Interpreting A-level Mathematics grades – as easy as A, B, C?

Many concerns have been expressed that students’ basic mathematical skills have deteriorated during the 1990s and there has been disquiet that current A-level grading does not distinguish adequately between the more able students. This study reports the author’s experiences of teaching maths to large classes of first-year engineering students and aims to enhance understanding of levels of mathematical competence in more recent years. Over the last four years, the classes have consisted of a very large proportion of highly qualified students – about 91% of them had at least grade B in A-level Mathematics. With a small group of students having followed a non-traditional route to university (no A-level maths) and another group having benefitted through taking A-level Further Mathematics at school, the classes have contained a very wide range of mathematical backgrounds. Despite the introductory maths course at university involving mainly repetition of A-level material, students’ marks were spread over a very wide range – for example, A-level Mathematics grade B students have scored across the range 16 – 97%. Analytical integration is the topic which produced the largest variation in performance across the class but, in contrast, the A-level students generally performed well in differentiation. Initial analysis suggests some stability in recent years in the mathematical proficiency of students with a particular A-level Mathematics grade. Allowing choice of applied maths modules as part of the A-level maths qualification increases the variety of students’ mathematical backgrounds and their selection from mechanics, statistics or decision maths is not clear from the final qualification.

A narrow-band ultraviolet B course improves vitamin D balance and alters cutaneous CYP27A1 and CYP27B1 mRNA expression levels in haemodialysis patients supplemented with oral vitamin D

Background: Chronic kidney disease (CKD) patients on dialysis are prone to vitamin D insufficiency despite oral vitamin D supplementation. Here, we studied whether narrow-band ultraviolet B (NB-UVB) exposures improve vitamin D balance.

Methods: 14 haemodialysis patients and 15 healthy subjects receiving oral cholecalciferol 20 µg daily got nine NB-UVB exposures on the entire body. Serum 25-hydroxyvitamin D (25(OH)D) was measured by radioimmunoassay. Cutaneous mRNA expression levels of CYP27A1 and CYP27B1, two enzymes required for hydroxylation of vitamin D into its active metabolite, were also measured.

Results: The baseline serum 25(OH)D concentration was 57.6 ± 18.2 nmol/l in the CKD patients and 74.3 ± 14.8 nmol/l in the healthy subjects. The NB-UVB course increased serum 25(OH)D by 14.0 nmol/l (95% CI 8.7-19.5) and 17.0 nmol/l (CI 13.7-20.2), respectively. At baseline the CKD patients showed significantly increased CYP27B1 levels compared to the healthy subjects.

Conclusions: A short NB-UVB course is an efficient way to improve vitamin D balance in CKD patients on dialysis who are receiving oral vitamin D supplementation. The increased cutaneous CYP27B1 levels in the CKD patients suggest that the loss of renal activity of this enzyme is at least partially compensated for by the skin.

Physicochemical characterization of bioactive polyacrylic acid organogels as potential antimicrobial implants for the buccal cavity

This study describes the formulation and physicochemical characterization of poly(acrylic acid) (PAA) organogels, designed as bioactive implants for improved treatment of infectious diseases of the oral cavity. Organogels were formulated containing a range of concentrations of PAA (3-10% w/w) and metronidazole (2 or 5% w/w, representing a model antimicrobial agent) in different nonaqueous solvents, namely, glycerol (Gly), polyethylene glycol (PEG 400), or propylene glycol (PG). Characterization of the organogels was performed using flow rheometry, compressional analysis, oscillatory rheometry, in vitro mucoadhesion, moisture uptake, and drug release, methods that provide information pertaining to the nonclinical and clinical use of these systems. Increasing the concentration of PAA significantly increased the consistency, compressibility, storage modulus, loss modulus, dynamic viscosity, mucoadhesion, and the rate of drug release. These observations may be accredited to enhanced molecular polymer entanglement. In addition, the choice of solvent directly affected the physicochemical parameters of the organogels, with noticeable differences observed between the three solvents examined. These differences were accredited to the nature of the interaction of PAA with each solvent and, importantly, the density of the resultant physical cross-links. Good correlation was observed between the viscoelastic properties and drug release, with the exception of glycerol-based formulations containing 5 and 10% w/w PAA. This disparity was due to excessive swelling during the dissolution analysis. Ideally, formulations should exhibit controlled drug release, high viscoelasticity, and mucoadhesion, but should flow under minimal stresses. Based on these criteria, PEG 400-based organogels composed of 5% or 10% w/w PAA exhibited suitable physicochemical properties and are suggested to be a potentially interesting strategy for use as bioactive implants designed for use in the oral cavity. © 2008 American Chemical Society.

