Relative efficiency measurement in the public sector with data envelopment analysis

PhDTraditional efficiency measures have two significant drawbacks. Firstly, they fail to recognise that output is the result of all inputs operating in combination; thus output per head is a misleading indicator of intrinsic labour productivity. Secondly, they have often been defined in terms of average levels of performance in least squares production functions. In practice, average performance norms may institutionalise some level of inefficiency. The first of these problems may be overcome in a total-factor view of efficiency. This implies the extension of traditional ratio measures to include all inputs and outputs simultaneously. The second requires the comparison of performance with frontier possibilities. Both of these improvements are embodied in Data Envelopment Analysis (DEA). Two applications of DEA are undertaken on U. K. public sector data. The first of these defines frontier efficiency in local education authorities (LEAs). It develops an 8 variable model with 3 outputs (based on exam pass rates) and 5 inputs. Four of the inputs are uncontrollable background variables allowing for differences in student catchment area; the fifth, teaching expenditure, is under LEA control and can be targeted. The results suggest that 44 authorities are best-practice and at the remainder spending per pupil could have been reduced by an average of 6.8%. These results are replicated on smaller clusters of LEAs to examine the sensitivity of DEA to the size of the performance comparison. The clustering procedure produces marked effects on targets, peer groups and the efficiency status of certain authorities. A second case study investigates the performance of a sample of 33 prisons with a high remand population. The model separately identifies the effects of remand prisoners on costs, and includes separate variables to reflect the levels of overcrowding and offences. In 1984/85 the combined budget of these prisons was overspent by 4.6% vis a vis best-practice costs. Using an alternative constant returns technology this overspend rises to 13.1%. Two aspects of DEA targets are explored. A model of Leibenstein's inert area suggests reasons for the persistence of inefficiency and hence that targets may be unattainable without coercion. Secondly, the literature has justified the recommendation of DEA targets in their being Pareto efficient. This interpretation is disputed and an alternative DEA-Dominance criterion is proposed as a more appropriate basis for targeting

A Preliminary Investigation of the Comparative Expectations of Parents of Children with Autism and Chairpersons in the Committee on Preschool Special Education (CPSE) and/or Committee on Special Education (CSE) Process

This qualitative study explored the underlying beliefs of parents who have children with autism and chairpersons of the Committee on Preschool Special Education (CPSE)/Committee on Special Education (CSE). Specifically, beliefs that promote trust and diminish conflict were of primary interest, as high rates of litigation were well documented with this group of parents in the United States. The theory of defensive reasoning (Argyris, 1999) was the lens used to analyze the dynamic. The themes identified provide insight into the promotion of trust and the reduction of conflict at the CPSE/CSE. The findings revealed two distinctly different expectations within the parent group of participants: parents who expect the worst (n=3), and parents who expect to figure it out (n=9). The chairperson participants reported that most parents, new to the process, expected the worst. Chairpersons (n=9) reported that they were able to form collaborative relationships with most parents. Chairpersons and most parents reported common underlying beliefs that they attributed to the formation of collaborative relationships. This study revealed new insights associated with the underlying beliefs of each group of participants. Most parents in this study reported a lack of conflict and described the chairperson as an ally. It was also found that chairpersons may falsely believe in potential threat at the CPSE/CSE, as chairperson expectations and beliefs were ultimately well aligned with those of most parents. The sharing of underlying beliefs between parents and chairpersons is not uniformly practiced at the CPSE/CSE. These findings are discussed including implications for parents, parent advocates, chairpersons, and future research

Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells

Mutations to fibroblast growth factor receptor 3 (FGFR3) and phosphatase and tensin homologue (PTEN) signalling pathway components (for example, PTEN loss, PIK3CA, AKT1, TSC1/2) are common in bladder cancer, yet small-molecule inhibitors of these nodes (FGFR/PTENi) show only modest activity in preclinical models. As activation of autophagy is proposed to promote survival under FGFR/PTENi, we have investigated this relationship in a panel of 18 genetically diverse bladder cell lines. We found that autophagy inhibition does not sensitise bladder cell lines to FGFR/PTENi, but newly identify an autophagy-independent cell death synergy in FGFR3-mutant cell lines between mTOR (mammalian target of rapamycin) pathway inhibitors and chloroquine (CQ)—an anti-malarial drug used as a cancer therapy adjuvant in over 30 clinical trials. The mechanism of synergy is consistent with lysosomal cell death (LCD), including cathepsin-driven caspase activation, and correlates with suppression of cSREBP1 and cholesterol biosynthesis in sensitive cell lines. Remarkably, loss of viability can be rescued by saturating cellular membranes with cholesterol or recapitulated by statin-mediated inhibition, or small interfering RNA knockdown, of enzymes regulating cholesterol metabolism. Modulation of CQ-induced cell death by atorvastatin and cholesterol is reproduced across numerous cell lines, confirming a novel and fundamental role for cholesterol biosynthesis in regulating LCD. Thus, we have catalogued the molecular events underlying cell death induced by CQ in combination with an anticancer therapeutic. Moreover, by revealing a hitherto unknown aspect of lysosomal biology under stress, we propose that suppression of cholesterol metabolism in cancer cells should elicit synergy with CQ and define a novel approach to future cancer treatments

