Monitoring population‐level responses of marine mammals to human activities

We provide guidance for monitoring whether human activities affect the physiology or behavior of marine mammals and, if so, whether those effects may lead to changes in survival and reproduction at the population level. We suggest that four elements be included in designing and implementing such a monitoring program. The first is development of a theory of change: a set of mechanistic hypotheses that outline why a given activity might be expected to have one or more measurable effects on individuals and populations, and ideally the magnitude, timing, and duration of the effects. The second element, definition of biologically meaningful effect sizes, ultimately facilitates the development of a monitoring program that can detect those magnitudes of effect with the desired levels of precision. The third element, selection of response variables for monitoring, allows inference to whether observed changes in the status of individuals or populations are attributable to a given activity. Visual observations, passive acoustic and tagging instruments, and direct physical measurements all can provide data that facilitate quantitative hypothesis testing. The fourth element is specification of the temporal sequence of monitoring. These elements also can be used to inform monitoring of the responses of other taxonomic groups to human activities.     

Models of climate associations and distributions of amphibians in Italy

Analyzing the relationships between the distribution of animal species and climatic variables is not only important for understanding which factors govern species distribution but also for improving our ability to predict future ecological responses to climate change. In the context of global climate change, amphibians are of particular interest because of their extreme sensitivity to the variation of temperature and precipitation regimes. We analyzed species–climate relationships for 17 amphibian species occurring in Italy using species distribution data at the 10 × 10 km resolution. A machine learning method, Random Forests, was used to model the distribution of amphibians in relation to a set of 18 climatic variables. The results showed that the variables which had the highest importance were those related to precipitation, indicating that precipitation is an important factor in determining amphibian distribution. Future projections showed a complex response of species distributions, emphasizing the potential severity of climate change on the distributions of amphibians in Italy. The species that will decrease the most are those occurring in mountainous and Mediterranean areas. Our results provide some preliminary information that could be useful for amphibian conservation, indicating if future conservation priorities for some species should be enhanced.     

Fabrication of Nano-engineered Transparent Conducting Oxides by Pulsed Laser Deposition

Nanosecond Pulsed Laser Deposition (PLD) in the presence of a background gas allows the deposition of metal oxides with tunable morphology, structure, density and stoichiometry by a proper control of the plasma plume expansion dynamics. Such versatility can be exploited to produce nanostructured films from compact and dense to nanoporous characterized by a hierarchical assembly of nano-sized clusters. In particular we describe the detailed methodology to fabricate two types of Al-doped ZnO (AZO) films as transparent electrodes in photovoltaic devices: 1) at low O₂ pressure, compact films with electrical conductivity and optical transparency close to the state of the art transparent conducting oxides (TCO) can be deposited at room temperature, to be compatible with thermally sensitive materials such as polymers used in organic photovoltaics (OPVs); 2) highly light scattering hierarchical structures resembling a forest of nano-trees are produced at higher pressures. Such structures show high Haze factor (>80%) and may be exploited to enhance the light trapping capability. The method here described for AZO films can be applied to other metal oxides relevant for technological applications such as TiO₂, Al₂O₃, WO₃ and Ag₄O₄.     

Anti-cyclic citrullinated peptide antibody titer predicts time to rheumatoid arthritis onset in patients with undifferentiated arthritis: results from a 2-year prospective study

Introduction

The diagnostic, predictive and prognostic role of anti-cyclic citrullinated peptide (CCP) antibodies in rheumatoid arthritis (RA) patients is widely accepted. Moreover, detection of these antibodies in subjects presenting with undifferentiated arthritis (UA) is associated with a significant risk to develop the disease. On the other hand, clinical and prognostic significance of evaluating anti-CCP levels in subjects with inflammatory arthritis at disease onset has not been fully clarified. The goal of this prospective study is to analyze the value and prognostic significance of anti-CCP titer quantification in UA subjects.

Methods

Serial anti-CCP assays were measured in 192 consecutive patients presenting with UA lasting less than 12 weeks. Clinical and serological data and arthritis outcome were evaluated every 6 months until two years of follow-up.

Results

Anti-CCP positivity, at both low and high titer, and arthritis of hand joints significantly predicted RA at two years, risk increasing in subjects with high anti-CCP titers at baseline. Moreover, time to RA diagnosis was shorter in patients with high anti-CCP2 titers at enrollment with respect to those with low antibody concentration.

Conclusions

Presence of anti-CCP antibodies, at both low and high concentration, is significantly associated with RA development in subjects with recent onset UA. However, time interval from the onset of the first symptoms to the fulfilment of the classification criteria appears to be directly related to the initial anti-CCP level.     

A Re-Emerging Marker for Prognosis in Hepatocellular Carcinoma: The Add-Value of FISHing c-myc Gene for Early Relapse

Hepatocellular carcinoma is one leading cause of cancer-related death and surgical resection is still one of the major curative therapies. Recently, there has been a major effort to find mechanisms involved in carcinogenesis and early relapse. c-myc gene abnormality is found in hepatocarcinogenesis. Our aim was to analyze the role of c-myc as prognostic factor in terms of overall survival and disease-free survival and to investigate if c-myc may be an important target for therapy. We studied sixty-five hepatocellular carcinomas submitted to surgical resection with curative intent. Size, macro-microvascular invasion, necrosis, number of nodules, grading and serum alfa-fetoprotein level were registered for all cases. We evaluated the c-myc aberrations by using break-apart FISH probes. Probes specific for the centromeric part of chromosome 8 and for the locus specific c-myc gene (8q24) were used to assess disomy, gains of chromosomes (polysomy due to polyploidy) and amplification. c-myc gene amplification was scored as 8q24/CEP8 > 2. Statistical analysis for disease-free survival and overall survival were performed. At molecular level, c-myc was amplified in 19% of hepatocellular carcinoma, whereas showed gains in 55% and set wild in 26% of cases. The 1- and 3-year disease-free survival and overall survival for disomic, polysomic and amplified groups were significantly different (p=0.020 and p=.018 respectively). Multivariate analysis verified that the AFP and c-myc status (amplified vs. not amplified) were significant prognostic factors for overall patients survival. c-myc gene amplification is significantly correlated with disease-free survival and overall survival in patients with hepatocellular carcinoma after surgical resection and this model identifies patients with risk of early relapse (≤12 months). We suggest that c-myc assessment may be introduced in the clinical practice for improving prognostication (high and low risk of relapse) routinely and may have be proposed as biomarker of efficacy to anti-c-myc targeted drugs in clinical trials.     

Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL,MLL, DDB1 and LMO2

Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized.     

Mode of delivery is associated with different hematological profiles in the newborn calf

Several studies on babies have shown that the type of delivery can influence the hematological and immune status of the newborn. In bovine medicine, some authors reported the hematological pattern of the newborn calf, but never related it with the calving process or other perinatal factors. The purpose of the present study was to evaluate the hematological profile in newborn calves in relation to the type of delivery. A total of 41 healthy calves were enrolled; 16 Friesian calves which were born by vaginal delivery without assistance (VD), and 25 Belgian Blue calves that were born by elective Caesarean section (CS). As soon as the calves were born, a complete clinical examination was performed to verify viability and maturity. At 10 min after birth, 2 mL venous blood was collected to perform the blood gas and acid-base evaluation. Blood samples were subsequently collected from the jugular vein within 30 min after birth, and at 1, 2, 3, 7, and 14 days of age. An automatic analyzer was used to determine hemoglobin concentration (Hb), hematocrit (Ht), and red and white blood cell counts, while differential leukocyte count was performed microscopically. Statistical analysis was applied to assess differences between the groups and within the group for all parameters between each sampling time (P ≤ 0.05). All the calves were born alive, viable, and mature. There were no acidotic calves, but statistical analysis revealed many differences, as higher pH, base excess (BE) (P ≤ 0.05), PO₂ (P < 0.001), and sO₂ (P < 0.0001) in the VD group. Levels of hemoglobin concentration, hematocrit, and red blood cell number were constantly higher in CS calves (P < 0.001). In comparison with the VD calves, white blood cell and neutrophil absolute number were higher at birth and at 14 days of age in the CS group (P < 0.001 and P ≤ 0.05). The mode of delivery, therefore, seems to have an influence on the oxygenation levels and on the hematological and nonspecific immunity profile of the newborn calf.     

Hydroxybutyrate prevents protein aggregation in the halotolerant bacterium <Emphasis Type="Italic">Pseudomonas</Emphasis> sp. CT13 under abiotic stress

Polyhydroxybutyrate (PHB), a typical carbon and energy storage compound, is widely found in Bacteria and Archae domains. This polymer is produced in response to conditions of physiological stress. PHB is composed of repeating units of β-hydroxybutyrate (R-3HB). It has been previously shown that R-3HB functions as an osmolyte in extremophile strains. In this study, Pseudomonas sp. CT13, a halotolerant bacterium, and its PHB synthase-minus mutant (phaC) were used to analyze the chaperone role of R-3HB. The production of this compound was found to be essential to salt stress resistance and positively correlated with salt concentration, suggesting that PHB monomer acts as a compatible solute in Pseudomonas sp. CT13. R-3HB accumulation was also associated with the prevention of protein aggregation under combined salt and thermal stresses in Pseudomonas sp. CT13. Physiological concentrations of R-3HB efficiently reduced citrate synthase (CS) aggregation and stabilized the enzymatic activities of CS during thermal stress. Docking analysis of the CS/R-3HB interaction predicted the stability of this complex under physiological concentrations of R-3HB. Thus, in vivo, in vitro and in silico analyses suggest that R-3HB can act as a chemical chaperone.     

Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats

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Multiple imputation methods for handling incomplete longitudinal and clustered data where the target analysis is a linear mixed effects model

Multiple imputation (MI) is increasingly popular for handling multivariate missing data. Two general approaches are available in standard computer packages: MI based on the posterior distribution of incomplete variables under a multivariate (joint) model, and fully conditional specification (FCS), which imputes missing values using univariate conditional distributions for each incomplete variable given all the others, cycling iteratively through the univariate imputation models. In the context of longitudinal or clustered data, it is not clear whether these approaches result in consistent estimates of regression coefficient and variance component parameters when the analysis model of interest is a linear mixed effects model (LMM) that includes both random intercepts and slopes with either covariates or both covariates and outcome contain missing information. In the current paper, we compared the performance of seven different MI methods for handling missing values in longitudinal and clustered data in the context of fitting LMMs with both random intercepts and slopes. We study the theoretical compatibility between specific imputation models fitted under each of these approaches and the LMM, and also conduct simulation studies in both the longitudinal and clustered data settings. Simulations were motivated by analyses of the association between body mass index (BMI) and quality of life (QoL) in the Longitudinal Study of Australian Children (LSAC). Our findings showed that the relative performance of MI methods vary according to whether the incomplete covariate has fixed or random effects and whether there is missingnesss in the outcome variable. We showed that compatible imputation and analysis models resulted in consistent estimation of both regression parameters and variance components via simulation. We illustrate our findings with the analysis of LSAC data.