurred in 95 (25.6%) of 371 patients. AEs of special interest were limited and included pneumonia (29 of 371 [7.8%]), noninfectious colitis (9 of 371 [2.4%]), and pneumonitis (4 of 371 [1.1%]). AEs led to discontinuation of umbralisib in 51 patients (13.7%). Four patients (1.1%) died of AEs, none of which was deemed related to umbralisib. No cumulative toxicities were reported. The favorable long-term tolerability profile and low rates of immune-mediated toxicities support the potential use of umbralisib for the benefit of a broad population of patients with lymphoid malignancies

Synergistic activity of troxacitabine (Troxatyl™) and gemcitabine in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials.</p> <p>Methods</p> <p>The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For <it>in vivo </it>studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired <it>t </it>test using GraphPad prism software.</p> <p>Results</p> <p>Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug concentrations, there was no effect on phosphorylated pools at drug combinations that were synergistic. The amount of troxacitabine incorporated into DNA was also not affected by the presence of gemcitabine. <it>In vivo </it>testing against a human pancreatic (AsPC-1) xenograft mouse tumor model indicated that both drugs were more than additive at well-tolerated doses and schedule. The biological basis for this synergy is unclear as we did not observe changes in apoptosis, DNA repair, troxacitabine incorporation into DNA or troxacitabine metabolism in the presence of gemcitabine.</p> <p>Conclusion</p> <p>These data, together with phase I clinical data showing tolerability of both agents when combined, suggest combination therapy with troxacitabine and gemcitabine warrants further evaluation in advanced pancreatic cancer patients.</p

Holoprosencephaly

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life

Targeting histone deacetyalses in the treatment of B- and T-cell malignancies

HDAC inhibitors (HDACI) are now emerging as one of the most promising new classes of drugs for the treatment of select forms of non-Hodgkin’s lymphoma (NHL). They are particularly active in T-cell lymphomas, possibly hodgkin’s lymphoma and indolent B cell lymphomas. Presently, two of these agents, vorinostat and romidepsin, have been approved in the US for the treatment of relapsed and refractory cutaneous T cell lymphomas (CTCL). Initially, these agents were developed with the idea that they affected transcriptional activation and thus gene expression, by modulating chromatin condensation and decondensation. It is now clear that their effects go beyond chromatin and by affecting the acetylation status of histones and other intra-cellular proteins, they modify gene expression and cellular function via multiple pathways. Gene expression profiles and functional genetic analysis has led to further understanding of the various molecular pathways that are affected by these agents including cell cycle regulation, pathways of cellular proliferation, apoptosis and angiogenesis all important in lymphomagenesis. There is also increasing data to support the effects of these agents on T cell receptor and immune function which may explain the high level of activity of these agents in T cell lymphomas and hodgkin’s lymphoma. There is ample evidence of epigenetic dysregulation in lymphomas which may underlie the mechanisms of action of these agents but how these agents work is still not clear. Current HDAC inhibitors can be divided into at least four classes based on their chemical structure. At present several of these HDAC inhibitors are in clinical trials both as single agents and in combination with chemotherapy or other biological agents. They are easy to administer and are generally well tolerated with minimal side effects. Different dosing levels and schedules and the use of isospecific HDAC inhibitors are some of the strategies that are being employed to increase the therapeutic effect of these agents in the treatment of lymphomas. There may also be class differences that translate into specific activity against different lymphoma. HDAC inhibitors will likely be incorporated into combinations of targeted therapies both in the upfront and relapsed setting for lymphomas

Contextualizing privilege and disadvantage: lessons from women expatriates in the Middle East

This article explores how the simultaneity of privilege and disadvantage shapes the experiences of women expatriates in the Middle East. The article problematizes the simultaneity of being an elite group (e.g. expatriates) and a disadvantaged group (e.g. women) within the context of Gulf Cooperation Council countries. Drawing on the literature about women and work expatriation, the article analyses the narratives of women expatriates to highlight the complexity and multidimensionality of their experiences, positioning the discussion within the framework of gendered institutions. The article concludes that privilege and disadvantage are inseparable to the way the experiences of women expatriates unfold in the Middle East, and that institutional settings articulate this inseparability in order to regulate and help to maintain the gender social order. The article contributes a nuanced understanding of the experiences of women expatriates, challenging dominant views that present this group as generally privileged by virtue of their skilled and mobile status