Work and Retirement Among Women: The Health and Employment After Fifty Study.

BACKGROUND: Women increasingly work beyond age 50+ but their occupational health is under-researched. AIMS: To investigate what jobs older contemporary women do, when they exit their jobs and what factors predict job exit. METHODS: Data came from the Health and Employment After Fifty cohort, which recruited women aged 50-64 at baseline in 2013-14 and has followed them up annually collecting: demographic, lifestyle and work information. Exits from employment were mapped longitudinally over five follow-ups. Time-to-first event Cox regression analyses were used to identify risk factors for job exit. RESULTS: At baseline, 4436 women participated, 64% of whom were working. The proportions of women working at 50-54, 55-60 and over 60 years were 86%, 79% and 38%, respectively. Amongst all women, after adjustment for age, managing comfortably financially and not coping with the mental demands of the job were associated with exit. Risk factors for job exit differed in the age bands: 50-54; 55-59 and >60 years, reflecting socio-economic status, markers of health (musculoskeletal pain and poor self-rated health) and work factors (under-appreciation, job dissatisfaction, temporary/permanent contracts, coping with work's physical demands). CONCLUSIONS: Factors contributing to exit from work among older women differ by age group, after controlling for perceived financial position, age and mental demands of the job. A number of work characteristics predict job exit and suggest that employers can play an important role in supporting women to continue working until older ages. Identification and treatment of musculoskeletal pain could also enable work amongst older women.

Can different degrees of resistance training improve mood states in patients with fibromyalgia? A randomized controlled trial.

The purpose of this study was to look at the effects of low and high intensity resistance training (RT) on the mood states of fibromyalgia patients (FM). A total of 69 women participated in the study, with 31 healthy women serving as control group (HC), and 28 women diagnosed with FM being randomly assigned to one of two RT groups: low intensity or high intensity. Ten women diagnosed with FM formed a group of preferred intensity (PI). FM patients were subjected to 8 weeks of supervised RT with low, high, or PI doses. The exercise protocol was the same for both groups, with large muscle group exercises. Each intervention group performed a specific number of repetitions and rest periods based on the intensity. Training sessions took place twice a week. The HC received no type of intervention. The Brunel mood scale was used to assess mood states. When the mood profiles of patients with FM and healthy women were compared, patients with FM showed a worse mood profile. Low and high intensity RT for eight weeks did not improve the mood profile of FM patients. Anger showed a significant difference between LIRT and HIRT groups in the follow-up period (p=0.01); similarly significant differences between HIRT and HC were seen at baseline and at the 4 week evaluation in vigor (p=0.01 and p=0.001) and fatigue (p=0.01 and p=0.03). FM patients have a worse mood profile than healthy women, and eight weeks of low and high intensity RT did not result in significant improvements.

Shift work amongst older UK workers and job exit.

BACKGROUND: Night/shift work may be increasing but there are few data about the prevalence amongst older workers. With governments encouraging people to work to older ages, it is important to know how feasible night/shift work is for them and whether there are any adverse health consequences. AIMS: Amongst current older workers (aged 50-64 years), to explore the prevalence of night/shift working and evaluate its health impacts and sustainability over 4 years of follow-up. METHODS: Data from the Health and Employment After Fifty cohort were used to describe the demographic, job and health characteristics of men and women undertaking night/shift work. Longitudinal data were used to examine the number and nature of exits annually thereafter. RESULTS: Amongst the 5409 working at baseline, 32% reported night/shift work in sectors which differed by sex. Night/shift workers were more likely to be: current smokers; doing physically demanding work; struggling to cope at work; dissatisfied with their hours; depressed; sleeping poorly; rating their health poorly. Women whose job involves night work were more likely to exit the workforce over 4 years. CONCLUSIONS: Almost one in three contemporary UK older workers report night/shift work. We found some evidence of adverse impacts on health, sleep and well-being and higher rates of job exit amongst women. More research is needed but night/shift work may be challenging to sustain for older workers and could have health consequences.

Parametric Amplification and Noise Squeezing in Room Temperature Atomic Vapors.

