Context
The mountain pine beetle (MPB;
Dendroctonus ponderosae
) is a native bark beetle whose outbreaks leads to widespread conifer forest mortality. Of particular concern to forest and wildfire ...managers is the influence of MPB outbreaks on wildfire via spatial legacies left in impacted forest stands. There is, however, limited consensus in the literature regarding how MPB outbreaks affect wildfire across western North America.
Objectives
This meta-analysis aims to (1) summarize available evidence regarding MPB-wildfire interactions, and (2) identify environmental and methodological indicators associated with various wildfire responses (i.e., amplified, neutral, or dampened) post-outbreak.
Methods
We include peer-reviewed publications focusing on MPB outbreaks and subsequent wildfire activity in forests across western Canada and the USA between 2000 and 2021. A classification scheme was used to examine attributes of each publication to assess which indicators contribute most to their associated wildfire response.
Results
We found that spatial scale, forest fuels, and weather are main drivers of variation in wildfire response post-outbreak. Metrics of forest fuels and inclusion of weather data on a stand-scale are related to amplified fire responses, whereas dampened responses correspond to landscape-scale analyses. Furthermore, red-stage stands are associated with amplified fire response, whereas other stages are associated with dampened response—supporting current conceptual models of the importance of outbreak stage on wildfire.
Conclusions
Advancing our understanding regarding drivers of wildfire responses post-MPB outbreak is key to developing accurate, and comparative research studies. These findings provide crucial information for wildfire, and forest management agencies, especially in forests newly exposed to this disturbance interaction under climate change.
MAGIA (miRNA and genes integrated analysis) is a novel web tool for the integrative analysis of target predictions, miRNA and gene expression data. MAGIA is divided into two parts: the query section ...allows the user to retrieve and browse updated miRNA target predictions computed with a number of different algorithms (PITA, miRanda and Target Scan) and Boolean combinations thereof. The analysis section comprises a multistep procedure for (i) direct integration through different functional measures (parametric and non-parametric correlation indexes, a variational Bayesian model, mutual information and a meta-analysis approach based on P-value combination) of mRNA and miRNA expression data, (ii) construction of bipartite regulatory network of the best miRNA and mRNA putative interactions and (iii) retrieval of information available in several public databases of genes, miRNAs and diseases and via scientific literature text-mining. MAGIA is freely available for Academic users at http://gencomp.bio.unipd.it/magia.
Neoadjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum ...(Pt) response in NACT settings have hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were investigated to identify miRNA families with prognostic role in high-grade serous EOC patients who received the NACT regimen.
One hundred sixty-four matched tumor biopsies taken at initial laparoscopic evaluation and at interval-debulking surgery (IDS) after four courses of Pt-based therapy were selected from 82 stage IIIC–IV high-grade serous-EOC patients that were judged unsuitable for complete primary debulking and subjected the NACT protocol. miRNA profiling by microarray, real-time PCR and immuno-histochemical staining for Smad2 phosphorylation (P-Smad2) were used for data analysis.
Analysis revealed that 369 miRNAs were differentially expressed in matched biopsies (referred to as DEMs). DEMs were not scattered across the genome, but clustered into families: miR-199, let-7, miR-30, miR-181 and miR-29. Multivariate analysis showed that miR-199a-3p, miR-199a-5p, miR-181a-5p and let-7g-5p associated with overall and progression-free survival (P < 0.05); miR-199a-3p, miR-199a-5p and miR-181a-5p associated with residual tumor volume and Pt-free interval (P < 0.05). Immuno-histochemical staining confirmed an enrichment of P-Smad2, a marker of transforming growth factor-&bgr; activation, in tumors from patients with shorter PFS and OS, and with high levels of expression of miR-181a-5p (P < 0.05). Kaplan–Meier curves plotting concomitant expression of P-Smad2 and miR-181a-5p show significant differences in PFS and OS compared with those depicting the expression of each biomarker alone (P < 0.001).
This study describes several miRNA families with a prognostic role in the NACT setting. It also confirms that concomitant analysis of P-Smad2 and miR-181a-5p in surgical samples may be capable of identifying those ovarian cancer patients with poor outcome and little chance of response to Pt-based NACT.
The majority of patients with stage III–IV epithelial ovarian cancer (EOC) relapse after initially responding to platinum-based chemotherapy, and develop resistance. The genomic features involved in ...drug resistance are unknown. To unravel some of these features, we investigated the mutational profile of genes involved in pathways related to drug sensitivity in a cohort of matched tumors obtained at first surgery (Ft-S) and second surgery (Sd-S).
Matched biopsies (33) taken at Ft-S and Sd-S were selected from the ‘Pandora’ tumor tissue collection. DNA libraries for 65 genes were generated using the TruSeq Custom Amplicon kit and sequenced on MiSeq (Illumina). Data were analyzed using a high-performance cluster computing platform (Cloud4CARE project) and independently validated.