MUBs inequivalence and affine planes

There are fairly large families of unitarily inequivalent complete sets of N+1 mutually unbiased bases (MUBs) in C^N for various prime powers N. The number of such sets is not bounded above by any polynomial as a function of N. While it is standard that there is a superficial similarity between complete sets of MUBs and finite affine planes, there is an intimate relationship between these large families and affine planes. This note briefly summarizes "old" results that do not appear to be well-known concerning known families of complete sets of MUBs and their associated planes.Comment: This is the version of this paper appearing in J. Mathematical Physics 53, 032204 (2012) except for format changes due to the journal's style policie

Examining the Factor Structure of the Home Mathematics Environment to Delineate Its Role in Predicting Preschool Numeracy, Mathematical Language, and Spatial Skills

A growing body of evidence suggests that the ways in which parents and preschool children interact in terms of home-based mathematics activities (i.e., the home mathematics environment; HME) is related to children’s mathematics development (e.g., primarily numeracy skills and spatial skills); however, this body of evidence is mixed with some research supporting the relation and others finding null effects. Importantly, few studies have explicitly examined the factor structure of the HME and contrasted multiple hypothesized models. To develop more precise models of how the HME supports children’s mathematics development, the structure of the HME needs to be examined and linked to mathematics performance. The purpose of this study was to extend prior work by replicating the factor structure of the HME (as one general HME factor and three specific factors of direct numeracy, indirect numeracy, and spatial) and using those factors to predict direct assessments of children’s numeracy, mathematical language, and spatial skills. It was hypothesized that the general HME factor would be related to each direct assessment, the direct numeracy factor would be related to both numeracy and mathematical language, and the spatial factor would be related to spatial skills. Using a sample of 129 preschool children (M age = 4.71 years, SD = 0.55; 46.5% female), a series of confirmatory factor analyses were conducted. Results diverged somewhat from prior work as the best fitting model was a bifactor model with a general HME factor and two specific factors (one that combined direct and indirect numeracy activities and another of spatial activities) rather than three specific factors as had previously been found. Further, structural equation modeling analyses suggested that, in contrast to expectations, only the direct + indirect numeracy factor was a significant predictor of direct child assessments when accounting for age, sex, and parental education. These findings provide evidence that a bifactor model is important in understanding the structure of the HME, but only one specific factor is related to children’s outcomes. Delineating the structure of the HME, and how specific facets of the HME relate to children’s mathematics skills, provides a strong foundation for understanding and enhancing the mechanisms that support mathematics development

Clearance of damaged mitochondria via mitophagy is important to the protective effect of ischemic preconditioning in kidneys

