Breast cancer in lesbians and bisexual women: Systematic review of incidence, prevalence and risk studies

This article is made available through the Brunel Open Access Publishing Fund. © 2013 Meads and Moore; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The UK Parliamentary Enquiry and USA Institute of Medicine state that lesbians may be at a higher risk of breast cancer but there is insufficient information. Lesbians and bisexual (LB) women have behavioural risk-factors at higher rates compared to heterosexuals such as increased alcohol intake and higher stress levels. Conversely, breast cancer rates are higher in more affluent women yet income levels in LB women are relatively low. This systematic review investigated all evidence on whether there is, or likely to be, higher rates of breast cancer in LB women. Methods: Cochrane library (CDSR, CENTRAL, HTA, DARE, NHSEED), MEDLINE, EMBASE, PsychINFO, CAB abstracts, Web of Science (SCI, SSCI), SIGLE and Social Care Online databases were searched to October 2013. Unpublished research and specific lesbian, gay and bisexual websites were checked, as were citation lists of relevant papers. Included were studies in LB populations reporting breast cancer incidence or prevalence rates, risk model results or risk-factor estimates. Inclusions, data-extraction and quality assessment were by two reviewers with disagreements resolved by discussion. Results: Searches found 198 references. No incidence rates were found. Nine studies gave prevalence estimates - two showed higher, four showed no differences, one showed mixed results depending on definitions, one had no comparison group and one gave no sample size. All studies were small with poor methodological and/or reporting quality. One incidence modelling study suggested a higher rate. Four risk modelling studies were found, one Rosner-Colditz and three Gail models. Three suggested higher and one lower rate in LB compared to heterosexual women. Six risk-factor estimates suggested higher risk and one no difference between LB and heterosexual women. Conclusions: The only realistic way to establish rates in LB women would be to collect sexual orientation within routine statistics, including cancer registry data, or from large cohort studies

2012 Wild Blueberry Project Reports

The 2012 edition of the Wild Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Do wild blueberries alleviate risk factors related to the Metabolic Syndrome? 2. Development of effective intervention measures to maintain and improve food safety for wild blueberries 3. Control tactics for blueberry pest insects, 2012 4. Development and implementation of a wild blueberry thrips IPM program, 2012 5. IPM 6. Biology of blueberry and pest insects, 2012 7. Biology of beneficial insects and blueberry pollination, 2012 8. Pesticide residues on lowbush blueberry, 2012 9. Maine wild blueberry –mummy berry research and extension 10. Efficacy of Apogee growth regulator for stimulating rhizome growth into bare spots in wild blueberry fields 11. Velpar by Matrix pre and post-emergence applications - demonstration plots 12. Wild blueberry Extension Education Program in 2012 INPUT SYSTEMS STUDY: 13. Systems approach to improving the sustainability of wild blueberry production, Year Three of a four-year study – experimental design 14. Food safety- Prevalence study of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella spp. on lowbush blueberries (Vaccinium angustifolium) 15. Abundance of insect pest species and natural enemies in lowbush blueberry fields maintained under different management practices 16. Input Systems Study: Systems approach to improving the sustainability of wild blueberry production, Year 3 of a four-year study, disease management results 17. Plant productivity, Year Three of a four-year study 18. Systems approach to improving the sustainability of wild blueberry production, Year Three of a four-year study, weed management results 19. Effects of organic and conventional management systems on the phosphorus solubility of lowbush blueberry barren soils 20. Systems approach to improving sustainability of wild blueberry production – soil health and chemistry measures 21. Evaluation of fungicides for control of mummy berry disease (ancillary study) 22. Systems approach to improving the sustainability of wild blueberry production – Ancillary land-leveling study, Year Two of a four-year study (ancillary study) 23. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2012 results from the 2011 trial (ancillary study) 24. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2012 trial (ancillary study) 25. Evaluation of herbicides for control of fineleaf sheep fescue for grass control in wild blueberries (ancillary study) 26. Pre-emergence application timing and rate of Alion and Sandea in combination with Velpar or Sinbar on weed control and injury to wild blueberry (ancillary study) 27. Compost and mulch effects on soil health and nutrient dynamics in wild blueberry (ancillary study

Falls and mobility in Parkinson's disease: protocol for a randomised controlled clinical trial

Background Although physical therapy and falls prevention education are argued to reduce falls and disability in people with idiopathic Parkinson\u27s disease, this has not yet been confirmed with a large scale randomised controlled clinical trial. The study will investigate the effects on falls, mobility and quality of life of (i) movement strategy training combined with falls prevention education, (ii) progressive resistance strength training combined with falls prevention education, (iii) a generic life-skills social program (control group). Methods/Design People with idiopathic Parkinson\u27s disease who live at home will be recruited and randomly allocated to one of three groups. Each person shall receive therapy in an out-patient setting in groups of 3-4. Each group shall be scheduled to meet once per week for 2 hours for 8 consecutive weeks. All participants will also have a structured 2 hour home practice program for each week during the 8 week intervention phase. Assessments will occur before therapy, after the 8 week therapy program, and at 3 and 12 months after the intervention. A falls calendar will be kept by each participant for 12 months after outpatient therapy. Consistent with the recommendations of the Prevention of Falls Network Europe group, three falls variables will be used as the primary outcome measures: the number of fallers, the number of multiple fallers and the falls rate. In addition to quantifying falls, we shall measure mobility, activity limitations and quality of life as secondary outcomes. Discussion This study has the potential to determine whether outpatient movement strategy training combined with falls prevention education or progressive resistance strength training combined with falls prevention education are effective for reducing falls and improving mobility and life quality in people with Parkinson\u27s disease who live at home