A total of 2270 somatic mutations were identified (89.85% base substitutions 8.19% indels, and 1.92% unknown). Homologous recombination (HR) genes and TP53 were mutated in the majority of Ft-S, while ATM, ATR, TOP2A and TOP2B were mutated in the entire dataset. Only 2% of mutations were conserved between matched Ft-S and Sd-S. Mutations detected at second surgery clustered patients in two groups characterized by different mutational profiles in genes associated with HR, PI3K, miRNA biogenesis and signal transduction.
There was a low level of concordance between Ft-S and Sd-S in terms of mutations in genes involved in key processes of tumor growth and drug resistance. This result suggests the importance of future longitudinal analyses to improve the clinical management of relapsed EOC.
IntroductionThe cause of epilepsy in multiple sclerosis (MS) has not yet been elucidated. The relevance of cortical pathology (cortical lesions and thickness) in MS patients with and without epilepsy ...was evaluated in a longitudinal study.Methods32 relapsing–remitting MS patients with epilepsy (RRMS/E) and 60 matched RRMS patients without epilepsy were included in a 3 year longitudinal study. The following clinical and MR parameters were analysed: Expanded Disability Status Scale (EDSS), cognitive score (CS), cortical lesion (CL) number and volume, grey matter fraction (GMf), global cortical thickness (CTh), T2 white matter lesion volume (T2WMLV), new CLs and new WM lesions.ResultsAt baseline (T0), CLs were observed in 27/32 (84.4%) RRMS/E and in 26/60 (43.3%) RRMS (p<0.001) patients, and the RRMS/E group had a higher number (10.2±8.9 vs 4.5±2.4; p<0.001) and total volume (2.0±1.3 vs 0.7±0.8 cm3; p<0.001) of CLs compared with the RRMS group. No significant difference in T2WMLV was observed. Global CTh was lower in RRMS/E (2.12±0.19 vs 2.35±0.14 mm; p<0.001), and this group also showed a decline in cognition (CS 10.9±6.3 vs 6.2±3.5; p<0.001). After 3 years (T1), the RRMS/E group had a higher accumulation of new CLs (3.4±3.2 vs 1.2±1.1; p<0.001) and faster reduction of GMf (p=0.022) while the two groups did not differ in the number of new WM and new Gad+ lesions.DiscussionRRMS/E had a more severe and rapidly evolving cortical pathology (CLs and atrophy) compared with RRMS without epilepsy. The RRMS/E group was also characterised by more pronounced cognitive decline, higher EDSS and higher prevalence of men.
Introduction
The heterogeneity of von Willebrand disease (VWD) makes its diagnosis a difficult task.
Methods
We report here on the usefulness of a microchip‐based flow‐chamber system, the total ...thrombus‐formation analysis system (T‐TAS), in the identification and characterization of VWD. Thirty VWD patients and 20 healthy subjects were studied with the T‐TAS platelet (PL) and atherome (AR) microchips developed for the in vitro assessment of platelet thrombus formation and fibrin‐rich platelet thrombus formation respectively.
Results
Samples from severe type 1 VWD, characterized by von Willebrand factor (VWF) levels below 10 U dL−1, failed to occlude either the PL or the AR chip capillaries, while the occlusion times were normal in patients with mild type 1 VWD (VWF above 25 U dL−1). PL and/or AR chip occlusion occurred, but took longer than normal, for samples from type Vicenza and type 1 VWD patients, whose VWF levels ranged between 10 and 25 U dL−1. No PL or AR chip capillary occlusion was seen for samples from patients with type 2A or 2B VWD featuring the absence of large VWF multimers, whereas no abnormalities emerged for type 2B patients with normal multimer patterns.
Conclusion
The T‐TAS appears to be sensitive mainly to plasma VWF concentration and the presence of large multimers. Failure of the PL and AR chips to become occluded points to a lack of large VWF multimers, or type 1 VWD with VWF levels below 10 U dL−1. Although the T‐TAS does not assure a precise VWD diagnosis, it does point us in the right direction, and thus seems a useful global preliminary test.
Although cognitive dysfunction affects a relevant portion of patients with multiple sclerosis (MS), its pathologic substrate has not been clarified and it does not seem entirely explained by white ...matter changes.
A total of 100 consecutive patients with relapsing remitting MS (RRMS) and 42 normal controls (NC) were enrolled in the study. Cognitive performance was assessed by Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB). Regional cortical thickness (CTh) was evaluated by Freesurfer.
Thirty-one patients with RRMS failed 1 or 2 tests of BRB and were considered to have a mild cognitive impairment (mCI-RRMS), while 8 patients failed at least 3 tests and were classified as markedly impaired (sCI-RRMS). The mean CTh of mCI-RRMS and sCI-RRMS group was significantly lower than in NC (p < 0.001) and cognitively normal patients with RRMS (CN-RRMS) (p < 0.001). The regional analysis revealed significant cortical thinning in frontal and temporal regions (frontotemporal thinning) of CN-RRMS compared to NC, while a widespread pattern of cortical thinning was observed in mCI-RRMS and in sCI-RRMS compared to both CN-RRMS and NC. A correlation was observed between cognitive score (CS) and the mean CTh (r = -0.69, p < 0.001) and between CS and CTh of almost all the cortical areas analyzed (r value between -0.20 and -0.65, p < 0.01). A correlation was found between T2-WM-LV and mean CTh (r = -0.31, p = 0.004) or CS (r = 0.21, p = 0.031). The multivariate analysis confirmed a widespread cortical thinning as the best predictor of cognitive impairment.
A widespread pattern of cortical thinning characterizes patients with cognitive dysfunction, suggesting such dysfunction as expression of a more aggressive and widespread cortical pathology.
The microbiological contamination of retrieved tissues has become a very important topic and it is a critical aspect in the safety of allografts, especially from multi-tissue donors whose tissues are ...frequently contaminated as a consequence of retrieval. We analysed a total of 10,107 tissues, 8178 musculoskeletal and 1929 cardiovascular tissues, retrieved from 978 multi-tissue donors. Of these, 159 heart-beating donors (HBD) were also organ donors, while the remaining 819 non-heart-beating donors (NHBD) were tissue donors only. A multivariate logistic model was used to determine the factors affecting contamination risk during retrieval. In the model, the dependent variable was the presence/absence of contamination while the covariates included were: gender, type of donor, age of donor, cause of death, previous skin donation, cadaver time, number of people attending the retrieval, number of tissues retrieved. Moreover, a second log-linear model was used to determine the number of strains isolated per tissue. Tissue contamination was statistically correlated with gender, type of donor, cadaver time, number of people attending the retrieval and season. In conclusion, to minimize the risk of bacterial contamination, aseptic techniques should be used at retrieval, with the number of retrieval team members kept to a minimum. In addition, cadaver time should be as short as possible and the donor should be refrigerated within a few hours after death.
In primary progressive multiple sclerosis (PPMS), a discrepancy exists between the modest brain white matter (WM) lesion burden and the severity of neurologic disability. Double-inversion recovery ...(DIR) sequences have improved MRI sensitivity in the detection of cortical lesions (CLs) in patients with relapsing-onset MS.
This 2-year longitudinal study was designed to assess the frequency, extent, and rate of formation of CLs in PPMS and their relationship with T2 lesion volume (LV), gray matter (GM) atrophy, and disability.
Forty-eight patients with PPMS underwent clinical and magnetic resonance examinations at baseline and after 2 years. The number and volume of CLs, WM T2 LV, and GM fraction (GMf) were assessed at baseline and at follow-up.
At baseline, CLs were detected in 81.2% of patients with PPMS. At least one new CL was found in 28 patients during the follow-up. In patients with PPMS, CL and T2 WM LVs increased over the follow-up. At baseline, CL number and volumes were significantly correlated with T2 WM LV, GMf, disease duration, and Expanded Disability Status Scale score, as well as with increasing GM atrophy and disability during the follow-up. A multivariate analysis showed that CL volume at baseline was an independent predictor of percentage GM volume change and disability accumulation during the subsequent 2-year period.
Cortical lesions are a frequent finding in primary progressive multiple sclerosis. The extent of such abnormalities is associated with the extent of cortical atrophy and clinical disability, and is able to predict their changes over a medium time period.
Background
Using double inversion recovery (DIR) MRI, cortical lesions can be seen in the brain of patients with multiple sclerosis (MS). The burden of such lesions seems to be well correlated with ...the severity of MS-related disability.
Objective
To investigate whether the extent of cortical damage in patients with benign MS (BMS) might contribute to explain their favorable clinical status.
Methods
Forty-eight patients with BMS (Expanded Disability Status Scale EDSS score ≤3.0 and disease duration ≥15 years) and 96 patients with non-disabling, early relapsing–remitting (RR) MS (EDSS score ≤3.0 and disease duration ≤5 years) were studied. Brain MRI, including a DIR and a fluid-attenuated inversion recovery (FLAIR) sequence, was acquired at baseline and after 12 months. On DIR images, intracortical (ICL) and cortical-subcortical lesions (CSL) were identified and their number and volume calculated. Total white matter (WM) lesion volume was quantified on FLAIR images.
Results
Compared with early RRMS, patients with BMS had lower number of ICL at both study time points (P ≤ 0.001 for both comparisons). At one-year follow-up, a significant increase of ICL and CSL number and total volume was observed only in early patients with RRMS. The number and volume of cortical lesions was not correlated with WM lesion volume. Total ICL number at baseline, total cortical lesion volume at baseline, and total cortical lesion volume change were independent predictors of MS phenotype.
Conclusion
In patients with BMS, the selective sparing of the cortex from disease-related focal pathology might be one of the factors associated to their favorable clinical status, independently of the (possible) accrual of WM lesions.
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