Public sector performance auditing: Emergence, purpose and meaning

The purpose of this paper is to evaluate the extant Anglo-American literature on 'performance auditing for the public sector', in order to identify the socio-economic and political themes that influenced the emergence of public sector performance auditing. The paper also seeks to develop an understanding of the role and practice of performance auditing in the public sector. Common catalysts for change appear to rest in the influence of the local governmental senior auditor (e.g. Auditor General), the existence of public sector reform and changes in standardisation generally. The traditional role of the public sector auditor has undergone significant change over time. In particular, the scope of the public sector audit now exceeds the expectation that the auditor only check for regulatory and procedural compliance. It is now expected that the auditor enhance accountability in the management of public sector resources. The perceived objectives of performance auditing (economy, efficiency and effectiveness) emerge as a strong theme, one which seems to comply with these more modern expectations of performance

Distal occurrence of mid-Holocene Whakatane Tephra on the Chatham Islands, New Zealand, and potential for cryptotephra studies

The Whakatane Tephra, a rhyolitic tephra erupted ca. 5500 cal. BP from Okataina Volcanic Centre, central North Island, has been identified on the Chatham Islands which lie ˜900 km east of Christchurch, New Zealand. The visible tephra layer, ˜5 mm in thickness and preserved within peat on Pitt Island, was identified using both radiocarbon dating and analysis of glass shards by electron microprobe. Whakatane Tephra is the first Holocene tephra to be identified on the Chatham Islands, and it is the most distal Holocene tephra yet recorded in the New Zealand region, being ˜850 km from source. The Pitt Island occurrence extends the tephra's dispersal area markedly, by an order of magnitude, possibly to ˜300,000 km2. An estimated dispersal index (D) of approximately 105 km2 indicates that the eruption generated a very high plinian column, possibly exceeding ˜30 km in height, with strong winds blowing the ash plume southeastwards. This new discovery of distal Whakatane Tephra as a thin but visible layer strongly implies that cryptotephras are likely to be preserved on the Chatham Islands and within adjacent ocean floor sediments. Therefore the potential exists to develop enhanced cryptotephrostratigraphic records from these distal areas, which in turn would help facilitate precise correlation via tephrochronology of palaeoenvironmental records (such as NZ-INTIMATE) from mainland New Zealand, the southwest Pacific Ocean, and the Chatham Islands

Evaluating the character and preservation of DNA within allophane clusters in buried soils on Holocene tephras, northern New Zealand

Clay minerals possess sorptive capacities for organic and inorganic matter, including DNA (Lorenz and Wackernagel, 1994), and hence reduce the utilization and degradation of organic matter or DNA by microorganisms. Buried allophane-rich soils on tephras (volcanic-ash beds) on the North Island, dated using tephrochronology, provide a valuable paleobiological ‘laboratory’ for studying the preservation of ancient DNA (aDNA) (Haile et al., 2007). Allophane comprises Al-rich nanocrystalline spherules ~3.5-5 nm in diameter (Fig. 1) with extremely large surface areas (up to 1000 m2 g-1). Moreover, allophanic soils are strongly associated with organic matter (Parfitt, 2009), and so we hypothesize that allophane also plays an important role for DNA protection within such soils

Single-cell approaches to cell competition: high-throughput imaging, machine learning and simulations

Cell competition is a quality control mechanism in tissues that results in the elimination of less fit cells. Over the past decade, the phenomenon of cell competition has been identified in many physiological and pathological contexts, driven either by biochemical signaling or by mechanical forces within the tissue. In both cases, competition has generally been characterized based on the elimination of loser cells at the population level, but significantly less attention has been focused on determining how single-cell dynamics and interactions regulate population-wide changes. In this review, we describe quantitative strategies and outline the outstanding challenges in understanding the single cell rules governing tissue-scale competition dynamics. We propose quantitative metrics to characterize single cell behaviors in competition and use them to distinguish the types and outcomes of competition. We describe how such metrics can be measured experimentally using a novel combination of high-throughput imaging and machine learning algorithms. We outline the experimental challenges to quantify cell fate dynamics with high-statistical precision, and describe the utility of computational modeling in testing hypotheses not easily accessible in experiments. In particular, cell-based modeling approaches that combine mechanical interaction of cells with decision-making rules for cell fate choices provide a powerful framework to understand and reverse-engineer the diverse rules of cell competition

Stratigraphy and chronology of late Quaternary tephras in Lake Maratoto, Hamilton, New Zealand

A 3 m piston core from Lake Maratoto (37°53’S 175°18’E) near Hamilton shows at least 12 thin, well-preserved distal airfall tephras intercalated with humic copropel (dy) deposits. Most of the tephras have been identified by their dominant ferromagnesian mineralogy, their stratigraphic position, and 5 radiocarbon dates. The majority of the tephras are derived from the Taupo and Okataina Volcanic Centres, while others originate from Mayor Island, Tongariro, and possibly Mount Egmont sources. The tephras dated (Libby ages) are: Taupo Pumice (Wk215) 1730 ± 60 years B.P., Tuhua Tephra (Wk214) 6210 ± 70 years B.P., Mangamate Tephra (Wk213) 10 120 ± 100 years B.P., and Rerewhakaaitu Ash (2 dates) (Wk237) 14 700 ± 220 years B.P. and (Wk238) 14 700 ± 180 years B.P. The identification of the tephras in Lake Maratoto extends the previously mapped distribution of North Island post-glacial (Holocene) tephras, and complements studies of soil genesis and weathering in the Waikato region. The core also provides a geochronological basis for further multidisciplinary studies of the paleolimnology, paleoclimate, and sedimentological history of the region

