Abstract:Conservation Biology 41In an attempt to provide a state of the art of the effect of forest management on biodiversity, 42we performed a MA comparing the species richness of managed and unmanaged forests in 47Our MA provides basic ecological knowledge needed for conservation and ecologically 48 sustainable forestry. In this paper, we showed that forest management has a negative effect 49 on the biodiversity of forest dwelling species. Because we were aware of the limitations of 50 our MA, we used caution when discussing the results considering that: (i) the effect is 51 strongly heterogeneous between different taxa; (ii) there is a trend for recovery of biodiversity 52 once management has been abandoned; (iii) no strong conclusion on the effect of different 53 management types could be drawn from our data due to low replication number. The obvious 54 main conclusion of this paper was that research on the subject in Europe was scarce and 55 that more controlled studies may help answer the questions raised. 113always provided negative slopes, except for bryophytes and birds (see Table 3, p. 107). 114Finally, even if the effect of TSA was significant only for carabids, saproxylic beetles and 115 fungi, most of the negative slopes for taxa have much higher value than the slope for all 160(2002): this paper compares old growth with 15 years-old stands, which were not considered 161 as "young regeneration phases" nor "clearfelling stands" in our protocol. We assume that our 162 selection protocol was restrictive enough regarding the number of studies finally included in 163 our MA; if we had been more restrictive in our inclusion criteria (i.e. excluding young stands), 164we would have rejected this paper. 166 Conclusions 167The paper we published does not aim at influencing European forest and conservation 168 policies in any way, but to provide decision-making tools based on scientific facts. Both 169 managed and unmanaged forests are needed to preserve European forest biodiversity, but 170 since there are many managed forests and very few old-growth ones, a special effort should 171 be allocated to create protected reserves, as suggested by Paillet et al. (2010).

Background & Aims Immunotherapies that induce T-cell responses have shown efficacy against some solid malignancies in patients and mice, but these have little effect on pancreatic ductal adenocarcinoma (PDAC). We investigated whether the ability of PDAC to evade T-cell responses induced by immunotherapies results from the low level of immunogenicity of tumor cells, the tumor's immunosuppressive mechanisms, or both. Methods KrasG12D/+; Trp53R172H/+; Pdx-1-Cre (KPC) mice, which develop spontaneous PDAC, or their littermates (controls) were given subcutaneous injections of a syngeneic KPC-derived PDAC cell line. Mice were then given gemcitabine and an agonist of CD40 to induce tumor-specific immunity mediated by T cells. Some mice were also given clodronate-encapsulated liposomes to deplete macrophages. Tumor growth was monitored. Tumor and spleen tissues were collected and analyzed by histology, flow cytometry, and immunohistochemistry. Results Gemcitabine in combination with a CD40 agonist induced T cell-dependent regression of subcutaneous PDAC in KPC and control mice. In KPC mice given gemcitabine and a CD40 agonist, CD4+ and CD8+ T cells infiltrated subcutaneous tumors, but only CD4+ T cells infiltrated spontaneous pancreatic tumors (not CD8+ T cells). In mice depleted of Ly6Clow F4/80+ extra-tumor macrophages, the combination of gemcitabine and a CD40 agonist stimulated infiltration of spontaneous tumors by CD8+ T cells and induced tumor regression, mediated by CD8+ T cells. Conclusions Ly6Clow F4/80+ macrophages that reside outside of the tumor microenvironment regulate infiltration of T cells into PDAC and establish a site of immune privilege. Strategies to reverse the immune privilege of PDAC, which is regulated by extra-tumor macrophages, might increase the efficacy of T cell immunotherapy for patients with PDAC.

BackgroundData regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels.MethodsA prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria.ResultsOne hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When Cmin was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT.ConclusionsWhen using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. Cmin levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and Cmin might be a new useful tool to predict AKI.

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Knowledge of the variables associated with DRP could aid their early detection in at-risk patients. The use of an application that can be continually updated in daily clinical practice helps to optimize resources.

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The accurate evaluation of donor-specific antibodies (DSAs) has allowed a precise identification of sensitized patients at risk of antibody-mediated rejection (ABMR). However, the scale of the humoral response is not always fully addressed, as it excludes the complete memory B-cell (mBC) pool such as that caused by antigen-specific mBC. Using a novel B-cell ELISpot assay approach, we assessed circulating mBC frequencies against class I and II HLA antigens in highly sensitized and nonsensitized patients in the waiting list for kidney transplantation. Also, kidney transplant patients undergoing ABMR were evaluated for the presence of donor-specific mBCs both at the time of rejection and before transplantation. For this purpose, 278 target HLA-sp antigens from 70 patients were studied and compared to circulating HLA-sp antibodies. Both class I and II HLA-sp mBC frequencies were identified in highly sensitized individuals but not in nonsensitized and healthy individuals, many years after first sensitization. Also, high donor-specific mBC responses were clearly found both during ABMR and before transplantation, regardless of circulating DSA. The higher the donor-specific mBC response, the more aggressive the allograft rejection. Thus, assessing donor-specific mBC frequencies may be relevant to better refine patient alloimmune-risk stratification, and provides new insight into the mechanisms of the adaptive humoral alloimmune response taking place in kidney transplantation.

BackgroundBecause of the high incidence of drug-related problems (DRPs) among hospitalized patients with cardiovascular diseases and their potential impact on morbidity and mortality, it is important to identify the most susceptible patients, who therefore require closer monitoring of drug therapy.PurposeTo identify the profile of patients at higher risk of developing at least one DRP during hospitalization in a cardiology ward.MethodWe consecutively included all patients hospitalized in the cardiology ward of a teaching hospital in 2009. DRPs were identified through a computerized warning system designed by the pharmacy department and integrated into the electronic medical record.ResultsA total of 964 admissions were included, and at least one DRP was detected in 29.8%. The variables associated with a higher risk of these events were polypharmacy (odds ratio [OR]=1.228; 95% confidence interval [CI]=1.153–1.308), female sex (OR=1.496; 95% CI=1.026–2.180), and first admission (OR=1.494; 95% CI=1.005–2.221).ConclusionMonitoring patients through a computerized warning system allowed the detection of at least one DRP in one-third of the patients. Knowledge of the risk factors for developing these problems in patients admitted to hospital for cardiovascular problems helps in identifying the most susceptible patients.