Short-term effects of visitor trampling on macroinvertebrates in karst streams in an ecotourism region

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cumulative influences of a small city and former mining activities on the sediment quality of a subtropical estuarine protected area

This study aimed to evaluate the sediment quality in the estuarine protected area known as Canan,ia-Iguape-Peruibe (CIP-PA), located on the southeastern coast of Brazil. The study was designed considering possible negative effects induced by the city of Canan,ia on the sediment quality of surrounding areas. This evaluation was performed using chemical and ecotoxicological analyses. Sediments were predominantly sandy, with low CaCO3 contents. Amounts of organic matter varied, but higher contents occurred closer to the city, as well as did Fe and Total Recoverable Oils and Greases (TROGs) concentrations. Contamination by Cd and Cu was revealed in some samples, while concentrations of Zn were considered low. Chronic toxicity was detected in all tested sediments and acute toxicity occurred only in sediments collected near the city. The principal component analysis (PCA) revealed an association among Cd, Cu, Fe, TROG, fines, organic matter, CaCO3, and chronic toxicity, whereas acute toxicity was found to be associated with Zn and mud. However, because Zn levels were low, acute toxicity was likely due to a contaminant that was not measured. Results show that there is a broad area within the CIP-PA that is under the influence of mining activities (chronic toxicity, moderate contamination by metals), whereas poorer conditions occur closer to Canan,ia (acute toxicity); thus, the urban area seems to constitute a relevant source of contaminants for the estuarine complex. These results show that contamination is already capable of producing risks for the local aquatic biota, which suggests that the CIP-PA effectiveness in protecting estuarine biota may be threatened.

In vitro effects of bethanechol on specimens of intestinal smooth muscle obtained from the duodenum and jejunum of healthy dairy cows

OBJECTIVE: To describe the in vitro effects of bethanechol on contractility of smooth muscle preparations from the small intestines of healthy cows and define the muscarinic receptor subtypes involved in mediating contraction. SAMPLE POPULATION: Tissue samples from the duodenum and jejunum collected immediately after slaughter of 40 healthy cows. PROCEDURES: Cumulative concentration-response curves were determined for the muscarinic receptor agonist bethanechol with or without prior incubation with subtype-specific receptor antagonists in an organ bath. Effects of bethanechol and antagonists and the influence of intestinal location on basal tone, maximal amplitude (A(max)), and area under the curve (AUC) were evaluated. RESULTS: Bethanechol induced a significant, concentration-dependent increase in all preparations and variables. The effect of bethanechol was more pronounced in jejunal than in duodenal samples and in circular than in longitudinal preparations. Significant inhibition of the effects of bethanechol was observed after prior incubation with muscarinic receptor subtype M(3) antagonists (more commonly for basal tone than for A(max) and AUC). The M(2) receptor antagonists partly inhibited the response to bethanechol, especially for basal tone. The M(3) receptor antagonists were generally more potent than the M(2) receptor antagonists. In a protection experiment, an M(3) receptor antagonist was less potent than when used in combination with an M(2) receptor antagonist. Receptor antagonists for M(1) and M(4) did not affect contractility variables. CONCLUSIONS AND CLINICAL RELEVANCE: Bethanechol acting on muscarinic receptor sub-types M(2) and M(3) may be of clinical use as a prokinetic drug for motility disorders of the duodenum and jejunum in dairy cows.

In vitro effects of bethanechol on smooth muscle preparations from abomasal fundus, corpus, and antrum of dairy cows

Abomasal displacement has been associated with gastric hypomotility. The supply of prokinetic drugs available to address this problem is insufficient. The goal of the study was to investigate the effect of the muscarinic agonist bethanechol (BeCh) on contractility parameters of smooth muscle preparations from several regions of the bovine abomasum (fundus, corpus, and antrum). Cumulative concentration-response curves were constructed using BeCh in vitro with and without pre-incubation with antagonists targeted at M(2) and M(3) muscarinic acetylcholine receptor (mAChR) subtypes. In all preparations investigated, BeCh induced a significant and concentration-dependent increase in all contractility parameters investigated. The maximal attainable effect (V(max)) was more pronounced in circular specimens, and V(max) of antral specimens in circular orientation were significantly lower when compared to the other preparations. Both antagonists caused a rightward shift of the concentration-response curve, suggesting that the effect of BeCh is mediated at least partly by M(2) and M(3) AChRs.

Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial

PURPOSE: The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. PATIENTS AND METHODS: The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF > or = 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. RESULTS: Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m(2) v 257 mg/m(2)) or epirubicin (480 mg/m(2) v 422 mg/m(2)) and had a lower screening LVEF and a higher body mass index. CONCLUSION: Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

Effects of Pasture Conditions in Spring on Seasonal Forage Productivity

Fifteen beef cow-calf producers in southern Iowa were selected based on locality, management level, historical date of grazing initiation and desire to participate in the project. In 1997 and 1998, all producers kept records of production and economic data using the Integrated Resource Management-Standardized Performance Analysis (IRM-SPA) records program. At the initiation of grazing on each farm in 1997 and 1998, Julian date, degree-days, cumulative precipitation, and soil moisture, phosphorus, and potassium concentrations were determined. Also determined were pH, temperature, and load-bearing capacity; and forage mass, sward height, morphology and dry matter concentration. Over the grazing season, forage production, measured both by cumulative mass and sward height, forage in vitro digestible dry matter concentration, and crude protein concentration were determined monthly. In the fall of 1996 the primary species in pastures on farms used in this project were cool-season grasses, which composed 76% of the live forage whereas legumes and weeds composed 8.3 and 15.3%, respectively. The average number of paddocks was 4.1, reflecting a low intensity rotational stocking system on most farms. The average dates of grazing initiation were May 5 and April 29 in 1997 and 1998, respectively, with standard deviations of 14.8 and 14.1 days. Because the average soil moisture of 23% was dry and did not differ between years, it seems that most producers delayed the initiation of grazing to avoid muddy conditions by initiating grazing at a nearly equal soil moisture. However, Julian date, degree-days, soil temperature and morphology index at grazing initiation were negatively related to seasonal forage production, measured as mass or sward height, in 1998. And forage mass and height at grazing initiation were negatively related to seasonal forage production, measured as sward height, in 1997. Moreover, the concentrations of digestible dry matter at the initiation of and during the grazing season and the concentrations of crude protein during the grazing season were lower than desired for optimal animal performance. Because the mean seasonal digestible dry matter concentration was negatively related to initial forage mass in 1997 and mean seasonal crude proteins concentrations were negatively related to the Julian date, degree-days, and morphology indeces in both years, it seems that delaying the initiation of grazing until pasture soils are not muddy, is limiting the quality as well as the quantity of pasture forage. In 1997, forage production and digestibility were positively related to the soil phosphorus concentration. Soil potassium concentration was positively related to forage digestibility in 1997 and forage production and crude protein concentration in 1998. Increasing the number of paddocks increased forage production, measured as sward height, in 1997, and forage digestible dry matter concentration in 1998. Increasing yields or the concentrations of digestible dry matter or crude protein of pasture forage reduced the costs of purchased feed per cow.

Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo

Alpha interferon (IFN-α) suppresses human immunodeficiency virus type 1 (HIV-1) replication in vitro by inducing cell-intrinsic retroviral restriction mechanisms. We investigated the effects of IFN-α/ribavirin (IFN-α/riba) treatment on 34 anti-HIV-1 restriction factors in vivo. Expression of several anti-HIV-1 restriction factors was significantly induced by IFN-α/riba in HIV/hepatitis C virus (HCV)-coinfected individuals. Fold induction of cumulative restriction factor expression in CD4+ T cells was significantly correlated with viral load reduction during IFN-α/riba treatment (r2 = 0.649; P < 0.016). Exogenous IFN-α induces supraphysiologic restriction factor expression associated with a pronounced decrease in HIV-1 viremia.

