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SHARED CARE PLANNING FOR ADULTS WHO ARE WHOLLY OR PARTIALLY LACKING IN AUTONOMY
Shared care planning poses several interpretative and implementation prob-lems when the patient lacks, in whole or in part, the capacity to make informed deci-sions about their health. This essay aims to investigate whether and under what con-ditions access to shared care planning is allowed for non-autonomous individuals. A superficial reading of the law might lead one to believe that only adult and legally com-petent persons can undertake care planning. On the contrary, the general structure and spirit of Law No. 219 leads to interpreting the rules on capacity in the sense that even patients who are wholly or partially lacking in autonomy can be protagonists in planning, with the support of those who have decision-making powers over their health.
La pianificazione condivisa delle cure pone diversi problemi interpretativi e attuativi quando il paziente è privo, in tutto o in parte, della capacità di prendere de-cisioni consapevoli sulla sua salute. Il saggio si propone di indagare se, e a quali condi-zioni, l’accesso alla pianificazione condivisa delle cure è ammesso a favore delle per-sone non autonome. Una lettura superficiale della legge potrebbe infatti portare a ri-tenere che solo le persone adulte e capace di agire possano intraprendere una pianifi-cazione delle cure. Al contrario, l’impianto generale e lo spirito della l. n. 219 porta ad interpretare le regole sulla capacità nel senso che anche i pazienti privi in tutto o in parte di autonomia possono essere protagonisti di una pianificazione, con il sostegno di coloro che hanno poteri di scelta sulla loro salute
What impact do master's degree programs have on career trajectories and professional development in nursing and midwifery? An explanatory mixed-methods study
Background: Master's programs in nursing and midwifery enhance professional skills and disciplinary content, though their impact on clinical application, career progression, and skill utilization remains underexplored. Purpose: This study investigates graduates' motivations, perceptions of program quality, and professional outcomes after a master's in nursing and midwifery sciences. Methods: Using an explanatory sequential mixed-methods design, we surveyed 110 graduates (50% response rate) from 2018 to 2023, followed by semistructured interviews with 17 participants. Discussion: Graduates reported high satisfaction with program quality, especially in research, management, and education, but noted limited clinical use of research and management skills. Career progression was achieved, though without corresponding professional recognition or financial reward. Six themes emerged from interviews, highlighting both program strengths and professional challenges. Conclusion: The program effectively builds advanced skills, yet structural barriers limit practical application. Aligning program objectives with workplace needs could enhance the impact of advanced nursing and midwifery degrees
Genetic and nongenetic variation of multiple births in Austrian dual-purpose cows
In recent decades, a general increase in multiple birth (MB) rate has been reported in both dairy and dual-purpose cattle breeds. As there is evidence that MB has negative effects on economically important traits in dairy cows, the aims of this study were to (i) investigate environmental and genetic factors affecting MB rate and (ii) assess the impact of MB on productive and nonproductive traits of the Austrian dual-purpose breeds Pinzgauer and Tyrol Grey. The dataset included 99,141 calvings of 33,791 Pinzgauer and 68,454 calvings of 19,244 Tyrol Grey cows recorded from 2000 to 2022. Environmental factors affecting MB were investigated using logistic regression, and genetic parameters of MB were estimated using linear and threshold animal models. In addition, the effects of MB on milk, fat, and protein yields and calving ease were analyzed using a linear mixed model, whereas stillbirth and cow survival (binary traits) were analyzed by logistic regression. The average MB rate from 2000 to 2022 was 5.80% for Pinzgauer and 3.89% for Tyrol Grey. The lowest MB rate was observed in primiparous cows in both breeds, and the highest in fourth-parity Pinzgauer and seventh-parity Tyrol Grey cows. The highest MB rate was in summer regardless of the breed. In Pinzgauer, the MB negatively affected dairy traits and survival, and in Tyrol Grey, it affected fat yield and calving ease. Stillbirth was notably higher when MB occurred than in single births in both breeds. In Pinzgauer, the estimated heritability was 0.029 (linear) and 0.138 (threshold), whereas in Tyrol Grey, it was 0.040 (linear) and 0.200 (threshold). Low additive genetic variation exists for this trait, but it is still exploitable in genetic programs aimed at curbing the MB rate
Characterization of Markarian 421 during its most violent year: Multiwavelength variability and correlations
Aims. Mrk 421 was in its most active state around early 2010, which led to the highest TeV gamma-ray flux ever recorded from any active galactic nuclei (AGN).We aim to characterize the multiwavelength behavior during this exceptional year for Mrk 421, and evaluate whether it is consistent with the picture derived with data from other less exceptional years. Methods. We investigated the period from November 5, 2009, (MJD 55140) until July 3, 2010, (MJD 55380) with extensive coverage from very-high-energy (VHE; E > 100 GeV) gamma rays to radio with MAGIC, VERITAS, Fermi-LAT, RXTE, Swift, GASP-WEBT, VLBA, and a variety of additional optical and radio telescopes. We characterized the variability by deriving fractional variabilities as well as power spectral densities (PSDs). In addition, we investigated images of the jet taken with VLBA and the correlation behavior among di_erent energy bands. Results. Mrk 421 was in widely di_erent states of activity throughout the campaign, ranging from a low-emission state to its highest VHE flux ever recorded. We find the strongest variability in X-rays and VHE gamma rays, and PSDs compatible with power-law functions with indices around 1.5. We observe strong correlations between X-rays and VHE gamma rays at zero time lag with varying characteristics depending on the exact energy band. We also report a marginally significant (_3_) positive correlation between high-energy (HE; E > 100 MeV) gamma rays and the ultraviolet band. We detected marginally significant (_3_) correlations between the HE and VHE gamma rays, and between HE gamma rays and the X-ray, that disappear when the large flare in February 2010 is excluded from the correlation study, hence indicating the exceptionality of this flaring event in comparison with the rest of the campaign. The 2010 violent activity of Mrk 421 also yielded the first ejection of features in the VLBA images of the jet of Mrk 421. Yet the large uncertainties in the ejection times of these unprecedented radio features prevent us from firmly associating them to the specific flares recorded during the 2010 campaign. We also show that the collected multi-instrument data are consistent with a scenario where the emission is dominated by two regions, a compact and extended zone, which could be considered as a simplified implementation of an energy-stratified jet as suggested by recent IXPE observations
Metasomatismo del mantello dell'avambraccio mediato dai fluidi: approfondimenti dalla modellazione termomeccanica petrologica
Mantle metasomatism and associated fluid-aided mass transfer have wide-ranging implications for geochemical, rheological and dynamical aspects of the shallow Earth interior. However, large uncertainties remain due to the inaccessibility of metasomatic processes over geologic timescales, scarcity of samples and the fragmentary nature of outcrops. Despite chemically open-system behavior has been evidenced from geochemical and petrological records, most geodynamical modelling approaches rely on a chemically closed-system. Taking advantage of improved numerical techniques, and thermodynamic theories, we developed a new petrological–thermo–mechanical code to overcome such a closed-system limitation. This code use thermodyamically predicted rock solubility to monitor the mass exchange between rocks and coexisting fluids, and thermomechanically determined fluid and solid flow to simulate advection and potential dynamic feedbacks. Comparison with previously published numerical results justifies the robustness of this new method in spite of the differences in the employed solid solution models, thermodynamic database and coarser resolution (0.50.5km), which cause minor compositional differences mainly due to smoothing effects along lithological boundaries. We utilize this new code to explore the first-order redistribution patterns of rock-forming elements and newly formed metasomatic minerals as a function of convergence rates, slab ages and subducted sediment compositions. Youngest and slowest subduction zones with an abundant water supply from the slab experience the most notable element mobility. The progressive thermal cooling of subduction zones enhances the extent of mantle alteration. Lithological boundaries with steep compositional gradients are often affected by intensive fluid-mediated alterations and formation of metasomatinites as slab-derived elements are mostly absorbed along such boundaries. The multicomponent fluid compositions emanated from slabs evolve with slab depth, and associated alteration zones are characterized by a decrease in the phase proportions of antigorite, chlorite, and an increase of that of talc with depth near the slab-mantle interface. C- and Si-bearing fluids infiltration facilitates the formation of talc-rich metasomatinites at cold slab top conditions, whereas substantial carbon-poor fluids infiltration decomposes talc as slap top temperatures approach the solidus. Talc together with antigorite and chlorite likely play a significant role in element circulation as well as in controlling the bulk mechanical properties and seismicity along the plate interface at subduction zones. Overall, the obtained results are consistent with geophysical observations, petrological records, petrological experiments and reaction path model results. This work provides a promising tool for exploring the complex interplay among geodynamics of subduction zones, geochemical recycling occurring within the shallow planetary interior, and magmatic processes
Plant Behavior: Theoretical and Technological Advances
The widespread disregard for plant behavior is gradually being overcome through more inclusive theoretical approaches and the development of appropriate and advanced technologies.
In this paper we review scientific evidence on recent contributions to the study of plants, such as movement and communication as well as potential forms of attention. Some of the most recent contributions to the study of plant abilities come from comparative studies on biocommunication and research on the accuracy of plants in responding to different environmental stimuli through electrophysiological and kinematical analyses in different context (e.g., individual and social). Further, an underexplored area that warrants further investigation is plants’ multisensory perception and its potential link to multimodal communication capabilities.
Research into this set of abilities could help to clarify the degree of behavioral flexibility in sessile organisms without a nervous system and enhance discussions on interactive behavior as expressed in nature. This, in turn, will help to bridge the gap between studies on animal organisms and the rest of the living world
Wear behaviour of additively manufactured Nitinol cryogenically machined at different cutting speeds
Nitinol is a distinctive nickel-titanium alloy renowned for its superelasticity, shape memory properties, and biocompatibility, making it highly suitable for applications in the biomedical and aerospace sectors. The performance and service life of Nitinol components are strongly influenced by the process chain and the associated manufacturing parameters. However, existing studies often focus on the effects of individual steps in the process chain, overlooking the combined impact of multiple steps on the material's properties. In this context, the study explores the combined effects of additive manufacturing, heat treatment, and cryogenic machining on the wear performance of a Ni-rich Nitinol alloy. The material was systematically assessed in its as-built and heat-treated conditions for microstructure, transformation temperatures, nano-hardness, superelasticity, and surface roughness. Key findings show that heat treatment following additive manufacturing significantly enhanced the superelasticity and mechanical strength of the alloy, underlining the importance of heat treatment after additive manufacturing of Ni-rich Nitinol. On the contrary, the cryogenic machining step reduced the material superelasticity, with the influence of the cutting speed to be taken into account. Wear tests further demonstrate the superelasticity effect in assessing Nitinol's wear resistance, with surface roughness also playing a significant role. The study underscores the potential of heat-treated NiTi in applications requiring high mechanical strength, wear resistance, and superelasticity, such as biomedical devices and aerospace components
Progranulin measurement with a new automated method: a step forward in the diagnostic approach to neurodegenerative disorders
Mutations in the GRN gene encoded glycoprotein progranulin (PGRN), cause 5-10 % of all cases of frontotemporal lobar degeneration (FTLD). The aim of our study was to verify the analytical and clinical performance of an automated chemiluminescent immunoassay method for PGRN measurement recently developed (Chorus Evo, Diesse Diagnostica, Italy). Five plasma pools and residual plasma samples (K2EDTA) from 25 control subjects (11 males, 62-79 years; 14 females, 54-76 years) and 151 patients (70 males, 53-81 years; 81 females, 44-82 years) with different neurodegenerative disorders (NDs), were assayed. In 61 out of 151 patients, genetic GRN screening was carried. Within-run imprecision (CV%) ranged from 3.8 % (11.5 pg/L) to 10.8 % (2.5 pg/L), and between-run, from 5.6 % (68.7 pg/L) to 10.7 % (2.8 pg/L). At genetic screening, 3 out of 61 patients were classified as GRN+ carriers, 18 as "other mutations"and 40 as "no-mutations"carriers. The PGRN median level in GRN+ carriers (15.9 pg/L) was significantly lower than that in control subjects (32.8 pg/L; p=0.006), in GRN- (27.50 pg/L; p=0.007), in other mutation carriers (24.80 pg/L; p=0.05) and in NDs patients (22.40 pg/L; p=0.05) ROC analysis, demonstrates the accuracy of progranulin levels in discriminating between "GRN+"and "GRN-"carriers (AUC 0.985) as well as "GRN+"and "other mutations"carriers (AUC 0.870). The new automated progranulin method, for robust analytical performance, is suitable for use in the clinical setting, supporting clinicians in making a differential diagnosis in patients with neurodegenerative disorder
Aspirin-triggered DHA metabolites inhibit angiogenesis
Background and aim: Blood vessels supply oxygen, nutrients and provide gateways for immune surveillance. Since this network nourishes all tissues, vessel abnormalities contribute to many diseases, such as cancer. One of the potential targets for Docosahexaenoic Acid (DHA) in cancer is suppressing angiogenesis, a process of new blood vessel formation within tumors. In addition, aspirin (ASA) has antineoplastic effects that may be mediated, at least in part, by metabolites derived from acetylated COX-2. We aimed at determining the effect of DHA as well as its metabolites in angiogenesis, using in vitro as well as in vivo models.
Methods: Endothelial cell (EC) proliferation, motility and capillary-like tube formation were determined by MTT, wound healing, Boyden and Matrigel assays, respectively. In vivo angiogenesis was measured by the Matrigel sponge model in mice. The biosynthesis of proresolving lipid mediators by ECs was determined by LC-MS-MS.
