The Escalating Crisis of Health and Safety Law Enforcement in Great Britain: What Does Brexit Mean?

This paper explores occupational safety and health regulation in Great Britain following the UK's exit from the European Union. In particular, the paper focuses on the credibility of regulatory enforcement. The prospects raised by the UK's exit from the European Union have long been part of a free-market fantasy-even obsession-of right-wing politicians and their ideologues. As the UK's relationship with the EU is recalibrated, this will present right-wing opportunists with a new rationale for undermining health and safety law and enforcement. The paper uses empirical evidence of Great Britain's record in health and safety law enforcement to evidence a drift towards an extreme form of self-regulation. It deepens this evidence with a detailed analysis of key international policy debates, arguing that Brexit now raises an imminent threat of the UK entering a 'race to the bottom'. The paper concludes that the 2021 EU/UK Trade and Co-operation Agreement may enable the UK to evade its formal health and safety responsibilities under the treaty because of the lack of the prospect of significant retaliatory 'rebalancing' measures. Should minimal health and safety requirements cease to apply in the post-EU era, then the UK Government will be free to pursue a system of self-regulation that will allow health and safety standards to fall even further behind those of other developed economies.

Slow crystallisation of a monodisperse foam stabilised against coarsening.

The evolution of a three-dimensional monodisperse foam was investigated using X-ray tomography over the course of seven days. The coarsening of the sample was inhibited through the use of perfluorohexane gas. The internal configuration of bubbles is seen to change markedly, evolving from a disordered arrangement towards a more ordered state. We chart this ordering process through the use of the coordination number, the bond orientational order parameter (BOOP) and the translational order parameter.

Z-cone model for the energy of an ordered foam.

We develop the Z-Cone Model, in terms of which the energy of a foam may be estimated. It is directly applicable to an ordered structure in which every bubble has Z identical neighbours. The energy (i.e. surface area) may be analytically related to liquid fraction. It has the correct asymptotic form in the limits of dry and wet foam, with prefactors dependent on Z. In particular, the variation of energy with deformation in the wet limit is consistent with the anomalous behaviour found by Morse and Witten [Europhysics Letters, 1993, 22, 549] and Lacasse et al. [Physical Review E, 54, 5436], with a prefactor Z/2.

Association between class III ß-tubulin expression and response to paclitaxel/vinorebine-based chemotherapy for non-small cell lung cancer: a meta-analysis.

BACKGROUND: It has been proposed that the level of class III ß-tubulin gene expression can be used to predict clinical sensitivity to paclitaxel/vinorebine-based chemotherapy in non-small cell lung cancer (NSCLC) patients. However, whereas there are published reports supporting this association, there are also reports of studies that failed to find such an association. We conducted a meta-analysis of all relevant published data to provide a combined statistical assessment of the proposed association of expression variations of class III ß-tubulin with objective response and median survival in patients with NSCLC treated with paclitaxel/vinorebine-based chemotherapy. METHODS: We conducted the meta-analysis using data from ten studies, each of which evaluated the correlation between class III ß-tubulin expression levels and objective response in patients treated with paclitaxel/vinorebine-based chemotherapy for NSCLC patients. All eligible studies were searched by MEDLINE, EMBASE and CNKI databases. Overall odds ratios (ORs) of the objective response were calculated using the method of Mantel-Haenszel. The differences in objective responses between Caucasian and Asian patients treated with paclitaxel/vinorebine-based chemotherapy were compared. We also compared outcomes for patients treated with paclitaxel to those treated with vinorebine. RESULTS: There were a total of 552 patients in the ten studies that met our criteria for evaluation. High/positive expression of class III ß-tubulin was found in 279 patients (50.5%), and low/negative expression for this gene was found in 273 (49.5%) patients. The objective response rate for paclitaxel/vinorebine-based chemotherapy was significantly higher in patients with low/negative class III ß-tubulin expression (OR=0.28; 95% CI, 0.20-0.41; P<0.00001). Median survival time was longer for patients with low/negative expression of class III ß-tubulin compared with patients with high/positive expression (MR=1.40; CI, 0.89-0.90; P<0.00001). There was no significant difference in therapy between Caucasian and Asian patients treated with paclitaxel/vinorebine-based chemotherapy (Chi(2)=0.02, P=0.88). In our analysis, NSCLC patients treated with paclitaxel had more favorable clinical outcomes than those treated with vinorelbine (Chi(2)=3.69, P=0.05). CONCLUSIONS: By combining data from ten different studies, we found a correlation between low TUBB3 gene expression and favorable clinical outcome to anti-tubulin therapy. The correlation for the combined data was significantly stronger than it was for any of the individual studies. This result supports the usefulness of class III ß-tubulin mRNA level as a biomarker for sensitivity to paclitaxel/vinorebine-based chemotherapy in NSCLC patients.

GEN-SNiP: an online tool to find polymorphisms in a genome.

An online tool named GEN-SNiP that identifies variations in a set of test DNA sequences with respect to a standard reference sequence is developed and deployed successfully. The tool generates a list of substitutions, insertions and deletions for each test sequences, determined by the reference sequence. In the key batch mode feature, the tool allows multiple sequences to be compared and contrasted even when small insertions and deletions are present, with results sent to the user via email. Other distinguishing features of the tool are grouping of continuous deletions or insertions in the test sequence into a single entity for better output handling, displaying of the alignment of test and reference sequence and the input sequence. The tool has been reported as unique in recent literature.