Cyclophosphamide: As bad as its reputation? Long-term single centre experience of cyclophosphamide side effects in the treatment of systemic autoimmune diseases

OBJECTIVES Despite new treatment modalities, cyclophosphamide (CYC) remains a cornerstone in the treatment of organ or life-threatening vasculitides and connective tissue disorders. We aimed at analysing the short- and long-term side-effects of CYC treatment in patients with systemic autoimmune diseases. METHODS Chart review and phone interviews regarding side effects of CYC in patients with systemic autoimmune diseases treated between 1984 and 2011 in a single university centre. Adverse events were stratified according to the "Common Terminology Criteria for Adverse Events" version 4. RESULTS A total of 168 patients were included. Cumulative CYC dose was 7.45 g (range 0.5-205 g). Gastro-intestinal side effects were seen in 68 events, hair loss occurred in 38 events. A total of 58 infections were diagnosed in 44/168 patients (26.2%) with 9/44 suffering multiple infections. Severity grading of infections was low in 37/58 cases (63.8%). One CYC-related infection-induced death (0.6%) was registered. Amenorrhoea occurred in 7/92 females (7.6%) with 5/7 remaining irreversible. In females with reversible amenorrhoea, prophylaxis with nafarelin had been administered. Malignancy was registered in 19 patients after 4.7 years (median, range 0.25-22.25) presenting as 4 premalignancies and 18 malignancies, 3 patients suffered 2 premalignancies/malignancies each. Patients with malignancies were older with a higher cumulative CYC dose. Death was registered in 28 patients (16.6%) with 2/28 probably related to CYC. CONCLUSIONS Considering the organ or life-threatening conditions which indicate the use of CYC, severe drug-induced health problems were rare. Our data confirm the necessity to follow-up patients long-term for timely diagnosis of malignancies. CYC side-effects do not per se justify prescription of newer drugs or biologic agents in the treatment of autoimmune diseases.

Promoting Pollinating Insects in Intensive Agricultural Matrices: Field-Scale Experimental Manipulation of Hay-Meadow Mowing Regimes and Its Effects on Bees

Bees are a key component of biodiversity as they ensure a crucial ecosystem service: pollination. This ecosystem service is nowadays threatened, because bees suffer from agricultural intensification. Yet, bees rarely benefit from the measures established to promote biodiversity in farmland, such as agri-environment schemes (AES). We experimentally tested if the spatio-temporal modification of mowing regimes within extensively managed hay meadows, a widespread AES, can promote bees. We applied a randomized block design, replicated 12 times across the Swiss lowlands, that consisted of three different mowing treatments: 1) first cut not before 15 June (conventional regime for meadows within Swiss AES); 2) first cut not before 15 June, as treatment 1 but with 15% of area left uncut serving as a refuge; 3) first cut not before 15 July. Bees were collected with pan traps, twice during the vegetation season (before and after mowing). Wild bee abundance and species richness significantly increased in meadows where uncut refuges were left, in comparison to meadows without refuges: there was both an immediate (within year) and cumulative (from one year to the following) positive effect of the uncut refuge treatment. An immediate positive effect of delayed mowing was also evidenced in both wild bees and honey bees. Conventional AES could easily accommodate such a simple management prescription that promotes farmland biodiversity and is likely to enhance pollination services.

Assessing the Environmental Protection Agency's guidelines for cumulative risk assessment: Are they suitable for state agencies and EPA regional offices?

In the field of health risk analysis, cumulative risk assessment (CRA) is a necessary, although undeniably more complex approach to understanding the mixture of stressors, whether chemical or psychosocial, that exist in our environment, in all the pathways through which the chemicals may evolve—air, soil, or water, as well as the accumulation of these exposures over time. Related, or attached to the developing awareness of scientists understanding this mix of combined health effects is the burgeoning of the environmental justice movement, in which educated community advocates and even affected community members have called attention to evidence of a higher pollution burden in minority and/or lower SES communities. The intention of this paper is to 1) examine the development and understanding of CRA, primarily by the U.S. Environmental Protection Agency; 2) to assess several states agencies and some EPA regional offices' interpretation of CRA, again based primarily on EPA guidance, and 3) to analyze how CRA might be refined in its implementation—giving some cues as to how the EPA may more effectively interact with communities interested in CRA.^

Online Reputation Systems and Cumulative Advantage

The study of online reputation systems and their importance for promoting trust and cooperation and, therefore, the smooth functioning of online markets has received considerable attention over the last few years. In the first part of our talk we will try to give a brief overview of the existing theoretical and empirical work in this field, summarize the main findings from this research and identify open questions where results are either controversial or do not yet exist. The second part of our talk will focus on one of these issues that deserve further research, namely the relation between online reputation systems and processes of "cumulative advantage." Cumulative advantage is the mechanism where a favorable relative position of having a good reputation becomes a resource for further relative gains. The process leads to increased status inequality and a heavily skewed distribution of number of feedbacks, i.e. the ties in the reputation network. We present empirical evidence for direct and indirect reputation effects on the micro level of an auction reputation system and discuss the distributional consequences for the market level.

Effects of sublethal doses of methoxyfenozide on the development, survival and reproduction of Spodoptera frugiperda.

The lethal and sublethal effects of the ecdysone agonist methoxyfenozide on the fall armyworm, Spodoptera frugiperda (J. E. Smith), were investigated by feeding a methoxyfenozide-treated diet to ϐifth instars until pupation in doses corresponding to the LC 10 and LC 25 for the compound. Larval mortality reached 8% and 26% in the low and high concentration groups, respectively, on the seventh day of the experiment. A progressive larval mortality of 12% for the LC 10 and 60% for the LC 25 was observed before pupation. Treated larvae exhibited lower pupal weights, higher pupal mortality, presence of deformed pupae, and more deformed adults than untreated larvae. The incorporation of methoxyfenozide into the diet had a signiϐicant effect on the timing of larval development. The development period for males and females was about seven days longer than the controls for both concentrations tested. In contrast, the compound affected neither pupae nor adult longevity. Finally, S. frugiperda adults that resulted from ϐifth instars treated with methoxyfenozide were not affected in their mean cumulative number of eggs laid per female (fecundity), nor percentages of eggs hatched (fertility), or the sex ratio. Our results suggest that the combination of lethal and sublethal effects of methoxyfenozide may have important implications for the population dynamics of the fall armyworm

Toxicity and sublethal effects of six insecticides to last instar larvae and adults of the biocontrol agents Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae) and Adalia bipunctata (L.) (Coleoptera: Coccinellidae)

To further develop Integrated Pest Management (IPM) strategies against crop pests, it is important to evaluate the effects of insecticides on biological control agents. Therefore, we tested the toxicity and sublethal effects (fecundity and fertility) of flonicamid, flubendiamide, metaflumizone, spirotetramat, sulfoxaflor and deltamethrin on the natural enemies Chrysoperla carnea and Adalia bipunctata. The side effects of the active ingredients of the insecticides were evaluated with residual contact tests for the larvae and adults of these predators in the laboratory. Flonicamid, flubendiamide, metaflumizone and spirotetramat were innocuous to last instar larvae and adults of C. carnea and A. bipunctata. Sulfoxaflor was slightly toxic to adults of C. carnea and was highly toxic to the L4 larvae of A. bipunctata. For A. bipunctata, sulfoxaflor and deltamethrin were the most damaging compounds with a cumulative larval mortality of 100%. Deltamethrin was also the most toxic compound to larvae and adults of C. carnea. In accordance with the results obtained, the compounds flonicamid, flubendiamide, metaflumizone and spirotetramat might be incorporated into IPM programs in combination with these natural enemies for the control of particular greenhouse pests. Nevertheless, the use of sulfoxaflor and deltamethrin in IPM strategies should be taken into consideration when releasing either of these biological control agents, due to the toxic behavior observed under laboratory conditions. The need for developing sustainable approaches to combine the use of these insecticides and natural enemies within an IPM framework is discussed.

Increasing DNA repair methyltransferase levels via bone marrow stem cell transduction rescues mice from the toxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, a chemotherapeutic alkylating agent.

The chloroethylnitrosourea (CNU) alkylating agents are commonly used for cancer chemotherapy, but their usefulness is limited by severe bone marrow toxicity that causes the cumulative depletion of all hematopoietic lineages (pancytopenia). Bone marrow CNU sensitivity is probably due to the inefficient repair of CNU-induced DNA damage; relative to other tissues, bone marrow cells express extremely low levels of the O6-methylguanine DNA methyltransferase (MGMT) protein that repairs cytotoxic O6-chloroethylguanine DNA lesions. Using a simplified recombinant retroviral vector expressing the human MGMT gene under control of the phosphoglycerate kinase promoter (PGK-MGMT) we increased the capacity of murine bone marrow-derived cells to repair CNU-induced DNA damage. Stable reconstitution of mouse bone marrow with genetically modified, MGMT-expressing hematopoietic stem cells conferred considerable resistance to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a CNU commonly used for chemotherapy. Bone marrow harvested from mice transplanted with PGK-MGMT-transduced cells showed extensive in vitro BCNU resistance. Moreover, MGMT expression in mouse bone marrow conferred in vivo resistance to BCNU-induced pancytopenia and significantly reduced BCNU-induced mortality due to bone marrow hypoplasia. These data demonstrate that increased DNA alkylation repair in primitive hematopoietic stem cells confers multilineage protection from the myelosuppressive effects of BCNU and suggest a possible approach to protecting cancer patients from CNU chemotherapy-related toxicity.