Results and conclusion: DHA, but not arachidonic acid (AA), at concentrations consistent with those reached in blood after fish oil supplementation, decreased EC migration in a time- and concentration-dependent manner. Pretreatment with ASA modulated cell migration already after 24 h, while both DHA and ASA decreased migration at longer incubation times without affecting viability. 17-hydroxy-DHA was detected upon incubation with DHA, and increased amounts were observed upon combined treatment with DHA and ASA, an increase that was associated to a synergic effect on EC migration. 17(R)-hydroxy-DHA (17R-HDHA), the metabolite resulting from acetylated COX-2 activity of DHA, reduced EC migration in a concentration-dependent manner. DHA in the presence of ASA, as well as 17R-HDHA, also reduced EC tube formation. These results were confirmed in vivo where both 17R-HDHA or its downstream metabolite 17RResolvinD1 were able to decrease microvessels density in a Matrigel sponge model. Overall, we demonstrated that DHA in the presence of ASA-dependent acetylation of COX-2 showed increased antiangiogenic effects, possibly resulting from its conversion to its hydroxylated derivatives
Towards a mechanistic understanding of Von Hippel-Lindau syndrome in different tissues. Computational simulation and analysis of enzymatic systems to characterize the anti-cancer effect of α-ketoglutarate mimetic molecules
Von Hippel-Lindau (VHL) syndrome is a hereditary cancer disorder characterized by the development of benign and malignant tumors, caused by mutations in the VHL gene. This gene encodes for the tumor suppressor protein pVHL, which is crucial in regulating oxygen sensing. Under normal conditions, prolyl hydroxylase domain (PHD) enzymes hydroxylate hypoxia-inducible factors (HIFs-α), allowing pVHL to bind HIFs-α, driving their degradation. Hypoxia inhibits PHD activity, leading to HIFs-α stabilization and cell adaptation to hypoxia. As a hallmark of cancer, hypoxia promotes neo-angiogenesis and cell proliferation. In VHL syndrome, the loss of pVHL function results in abnormal HIF-α activation, driving tumor growth. PHD isoforms (PHD1,2,3) hydroxylate HIF-α subunits (HIF-1,2,3α) with different affinities and effects on tumor progression. However, the mechanisms determining these differences poorly understood. In this thesis, molecular dynamics (MD) simulations were employed to the molecular details governing PHDs/HIFs-α interactions focusing on PHD2 and PHD3, in complexes with HIF-1α and HIF-2α. Conservation analysis and binding free energy calculations were also performed to better understand PHDs substrate affinity. The results showed distinct affinities of PHD2 and PHD3 for HIFs-α substrates, with the PHD2 C-terminus playing a critical role in substrate binding and stabilization. MD simulations revealed that the PHD2 C-terminus exists in an equilibrium between folded and unfolded states. In its unfolded state, PHD2 enhances interactions with HIF-1α, while the folded state binds more strongly to HIF-2α. These findings challenge earlier assumptions that PHD2 preferentially binds HIF-1α, showing that under certain conditions, it binds more strongly to HIF-2α. Phosphorylation of the PHD2 residue Thr405, located in the C-terminus, influences binding energy without having a significant structural impact on PHD2/HIFs-α complexes. For PHD3, the study revealed that interactions with HIF-1α are primarily stabilized by the β2β3-loop, while its C-terminal region primarily binds HIF-2α. Despite this, binding free energy calculations suggest that PHD3 has a stronger affinity for HIF-1α, contrasting with reports that emphasize its role in regulating HIF-2α in hypoxic conditions. The study also identified cancer-associated mutations at specific interaction sites in the PHD2/HIFs-α and PHD3/HIFs-α complexes, with potential implications for drug development. Targeting specific residues could selectively modulate PHDs substrate specificity in tumors without affecting overall enzyme function. In addition, the effects of several PHDs inhibitors were examined, including N-oxalylglycine (NOG), dimethyloxalylglycine (DMOG), fumarate (FUM), Molidustat, and Vadadustat. NOG and Vadadustat were the most effective at stabilizing HIF-1α and HIF-2α complexes, while DMOG and Molidustat showed instability, even exiting the binding pocket during simulations. Overall, these findings advance our understanding of VHL syndrome’s molecular mechanisms and highlights the C-terminal region as a potential regulator of PHDs activity and suggest avenues for developing targeted therapies to modulate PHDs function in cancer and hypoxia-related diseases