We report on the use of parametric excitation to coherently manipulate the collective spin state of an atomic vapor at room temperature. Signatures of the parametric excitation are detected in the ground-state spin evolution. These include the excitation spectrum of the atomic coherences, which contains resonances at frequencies characteristic of the parametric process. The amplitudes of the signal quadratures show amplification and attenuation, and their noise distribution is characterized by a strong asymmetry, similar to those observed in mechanical oscillators. The parametric excitation is produced by periodic modulation of the pumping beam, exploiting a Bell-Bloom-like technique widely used in atomic magnetometry. Notably, we find that the noise squeezing obtained by this technique enhances the signal-to-noise ratio of the measurements up to a factor of 10, and improves the performance of a Bell-Bloom magnetometer by a factor of 3.

Top Quark Pair Production in Association with a Jet with Next-to-Leading-Order QCD Off-Shell Effects at the Large Hadron Collider.

We present a complete description of top quark pair production in association with a jet in the dilepton channel. Our calculation is accurate to next-to-leading order (NLO) in QCD and includes all nonresonant diagrams, interferences, and off-shell effects of the top quark. Moreover, nonresonant and off-shell effects due to the finite W gauge boson width are taken into account. This calculation constitutes the first fully realistic NLO computation for top quark pair production with a final state jet in hadronic collisions. Numerical results for differential distributions as well as total cross sections are presented for the Large Hadron Collider at 8 TeV. With our inclusive cuts, NLO predictions reduce the unphysical scale dependence by more than a factor of 3 and lower the total rate by about 13% compared to leading-order QCD predictions. In addition, the size of the top quark off-shell effects is estimated to be below 2%.

Association between RAD 51 rs1801320 and susceptibility to glioblastoma.

Glioblastoma is the most common and aggressive malignant primary brain tumor. Despite decades of research and the advent of new therapies, patients with glioblastoma continue to have a very poor prognosis. Radiation therapy has a major role as adjuvant treatment for glioblastoma following surgical resection. Many studies have shown that polymorphisms of genes involved in pathways of DNA repair may affect the sensitivity of the cells to treatment. Although the role of these polymorphisms has been investigated in relation to response to radiotherapy, their role as predisposing factors to glioblastoma has not been clarified yet. In the present study, we evaluated the association between polymorphisms in DNA repair genes, namely: XRCC1 rs25487, XRCC3 rs861539 and RAD51 rs1801320, with the susceptibility to develop glioblastoma. Eighty-five glioblastoma patients and 70 matched controls were recruited for this study. Data from the 1000 Genomes Project (98 Tuscans) were also downloaded and used for the association analysis. Subjects carrying RAD51 rs1801320 GC genotype showed an increased risk of glioblastoma (GC vs GG, χ(2) = 10.75; OR 3.0087; p = 0.0010). The C allele was also significantly associated to glioblastoma (χ(2) = 8.66; OR 2.5674; p = 0.0032). Moreover, RAD51 rs1801320 C allele increased the risk to develop glioblastoma also when combined to XRCC1 rs25487 G allele and XRCC3 rs861539 C allele (χ(2) = 6.558; p = 0.0053).

From farm to fork and beyond! UV enhances Aryl hydrocarbon receptor-mediated activity of cruciferous vegetables in human intestinal cells upon colonic fermentation.

While the "farm to fork" strategy ticks many boxes in the sustainability agenda, it does not go far enough in addressing how we can improve crop nutraceutical quality. Here, we explored whether supplementary ultraviolet (UV) radiation exposure during growth of broccoli and Chinese cabbage can induce bioactive tryptophan- and glucosinolate-specific metabolite accumulation thereby enhancing Aryl hydrocarbon receptor (AhR) activation in human intestinal cells. By combining metabolomics analysis of both plant extracts and in vitro human colonic fermentation extracts with AhR reporter cell assay, we reveal that human colonic fermentation of UVB-exposed Chinese cabbage led to enhanced AhR activation in human intestinal cells by 23% compared to plants grown without supplementary UV. Thus, by exploring aspects beyond "from farm to fork", our study highlights a new strategy to enhance nutraceutical quality of Brassicaceae, while also providing new insights into the effects of cruciferous vegetables on human intestinal health.

Dominant QCD backgrounds in Higgs boson analyses at the LHC: a study of pp --> tt + 2 jets at next-to-leading order.

We report the results of a next-to-leading order simulation of top quark pair production in association with two jets. With our inclusive cuts, we show that the corrections with respect to leading order are negative and small, reaching 11%. The error obtained by scale variation is of the same order. Additionally, we reproduce the result of a previous study of top quark pair production in association with a single jet.

Experimental observation of Faraday waves in soft gels.

We report the experimental observation of Faraday waves on soft gels. These were obtained using agarose in a mechanically vibrated cylindrical container. Low driving frequencies induce subharmonic standing waves with spatial structure that conforms to the geometry of the container. We report the experimental observation of the first 15 resonant Faraday wave modes that can be defined by the mode number (n,ℓ) pair. We also characterize the shape of the instability tongue and show the complex dependence upon material properties can be understood as an elastocapillary effect.

Two mutations of BRCA2 gene at exon and splicing site in a woman who underwent oncogenetic counseling.

BACKGROUND: Although most BRCA sequence variants are clearly deleterious and unequivocally pathogenetic, several are still classified as variants of unknown significance. PATIENTS AND METHODS: We followed families undergoing oncogenetic counseling from risk identification to risk definition by genetic testing and risk management. RESULTS: We identified two germline mutations in the BRCA2 gene in a woman with breast and ovarian cancer. One sequence alteration was 859/G>A in exon 7 (V211I). The other second sequence alteration (IVS13-2A>T) affected the splicing site in intron 13. The latter alteration is not yet listed in the Breast Cancer Information Core database. RT-PCR resulted in transcription of a sequence lacking exon 7 and a subsequent anomalous stop codon in exon 9 thereby confirming altered messenger RNA (mRNA) maturation. Amplification of the mutation in intron 13 resulted in transcription of a sequence lacking exon 14 and an anomalous stop codon in exon 15 thereby confirming altered mRNA maturation. Both mutations led to a truncated BRCA2 protein in its carboxy-terminal region. CONCLUSION: The two BRCA2 mutations identified affect mRNA splicing fidelity and play a pathogenetic role in breast and ovarian cancer.

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program.

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

Correlation of recurrence rates and times with posttreatment human papillomavirus status in patients treated with loop electrosurgical excision procedure conization for cervical squamous intraepithelial lesions.

The aim of the present study was to assess recurrence rates and times in patients with squamous intraepithelial lesion (SIL) of the uterine cervix treated with loop electrosurgical excision procedure (LEEP) conization, in order to define categories of patients who have a different risk of recurrence and who need a different surveillance protocol. This study was carried out on 119 consecutive patients who underwent LEEP. All patients were followed up with cervical smear and colposcopy after 3, 6, and 12 months in the first-year posttreatment, and every 6-12 months afterwards. Human papillomavirus (HPV) testing was performed at the time of LEEP and repeated 3-6 months later. The histologic examination of LEEP specimens revealed stage IA1 squamous cell cervical cancer in 4 (3.4%) cases, high-grade SIL in 75 (63%) cases, and low-grade SIL in 40 (33.6%) cases. The four patients with stage IA1 cervical cancer were not included in the further analyses. Disease recurred in none of the 50 patients with negative posttreatment HPV testing, in 4 (9.3%) of the 43 patients with positive posttreatment HPV testing and negative surgical margins, and in 8 (36.4%) of 22 patients with positive posttreatment HPV testing and positive margins. The combined evaluation of surgical margin status and posttreatment HPV testing could allow to subdivide patients treated with LEEP into categories at different risk of recurrence, requiring new tailored surveillance procedures.

Endoscopic management of symptomatic choledocholithiasis in pregnancy without the use of radiations.

We report a case of 26-year-old woman at 10th week of gestation with cholestatic jaundice due to a common bile duct (CBD) stone managed by endoscopical retrograde cholangiopancreatography (ERCP). The procedure was successfully carried out without the use of ionizing radiations and under trans-abdominal ultrasonographical (US) control. A few cases are reported in literature in which ERCP was performed without fluoroscopy examination. We believe that ERCP with US guidance is an effective and safe procedure to treat symptomatic choledocholithiasis in pregnant women.

HPV testing and Pap test: role for a combined approach in a non-screened population.

