The Search for Smart Schools: Identifying Texas School Districts’ Best Practices

This report outlines findings from the TXSmartSchools.org (TSS) Capstone Team’s mixed methodology study identifying best practices in high performing and cost-efficient school districts. TSS was particularly interested in finding best practices transferable from high performing school districts to low performing districts. The Capstone Team accomplished this using the TSS concept of “fiscal peers.” After completing a narrative literature review on the best practices in public education, the Capstone Team examined the effect of various school district expenditures on academic performance and cost efficiency through quantitative methods. The Capstone Team’s findings suggest the amount of money invested in practices are not indicative of the quality of the programs. Additional findings demonstrate the administrative cost ratio caps do not improve cost efficiency, and investments in bilingual education are associated with improved academic performance. To better describe the practices employed in school districts, semistructured interviews were conducted with school district officials. The findings from interviews with chief business officers and superintendents capture the importance of culture in district practices and operations. Based on the quantitative and qualitative findings, the Capstone Team makes recommendations that can be implemented at the district and state level. Further research is needed that will allow educators and researchers to better identify the best practices that will improve Texas schools’ and districts’ student academic achievement and fiscal efficiency

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH®liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m−2by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin. © 2001 Cancer Research Campaign http://www.bjcancer.co

Long-term agricultural experiments inform the development of climate-smart agricultural practices

California's Mediterranean agro-ecosystems are a major source of U.S. fruits and vegetables, and vulnerable to future extremes of precipitation and temperature brought on by climate change, including increased drought and flooding, and more intense and longer heat waves. To develop resilience to these threats, strategies are necessary for climate-smart management of soil and water. Long-term, large-scale, replicated ecological experiments provide unique testbeds for studying such questions. At the UC Davis Russell Ranch Sustainable Agriculture Facility (RRSAF), the 100-year Century Experiment, initiated in 1992, is investigating the effects of multiple farming practices in a farm-scale replicated study of 10 row crop cropping systems. It includes different fertility management systems: organic, conventional and hybrid (conventional plus winter cover crop) systems; different crops: wheat, tomatoes, corn, alfalfa, cover crops and grasslands; and different irrigation systems: rainfed, flood irrigated and drip irrigated. We briefly describe and report on a selection of long-term experiments conducted at RRSAF investigating soil management and irrigation practices, which are an important focus for developing climate-smart strategies in Mediterranean systems. For example, long-term monitoring of soil carbon content revealed that most crop systems have experienced a small increase in soil carbon since 1993, and increases in organically managed plots were substantially higher. As RRSAF continues to build upon this rich dataset from one of a very few long-term row crop experiments in Mediterranean ecosystems, it provides a testbed for identifying climate-smart solutions for these agronomically important ecosystems

Systematic LREE enrichment of mantle harzburgites: The petrogenesis of San Carlos xenoliths revisited

We are grateful to K. Itano for fruitful discussion of the ideas developed in this paper and K. Ozawa for support on the use of his opensystem melting model. The manuscript benefited from constructivecomments provided by Q. Xiong and three anonymous reviewers as well as from the editor X.-H. Li. This work was funded by a Japan Society for the Promotion of Science (JSPS) fellowship.The dichotomy between partial melting and metasomatism is a paradigm of mantle geochemistry since the pioneering work of Frey and Prinz (1978) on the occurrence of LREE-enriched harzburgites. However, the thermo-chemical implications of such two-stage scenarios are often poorly considered, and the latter fail to explain why trace-element enrichment and major-element depletion are often proportional.We here re-envisage the petrogenesis of the famous San Carlos peridotites based on new petrographic observations and detailed modal, major- and trace-element compositions. The lherzolites (and pyroxenites) are characterized by homogeneously fertile mineral chemistry and LREE-depleted patterns consistent with low degrees of partial melting of the lherzolitic protolith. Bulk compositions and mineral zoning suggest that opx-rich pyroxenites formed by pressure-solution creep during melt-present deformation, locally accompanied by magmatic segregations of cpx. The harzburgites are characterized by stronger mineral zoning with low-Mg# and Na-, Al- and Cr-rich cpx rims, and can be discriminated in a low-Jd and high-Jd cpx groups. The high-Jd group is interpreted as the result of local elemental redistribution in the presence of a low-degree hydrous melt, in good agreement with their wide range of LREE enrichment. In contrast, the MREE-to-HREE fractionation and increasing Cr# in spinel of the low-Jd group indicate that they experienced higher degrees of melting. Open-system melting simulations of trace-element fractionation during hydrous flux melting suggests that the high-Jd harzburgites are the result of low fluid influx producing poorly extracted melt, while higher influx led to higher melting degrees and efficient melt extraction in the low-Jd harzburgites; the lherzolites mostly remained below or near solidus during that process. The lithological and chemical heterogeneity of San Carlos mantle is thus compatible with a single-stage evolution, which is also supported by the striking consistency between Fe-Mg exchange and REE thermometric estimates (1057 and 1074 °C on average, respectively), indicating that harzburgites and lherzolites probably followed a similar P-T path and relatively little sub-solidus re-equilibration. These interpretations suggest that the development ofmelt extraction pathways promoted by reactive channeling instability is able to produce complex lithological heterogeneities during hydrous flux melting. This process provides a self-consistent explanation for the systematic enrichment of harzburgites observed in many mantle terranes and xenoliths worldwide. We argue that San Carlos is one of such examples where a ca 1.5-Ga continental lithosphere experienced localized flux melting and deformation during the tectonic reactivation of a Proterozoic subduction zone, providing new constraints on the mantle sources of volcanic activity in the Jemez Lineament.Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Scienc

