Performance indicators: good, bad, and ugly Bird, Sheila M.; Sir David, Cox; Farewell, Vern T. ...
Journal of the Royal Statistical Society. Series A, Statistics in society,
01/2005, Letnik:
168, Številka:
1
Journal Article
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A striking feature of UK public services in the 1990s was the rise of performance monitoring (PM), which records, analyses and publishes data in order to give the public a better idea of how ...Government policies change the public services and to improve their effectiveness. PM done well is broadly productive for those concerned. Done badly, it can be very costly and not merely ineffective but harmful and indeed destructive. Performance indicators (PIs) for the public services have typically been designed to assess the impact of Government policies on those services, or to identify well performing or under-performing institutions and public servants. PIs' third role, which is the public accountability of Ministers for their stewardship of the public services, deserves equal recognition. Hence, Government is both monitoring the public services and being monitored by PIs. Especially because of the Government's dual role, PM must be done with integrity and shielded from undue political influence, in the way that National Statistics are shielded. It is in everyone's interest that Ministers, Parliament, the professions, practitioners and the wider public can have confidence in the PM process, and find the conclusions from it convincing. Before introducing PM in any public service, a PM protocol should be written. This is an orderly record not only of decisions made but also of the reasoning or calculations that led to those decisions. A PM protocol should cover objectives, design considerations and the definition of PIs, sampling versus complete enumeration, the information to be collected about context, the likely perverse behaviours or side-effects that might be induced as a reaction to the monitoring process, and also the practicalities of implementation. Procedures for data collection, analysis, presentation of uncertainty and adjustment for context, together with dissemination rules, should be explicitly defined and reflect good statistical practice. Because of their usually tentative nature, PIs should be seen as 'screening devices' and not overinterpreted. If quantitative performance targets are to be set, they need to have a sound basis, take account of prior (and emerging) knowledge about key sources of variation, and be integral to the PM design. Aspirational targets have a distinctive role, but one which is largely irrelevant in the design of a PM procedure; motivational targets which are not rationally based may demoralize and distort. Anticipated and actual side-effects of PM, including on individuals' behaviour and priorities, may need to be monitored as an intrinsic part of the PM process. Independent scrutiny of PM schemes for the public services should be set up and must report publicly. The extent and nature of this scrutiny should be related to the assessed drawbacks and benefits, reflect ethical concerns, and conform with good statistical practice. Research is needed into the merits of different strategies for identifying institutions or individuals in the public release of PM data, into how new PM schemes should be evaluated, and into efficient designs for evaluating a series of new policies which are monitored by PIs. The Royal Statistical Society considers that attempts to educate the wider public, as well as policy makers, about the issues surrounding the use of PIs are very important. High priority should be given to sponsoring well-informed public debate, and to disseminating good practices by implementing them across Government.
The role of the cell wall hydrolase polygalacturonase (PG) during fruit ripening was investigated using novel mutant tomato lines in which expression of the PG gene has been down regulated by ...antisense RNA. Tomato plants were transformed with chimaeric genes designed to express anti-PG RNA constitutively. Thirteen transformed lines were obtained of which five were analysed in detail. All contained a single PG antisense gene, the expression of which led to a reduction in PG enzyme activity in ripe fruit to between 5% and 50% that of normal. One line, GR16, showed a reduction to 10% of normal PG activity. The reduction in activity segregated with the PG antisense gene in selfed progeny of GR16. Plants homozygous for the antisense gene showed a reduction of PG enzyme expression of greater than 99%. The PG antisense gene was inherited stably through two generations. In tomato fruit with a residual 1% PG enzyme activity pectin depolymerisation was inhibited, indicating that PG is involved in pectin degradation in vivo. Other ripening parameters, such as ethylene production, lycopene accumulation, polyuronide solubilisation, and invertase activity, together with pectinesterase activity were not affected by the expression of the antisense gene.
