Modelling the US Federal Spending Process: Overview and Implications

The object of study is the US Federal budget process - an institutional process of increasing prominence in US and world affairs - which is unique in generating quantitative data for scholarly research. The authors first outline their rigorous, but simple, econometric models of how budget decisions are made, coordinated, and implemented and then trace the implications of their high-inertia view of the process for the US economic cycle. They propound a presidential and Congressional ambition model of current and postwar cyclical economic difficulties, including stagflation, in terms of a macroeconomic model of the US economy in which federal governmental expenditure is endogenous. The chapter concludes with speculation on the disastrous consequences for society of the growth of a sluggishly adaptable bureaucratic process operating in a rapidly changing economic and social environment

KDM5A mutations identified in autism spectrum disorder using forward genetics.

Autism spectrum disorder (ASD) is a constellation of neurodevelopmental disorders with high phenotypic and genetic heterogeneity, complicating the discovery of causative genes. Through a forward genetics approach selecting for defective vocalization in mice, we identified Kdm5a as a candidate ASD gene. To validate our discovery, we generated a Kdm5a knockout mouse model (Kdm5a-/-) and confirmed that inactivating Kdm5a disrupts vocalization. In addition, Kdm5a-/- mice displayed repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis. Loss of KDM5A also resulted in dysregulation of the hippocampal transcriptome. To determine if KDM5A mutations cause ASD in humans, we screened whole exome sequencing and microarray data from a clinical cohort. We identified pathogenic KDM5A variants in nine patients with ASD and lack of speech. Our findings illustrate the power and efficacy of forward genetics in identifying ASD genes and highlight the importance of KDM5A in normal brain development and function

The myth and therapeutic potentials of postbiotics

Postbiotics (bioactives) are nonviable metabolites produced by probiotics that exert biological effects on the hosts. The myriad beneficial effects of postbiotics produced by six novel bacteriocinogenic Lactobacillus plantarum strains have been proven extensively since 2004, with the broad bacteriocin inhibitory activity against various pathogens, as they harbor two classes of bacteriocin structural genes (plnEF and pln W). The supplementation of the postbiotics to various animal models has significantly improved serum cholesterol, immune response, overall health, and growth, while suppressing the population of pathogenic bacteria in the digestive tract. Additionally, the postbiotics of these lactobacilli strains demonstrated novel antiproliferation and anticancer activity against various human cancer cell lines by inducing cytotoxicity via apoptotic pathway

Parameters for the mathematical modelling of Clostridium difficile acquisition and transmission: a systematic review

INTRODUCTION: Mathematical modelling of Clostridium difficile infection dynamics could contribute to the optimisation of strategies for its prevention and control. The objective of this systematic review was to summarise the available literature specifically identifying the quantitative parameters required for a compartmental mathematical model of Clostridium difficile transmission. METHODS: Six electronic healthcare databases were searched and all screening, data extraction and study quality assessments were undertaken in duplicate. Results were synthesised using a narrative approach. RESULTS: Fifty-four studies met the inclusion criteria. Reproduction numbers for hospital based epidemics were described in two studies with a range from 0.55 to 7. Two studies provided consistent data on incubation periods. For 62% of cases, symptoms occurred in less than 4 weeks (3-28 days) after infection. Evidence on contact patterns was identified in four studies but with limited data reported for populating a mathematical model. Two studies, including one without clinically apparent donor-recipient pairs, provided information on serial intervals for household or ward contacts, showing transmission intervals of <1 week in ward based contacts compared to up to 2 months for household contacts. Eight studies reported recovery rates of between 75%-100% for patients who had been treated with either metronidazole or vancomycin. Forty-nine studies gave recurrence rates of between 3% and 49% but were limited by varying definitions of recurrence. No study was found which specifically reported force of infection or net reproduction numbers. CONCLUSIONS: There is currently scant literature overtly citing estimates of the parameters required to inform the quantitative modelling of Clostridium difficile transmission. Further high quality studies to investigate transmission parameters are required, including through review of published epidemiological studies where these quantitative estimates may not have been explicitly estimated, but that nonetheless contain the relevant data to allow their calculation

Rethinking the theory and practice of land-use regulation: towards nomocracy

It is often held that planning theory has little influence on planning practice. Some speak of an evident ‘theory-practice gap’. In reality, the opposite seems to be the case. The so-called ‘theorypractice gap’ is not the main issue at all; the real question is ‘which theory for what kind of practice’? Assuming this view, the article presents two different theories of public regulation: the teleocratic approach and the nomocratic approach.They can be interpreted as general approaches regarding the role of the state, but the article focus particularly on the consequences of accepting them in the specific field of land-use regulation. For the teleocratic approach, planning must be the central and most important instrument of land-use regulation, while for the nomocratic approach planning has only a secondary role and different kind of regulative instruments are proposed