Information transmission and the bounds to growth

This paper studies the long run growth implications of the presence of information acquisition and transmission costs. We assume that vertical innovation requires researchers to be informed on the current version of the product they want to improve upon; and we also assume that quasi-fixed managerial inputs are required for production in the manufacturing sector. Despite the fact the increases in total factor productivity cause R&D and managerial quasi-fixed labor costs to decrease in the same way as variable labor costs, the presence of these costs is sufficient to rule out the strong scale effect at all levels of the intertemporal returns to ideas. More importantly, the upper bound of long run growth rates crucially depends on information transmission costs

AN EXPLORATIVE ASSESSMENT OF POTENTIAL NOVEL DIAGNOSTIC AND PROGNOSTIC BIOMARKERS FOR IDENTIFICATION OF PRODROMAL PARKINSON¿S DISEASE

ABSTRACT Background - Parkinson\u2019s disease (PD) is the second most common neurodegenerative disorder after Alzheimer, primarily affecting about 6 million people worldwide. An early identification of PD is one of the main challenges in neurological research because to date, its diagnosis is still largely based on the clinical assessment of cardinal motor signs (bradykinesia, rigidity, resting tremor and postural instability) resulting by a progressive degeneration of dopaminergic neurons of the substantia nigra and locus coeruleus. However, impaired motor function appears when over 60% of the dopaminergic neurons are degenerated in the brain. In recent years, several evidence indicates that the onset of PD happens years to decades before the occurrence of classic motor symptoms. Pathological and imaging studies, for example, suggest that signs of nigrostriatal lesion can be detected 5\u201310 years before this clinical stage, and various observational prospective studies reveal that several non-motor symptoms (NMS) occur in this pre-diagnostic phase. Actually NMS such as olfactory impairment, cardiovascular dysautonomia such as orthostatic hypotension (OH) and rapid eye movement (REM) behaviour disorder (RBD) are currently being studied as features of prodromal PD and seem to be correlated to the early neuropathological process of disease. Beside these clinical manifestations, other biological alterations such as elevated oxidative stress and pro-inflammatory response have been involved in the cascade of events leading to degeneration of dopaminergic neurons. Recently, microRNAs (miRNAs) have been recognized as potent post-transcriptional regulators of PD-related gene expression. Consequently, the characterization of several NMS together with the assessment of molecular biomarkers linked to inflammation and oxidative damage, could be a potential methodological approach for the early identification of PD patients. Objectives - The main objective of my study was to explore potential novel diagnostic and prognostic biomarkers of PD. Specific study aims were, in patients with prodromal and established PD: a) to evaluate clinical markers such as olfactory and cardiovascular autonomic functions; b) to measure circulating mediators of oxidative stress and inflammatory response as early biomarkers of organ failure; c) to correlate biological findings with clinical functional alterations; d) to characterize specific circulating miRNA profiles in plasma samples. Methods - For this purpose, we recruited 15 patients with overt PD (Hoehn and Yahr stage I-III, on L-DOPA and dopamine agonists combination therapy), 11 subjects diagnosed with idiopathic RBD (iRBD) confirmed by lack of atonia during the REM sleep phase on polysomnography and 12 age- and gender-matched controls (CTRL). All enrolled subjects underwent the following assessments: total olfactory score (TOS) using Sniffin' Sticks Extended Test; autonomic function by measuring heart rate variability during deep breathing (DB) test, which expresses parasympathetic function, lying to standing (LS) test and the Valsalva manoeuvre (VM), that gives information about both sympathetic and parasympathetic function; antioxidant/oxidative stress mediators [glutathione (GSH), the most important endogenous scavenger, assessed in total and reduced form and in plasma and blood samples according to a high performance liquid chromatographic (HPLC) method; plasma malondialdehyde (MDA), a marker of lipid peroxidation, assayed by HPLC with fluorescence detection; 8-hydroxy-2-deoxyguanosine (8-OHdG), index of oxidative DNA damage, and 3-nitrotyrosine (3-NT), a stable end product of peroxynitrite oxidation, analyzed by commercial ELISA kits]; inflammatory response [plasma concentrations of tumor necrosis factor alpha (TNF\uf061) and interleukin 1-beta (IL1\uf062), the most important inflammatory cytokines, by ELISA commercial kits, while urine neopterin levels, a sensitive marker of cellular-mediated inflammation, were measured by an isocratic HPLC method]. Biochemical parameters were than correlated with clinical functional results. The miRNA profiling was performed in a subpopulation of the enrolled subjects (4 PD, 4 iRBD and 4 CTRL) by small RNA Sequencing, using Miseq sequencer (Illumina). The differentially expressed (DE) miRNAs analysis, based on the negative binomial distribution, was performed with DE Seq2 by performing three comparisons:1) iRBD versus CTRL; 2) PD versus iRBD; 3) PD versus CTRL. Subsequently, the relative expressions of specific miRNAs were validated in all study population by quantitative real-time (qRT) PCR using miScript PCR System kit (Qiagen). Results - A significant worsening trend was observed in total olfactory score, blood reduced GSH, LS and VM ratio and neopterin from the reference controls to iRBD and PD groups. In the multivariable ordinal logistic regression model, only low blood reduced GSH levels (p=0.037, OR=0.994; 95% CI 0.988 \u2013 1.000), adjusted by history of hypertension, total olfactory score, LS ratio and VM ratio, were associated to PD status. Functional anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but was absent in CTRL (p= 0.097). OH was more common among iRBD (73%) and PD (60%) than in controls (25%) (p=0.055), independently of antihypertensive treatment. A direct correlation was observed between total olfactory score and blood reduced GSH concentrations (R=0.034, p=0.037) and with VM ratio (R=0.43 p=0.015). Conversely, an inverse relation was found between total olfactory score and urine neopterin levels (R=-0.39 p=0.016). The results on circulating miRNA profiles found about 889 thousand sequenced reads mapped to mature miRNA sequences annotated in miRBase v21, by small RNA sequencing analysis. After data processing, no statistically significant DE miRNA was observed in the PD versus CTRL, whereas we found 33 DE miRNAs (18 downregulated, 15 upregulated, p-value <0.005) in the comparison between PD and iRBD and 6 (3 downregulated, 3 upregulated, p-value <0.005) in iRBD versus CTRL. Four common DE miRNAs (miR-101, miR-1260a, miR-142, miR15a) were dysregulated between the two different comparisons. In the PD patients, three miRNAs (miR-101, mir-142 and miR15a) were downregulated (Fold Change 0.5) with respect to iRBD. Conversely, miR-101, miR-142 and miR15a were upregulated and miR-1260a downregulated in iRBD compared to CTRL. The NGS results have not been validated by RT-PCR analysis till now because these miRNAs are poorly expressed in plasma. This condition makes very difficult, from a methodological point of view, their extraction. Discussion - The main findings of the present study are that reduced systemic antioxidant capacity is independently associated to overt PD and iRBD, a condition now established as prodromal PD, and correlates with olfactory and sympathetic dysfunction. Moreover, progressive cardiovascular autonomic dysfunction, expressed as altered sympathetic (VM ratio, OH) or parasympathetic (LS ratio) response to testing, is found from prodromal state to overt disease and correlates with olfactory dysfunction. Increased concentrations of neopterin, an inflammatory biomarker, are associated with worse olfactory dysfunction. The NGS analysis highlights a miRNA profiling in PD and iRBD subjects that needs to be verify, by changing and modifying the methodological approach for miRNA quantification. Conclusions - Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular autonomic dysfunction, a useful additive biomarker of disease. Our pilot findings need to be confirmed in a larger population to establish their actual clinical value for an early diagnosis of PD