Rheology of the gel formed in the California Mastitis Test.

The California Mastitis Test has previously been adapted for use in an inline, cow-side sensor and relies on the fact that the viscosity of the gel formed during the test is proportional to the somatic cell concentration. In this paper, the use of capillary and rotational viscometry was compared in light of the expected rheology of the gel formed during the test. It was found that the gel is non-Newtonian, but the initial phase of viscosity increase was not due to shear dependence, but rather due to the gelation reaction. The maximum apparent viscosity of the gel was shear dependent while the time it took to reach the maximum was not truly shear dependent, but was rather dependent on the degree of mixing during gelation. This was confirmed by introducing a delay time prior to viscosity measurement, in both capillary and rotational viscometry. It was found that by mixing the reagent and infected milk, then delaying viscosity measurement for 30 s, shortened the time it took to reach maximum viscosity by more than 60 s. The maximum apparent viscosity, however, was unaffected. It was found that capillary viscometry worked well to correlate relative viscosity with somatic cell count, but that it was sensitive to the reagent concentration. It can therefore be deduced that the rheology of the gel is complicated not only by it being non-Newtonian, but also by the strong dependence on test conditions. These make designing a successful sensor much more challenging.

Correlation of PIK3Ca mutations with gene expression and drug sensitivity in NCI-60 cell lines.

The gene that encodes the alpha-isoform of phosphatidylinositol 3-kinase (PIK3Ca) is frequently mutated in human cancers. We profiled the mutation status of the PIK3Ca gene in the National Cancer Institute (NCI)-60 panel of human cancer cell lines maintained by the Developmental Therapeutics Program of the NCI. Mutation hotspots on the gene were PCR amplified and sequenced, and the trace data were analyzed with software designed to detect mutations. Seven of the cell lines tested have PIK3Ca mutations: two lines derived from breast cancer, two from colon cancer, two from ovarian cancer, and one from lung cancer. BRAF and EGFR genes were normal in the PIK3Ca mutant lines. Two of the cell lines with mutant PIK3Ca also have a mutant version of the KRAS gene. The mutation status was correlated with array-based gene expression that is publicly available for the NCI-60 cell lines. We found increased expression levels for estrogen receptor (ER) and ERBB2 in PIK3Ca mutant lines. The PIK3Ca mutation status was also correlated with compound screening data for the cell lines. PIK3Ca-mutant cell lines were relatively more sensitive than PIK3Ca-normal cell lines to the ER inhibitor tamoxifen and the AKT inhibitor triciribine, among other compounds. The results provide insights into the role of mutant PIK3Ca in oncogenic signaling and allow preliminary identification of novel targets for therapeutic intervention in cancers harboring PIK3Ca mutations.

Chemical and rheological aspects of gel formation in the California Mastitis Test.

The rheological properties of the CMT gel were analysed. Data are presented to demonstrate that the gel is a non-homogenous, visco-elastic, non-Newtonian fluid with rheopectic, and rheodestructive behaviour. The fundamental chemistry of the CMT is reviewed and a modified theory of gel formation is presented. The implications of the rheological properties and modified theory of gel formation for an automatic sensor are discussed.

The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion.

HGK (hepatocyte progenitor kinase-like/germinal center kinase-like kinase) is a member of the human STE20/mitogen-activated protein kinase kinase kinase kinase family of serine/threonine kinases and is the ortholog of mouse NIK (Nck-interacting kinase). We have cloned a novel splice variant of HGK from a human tumor line and have further identified a complex family of HGK splice variants. We showed HGK to be highly expressed in most tumor cell lines relative to normal tissue. An active role for this kinase in transformation was suggested by an inhibition of H-Ras(V12)-induced focus formation by expression of inactive, dominant-negative mutants of HGK in both fibroblast and epithelial cell lines. Expression of an inactive mutant of HGK also inhibited the anchorage-independent growth of cells yet had no effect on proliferation in monolayer culture. Expression of HGK mutants modulated integrin receptor expression and had a striking effect on hepatocyte growth factor-stimulated epithelial cell invasion. Together, these results suggest an important role for HGK in cell transformation and invasiveness.

Requirement for PAK4 in the anchorage-independent growth of human cancer cell lines.

p21-activated protein kinase (PAK) serine/threonine kinases are important effectors of Rho family GTPases and have been implicated in the regulation of cell morphology and motility, as well as in cell transformation. To further investigate the possible involvement of PAK kinases in tumorigenesis, we analyzed the expression of several family members in tumor cell lines. Here we demonstrate that PAK4 is frequently overexpressed in human tumor cell lines of various tissue origins. We also have identified serine (Ser-474) as the likely autophosphorylation site in the kinase domain of PAK4 in vivo. Mutation of this serine to glutamic acid (S474E) results in constitutive activation of the kinase. Phosphospecific antibodies directed against serine 474 detect activated PAK4 on the Golgi membrane when PAK4 is co-expressed with activated Cdc42. Furthermore, expression of the active PAK4 (S474E) mutant has transforming potential, leading to anchorage-independent growth of NIH3T3 cells. A kinase-inactive PAK4 (K350A,K351A), on the other hand, efficiently blocks transformation by activated Ras and inhibits anchorage-independent growth of HCT116 colon cancer cells. Taken together, our data strongly implicate PAK4 in oncogenic transformation and suggest that PAK4 activity is required for Ras-driven, anchorage-independent growth.