Local cellular neighbourhood controls proliferation in cell competition

Cell competition is a quality control mechanism through which tissues eliminate unfit cells. Cell competition can result from short-range biochemical inductions or long-range mechanical cues. However, little is known about how cell-scale interactions give rise to population shifts in tissues, due to the lack of experimental and computational tools to efficiently characterise interactions at the single-cell level. Here, we address these challenges by combining long-term automated microscopy with deep learning image analysis to decipher how single-cell behaviour determines tissue make-up during competition. Using our high-throughput analysis pipeline, we show that competitive interactions between MDCK wild-type cells and cells depleted of the polarity protein scribble are governed by differential sensitivity to local density and the cell-type of each cell's neighbours. We find that local density has a dramatic effect on the rate of division and apoptosis under competitive conditions. Strikingly, our analysis reveals that proliferation of the winner cells is upregulated in neighbourhoods mostly populated by loser cells. These data suggest that tissue-scale population shifts are strongly affected by cellular-scale tissue organisation. We present a quantitative mathematical model that demonstrates the effect of neighbour cell-type dependence of apoptosis and division in determining the fitness of competing cell lines

Metabolic, inflammatory and haemostatic effects of a low-dose continuous combined HRT in women with type 2 diabetes: potentially safer with respect to vascular risk?

BACKGROUND Conventional hormone replacement therapy (HRT) containing conjugated equine oestrogen (CEE) and medroxyprogesterone acetate (MPA) increases triglyceride, C- reactive protein (CRP) and coagulation Factor VII concentrations, potentially explaining their increased coronary heart disease (CHD) and stroke risk. OBJECTIVE To assess the metabolic effects of a continuous combined HRT containing 1 mg oestradiol and 0.5 mg norethisterone or matching placebo. DESIGN Double-blind, randomized placebo-controlled trial. PATIENTS Fifty women with type 2 diabetes. MEASUREMENTS Classical and novel risk factors for vascular disease. RESULTS Triglyceride concentration was not altered (P = 0.31, change in active arm relative to placebo) and low-density lipoprotein (LDL) cholesterol concentration declined 13% (P = 0.018). IL-6 concentration (mean difference -1.42 pg/ml, 95% CI: -2.55 to - 0.29 IU/dl, P = 0.015), Factor VII (-32 IU/dl, -43 to -21 IU/l, P lt 0.001) and tissue plasminogen activator antigen (by 13%, P = 0.005) concentrations fell, but CRP was not significantly altered (P = 0.62). Fasting glucose (P = 0.026) also declined significantly, but there are no significant effects on HBA1c, Factor IX or APC resistance. CONCLUSIONS HRT containing 1 mg oestradiol and 0.5 mg norethisterone may avoid the adverse metabolic effects potentially implicated in the elevated CHD and stroke risk induced by conventional higher dose HRT. This type of preparation may therefore be more suitable than conventional HRT for women at elevated CHD risk such as those with type 2 diabetes. Large randomized controlled trials of such low dose preparations, powered for cardiovascular end points, are now needed

Mapping the topography of a protein energy landscape

Protein energy landscapes are highly complex, yet the vast majority of states within them tend to be invisible to experimentalists. Here, using site-directed mutagenesis and exploiting the simplicity of tandem-repeat protein structures, we delineate a network of these states and the routes between them. We show that our target, gankyrin, a 226-residue 7-ankyrin-repeat protein, can access two alternative (un)folding pathways. We resolve intermediates as well as transition states, constituting a comprehensive series of snapshots that map early and late stages of the two pathways and show both to be polarized such that the repeat array progressively unravels from one end of the molecule or the other. Strikingly, we find that the protein folds via one pathway but unfolds via a different one. The origins of this behavior can be rationalized using the numerical results of a simple statistical mechanics model that allows us to visualize the equilibrium behavior as well as single-molecule folding/unfolding trajectories, thereby filling in the gaps that are not accessible to direct experimental observation. Our study highlights the complexity of repeat-protein folding arising from their symmetrical structures; at the same time, however, this structural simplicity enables us to dissect the complexity and thereby map the precise topography of the energy landscape in full breadth and remarkable detail. That we can recapitulate the key features of the folding mechanism by computational analysis of the native structure alone will help toward the ultimate goal of designed amino-acid sequences with made-to-measure folding mechanisms—the Holy Grail of protein folding

Context-dependent energetics of loop extensions in a family of tandem-repeat proteins

Consensus-designed tetratricopeptide repeat proteins are highly stable, modular proteins that are strikingly amenable to rational engineering. They therefore have tremendous potential as building blocks for biomaterials and biomedicine. Here, we explore the possibility of extending the loops between repeats to enable further diversification, and we investigate how this modification affects stability and folding cooperativity. We find that extending a single loop by up to 25 residues does not disrupt the overall protein structure, but, strikingly, the effect on stability is highly context-dependent: in a two-repeat array, destabilization is relatively small and can be accounted for purely in entropic terms, whereas extending a loop in the middle of a large array is much more costly because of weakening of the interaction between the repeats. Our findings provide important and, to our knowledge, new insights that increase our understanding of the structure, folding, and function of natural repeat proteins and the design of artificial repeat proteins in biotechnology

Stability, Causality, and Lorentz and CPT Violation

Stability and causality are investigated for quantum field theories incorporating Lorentz and CPT violation. Explicit calculations in the quadratic sector of a general renormalizable lagrangian for a massive fermion reveal that no difficulty arises for low energies if the parameters controlling the breaking are small, but for high energies either energy positivity or microcausality is violated in some observer frame. However, this can be avoided if the lagrangian is the sub-Planck limit of a nonlocal theory with spontaneous Lorentz and CPT violation. Our analysis supports the stability and causality of the Lorentz- and CPT-violating standard-model extension that would emerge at low energies from spontaneous breaking in a realistic string theory.Comment: 20 pages, accepted for publication in Physical Review