An examination of the rheological and mucoadhesive properties of poly(Acrylic acid) organogels designed as platforms for local drug delivery to the oral cavity

This study examined the rheological/mucoadhesive properties of poly (acrylic acid) PAA organogels as platforms for drug delivery to the oral cavity. Organogels were prepared using PAA (3%, 5%, 10% w/w) dissolved in ethylene glycol (EG), propylene glycol (PG), 1,3-propylene glycol (1,3-PG), 1,5-propanediol (1,5-PD), polyethylene glycol 400 (PEG 400), or glycerol. All organogels exhibited pseudoplastic flow. The increase in storage (G') and loss (G '') moduli of organogels as a function of frequency was minimal, G '' was greater than G '' (at all frequencies), and the loss tangent <1, indicative of gel behavior. Organogels prepared using EG, PG, and 1,3-propanediol (1,3-PD) exhibited similar flow/viscoelastic properties. Enhanced rheological structuring was associated with organogels prepared using glycerol (in particular) and PEG 400 due to their interaction with adjacent carboxylic acid groups on each chain and on adjacent chains. All organogels (with the exception of 1,5-PD) exhibited greater network structure than aqueous PAA gels. Organogel mucoadhesion increased with polymer concentration. Greatest mucoadhesion was associated with glycerol-based formulations, whereas aqueous PAA gels exhibited the lowest mucoadhesion. The enhanced network structure and the excellent mucoadhesive properties of these organogels, both of which may be engineered through choice of polymer concentration/solvent type, may be clinically useful for the delivery of drugs to the oral cavity.

Exchange systems and style in the Central Mediterranean. 4500-1700 b.c..:Unpublished PhD. Cambridge University Library

Malone, C.A.T., 1986, Unpublished PhD, Cambridge University, Cambridge.

DEAD-box helicase DP103 defines metastatic potential of human breast cancers

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.

Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C).

PURPOSE: To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. PATIENTS AND METHODS: Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis. RESULTS: One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX+C arm. CONCLUSION: Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

CaII K interstellar observations towards early-type disc and halo stars

We present high-resolution (R = lambda/Deltalambda similar to 40 000) Ca II K interstellar observations (lambda(air) = 3933.66Angstrom) towards 88 mainly B-type stars, of which 74 are taken from the Edinburgh-Cape or Palomar-Green surveys, and 81 have > 25degrees. The majority of the data come from previously existing spectroscopy, although also included are 18 new observations of stars with echelle spectra taken with UVES on the Very Large Telescope UT2 (Kueyen). Some 49 of the sample stars have distance estimates above the Galactic plane (z) greater than or equal to 1 kpc, and are thus good probes of the halo interstellar medium. Of the 362 interstellar Ca K components that we detect, 75 (21 per cent) have absolute values of their LSR velocity values exceeding 40 km s(-1). In terms of the deviation velocity for the sightlines with distance estimates, 46/273 (17 per cent) of components have velocity values exceeding those predicted by standard Galactic rotation by more than 40 km s(-1). Combining this data set with previous observations, we find that the median value of the reduced equivalent width (REW) of stars with z greater than or equal to 1 kpc (EW x sin ) is similar to 115 mAngstrom (n = 80), similar to that observed in extragalactic sightlines by Bowen. Using data of all z distances, the REW at infinity is found to be similar to 130 mAngstrom, with the scaleheight (1) of the Ca II K column density distribution being;z 800 pc (n = 196) and reduced column density at infinity of log[N(Ca II K) cm(-2)] similar to 12.24. This implies that similar to30 per cent of Ca II K absorption occurs at distances exceeding similar to1 kpc. For nine sightlines, with distance exceeding 1 kpc and with a companion object within 5degrees, we find that all but two have values of Ca II reduced equivalent width the same to within similar to20 per cent, when the REW of the nearest object is extrapolated to the distance of the further of the pair, and assuming 1 = 800 pc. For 29 of our sightlines with z greater than or equal to 1 kpc and a H I detection from the Leiden-Dwingeloo survey (beamsize of 0.5degrees), we find log(N(Ca II K)IN(H I)) ranging from -7.4 to - 8.4. Values of the Ca II K abundance relative to neutral hydrogen (log[N(Ca II K) cm(-2)] - log[N(H I) cm(-2)]) are found to be more than similar to0.5 dex higher in stars with distances exceeding approximate to100 pc, when compared with the (log[N(Ca II K) cm(-2)] -log[N(H-tot) cm(-2)]) values found in nearby sightlines such as those in Wakker & Mathis (2000). Finally, stellar Ca II K equivalent widths of the sample are determined for 26 objects.

Enhanced sensitivity of protein kinase B/Akt to insulin in hypoxia is independent of HIF1 alpha and promotes cell viability

Maintenance of oxygen homeostasis is a key requirement to ensure normal mammalian cell growth and differentiation. Hypoxia arises when oxygen demand exceeds supply, and is a feature of multiple human diseases including stroke, cancer and renal fibrosis. We have investigated the effect of hypoxia on kidney cells, and observed that insulin-induced cell viability is increased in hypoxia. We have characterized the role of protein kinase B (PKB/ Akt) in these cells as a potential mediator of this effect. PKB/Akt activity was increased by low oxygen concentrations in kidney cells, and insulin-stimulated activation of PKB/Akt was stronger, more rapid and more sustained in hypoxia. Reduction of HIF1 alpha levels using antimycin-A or siRNA targeting HlF1 alpha did not affect PKB/Akt activation in hypoxia. Pharmacologic stabilization of HIF1 alpha independent of hypoxia did not increase insulin-stimulated PKB/Akt activation. Although increased insulin-stimulated cell viability was observed in hypoxia, no differences in the degree of insulin-stimulated glucose uptake were observed in L6 muscle cells in hypoxia compared to normoxia. Thus, PKB/Akt may regulate specific cellular responses to growth factors such as insulin under adverse conditions such as hypoxia. alpha 2007 Elsevier GmbH. All rights reserved.