The objective of this study was to measure levels of the toxin microcystin in different tissues of fish known to feed on cyanobacteria during toxic bloom events. Wild Nile and redbreast tilapia (
...Oreochromis niloticus and
Tilapia rendalli) were sampled from the catch of artisanal fishermen at eutrophic stations of Funil and Furnas reservoirs in southeastern Brazil. Phytoplankton communities in the two reservoirs were quite different taxonomically, but not dissimilar in microcystin content (200
μg
g dry weight (DW)
seston
−1 at Funil, 800
μg
gDW
seston
−1 at Furnas). All of the 27 fish sampled contained microcystin, ranging from 0.8 to 32.1
μg
g
liver
−1 and from 0.9 to 12.0
ng
g
muscle
−1. Most microcystin variants found in seston were also found in fish liver
. T. rendalli had the lowest concentration in both tissues when compared to
O. niloticus. In both reservoirs, one of every four fish sampled, always
O. niloticus, had a level of microcystins beyond the World Health Organization tolerable daily intake (8
ng
g
tissue
−1) and represented a risk for consumers. It is possible that closer study of inter-species variability in toxin burden in cyanobacteria-impacted water bodies will permit the development of guidelines for fish consumption that will better protect public health.
To examine the effect of exercise on overnight hypoglycemia in children with type 1 diabetes mellitus (T1DM).
At 5 clinical sites, 50 subjects with T1DM (age 11 to 17 years) were studied in a ...clinical research center on 2 separate days. One day included an afternoon exercise session on a treadmill. On both days, frequently sampled blood glucose levels were measured at the DirecNet central laboratory. Insulin doses were similar on both days.
During exercise, plasma glucose levels fell in almost all subjects; 11 (22%) developed hypoglycemia. Mean glucose level from 10
pm to 6
am was lower on the exercise day than on the sedentary day (131 vs 154 mg/dL;
P
=
.003). Hypoglycemia developed overnight more often on the exercise nights than on the sedentary nights (
P
=
.009), occurring on the exercise night only in 13 (26%), on the sedentary night only in 3 (6%), on both nights in 11 (22%), and on neither night in 23 (46%). Hypoglycemia was unusual on the sedentary night if the pre-bedtime snack glucose level was
>
130 mg/dL.
These findings indicate that overnight hypoglycemia after exercise is common in children with T1DM and support the importance of modifying diabetes management after afternoon exercise to reduce the risk of hypoglycemia.
Fast XPS and NEXAFS have been used to investigate the adsorption, desorption, and molecular conformation of styrene adsorbed on Ag(100) in order to determine whether single-crystal studies on the ...catalytic oxidation of this molecule do indeed provide valid information relevant to a fundamental understanding of the Ag-catalyzed epoxidation of terminal alkenes, especially ethene. Styrene adsorbs and desorbs from the metal surface without decomposition and three states are discerned in the desorption spectra, depending on the coverage. The strongest and weakest bound states are associated with molecules in multilayer and submonolayer environments, respectively. XPS data indicate that a desorption peak that appears at intermediate coverages is associated with tilted molecules in the contact layer. In the coverage regime relevant to the catalytic epoxidation reaction, the phenyl and vinyl groups are coplanar, and the molecule lies flat on the metal surface. These observations validate the use of styrene as a model adsorbate with which to investigate the catalytic chemistry of terminal alkenes.