Essays on the Effects of Corporate Taxation

Cette thèse est une collection de trois articles en macroéconomie et finances publiques. Elle développe des modèles d'Equilibre Général Dynamique et Stochastique pour analyser les implications macroéconomiques des politiques d'imposition des entreprises en présence de marchés financiers imparfaits. Le premier chapitre analyse les mécanismes de transmission à l'économie, des effets d'un ré-échelonnement de l'impôt sur le profit des entreprises. Dans une économie constituée d'un gouvernement, d'une firme représentative et d'un ménage représentatif, j'élabore un théorème de l'équivalence ricardienne avec l'impôt sur le profit des entreprises. Plus particulièrement, j'établis que si les marchés financiers sont parfaits, un ré-échelonnement de l'impôt sur le profit des entreprises qui ne change pas la valeur présente de l'impôt total auquel l'entreprise est assujettie sur toute sa durée de vie n'a aucun effet réel sur l'économie si l'état utilise un impôt forfaitaire. Ensuite, en présence de marchés financiers imparfaits, je montre qu'une une baisse temporaire de l'impôt forfaitaire sur le profit des entreprises stimule l'investissement parce qu'il réduit temporairement le coût marginal de l'investissement. Enfin, mes résultats indiquent que si l'impôt est proportionnel au profit des entreprises, l'anticipation de taxes élevées dans le futur réduit le rendement espéré de l'investissement et atténue la stimulation de l'investissement engendrée par la réduction d'impôt. Le deuxième chapitre est écrit en collaboration avec Rui Castro. Dans cet article, nous avons quantifié les effets sur les décisions individuelles d'investis-sement et de production des entreprises ainsi que sur les agrégats macroéconomiques, d'une baisse temporaire de l'impôt sur le profit des entreprises en présence de marchés financiers imparfaits. Dans un modèle où les entreprises sont sujettes à des chocs de productivité idiosyncratiques, nous avons d'abord établi que le rationnement de crédit affecte plus les petites (jeunes) entreprises que les grandes entreprises. Pour des entreprises de même taille, les entreprises les plus productives sont celles qui souffrent le plus du manque de liquidité résultant des imperfections du marché financier. Ensuite, nous montré que pour une baisse de 1 dollar du revenu de l'impôt, l'investissement et la production augmentent respectivement de 26 et 3,5 centimes. L'effet cumulatif indique une augmentation de l'investissement et de la production agrégés respectivement de 4,6 et 7,2 centimes. Au niveau individuel, nos résultats indiquent que la politique stimule l'investissement des petites entreprises, initialement en manque de liquidité, alors qu'elle réduit l'investissement des grandes entreprises, initialement non contraintes. Le troisième chapitre est consacré à l'analyse des effets de la réforme de l'imposition des revenus d'entreprise proposée par le Trésor américain en 1992. La proposition de réforme recommande l'élimination des impôts sur les dividendes et les gains en capital et l'imposition d'une seule taxe sur le revenu des entreprises. Pour ce faire, j'ai eu recours à un modèle dynamique stochastique d'équilibre général avec marchés financiers imparfaits dans lequel les entreprises sont sujettes à des chocs idiosyncratiques de productivité. Les résultats indiquent que l'abolition des impôts sur les dividendes et les gains en capital réduisent les distorsions dans les choix d'investissement des entreprises, stimule l'investissement et entraîne une meilleure allocation du capital. Mais pour être financièrement soutenable, la réforme nécessite un relèvement du taux de l'impôt sur le profit des entreprises de 34\% à 42\%. Cette hausse du taux d'imposition décourage l'accumulation du capital. En somme, la réforme engendre une baisse de l'accumulation du capital et de la production respectivement de 8\% et 1\%. Néanmoins, elle améliore l'allocation du capital de 20\%, engendrant des gains de productivité de 1.41\% et une modeste augmentation du bien être des consommateurs.