A case report and brief review of the literature on bilateral retinal infarction following cardiopulmonary bypass for coronary artery bypass grafting

Postoperative visual loss is a devastating perioperative complication. The commonest aetiologies are anterior ischaemic optic neuropathy (AION), posterior ischaemic optic neuropathy (PION), and central retinal artery occlusion (CRAO). These appear to be related to certain types of operation, most commonly spinal and cardiac bypass procedures; with the rest divided between: major trauma causing excessive blood loss; head/neck and nasal or sinus surgery; major vascular procedures (aortic aneurysm repair, aorto-bifemoral bypass); general surgery; urology; gynaecology; liposuction; liver transplantation and duration of surgery. The non-surgical risk factors are multifactorial: advanced age, prolonged postoperative anaemia, positioning (supine v prone), alteration of venous drainage of the retina, hypertension, smoking, atherosclerosis, hyperlipidaemia, diabetes, hypercoagulability, hypotension, blood loss and large volume resuscitation. Other important cardiac causes are septic emboli from bacterial endocarditis and emboli caused by atrial myxomata. The majority of AION cases occur during CPB followed by head/neck surgery and prone spine surgery. CPB is used to allow coronary artery bypass grafting on a motionless heart. It has many side-effects and complications associated with its use and we report here a case of bilateral retinal infarction during routine coronary artery bypass grafting in a young male patient with multiple risk factors for developing this complication despite steps to minimise its occurrence

Amplicon-Dependent CCNE1 Expression Is Critical for Clonogenic Survival after Cisplatin Treatment and Is Correlated with 20q11 Gain in Ovarian Cancer

Genomic amplification of 19q12 occurs in several cancer types including ovarian cancer where it is associated with primary treatment failure. We systematically attenuated expression of genes within the minimally defined 19q12 region in ovarian cell lines using short-interfering RNAs (siRNA) to identify driver oncogene(s) within the amplicon. Knockdown of CCNE1 resulted in G1/S phase arrest, reduced cell viability and apoptosis only in amplification-carrying cells. Although CCNE1 knockdown increased cisplatin resistance in short-term assays, clonogenic survival was inhibited after treatment. Gain of 20q11 was highly correlated with 19q12 amplification and spanned a 2.5 Mb region including TPX2, a centromeric protein required for mitotic spindle function. Expression of TPX2 was highly correlated with gene amplification and with CCNE1 expression in primary tumors. siRNA inhibition of TPX2 reduced cell viability but this effect was not amplicon-dependent. These findings demonstrate that CCNE1 is a key driver in the 19q12 amplicon required for survival and clonogenicity in cells with locus amplification. Co-amplification at 19q12 and 20q11 implies the presence of a cooperative mutational network. These observations have implications for the application of targeted therapies in CCNE1 dependent ovarian cancers

Lipidomics Analysis Reveals Efficient Storage of Hepatic Triacylglycerides Enriched in Unsaturated Fatty Acids after One Bout of Exercise in Mice

Background: Endurance exercise induces lipolysis, increases circulating concentrations of free fatty acids (FFA) and the uptake and oxidation of fatty acids in the working muscle. Less is known about the regulation of lipid metabolism in the liver during and post-exercise

Attitudes of Hong Kong residents to cars and public transport: some policy implications

Hong Kong currently has low levels of car ownership and use due to a combination of good public transport, high population densities and high private transport costs. However, levels are rising, contributing to congestion and environmental problems. A major response by the government is to seek to increase rail's share of public transport journeys from its current level of 33% to 45% by 2016. After reviewing the transport situation in Hong Kong, the paper discusses the appropriateness of these targets as well as questioning whether they are achievable. The results of a questionnaire survey of 595 residents of Hong Kong, designed to elicit people's attitudes to cars and public transport, are analysed. It is concluded that unless the government does more to curb car ownership and use, rail targets will have little chance of being achieved

UK National Parks: A Role for Road-Pricing?

This is an electronic version of an article published in the International Journal of Sustainable Transportation [© Taylor & Francis] and the definitive version is available at: www.tandf.co.uk/journals/titles/15568318.aspThe National Parks of the United Kingdom are characterised by their beautiful countryside and spectacular rural landscapes. They are also significant trip attracting locations, the dominant transport mode being the private car, which typically accounts for 90% of all journeys made to these destinations. Excessive car use in National Parks is problematic since traffic congestion, environmental degradation, vehicle noise and parking problems serve to undermine the natural and recreational values which they are intended to promote. Though not widely explored in a rural policy context, recent literature published by key stakeholders has called for research into the potential use of innovative measures such as road pricing in National Park settings. This paper reports on the findings of in-depth interviews with Transport Officers at eleven of the fourteen UK National Park Authorities, which seek to explore the attitudes of this key group of stakeholders in regard to road pricing and the UK National Parks. The paper concludes that the complexity of the transport planning process, the significance of relationships between key stakeholders, and perceptions of existing transport conditions ‘on the ground’ in National Parks, would appear to negate the possible application of road pricing in these settings for the foreseeable future. For policy makers and planners, who have long since called for an integrated transport planning approach consisting of incentives and, crucially, disincentives, the findings question the future direction of transport planning in economically attractive, yet environmentally sensitive locations

Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis.

Deregulated glucose metabolism fulfills the energetic and biosynthetic requirements for tumor growth driven by oncogenes. Because inhibition of oncogenic BRAF causes profound reductions in glucose uptake and a strong clinical benefit in BRAF-mutant melanoma, we examined the role of energy metabolism in responses to BRAF inhibition. We observed pronounced and consistent decreases in glycolytic activity in BRAF-mutant melanoma cells. Moreover, we identified a network of BRAF-regulated transcription factors that control glycolysis in melanoma cells. Remarkably, this network of transcription factors, including hypoxia-inducible factor-1α, MYC, and MONDOA (MLXIP), drives glycolysis downstream of BRAF(V600), is critical for responses to BRAF inhibition, and is modulated by BRAF inhibition in clinical melanoma specimens. Furthermore, we show that concurrent inhibition of BRAF and glycolysis induces cell death in BRAF inhibitor (BRAFi)-resistant melanoma cells. Thus, we provide a proof-of-principle for treatment of melanoma with combinations of BRAFis and glycolysis inhibitors

S ⁵: The Orbital and Chemical Properties of One Dozen Stellar Streams

Abstract We report the kinematic, orbital, and chemical properties of 12 stellar streams with no evident progenitors using line-of-sight velocities and metallicities from the Southern Stellar Stream Spectroscopic Survey (S 5), proper motions from Gaia EDR3, and distances derived from distance tracers or the literature. This data set provides the largest homogeneously analyzed set of streams with full 6D kinematics and metallicities. All streams have heliocentric distances between ∼10 and 50 kpc. The velocity and metallicity dispersions show that half of the stream progenitors were disrupted dwarf galaxies (DGs), while the other half originated from disrupted globular clusters (GCs), hereafter referred to as DG and GC streams. Based on the mean metallicities of the streams and the mass–metallicity relation, the luminosities of the progenitors of the DG streams range between those of Carina and Ursa Major I (−9.5 ≲ M V ≲ −5.5). Four of the six GC streams have mean metallicities of [Fe/H] &lt; −2, more metal poor than typical Milky Way (MW) GCs at similar distances. Interestingly, the 300S and Jet GC streams are the only streams on retrograde orbits in our dozen-stream sample. Finally, we compare the orbital properties of the streams with known DGs and GCs in the MW, finding several possible associations. Some streams appear to have been accreted with the recently discovered Gaia–Enceladus–Sausage system, and others suggest that GCs were formed in and accreted together with the progenitors of DG streams whose stellar masses are similar to those of Draco to Carina (∼105–106 M ⊙).</jats:p

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy