Constitutional Law - Article I, Section 9 - Privilege against Self-Incrimination - Right to Refuse a Field Sobriety Test

The Pennsylvania Supreme Court held that the privilege against self-incrimination grounded in Article I, Section 9 of the Pennsylvania Constitution does not encompass a right to refuse a field sobriety test. Commonwealth v. Hayes, 674 A.2d 677 (Pa. 1996

Predatory Organisms with Untapped Biosynthetic Potential:Descriptions of Novel Corallococcus Species C. aberystwythensis sp. nov., C. carmarthensis sp. nov., C. exercitus sp. nov., C. interemptor sp. nov., C. llansteffanensis sp. nov., C. praedator sp. nov., C. sicarius sp. nov., and C. terminator sp. nov

Corallococcus spp. are common soil-dwelling organisms which kill and consume prey microbes through the secretion of antimicrobial substances. Two species of Corallococcus have been described previously (Corallococcus coralloides and Corallococcus exiguus). A polyphasic approach was taken to characterise antimicrobial, biochemical and phenotypic properties of eight Corallococcus spp. strains and the two type strains. We also report here the genome sequence of the C. exiguus type strain (DSM 14696T). The genomes of the eight candidate strains, C. exiguus DSM 14696T and C. coralloides DSM 2259T, had an average nucleotide identity below 95% and digital DNA-DNA hybridisation scores less than the 70% lower bound for species identity, indicating they belong to distinct species. All ten strains, including the two type strains, were thoroughly characterised, including biochemical analysis of their fatty acid methyl esters, substrate utilisation and sugar assimilation. Each strain gave a distinct profile of properties, which together with their genomic differences supports the proposal of the eight candidate strains as novel species: Corallococcus exercitus sp. nov. (AB043AT = DSM 108849T = NBRC 113887T), Corallococcus interemptor sp. nov. (AB047AT = DSM 108843T = NBRC 113888T), Corallococcus aberystwythensis sp. nov. (AB050AT = DSM 108846T = NBRC 114019T), Corallococcus praedator sp. nov. (CA031BT = DSM 108841T = NBRC 113889T), Corallococcus sicarius sp. nov. (CA040BT = DSM 108850T = NBRC 113890T), Corallococcus carmarthenensis sp. nov. (CA043DT = DSM 108842T = NBRC 113891T), Corallococcus llansteffanensis sp. nov. (CA051BT = DSM 108844T = NBRC 114100T) and Corallococcus terminator sp. nov. (CA054AT = DSM 108848T = NBRC 113892T)

Changes in the total fecal bacterial population in individual horses maintained on a restricted diet over 6 weeks

Twelve mature (aged 5–16 years) horses and ponies of mixed breed and type were fed restricted (1.25% BM Dry matter) quantities of one of two fiber based diets formulated to be iso-caloric. Diet 1 comprised of 0.8% body mass (BM) of chaff based complete feed plus 0.45% BM low energy grass hay (the same hay used for both diets). Diet 2 comprised 0.1% BM of a nutrient balancer plus 1.15% BM grass hay. Fecal samples were collected at week 10 and week 16. DNA was extracted and the V1-V2 regions of 16SrDNA were 454-pyrosequenced to investigate the bacterial microbiome of the horse. The two most abundant phyla found in both diets and sampling periods were the Firmicutes and Bacteroidetes. There was a clear reduction in Bacteroidetes with a concordant increase in Firmicutes over time. There was a limited degree of stability within the bacterial community of the hindgut of horses, with 65% of bacteria retained, over a 6 week period whilst on a uniform diet. The presence of a core community defined by being present in all samples (each animal/diet combination) included in the study and being present at 0.1% relative abundance (or greater) was identified. In total 65 operational taxonomic units (OTUs) were identified that fit the definition of core making up 21–28% of the total sequences recovered. As with total population the most abundant phyla were the Bacteroidetes followed by the Firmicutes, however there was no obvious shift in phyla due to period. Indeed, when the relative abundance of OTUs was examined across diets and periods there was no significant effect of diet or period alone or in combination on the relative abundance of the core OTUs