Effectiveness of a commercial lure to attract red fox

In camera trap studies, attractants may be used to increase detection probabilities of wildlife, which may help to improve estimates of abundance and occupancy. Using a semi-experimental approach, we investigated if a commercial, strawberry scented lure increased detection probability and visiting time duration in red fox Vulpes vulpes, and the potential reasons for variation in these parameters. In September 2020, within the Stelvio National Park, central Italian Alps, 32 camera sites were randomly assigned to 4 different treatments: 8 to commercial lure, the target of our investigation; 8 to orange aroma, to test for the "curiosity" effect; 8 to cat kibble, to test for the "likability" effect; 8 to camera trap only, the control test. Detection probability and duration of visiting time were estimated using hurdle negative binomial regression models. Daily detection probability was significantly higher with lure (0.078), orange aroma (0.086), kibble (0.075) than with camera trap only (0.031); in the first day after treatment, the time an animal spent in front of the cameras significantly increased with orange aroma (16.61 s) and kibble (33.78 s) compared to lure (9.97 s) and camera trap only (0.38 s). Our results support the use of lures to improve detection probability and visit duration in red fox, but we could not disentangle the drivers of increased parameter estimates. When consumable costs are considered, the use of the commercial strawberry scented lure does not appear justified for both detection probability and visit duration, and cheaper alternatives may be preferable

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Behavior of Aeromonas hydrophila in Bottled Mineral Waters