<p>Ischemic preconditioning (IPC) affords tissue protection in organs including kidneys; however, the underlying mechanism remains unclear. Here we demonstrate an important role of macroautophagy/autophagy (especially mitophagy) in the protective effect of IPC in kidneys. IPC induced autophagy in renal tubular cells in mice and suppressed subsequent renal ischemia-reperfusion injury (IRI). The protective effect of IPC was abolished by pharmacological inhibitors of autophagy and by the ablation of <i>Atg7</i> from kidney proximal tubules. Pretreatment with BECN1/Beclin1 peptide induced autophagy and protected against IRI. These results suggest the dependence of IPC protection on renal autophagy. During IPC, the mitophagy regulator PINK1 (PTEN induced putative kinase 1) was activated. Both IPC and BECN1 peptide enhanced mitolysosome formation during renal IRI in mitophagy reporter mice, suggesting that IPC may protect kidneys by activating mitophagy. We further established an in vitro model of IPC by inducing ‘chemical ischemia’ in kidney proximal tubular cells with carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Brief treatment with CCCP protected against subsequent injury in these cells and the protective effect was abrogated by autophagy inhibition. In vitro IPC increased mitophagosome formation, enhanced the delivery of mitophagosomes to lysosomes, and promoted the clearance of damaged mitochondria during subsequent CCCP treatment. IPC also suppressed mitochondrial depolarization, improved ATP production, and inhibited the generation of reactive oxygen species. Knockdown of <i>Pink1</i> suppressed mitophagy and reduced the cytoprotective effect of IPC. Together, these results suggest that autophagy, especially mitophagy, plays an important role in the protective effect of IPC.</p> <p><b>Abbreviations</b>: ACTB: actin, beta; ATG: autophagy related; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; BUN: blood urea nitrogen; CASP3: caspase 3; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; COX4I1: cytochrome c oxidase subunit 4I1; COX8: cytochrome c oxidase subunit 8; DAPI: 4ʹ,6-diamidino-2-phenylindole; DNM1L: dynamin 1 like; EGFP: enhanced green fluorescent protein; EM: electron microscopy; ER: endoplasmic reticulum; FC: floxed control; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; H-E: hematoxylin-eosin; HIF1A: hypoxia inducible factor 1 subunit alpha; HSPD1: heat shock protein family D (Hsp60) member 1; IMMT/MIC60: inner membrane mitochondrial protein; IPC: ischemic preconditioning; I-R: ischemia-reperfusion; IRI: ischemia-reperfusion injury; JC-1: 5,5ʹ,6,6ʹ-tetrachloro-1,1ʹ,3,3ʹ-tetraethylbenzimidazolylcarbocyanine iodide; KO: knockout; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; mito-QC: mito-quality control; mRFP: monomeric red fluorescent protein; NAC: N-acetylcysteine; PINK1: PTEN induced putative kinase 1; PPIB: peptidylprolyl isomerase B; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; RPTC: rat proximal tubular cells; SD: standard deviation; sIPC: simulated IPC; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling</p

Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy

Autophagy is a cell-protective and degradative process that recycles damaged and long-lived cellular components. Cancer cells are thought to take advantage of autophagy to help them to cope with the stress of tumorigenesis; thus targeting autophagy is an attractive therapeutic approach. However, there are currently no specific inhibitors of autophagy. ULK1, a serine/threonine protein kinase, is essential for the initial stages of autophagy, and here we report that two compounds, MRT67307 and MRT68921, potently inhibit ULK1 and ULK2 in vitro and block autophagy in cells. Using a drug-resistant ULK1 mutant, we show that the autophagy-inhibiting capacity of the compounds is specifically through ULK1. ULK1 inhibition results in accumulation of stalled early autophagosomal structures, indicating a role for ULK1 in the maturation of autophagosomes as well as initiation

Targeting the interaction of GABAB_{B} receptors with CaMKII with an interfering peptide restores receptor expression after cerebral ischemia and inhibits progressive neuronal death in mouse brain cells and slices

Cerebral ischemia is the leading cause for long-term disability and mortality in adults due to massive neuronal death. Currently, there is no pharmacological treatment available to limit progressive neuronal death after stroke. A major mechanism causing ischemia-induced neuronal death is the excessive release of glutamate and the associated overexcitation of neurons (excitotoxicity). Normally, GABA$_{B}$ receptors control neuronal excitability in the brain via prolonged inhibition. However, excitotoxic conditions rapidly downregulate GABA$_{B}$ receptors via a CaMKII-mediated mechanism and thereby diminish adequate inhibition that could counteract neuronal overexcitation and neuronal death. To prevent the deleterious downregulation of GABA$_{B}$ receptors, we developed a cell-penetrating synthetic peptide (R1-Pep) that inhibits the interaction of GABA$_{B}$ receptors with CaMKII. Administration of this peptide to cultured cortical neurons exposed to excitotoxic conditions restored cell surface expression and function of GABA$_{B}$ receptors. R1-Pep did not affect CaMKII expression or activity but prevented its T286 autophosphorylation that renders it autonomously and persistently active. Moreover, R1-Pep counteracted the aberrant downregulation of G protein-coupled inwardly rectifying K$^{+}$ channels and the upregulation of N-type voltage-gated Ca$^{2+}$ channels, the main effectors of GABA$_{B}$ receptors. The restoration of GABA$_{B}$ receptors activated the Akt survival pathway and inhibited excitotoxic neuronal death with a wide time window in cultured neurons. Restoration of GABA$_{B}$ receptors and neuroprotective activity of R1-Pep was verified by using brain slices prepared from mice after middle cerebral artery occlusion (MCAO). Treatment with R1-Pep restored normal GABA$_{B}$ receptor expression and GABA receptor-mediated K$^{+}$ channel currents. This reduced MCAO-induced neuronal excitability and inhibited neuronal death. These results support the hypothesis that restoration of GABA$_{B}$ receptor expression under excitatory conditions provides neuroprotection and might be the basis for the development of a selective intervention to inhibit progressive neuronal death after ischemic stroke