In this study we describe the activation of a protein kinase which phosphorylates a peptide, T669, comprising amino acids 663-681 of the epidermal growth factor receptor and containing the phosphate ...acceptor site Pro-Leu-Thr669-Pro. In the human epidermoid carcinoma cell line KB, T669 kinase activity in cytosolic extracts peaked (up to 15-fold compared with basal levels) 15-30 min after addition of interleukin-1 (IL-1) and closely paralleled receptor occupancy with a half-maximally effective concentration of approximately 100 pM IL-1 alpha. IL-1 treatment elevated T669 kinase activity to a variable extent in selected fibroblast lines, the hepatoma cell line HepG2, and the murine thymoma EL4 6.1. An IL-1 receptor-negative EL4 variant and the B cell lines 70Z/3, CB23, and RPMI 1788 did not respond in this way. All of the cell lines except 70Z/3 showed increased levels of T669 kinase when treated with the protein kinase C activator phorbol myristate acetate and/or with epidermal growth factor. This finding is in agreement with a previous study (Countaway, J. L., Northwood, I. C., and Davis, R. J. (1989) J. Biol. Chem. 264, 10828-10835). Activators of protein kinase A did not mimic the ability of IL-1 to stimulate T669 kinase activity, nor did the protein kinase C inhibitor staurosporine abrogate the effect of IL-1. T669 kinase activity from IL-1-stimulated KB cells was partially purified by ion exchange, hydrophobic interaction, and size exclusion chromatography. The partially purified enzyme phosphorylated myelin basic protein, a characteristic substrate of microtubule-associated protein-2 kinase (MAP-2 kinase) and the peptide Arg-Arg-Arg-(Tyr-Ser-Pro-Thr-Ser-Pro-Ser)4 from RNA polymerase II. Western blotting of chromatographic fractions revealed that T669 kinase activity corresponded with two proteins of 43 and 45 kilodaltons which cross-reacted with antibodies raised against peptide sequences of rat extracellular signal-regulated kinase-1/microtubule-associated protein-2 kinase. T669 kinase activity was critically dependent on the presence of phosphatase inhibitors. Since both the 43- and 45-kDa proteins, immunoprecipitated from 32Pphosphate-labeled cells, demonstrated a dramatic increase in their levels of serine, threonine, and tyrosine phosphorylation after brief treatment with IL-1, we conclude that IL-1 modulates the activity of these extracellular signal-regulated kinase/microtubule-associated protein-2 kinases by altering the level of their phosphorylation.
Human GraB (hGraB) preferentially induces apoptosis via Bcl-2-regulated mitochondrial damage but can also directly cleave caspases and caspase substrates in cell-free systems. How hGraB kills cells ...when it is delivered by cytotoxic lymphocytes (CL) and the contribution of hGraB to CL-induced death is still not clear. We show that primary human natural killer (hNK) cells, which specifically used hGraB to induce target cell death, were able to induce apoptosis of cells whose mitochondria were protected by Bcl-2. Purified hGraB also induced apoptosis of Bcl-2-overexpressing targets but only when delivered at 5- to 10-fold the concentration required to kill cells expressing endogenous Bcl-2. Caspases were critical in this process as inhibition of caspase activity permitted clonogenic survival of Bcl-2-overexpressing cells treated with hGraB or hNK cells but did not protect cells that only expressed endogenous Bcl-2. Our data therefore show that hGraB triggers caspase activation via mitochondria-dependent and mitochondria-independent mechanisms that are activated in a hierarchical manner, and that the combined effects of Bcl-2 and direct caspase inhibition can block cell death induced by hGraB and primary hNK cells.
Previous studies of the pericentromeric region of the human X chromosome short arm (Xp) revealed an age gradient from ancient DNA that contains expressed genes to recent human-specific DNA at the ...functional centromere. We analyzed the finished sequence of this human genomic region to investigate its evolutionary history. Phylogenetic analysis of >1,500 alpha-satellite monomers from the region revealed the presence of five physical domains, each containing monomers from a distinct phylogenetic clade. The most distal domain contains long interspersed nucleotide element repeats that were active >35 million years ago, whereas the four proximal domains contain more recently active long interspersed nucleotide element repeats. An out-of-register, unequal recombination (i.e., crossover) detected at the edge of the X chromosome-specific alpha-satellite array (DXZ1) may reflect the most recent of a series of punctuating events during evolution that resulted in a proximal physical expansion of the X centromere. The first 18 kb of this array has 97-99% pairwise identity among all 2-kb repeat units. To perform more detailed evolutionary comparisons, we sequenced the junction between the ancient DNA of Xp and the primate-specific alpha satellite in chimpanzee, gorilla, orangutan, vervet, macaque, and baboon. The striking conservation found in all cases supports the ancestral nature of the alpha satellite at this location. These studies demonstrate that the primate X centromere appears to have evolved through repeated expansion events occurring within the central, active region of centromeric DNA, with the newly added sequences then conferring centromere function.
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