The aim of the present study was to test the polymerase chain reaction (PCR) as a tool to identify human papillomavirus (HPV) in routine cytological samples scraped from the uterine cervix. Moreover, attention has been focused on the correlation between HPV types and early intraepithelial lesions. The study involved 586 women who had undergone conventional Pap test. Analysis of HPV infection was performed by PCR and HPV typing by dot blot. In a group of 78 cases histologically diagnosed as high-grade squamous intraepithelial lesions (HSILs), the cytological diagnosis was correct in 92.3% and the HPV test was positive in 89.8% of cases; combined positivity at Pap and/or HPV tests raised this figure to 99.0%. In a group of 67 cases histologically diagnosed as low-grade squamous intraepithelial lesions (LSILs), the cytological diagnosis was correct in 73.1% and the PCR-based HPV test was positive in 64.2%; combined positivity at Pap and/or HPV tests raised this figure to 91.0%. This study confirms the limitations of screening programs based on Pap test only. Our results suggest, in fact, that adding the HPV test to primary screening could increase the yield of preinvasive cervical lesions.

Evidence for a novel gene associated with low tumor metastatic potential.

We describe a gene, NM23, that is associated with the tumor metastatic process. NM23 RNA levels were highest in cells and tumors of relatively low metastatic potential in two experimental systems: (1) murine K-1735 melanoma cell lines, in which the gene was identified, and (2) N-nitroso-N-methylurea-induced rat mammary carcinomas. NM23 RNA levels did not correlate with cell sensitivity to host immunological responses and may, therefore, be associated with intrinsic aggressiveness. The predicted carboxy-terminal protein sequence encoded by the pNM23 cDNA clone is novel compared with Genebank animal, bacterial, and viral sequences.

Angiogenesis as a prognostic indicator of survival in non-small-cell lung carcinoma: a prospective study.

BACKGROUND: Tumors acquire nutrients that are essential for continued growth and an avenue for dissemination to the rest of the body by inducing angiogenesis (i.e., the formation of new blood vessels). Preliminary studies involving a number of different kinds of cancer have indicated that an assessment of tumor angiogenesis may be useful in predicting disease outcome. PURPOSE: In a prospective study, we evaluated the relationship between tumor angiogenesis and survival for 407 patients with non-small-cell lung carcinoma who were treated with potentially curative surgery. METHODS: The study population consisted of 360 male and 47 female patients who underwent surgery consecutively at the Department of Surgery, University of Pisa, Italy, from March 1991 through December 1994. Follow-up lasted through February 1996, with a median follow-up for living patients of 29 months (range, 15-60 months). An anti-CD34 monoclonal antibody, which is specific for endothelial cells, and standard immunohistochemical techniques were used to measure angiogenesis in tumor samples. Angiogenesis was quantified in terms of microvessel counts; the counts for single, high-power microscopic fields (magnification x250) in the three most intense areas of blood vessel growth for each sample were averaged. The median microvessel count in this series was 20, and the counts were categorized as follows: 1) low versus high (< or =20 versus >20 microvessels) or 2) in five categories (1-10, 11-20, 21-30, 31-40, and > or =41 microvessels). Disease-free and overall survival during follow-up were assessed. Kaplan-Meier survival curves were modeled in a univariate analysis of patient and tumor characteristics; the Cox proportional hazards model was used in multivariate analysis. Reported P values are two-sided. RESULTS AND CONCLUSIONS: In the univariate analysis, patients with larger tumors (P for trend <.00001), a more advanced tumor stage (P for trend <.00001), a greater degree of regional lymph node involvement (P for trend <.00001), or more vascularized tumors (high versus low microvessel count, P<.00001) experienced significantly reduced overall survival. When microvessel counts were analyzed in five categories, a highly significant trend (P<.00001) toward worse prognosis was observed with increasing tumor vascularity. In multivariate analysis, tumor microvessel count (P<.00001), tumor size (P = .0006), and regional lymph node status (P<.00001) retained independent prognostic value with respect to overall survival; among these variables, tumor microvessel count, considered as a continuous variable, was the most important, with a relative hazard of death of 8.38 (95% confidence interval = 4.19-16.78) associated with the highest microvessel counts. IMPLICATIONS: An evaluation of tumor angiogenesis may be useful in the postsurgical staging of patients with non-small-cell lung carcinoma and in identifying subsets of patients who may benefit from different postsurgical treatments.

Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential.

Expression of a recently identified murine gene, nm23, has been previously proposed to be inversely correlated to tumor metastatic potential in rodent model systems. The present study was designed to investigate whether nm23 RNA was detectable in human tumor tissue, and if it was differentially expressed. nm23 RNA levels in 27 human primary infiltrating ductal breast carcinomas were determined by using Northern blots or in situ hybridization. These data were compared to traditional histopathological indicators of metastatic potential, including the number of involved (tumor bearing) lymph nodes, grade of differentiation, and hormone receptor status. A striking consistency was observed in all tumors from patients with involved lymph nodes. Using Northern blot or in situ hybridizations, all of these tumors expressed low levels of nm23 RNA. Quantitative in situ hybridization on tumors from patients with 0 involved lymph nodes identified two groups: (a) approximately 75% contained high nm23 RNA levels, and (b) 25% contained significantly (alpha = 0.05) lower nm23 RNA levels. Low nm23 RNA levels in the 0 involved lymph node tumors were accompanied by two additional histopathological indicators of high metastatic potential, low nuclear and cytoplasmic estrogen receptor content, and poorly differentiated histological grade. In contrast, none of the high nm23 RNA level tumors were both receptor negative and poorly differentiated. We conclude that nm23 RNA levels are differentially expressed in human breast tumors, and that low nm23 RNA levels are associated with histopathological indication of high metastatic potential. Short term (median follow-up of 16 months) clinical course data were consistent with nm23 RNA levels, in that 2 of 11 low nm23 RNA content patients (including one from the 0 involved lymph node group) developed metastases, while none of the high nm23 RNA patients have experienced recurrent disease.

Altered expression of NM23, a gene associated with low tumor metastatic potential, during adenovirus 2 Ela inhibition of experimental metastasis.

NM23, a novel gene associated with low tumor metastatic potential, has been investigated in an experimental system in which metastasis is inhibited by the transfection of viral and cellular oncogenes. The experimental system utilizes transfection of the Adenovirus 2 Ela gene to inhibit metastasis: rat embryo fibroblasts (REF) transfected with c-Ha-ras were highly metastatic, while REF cotransfected with ras and Ela were virtually nonmetastatic. NM23 RNA levels were higher in three independently ras + Ela-cotransfected, low metastatic REF lines than in three independently ras-transfected, highly metastatic REF line. Differences in hybridizable NM23 RNA levels between the two groups of transfected cell lines ranged from 2- to 8-fold. In situ hybridization demonstrated that the relatively high NM23 RNA levels in low metastatic ras + Ela-cotransfected REF cells were not due to overexpression of the NM23 gene by a subpopulation of cells. Thus, the metastasis-inhibitory effect of the exogenously added Ela gene has been associated with increased activation of the cellular NM23 gene. This associated is particularly significant in light of the very few changes observed in translatable steady-state RNA levels between ras- and ras + Ela-transfected REF lines. The data identify NM23 as a candidate for a gene that suppresses the malignant state.

Immunohistochemical markers of neural progenitor cells in the early embryonic human cerebral cortex.

The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development.  To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tß4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation.

p21 RNA and protein expression in non-small cell lung carcinomas: evidence of p53-independent expression and association with tumoral differentiation.

p21, the product of the WAF1/CIP1/SDI1/mda-6 gene, is an inhibitor of cyclin-dependent kinases. In cell cultures p21 is induced by p53-dependent and p53-independent pathways by DNA damage and induction of differentiation. We investigated p21 RNA and immunohistochemical expression in 43 non-small cell lung carcinomas and corresponding normal lung samples previously investigated for p53 and WAF1 gene status and p53 protein expression. p21 RNA and protein expression in normal and neoplastic tissues were strictly associated (p-0.0001). In normal tissue p21 RNA was expressed at low levels and p21 immunoreactivity was seen in scattered differentiated bronchial, alveolar and stromal cells. In the majority of neoplasms p21 protein and RNA were expressed at higher levels than in the corresponding normal tissues: p21 overexpression was seen in 27 (63%) and 28 (65%) cases respectively. p21 was expressed independently from p53 gene/protein alterations. p21 overexpression was more frequent in well differentiated tumors (P=0.01 and P=0.022 for RNA and protein respectively), and p21 immunoreactivity was usually seen in foci of more pronounced differentiation. We conclude that p21 expression is related to tumor differentiation, and that p53-independent p21 expression is a common feature of in vivo neoplasms.