Oncogenic EGFR Signaling Activates an mTORC2-NF- B Pathway That Promotes Chemotherapy Resistance

Although it is known that mTOR complex 2 (mTORC2) functions upstream of Akt, the role of this protein kinase complex in cancer is not well understood. Through an integrated analysis of cell lines, in vivo models and clinical samples, we demonstrate that mTORC2 is frequently activated in glioblastoma (GBM), the most common malignant primary brain tumor of adults. We show that the common activating epidermal growth factor receptor (EGFR) mutation (EGFRvIII) stimulates mTORC2 kinase activity, which is partially suppressed by PTEN. mTORC2 signaling promotes GBM growth and survival, and activates NF-κB. Importantly, this mTORC2-NF-κB pathway renders GBM cells and tumors resistant to chemotherapy in a manner independent of Akt. These results highlight the critical role of mTORC2 in GBM pathogenesis, including through activation of NF-κB downstream of mutant EGFR, leading to a previously unrecognized function in cancer chemotherapy resistance. These findings suggest that therapeutic strategies targeting mTORC2, alone or in combination with chemotherapy, will be effective in cancer

Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.

Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium. Antagonistically, ESX-1 is also essential to block the autophagic flux and deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize to the MCV in an ESX-1-dependent manner, suggesting an important role in the manipulation of autophagy by mycobacteria. Our findings suggest that the infection by M. marinum activates an autophagic response that is simultaneously repressed and exploited by the bacterium to support its survival inside the MCV

KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1

The mechanistic target of rapamycin complex 1 kinase (mTORC1) is a central regulator of cell growth that responds to diverse environmental signals and is deregulated in many human diseases, including cancer and epilepsy1–3. Amino acids are a key input, and act through the Rag GTPases to promote the translocation of mTORC1 to the lysosomal surface, its site of activation4. Multiple protein complexes regulate the Rag GTPases in response to amino acids, including GATOR1, a GTPase activating protein for RagA, and GATOR2, a positive regulator of unknown molecular function. Here, we identify a four-membered protein complex (KICSTOR) composed of the KPTN, ITFG2, C12orf66, and SZT2 gene products as required for amino acid or glucose deprivation to inhibit mTORC1 in cultured cells. In mice lacking SZT2, mTORC1 signaling is increased in several tissues, including in neurons in the brain. KICSTOR localizes to lysosomes; binds to GATOR1 and recruits it, but not GATOR2, to the lysosomal surface; and is necessary for the interaction of GATOR1 with its substrates, the Rag GTPases, and with GATOR2. Interestingly, several KICSTOR components are mutated in neurological diseases associated with mutations that lead to hyperactive mTORC1 signaling5–10. Thus, KICSTOR is a lysosome-associated negative regulator of mTORC1 signaling that, like GATOR1, is mutated in human disease11,12

Synthesis of Polybenzoquinolines as Graphene Nanoribbon Precursors

The bottom-up synthesis of graphene nanoribbons (narrow strips of sp2 hybridized carbon) has attracted much attention in recent years, with a number of contemporary demonstrations of the preparation of allcarbon systems. However, a limited number of studies have addressed the solution-phase synthesis of heteroatom-doped graphene nanoribbons; the design and preparation of such constructs is a significant challenge. We have recently developed new synthetic methodologies for the synthesis of oligobenzoquinolines via the aza-Diels???Alder (Povarov) reaction, producing oligobenzoquinoline precursors whose length and sequence are precisely controlled. Our straightforward approach also provides access to crowded macromolecular polybenzoquinoline scaffolds, which are key intermediates for the preparation of nitrogen-doped nanoribbons. Altogether, these findings hold implications for the bottom-up synthesis of graphene nanoribbons whose edge character, terminal functionalities, doping, and length are precisely defined

Synthesis of polybenzoquinolines as graphene nanoribbon precursors

The bottom-up synthesis of all-carbon graphene nanoribbons (narrow strips of sp2 hybridized carbon) has attracted much attention in recent years, with a number of contemporary demonstrations of the preparation of all-carbon systems. However, fewer studies have focused on the solution-phase synthesis of heteroatom-doped graphene nanoribbons, the preparation of which remains a significant synthetic challenge. We have developed an iterative route to oligobenzoquinolines based on the aza-Diels–Alder (Povarov) reaction and methodologies for controlling the length and sequence of our oligobenzoquinoline precursors. Our straightforward approach also provides access to crowded macromolecular polybenzoquinoline scaffolds with a unique architecture and connectivity, which are key intermediates for the preparation of nitrogen-doped nanoribbons. Our findings hold implications for the bottom-up synthesis of graphene nanoribbons whose edge character, terminal functionalities, doping, and length are precisely controllable

Synthesis of N-Heterocyclic Compounds: N-Doped Rubicene and Tetrabenzopentacene

Carbon-based materials, such as acenes, fullerenes, and graphene nanoribbons, are viewed as the potential successors to silicon in the next generation of electronics. Although a number of methodologies provide access to these materials all-carbon variants, relatively fewer strategies readily furnish their nitrogen-doped analogues. Herein, we report the synthesis of nitrogen-containing rubicene and tetrabenzopentacene via selective Heck-type reactions