The growth and survival of Aeromonas hydrophila in three types of natural mineral waters were investigated. Mineral waters with different levels of mineral content (low, medium, and high) were experimentally contaminated with A. hydrophila, stored at different temperatures (10 degrees C and 20 degrees C), and analyzed at intervals over a 60-day period. Water samples that were not experimentally contaminated were investigated for indigenous A. hydrophila. The results confirmed that A. hydrophila may occur naturally in mineral waters and showed that the level of mineral content, temperature, length of storage, and, in some cases, the type of container used may favor the growth of A. hydrophila. The greatest proliferation was observed in water with a low mineral content stored in PET bottles at 10 degrees C, in which A. hydrophila peaked at day 28 (4.47 +/- 0.01 log CFU/100 ml). At 20 degrees C, the same load was observed at day 60. The presence of high densities of A. hydrophila in bottled mineral water can constitute a risk for some groups of consumers, such as elderly and immunocompromised persons

Posttransplant lymphoproliferative disorders in neuronal xenotransplanted macaques

Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations that occur in the setting of depressed T-cell function due to immunosuppressive therapy used following solid organ transplantation, hematopoietic stem cell transplantation, and also xenotransplantation. In the present study, 28 immunosuppressed parkinsonian Macaca fascicularis were intracerebrally injected with wild-type or CTLA4-Ig transgenic porcine xenografts to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Nine of 28 (32%) immunosuppressed primates developed masses compatible with PTLD, located mainly in the gastrointestinal tract and/or nasal cavity. The masses were classified as monomorphic PTLD according to the World Health Organization classification. Immunohistochemistry and polymerase chain reaction (PCR) analyses revealed that the PTLDs were associated with macaca lymphocryptovirus as confirmed by double-labeling immunohistochemistry for CD20 and Epstein-Barr nuclear antigen 2 (EBNA-2), where the viral protein was located within the CD20+ neoplastic B cells. In sera from 3 distinct phases of the experimental life of the primates, testing by quantitative PCR revealed a progression of the viral load that paralleled the PTLD progression and no evidence of zoonotic transmission of porcine lymphotropic herpesvirus through xenoneuronal grafts. These data suggest that monitoring the variation of macaca lymphocryptovirus DNA in primates could be used as a possible early diagnostic tool for PTLD progression, allowing preemptive treatment such as immunosuppression therapy reduction

Age-related changes in the primary motor cortex of newborn to adult domestic pig sus scrofa domesticus

The pig has been increasingly used as a suitable animal model in translational neuroscience. However, several features of the fast-growing, immediately motor-competent cerebral cortex of this species have been adequately described. This study analyzes the cytoarchitecture of the primary motor cortex (M1) of newborn, young and adult pigs (Sus scrofa domesticus). Moreover, we investigated the distribution of the neural cells expressing the calcium-binding proteins (CaBPs) (calretinin, CR; parvalbumin, PV) throughout M1. The primary motor cortex of newborn piglets was characterized by a dense neuronal arrangement that made the discrimination of the cell layers difficult, except for layer one. The absence of a clearly recognizable layer four, typical of the agranular cortex, was noted in young and adult pigs. The morphometric and immunohistochemical analy-ses revealed age-associated changes characterized by (1) thickness increase and neuronal density (number of cells/mm2 of M1) reduction during the first year of life; (2) morphological changes of CR-immunoreactive neurons in the first months of life; (3) higher density of CR-and PV-immunopositive neurons in newborns when compared to young and adult pigs. Since most of the present findings match with those of the human M1, this study strengthens the growing evidence that the brain of the pig can be used as a potentially valuable translational animal model during growth and development

Deviation of behavioural and productive parameters in dairy cows due to a lameness event: a synthesis of reviews

Lameness is a widespread multifactorial condition affecting the health and performance of dairy cows. Despite the growing support by precision farming technologies, farmers still lack reliable data-driven tools to early identify lame cows. This study used a synthesis of reviews to identify cow’s behavioural and productive parameters most related to lameness and estimate their deviation due to a lameness event. The methodological approach used reviews as starting point to identify the most pertinent studies with the intention of extracting and analysing data from these primary studies. The final dataset used information collected from 31 research papers, cited in 15 reviews, and involved more than 25,000 dairy cows. Five parameters were suitable for the meta-analysis: one about eating behaviour (eating time), three regarding activity and resting behaviour (lying bouts, lying bout duration and lying time) and milk yield. The meta-analysis revealed that all parameters had a significant deviation in cows affected by lameness. The calculation of the pooled means allowed to quantify a mean value for the deviation imposed by a severe lameness event from the value recorded on nonlame cows. Compared to a nonlame animal, a lame cow had a significant negative deviation for eating time (−39 min/day), number of lying bouts (−0.5/day), and milk yield (−3 kg/day). Lame cows had positive deviations for lying bout duration (+12 min/bout) and daily lying time (+42 min/day). The individual or combined use of these mean deviation values as alarm reference thresholds could improve the accuracy of the current automated lameness detection systems