Do fiscal rules matter?

Fiscal rules are laws aimed at reducing the incentive to accumulate debt, and many countries adopt them to discipline local governments. Yet, their effectiveness is disputed because of commitment and enforcement problems. We study their impact applying a quasi-experimental design in Italy. In 1999, the central government imposed fiscal rules on municipal governments, and in 2001 relaxed them below 5,000 inhabitants. We exploit the before/after and discontinuous policy variation, and show that relaxing fiscal rules increases deficits and lowers taxes. The effect is larger if the mayor can be reelected, the number of parties is higher, and voters are older

Stomatitis and vR-TkI: a review of current literature in 4369 patients

the following review was performed to answer to the question \u201cWhat is the rate of incidence of oral stomatitis in patients treated with VegF tKis?\u201

Development of a nomogram for the prediction of periodontal tooth loss using the staging and grading system: A long- term cohort study

AimTo develop and internally validate a nomogram built on a multivariate prediction model including parameters from the new classification of periodontal diseases, able to predict, at baseline, the occurrence of tooth loss due to periodontal reason (TLP).Materials and MethodsA total of 315 individuals diagnosed with periodontal disease and receiving a minimum of one annual supportive periodontal therapy visit were included in the study. Patients were staged and graded based upon baseline data. The population was divided into a development (254 patients) and a validation (61 patients) cohort to allow subsequent temporal validation of the model. According to the TLP at the 10- year follow- up, patients were categorized as - low tooth loss- (- ¤ 1 TLP) or - high tooth loss- (- ¥ 2 TLP). Bootstrap internal validation was performed on the whole data set to calculate an optimism- corrected estimate of performance.ResultsThe generated nomogram showed a strong predictive capability (AUC = 0.81) and good calibration with an intercept = 0 and slope = 1. These findings were confirmed by internal validation using bootstrapping (average bootstrap AUC = 0.83).ConclusionsThe clinical implementation of the present nomogram guides the prediction of patients with high risk of disease progression and subsequent tooth loss for personalized care.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163380/2/jcpe13362.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163380/1/jcpe13362_am.pd

Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer

Background: Mutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC). However, it is not yet clear whether specific TP53 mutations bear distinct clinical and pathophysiological significance in different HNSCC subgroups. Methods: A systematic bioinformatics appraisal of TP53 mutations was performed on 415 HNSCC cases available on The Cancer Genome Atlas (TCGA). The following features were analysed and correlated with known clinicopathological variables: mutational profile of TP53, location (within secondary structure and predicted domains of p53 protein) and well-known hotspot mutations. Interactome–genome–transcriptome network analysis highlighted different gene networks. An algorithm was generated to develop a new prognostic classification system based on patients’ overall survival. Results: TP53 mutations in HNSCCs exhibited distinct differences in different anatomical sites. The mutational profile of TP53 was an independent prognostic factor in HNSCC. High risk of death mutations, identified by our novel classification algorithm, was an independent prognostic factor in TCGA HNSCC database. Finally, network analysis suggested that distinct p53 molecular pathways exist in a site- and mutation-specific manner. Conclusions: The mutational profile of TP53 may serve as an independent prognostic factor in HNSCC patients, and is associated with distinctive site-specific biological networks

Social, environmental and psychological factors associated with objective physical activity levels in the over 65s

Objective: To assess physical activity levels objectively using accelerometers in community dwelling over 65 s and to examine associations with health, social, environmental and psychological factors. Design: Cross sectional survey. Setting: 17 general practices in Scotland, United Kingdom. Participants: Random sampling of over 65 s registered with the practices in four strata young-old (65–80 years), old-old (over 80 years), more affluent and less affluent groups. Main Outcome Measures: Accelerometry counts of activity per day. Associations between activity and Theory of Planned Behaviour variables, the physical environment, health, wellbeing and demographic variables were examined with multiple regression analysis and multilevel modelling. Results: 547 older people (mean (SD) age 79(8) years, 54% female) were analysed representing 94% of those surveyed. Accelerometry counts were highest in the affluent younger group, followed by the deprived younger group, with lowest levels in the deprived over 80 s group. Multiple regression analysis showed that lower age, higher perceived behavioural control, the physical function subscale of SF-36, and having someone nearby to turn to were all independently associated with higher physical activity levels (R2 = 0.32). In addition, hours of sunshine were independently significantly associated with greater physical activity in a multilevel model. Conclusions: Other than age and hours of sunlight, the variables identified are modifiable, and provide a strong basis for the future development of novel multidimensional interventions aimed at increasing activity participation in later life.Publisher PDFPeer reviewe

Population genomic, olfactory, dietary, and gut microbiota analyses demonstrate the unique evolutionary trajectory of feral pigs

Domestication is an intriguing evolutionary process. Many domestic populations are subjected to strong human-mediated selection, and when some individuals return to the wild, they are again subjected to selective forces associated with new environments. Generally, these feral populations evolve into something different from their wild predecessors and their members typically possess a combination of both wild and human selected traits. Feralisation can manifest in different forms on a spectrum from a wild to a domestic phenotype. This depends on how the rewilded domesticated populations can readapt to natural environments based on how much potential and flexibility the ancestral genome retains after its domestication signature. Whether feralisation leads to the evolution of new traits that do not exist in the wild or to convergence with wild forms, however, remains unclear. To address this question, we performed population genomic, olfactory, dietary, and gut microbiota analyses on different populations of Sus scrofa (wild boar, hybrid, feral and several domestic pig breeds). Porcine single nucleotide polymorphisms (SNPs) analysis shows that the feral population represents a cluster distinctly separate from all others. Its members display signatures of past artificial selection, as demonstrated by values of FST in specific regions of the genome and bottleneck signature, such as the number and length of runs of homozygosity. Generalised FST values, reacquired olfactory abilities, diet, and gut microbiota variation show current responses to natural selection. Our results suggest that feral pigs are an independent evolutionary unit which can persist so long as levels of human intervention remain unchanged