Heart failure patients demonstrate impaired changes in brachial artery blood flow and shear rate pattern during moderate-intensity cycle exercise

New Findings What is the central question of this study? We explored whether heart failure (HF) patients demonstrate different exercise-induced brachial artery shear rate patterns compared with control subjects. What is the main finding and its importance? Moderate-intensity cycle exercise in HF patients is associated with an attenuated increase in brachial artery anterograde and mean shear rate and skin temperature. Differences between HF patients and control subjects cannot be explained fully by differences in workload. HF patients demonstrate a less favourable shear rate pattern during cycle exercise compared with control subjects. Repeated elevations in shear rate (SR) in conduit arteries, which occur during exercise, represent a key stimulus to improve vascular function. We explored whether heart failure (HF) patients demonstrate distinct changes in SR in response to moderate-intensity cycle exercise compared with healthy control subjects. We examined brachial artery SR during 40 min of cycle exercise at a work rate equivalent to 65% peak oxygen uptake in 14 HF patients (65 ± 7 years old, 13 men and one woman) and 14 control subjects (61 ± 5 years old, 12 men and two women). Brachial artery diameter, SR and oscillatory shear index (OSI) were assessed using ultrasound at baseline and during exercise. The HF patients demonstrated an attenuated increase in mean and anterograde brachial artery SR during exercise compared with control subjects (time × group interaction, P = 0.003 and P 0.05). In conclusion, HF patients demonstrate a less favourable SR pattern during cycle exercise than control subjects, characterized by an attenuated mean and anterograde SR and by increased OSI

Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome

The Plasmodium falciparum proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the P. falciparum 20S proteasome (Pf20S) beta5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth of P. falciparum compared with a human cell line and exhibit high potency against field isolates of P. falciparum and Plasmodium vivax They have a low propensity for development of resistance and possess liver stage and transmission-blocking activity. Exemplar compounds, MPI-5 and MPI-13, show potent activity against P. falciparum infections in a SCID mouse model with an oral dosing regimen that is well tolerated. We show that MPI-5 binds more strongly to Pf20S than to human constitutive 20S (Hs20Sc). Comparison of the cryo-electron microscopy (EM) structures of Pf20S and Hs20Sc in complex with MPI-5 and Pf20S in complex with the clinically used anti-cancer agent, bortezomib, reveal differences in binding modes that help to explain the selectivity. Together, this work provides insights into the 20S proteasome in P. falciparum, underpinning the design of potent and selective antimalarial proteasome inhibitors

Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance.

Despite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive external ophthalmoplegia remains unknown in a large proportion of patients. Here we show that mutations in SPG7 are a novel cause of progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. After excluding known causes, whole exome sequencing, targeted Sanger sequencing and multiplex ligation-dependent probe amplification analysis were used to study 68 adult patients with progressive external ophthalmoplegia either with or without multiple mitochondrial DNA deletions in skeletal muscle. Nine patients (eight probands) were found to carry compound heterozygous SPG7 mutations, including three novel mutations: two missense mutations c.2221G>A; p.(Glu741Lys), c.2224G>A; p.(Asp742Asn), a truncating mutation c.861dupT; p.Asn288*, and seven previously reported mutations. We identified a further six patients with single heterozygous mutations in SPG7, including two further novel mutations: c.184-3C>T (predicted to remove a splice site before exon 2) and c.1067C>T; p.(Thr356Met). The clinical phenotype typically developed in mid-adult life with either progressive external ophthalmoplegia/ptosis and spastic ataxia, or a progressive ataxic disorder. Dysphagia and proximal myopathy were common, but urinary symptoms were rare, despite the spasticity. Functional studies included transcript analysis, proteomics, mitochondrial network analysis, single fibre mitochondrial DNA analysis and deep re-sequencing of mitochondrial DNA. SPG7 mutations caused increased mitochondrial biogenesis in patient muscle, and mitochondrial fusion in patient fibroblasts associated with the clonal expansion of mitochondrial DNA mutations. In conclusion, the SPG7 gene should be screened in patients in whom a disorder of mitochondrial DNA maintenance is suspected when spastic ataxia is prominent. The complex neurological phenotype is likely a result of the clonal expansion of secondary mitochondrial DNA mutations modulating the phenotype, driven by compensatory mitochondrial biogenesis

The Biology of Cancer Stem Cells and Its Clinical Implication in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment options in its advanced state. The molecular mechanisms underlying HCC remain unclear because of the complexity of its multi-step development process. Cancer stem cells (CSCs) are defined as a small population of cells within a tumor that possess the capability for self-renewal and the generation of heterogeneous lineages of cancer cells. To date, there have been two theories concerning the mechanism of carcinogenesis, i.e., the stochastic (clonal evolution) model and the hierarchical (cancer stem cell-driven) model. The concept of the CSC has been established over the past decade, and the roles of CSCs in the carcinogenic processes of various cancers, including HCC, have been emphasized. Previous experimental and clinical evidence indicated the existence of liver CSCs; however, the potential mechanistic links between liver CSCs and the development of HCC in humans are not fully understood. Although definitive cell surface markers for liver CSCs have not yet been found, several putative markers have been identified, which allow the prospective isolation of CSCs from HCC. The identification and characterization of CSCs in HCC is essential for a better understanding of tumor initiation or progression in relation to signaling pathways. These markers could be used along with clinical parameters for the prediction of chemoresistance, radioresistance, metastasis and survival and may represent potential targets for the development of new molecular therapies against HCC. This review describes the current evidence for the existence and function of liver CSCs and discuss the clinical implications of CSCs in patients demonstrating resistance to conventional anti-cancer therapies, as well as clinical outcomes. Such data may provide a future perspective for targeted therapy in HCC