Designing for health – reducing occupational health risks in bored pile operations

Insitu concrete bored piling is a common foundation solution for both major building and civil engineering projects. The technique is used both for individual or grouped piles topped with a pile cap, or a line of piles, contiguous or secant, topped with a capping beam as part of a basement or abutment construction. There are many health hazards associated with bored piles. One of the main risks is the breaking down of the unwanted pile-top, typically using hand-held pneumatic breakers. This operation creates particular problems for hand arm vibration syndrome (HAVS), dust and noise. But there are several viable alternatives to this procedure that remove or significantly reduce these risks. These innovations have been developed by the construction supply chain and are readily available. D4h, a UK Government-funded research project by Loughborough University and the European Construction Institute, has demonstrated that designers can play their part in encouraging their adoption, without straying into the perceived danger of specifying means and methods. If designers are willing to identify pile-top break down as a significant residual risk in their health and safety assessment, thus requiring the Principal Contractor1 to provide proposals to address this risk – this may be the only push needed to get the industry to eliminate the major HAVS problem from insitu bored piles. This paper will benefit the health and safety research community, especially those working on designer intervention. The paper will also be of use to industry practitioners, providing innovative solutions to a significant occupational health risk as well as challenging designers to take construction health and safety more seriously

Attenuated sex steroid receptor expression in fallopian tube of women with ectopic pregnancy

CONTEXT: Sex steroid hormone receptor (SHR) dynamics are well-documented in human endometrium but have not been comprehensively studied in Fallopian tube (FT). OBJECTIVE: To compare expression patterns and hormonal regulation of SHR in FT with that described in endometrium, and determine whether SHR expression is altered in FT of women with ectopic pregnancy (EP). DESIGN: Tissue analysis and culture. PATIENTS OR OTHER PARTICIPANTS: Women undergoing surgery for benign gynaecological conditions (n=14) and EP (n=6). INTERVENTIONS: Q-RT-PCR and immunohistochemistry were used to determine SHR mRNA expression and protein localization, respectively. SHR levels were measured in tubal explant cultures stimulated with estrogen and progestogen. RESULTS: ERα and ERβ mRNAs were constitutively expressed in FT during the menstrual cycle. PR-AB and PR-B mRNAs were decreased in mid-luteal compared to follicular phase. ERα, PR-AB and PR-B mRNAs were downregulated in human FT in vitro by treatment with progestogen. ERα, ERβ1, ERβ2, PR and AR proteins localised to cell nuclei of epithelium, stroma and smooth muscle of non-pregnant FT. In FT from women with EP, PR-B mRNA was decreased when compared to mid-luteal FT, and ERα protein was not detected. CONCLUSIONS: SHR expression in FT is different from that observed in endometrium recovered at similar stages of the menstrual cycle and expression in FT from women with EP is also altered compared with normal FT. These data are an important benchmark for furthering understanding of normal human FT physiology, transcriptional changes in FT in response to progesterone, and disorders of FT function, such as EP

Placental Growth Factor:A Promising Diagnostic Biomarker for Tubal Ectopic Pregnancy

CONTEXT: Tubal ectopic pregnancy is common but accurate diagnosis is difficult and costly. There is currently no serum test to differentiate tubal from intrauterine implantation and an effective biomarker of ectopic pregnancy would be a major clinical advance. OBJECTIVE: A key feature of successful intrauterine implantation is the establishment of a supportive vascular network and this has been associated with the activity of placental growth factor (PIGF). We hypothesized that the local decidual environment facilitates PIGF-dependent angiogenesis and that this pathway is not active in tubal implantation. We aimed to determine whether tubal implantation is manifest by an attenuation of the normal trophoblast PIGF-response and whether serum PIGF levels are different in ectopic compared to intrauterine pregnancy. DESIGN: Tissue and serum analysis. SETTING: A large UK teaching hospital. PATIENTS: Gestation-matched pregnant women undergoing surgical termination of pregnancy (viable intrauterine) (n=15), evacuation of uterus for embryonic missed miscarriage (non-viable intrauterine) (n=10) and surgery for tubal ectopic pregnancy (n=15). INTERVENTIONS: Trophoblast was examined by immunohistochemistry and quantitative RT-PCR, and serum was analyzed by ELISA. RESULTS: PIGF was localized to the cytotrophoblast cells. Expression of PIGF mRNA was reduced in trophoblast isolated from women with ectopic compared to intrauterine pregnancies (P<0.05). Serum PIGF was undetectable in women with tubal ectopic pregnancies and reduced, or undetectable, in miscarriage compared to viable intrauterine pregnancies (P<0.01). CONCLUSIONS: Serum PIGF is a promising novel diagnostic biomarker for early pregnancy location and outcome, and large-scale studies are now required to determine its clinical utility

CB1 Expression Is Attenuated in Fallopian Tube and Decidua of Women with Ectopic Pregnancy