Binding of an antimicrobial peptide to bacterial cells: interaction with different species, strains and cellular components

Antimicrobial peptides (AMPs) selectively kill bacteria by disrupting their cell membranes, and are promising compounds to fight drug-resistant microbes. Biophysical studies on model membranes have characterized AMP/membrane interactions and the mechanism of bilayer perturbation, showing that accumulation of cationic peptide molecules in the external leaflet leads to the formation of pores ("carpet" mechanism). However, similar quantitative studies on real cells are extremely limited. Here, we investigated the interaction of the dansylated PMAP23 peptide (DNS-PMAP23) with a Gram-positive bacterium, showing that 10(7) bound peptide molecules per cell are needed to kill it. This result is consistent with our previous finding for Gram-negative strains, where a similar high threshold for killing was determined, demonstrating the general relevance of the carpet model for real bacteria. However, in the case of the Gram-positive strain, this number of molecules even exceeds the total surface available on the bacterial membrane. The high affinity of DNS-PMAP23 for the anionic teichoic acids of the Gram-positive cell wall, but not for the lipopolysaccharides of Gram-negative bacteria, provides a rationale for this finding. To better define the role of anionic lipids in peptide/cell association, we studied DNS-PMAP23 interaction with E. coli mutant strains lacking phosphatidylglycerol and/or cardiolipin. Surprisingly, these strains showed a peptide affinity similar to that of the wild type. This finding was rationalized by observing that these bacteria have an increased content of other anionic lipids, thus maintaining the total membrane charge essentially constant. Finally, studies of DNS-PMAP23 association to dead bacteria showed an affinity an order of magnitude higher compared to that of live cells, suggesting strong peptide binding to intracellular components that become accessible after membrane perturbation. This effect could play a role in population resistance to AMP action, since dead bacteria could protect the surviving cells by sequestering significant amounts of peptide molecules. Overall, our data indicate that quantitative studies of peptide association to bacteria can lead to a better understanding of the mechanism of action of AMPs

Tibiotalocalcaneal arthrodesis in a rare case of tuberculosis of the talus

Aim To assess our personal experience of a case of tuberculosis of the talus, and to provide an overview of the literature about this tuberculosis manifestations, including all its aspects: epidemiology, clinical and imaging presentation, and all the treatments available to the current state of knowledge. Methods We present our experience in a case of a 34-year-old patient, who came to our attention with difficulty in walking and pain due to a talar tuberculosis, with consequent bone disruption and reabsorption, and foot deformities. Results A tibiotalocalcaneal arthrodesis with retrograde nail and bone graft was performed after antibiotic therapy. Today, almost two years after treatment, the patient can walk independently with no major limitations in everyday life. Conclusion Tibiotalocalcaneal arthrodesis with bone graft showed good functional results in this case study, with complete graft fusion and good functional and radiological outcomes

Cross-sectional associations between sleep duration, sedentary time, physical activity, and adiposity indicators among Canadian preschool-aged children using compositional analyses

Abstract Background Sleep duration, sedentary behaviour, and physical activity are three co-dependent behaviours that fall on the movement/non-movement intensity continuum. Compositional data analyses provide an appropriate method for analyzing the association between co-dependent movement behaviour data and health indicators. The objectives of this study were to examine: (1) the combined associations of the composition of time spent in sleep, sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) with adiposity indicators; and (2) the association of the time spent in sleep, sedentary behaviour, LPA, or MVPA with adiposity indicators relative to the time spent in the other behaviours in a representative sample of Canadian preschool-aged children. Methods Participants were 552 children aged 3 to 4 years from cycles 2 and 3 of the Canadian Health Measures Survey. Sedentary time, LPA, and MVPA were measured with Actical accelerometers (Philips Respironics, Bend, OR USA), and sleep duration was parental reported. Adiposity indicators included waist circumference (WC) and body mass index (BMI) z-scores based on World Health Organization growth standards. Compositional data analyses were used to examine the cross-sectional associations. Results The composition of movement behaviours was significantly associated with BMI z-scores (p = 0.006) but not with WC (p = 0.718). Further, the time spent in sleep (BMI z-score: γ sleep  = −0.72; p = 0.138; WC: γ sleep  = −1.95; p = 0.285), sedentary behaviour (BMI z-score: γ SB  = 0.19; p = 0.624; WC: γ SB  = 0.87; p = 0.614), LPA (BMI z-score: γ LPA  = 0.62; p = 0.213, WC: γ LPA  = 0.23; p = 0.902), or MVPA (BMI z-score: γ MVPA  = −0.09; p = 0.733, WC: γ MVPA  = 0.08; p = 0.288) relative to the other behaviours was not significantly associated with the adiposity indicators. Conclusions This study is the first to use compositional analyses when examining associations of co-dependent sleep duration, sedentary time, and physical activity behaviours with adiposity indicators in preschool-aged children. The overall composition of movement behaviours appears important for healthy BMI z-scores in preschool-aged children. Future research is needed to determine the optimal movement behaviour composition that should be promoted in this age group