Tutorial on model selection and validation of model input into precision dosing software for model-informed precision dosing

There has been rising interest in using model-informed precision dosing to provide personalized medicine to patients at the bedside. This methodology utilizes population pharmacokinetic models, measured drug concentrations from individual patients, pharmacodynamic biomarkers, and Bayesian estimation to estimate pharmacokinetic parameters and predict concentration-time profiles in individual patients. Using these individualized parameter estimates and simulated drug exposure, dosing recommendations can be generated to maximize target attainment to improve beneficial effect and minimize toxicity. However, the accuracy of the output from this evaluation is highly dependent on the population pharmacokinetic model selected. This tutorial provides a comprehensive approach to evaluating, selecting, and validating a model for input and implementation into a model-informed precision dosing program. A step-by-step outline to validate successful implementation into a precision dosing tool is described using the clinical software platforms Edsim++ and MwPharm++ as examples.</p

Release from sheep-grazing appears to put some heart back into upland vegetation:A comparison of nutritional properties of plant species in long-term grazing experiments

Rewilding or wilding is a popularised means for enhancing the conservation value of marginal land. In the British uplands, it will involve a reduction, or complete removal, of livestock grazing (sheep), based on the belief that grazing has reduced plant species diversity, the ‘Wet Desert’ hypothesis. The hope is that if livestock is removed, diversity will recover. If true, we hypothesise that the species extirpated/reduced by grazing and then recover on its removal would more nutritious compared to those that persisted. We test this hypothesis at Moor House National Nature Reserve (North‐Pennines), where seven sets of paired plots were established between 1953 and 1967 to compare ungrazed/sheep‐grazed vegetation. Within these plot‐pairs, we compared leaf properties of seven focal species that occurred only, or were present in much greater abundance, in the absence of grazing to those of 10 common species that were common in both grazed and ungrazed vegetation. Each sample was analysed for macro‐nutrients, micro‐nutrients, digestibility, palatability and decomposability. We ranked the species with respect to 22 variables based on effect size derived from Generalised Linear Modelling (GLM) and compared species using a Principal Components Analysis. We also assessed changes in abundance of the focal species through time using GLMs. Our results support the ‘Wet Desert’ hypothesis, that is, that long‐term sheep grazing has selectively removed/reduced species like our focal ones and on recovery, they were more nutritious (macro‐nutrients, some micro‐nutrients) palatable, digestible and decomposable than common species. Measured changes in abundance of the focal species suggest that their recovery will take 10–20 years in blanket bog and 60 years in high‐altitude grasslands. Collectively, these results suggest that sheep grazing has brought about biotic homogenization, and its removal in (re)wilding schemes will reverse this process eventually! The ‘white woolly maggots’ have eaten at least part of the heart out of the highlands/uplands, and it will take some time for recovery

Strong Stability and Host Specific Bacterial Community in Faeces of Ponies

The horse, as a hindgut fermenter, is reliant on its intestinal bacterial population for efficient diet utilisation. However, sudden disturbance of this population can result in severe colic or laminitis, both of which may require euthanasia. This study therefore aimed to determine the temporal stability of the bacterial population of faecal samples from six ponies maintained on a formulated high fibre diet. Bacterial 16S rRNA terminal restriction fragment length polymorphism (TRFLP) analyses of 10 faecal samples collected from 6 ponies at regular intervals over 72 hour trial periods identified a significant pony-specific profile (P<0.001) with strong stability. Within each pony, a significantly different population was found after 11 weeks on the same diet (P<0.001) and with greater intra-individual similarity. Total short chain fatty acid (SCFA) concentration increased in all ponies, but other changes (such as bacterial population diversity measures, individual major SCFA concentration) were significant and dependent on the individual. This study is the first to report the extent of stability of microbes resident in the intestinal tract as represented with such depth and frequency of faecal sampling. In doing so, this provides a baseline from which future trials can be planned and the extent to which results may be interpreted

Cost-effectiveness of adoption strategies for point of care HIV viral load monitoring in South Africa

Background: Viral load (VL) testing is recommended for monitoring people on ART. The National Health Laboratory Service (NHLS) in South Africa conducts >5million laboratory-based VL tests but faces challenges with specimen integrity and results delivery. Point-of-care (POC) VL monitoring may improve VL suppression (VLS). We assessed the cost-effectiveness of different strategies for POC testing in South Africa. Methods: We developed a cost-outcome model utilizing NHLS data, including facility-level annual VL volumes, proportion with VLS, specimen rejection rates, turn-around-time, and the cost/test. We assessed the impact of adopting POC VL technology under 4 strategies: (1) status-quo; (2) targeted POC testing at facilities with high levels of viral failure; (3) targeted POC testing at low-performing facilities; (4) complete POC adoption. For each strategy, we determined the total cost, effectiveness (expected number of virally suppressed people) and incremental cost-effectiveness ratio (ICER) based on expected (>10%) VLS improvement. Findings: Existing laboratory-based VL testing costs $126 m annually and achieves 85.2$40/additional person suppressed, compared to the status-quo. Should resources allow, complete POC adoption may be cost-effective (ICER: $136/additional person suppressed), requiring an additional$49 m annually and achieving 94.5% VLS. All other strategies were dominated in the incremental analysis. Interpretation: Assuming POC VL monitoring confers clinical benefits, the most cost-effective strategy for POC adoption in South Africa is a targeted approach with POC VL technologies placed at facilities with high level of viral failure. Funding: Funding support from the Bill & Melinda Gates Foundation

RNF4 and VHL regulate the proteasomal degradation of SUMO-conjugated Hypoxia-Inducible Factor-2α

Hypoxia-inducible factors (HIFs) are critical transcription factors that mediate cell survival during reduced oxygen conditions (hypoxia). At regular oxygen conditions (normoxia), HIF-1α and HIF-2α are continuously synthesized in cells and degraded via the ubiquitin–proteasome pathway. During hypoxia, these proteins are stabilized and translocate to the nucleus to activate transcription of target genes that enable cell survival at reduced oxygen levels. HIF proteins are tightly regulated via post-translational modifications including phosphorylation, acetylation, prolyl-hydroxylation and ubiquitination. Here we show for the first time that exogenous and endogenous HIF-2α are also regulated via the ubiquitin-like modifier small ubiquitin-like modifiers (SUMO). Using mutational analysis, we found that K394, which is situated in the sumoylation consensus site LKEE, is the major SUMO acceptor site in HIF-2α. Functionally, sumoylation reduced the transcriptional activity of HIF-2α. Similar to HIF-1α, HIF-2α is regulated by the SUMO protease SENP1. The proteasome inhibitor MG132 strongly stabilized SUMO-2-conjugated HIF-2α during hypoxia but did not affect the total level of HIF-2α. The ubiquitin E3 ligases von Hippel–Lindau and RNF4 control the levels of sumoylated HIF-2α, indicating that sumoylated HIF-2α is degraded via SUMO-targeted ubiquitin ligases

Neoliberalism and University Education in Sub-Saharan Africa

This article reviews the history of university development in Sub-Saharan Africa (SSA) and discusses the impact of neoliberal policies. This will be followed by an examination of the problems facing universities in the region. The following questions will be explored: (a) Are the existing universities in SSA serving the development needs of the region? (b) Are these universities up to the task of moving SSA out of the predicaments it faces such as famine, HIV/AIDS, poverty, diseases, debt, and human rights abuses? Finally, the article argues that for universities to play a role in the development of the region, a new paradigm that makes university education a public good should be established