BACKGROUND: Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known. METHODS AND FINDINGS: Timed FT biopsies (n = 18) were collected from women undergoing gynecological procedures for benign conditions. Endometrial biopsies and whole blood were collected from women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA and protein expression levels/patterns were examined in FT and endometrial biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was higher in luteal compared to follicular-phase (p<0.05). CB1 protein was located in smooth muscle of the wall and of endothelial vessels, and luminal epithelium of FT. In FT from women with EP, CB1 mRNA expression was low. CB1 mRNA expression was also significantly lower (p<0.05) in endometrium of women with EP compared to intrauterine pregnancies (IUP). Although of 1359G/A (rs1049353) polymorphisms of CNR1 gene suggests differential distribution of genotypes between the small, available cohorts of women with EP and those with IUP, results were not statistically significant. CONCLUSIONS: CB1 mRNA shows temporal variation in expression in human FT, likely regulated by progesterone. CB1 mRNA is expressed in low levels in both the FT and endometrium of women with EP. We propose that aberrant endocannabinoid-signaling in human FT leads to EP. Furthermore, our finding of reduced mRNA expression along with a possible association between polymorphism genotypes of the CNR1 gene and EP, suggests a possible genetic predisposition to EP that warrants replication in a larger sample pool

Evidence of prokineticin dysregulation in fallopian tube from women with ectopic pregnancy

OBJECTIVE: To demonstrate expression and regulation of prokineticins (PROKs) and their receptors (PROKRs) in Fallopian tube (FT) from non-pregnant women and women with ectopic pregnancy (EP). DESIGN: Tissue analysis. SETTING: Large UK teaching hospital PATIENTS: Women undergoing hysterectomy for benign gynecological conditions (n=15) and surgery for EP (n=16). INTERVENTIONS: Quantitative RT-PCR and immunohistochemistry were used to determine FT PROK/PROKR mRNA expression and protein localization, respectively. PROK/PROKR levels were measured in tubal explant cultures stimulated with estrogen and progestogen. MAIN OUTCOME MEASURES: Differential expression of PROK and PROKR. RESULTS: FT PROK2 and PROKR1 mRNA levels were upregulated during the progesterone-dominant mid-luteal phase of the menstrual cycle. Increased PROKR1 expression was observed in tubal explant cultures treated with medroxyprogesterone acetate. PROK and PROKR proteins were localized to the epithelium and smooth muscle layers of the FT. PROKR1 and PROKR2 mRNA levels were lower in FT from women with EP compared to non-pregnant FT from the mid-luteal phase. CONCLUSION: These data suggest a potential role for PROKs in FT function. PROKs are known to affect smooth muscle contraction in the gut. Dysregulated PROK expression in FT could affect FT smooth muscle contractility and embryo-tubal transport, providing a potential cause for EP

Quantitative Serial MRI of the Treated Fibroid Uterus

There are no long-term medical treatments for uterine fibroids, and non-invasive biomarkers are needed to evaluate novel therapeutic interventions. The aim of this study was to determine whether serial dynamic contrast-enhanced MRI (DCE-MRI) and magnetization transfer MRI (MT-MRI) are able to detect changes that accompany volume reduction in patients administered GnRH analogue drugs, a treatment which is known to reduce fibroid volume and perfusion. Our secondary aim was to determine whether rapid suppression of ovarian activity by combining GnRH agonist and antagonist therapies results in faster volume reduction.Forty women were assessed for eligibility at gynaecology clinics in the region, of whom thirty premenopausal women scheduled for hysterectomy due to symptomatic fibroids were randomized to three groups, receiving (1) GnRH agonist (Goserelin), (2) GnRH agonist+GnRH antagonist (Goserelin and Cetrorelix) or (3) no treatment. Patients were monitored by serial structural, DCE-MRI and MT-MRI, as well as by ultrasound and serum oestradiol concentration measurements from enrolment to hysterectomy (approximately 3 months).A volumetric treatment effect assessed by structural MRI occurred by day 14 of treatment (9% median reduction versus 9% increase in untreated women; P = 0.022) and persisted throughout. Reduced fibroid perfusion and permeability assessed by DCE-MRI occurred later and was demonstrable by 2-3 months (43% median reduction versus 20% increase respectively; P = 0.0093). There was no apparent treatment effect by MT-MRI. Effective suppression of oestradiol was associated with early volume reduction at days 14 (P = 0.041) and 28 (P = 0.0061).DCE-MRI is sensitive to the vascular changes thought to accompany successful GnRH analogue treatment of uterine fibroids and should be considered for use in future mechanism/efficacy studies of proposed fibroid drug therapies. GnRH antagonist administration does not appear to accelerate volume reduction, though our data do support the role of oestradiol suppression in GnRH analogue treatment of fibroids.ClinicalTrials.gov NCT00746031

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression