Numerical instabilities of spherical shallow water models considering small equivalent depths

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Shallow water models are often adopted as an intermediate step in the development of atmosphere and ocean models, though they are usually tested only with fluid depths relevant to barotropic fluids. Here we investigate numerical instabilities emerging in shallow water models considering small fluid depths, which are relevant for baroclinic fluids. Different numerical instabilities of similar nature are investigated. The first one is due to the adoption of the vector invariant form of the momentum equations, related to what is known as the Hollingsworth instability. We provide examples of this instability with finite volume and finite element schemes used in modern quasi-uniform spherical grid based models. The second is related to an energy conserving form of discretization of the Coriolis term in finite difference schemes on latitude-longitude global models. Simple test cases with shallow fluid depths are proposed as a means of capturing and predicting stability issues that can appear in three-dimensional models using only twodimensional shallow-water codes.Peixoto acknowledges the Sao Paulo Research Foundation (FAPESP) under the grant number 2016/18445-7 and the National Science and Technology Development Council (CNPq) under grant number 441328/2014-8. Thuburn was funded by the Natural Environment Research Council under the “Gung Ho” project (grant NE/1021136/1). Bell was supported by the Joint UK DECC/Defra Met Office Hadley Centre Climate Programme (GA01101)

Gradient flux measurements of sea–air DMS transfer during the Surface Ocean Aerosol Production (SOAP) experiment

Direct measurements of marine dimethylsulfide (DMS) fluxes are sparse, particularly in the Southern Ocean. The Surface Ocean Aerosol Production (SOAP) voyage in February–March 2012 examined the distribution and flux of DMS in a biologically active frontal system in the southwest Pacific Ocean. Three distinct phytoplankton blooms were studied with oceanic DMS concentrations as high as 25 nmol L−1. Measurements of DMS fluxes were made using two independent methods: the eddy covariance (EC) technique using atmospheric pressure chemical ionization–mass spectrometry (API-CIMS) and the gradient flux (GF) technique from an autonomous catamaran platform. Catamaran flux measurements are relatively unaffected by airflow distortion and are made close to the water surface, where gas gradients are largest. Flux measurements were complemented by near-surface hydrographic measurements to elucidate physical factors influencing DMS emission. Individual DMS fluxes derived by EC showed significant scatter and, at times, consistent departures from the Coupled Ocean–Atmosphere Response Experiment gas transfer algorithm (COAREG). A direct comparison between the two flux methods was carried out to separate instrumental effects from environmental effects and showed good agreement with a regression slope of 0.96 (r2 = 0.89). A period of abnormal downward atmospheric heat flux enhanced near-surface ocean stratification and reduced turbulent exchange, during which GF and EC transfer velocities showed good agreement but modelled COAREG values were significantly higher. The transfer velocity derived from near-surface ocean turbulence measurements on a spar buoy compared well with the COAREG model in general but showed less variation. This first direct comparison between EC and GF fluxes of DMS provides confidence in compilation of flux estimates from both techniques, as well as in the stable periods when the observations are not well predicted by the COAREG model

The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 2: androgen-receptor cofactors and bypass pathways

Prostate cancer is the second leading cause of cancer related deaths in men from the western world. Treatment of prostate cancer has relied on androgen deprivation therapy for the past 50 years. Response rates are initially high (70-80%), however almost all patients develop androgen escape and subsequently die within 1-2 years. Unlike breast cancer, alternative approaches (chemotherapy and radiotherapy) do not increase survival time. The high rate of prostate cancer mortality is therefore strongly linked to both development of androgen escape and the lack of alternate therapies. AR mutations and amplifications can not explain all cases of androgen escape and post-translational modification of the AR has become an alternative theory. However recently it has been suggested that AR co-activators e.g. SRC-1 or pathways the bypass the AR (Ras/MAP kinase or PI3K/Akt) may stimulated prostate cancer progression independent of the AR. This review will focus on how AR coactivators may act to increase AR transactivation during sub-optimal DHT concentrations and also how signal transduction pathways may promote androgen escape via activation of transcription factors, e.g. AP-1, c-Myc and Myb, that induce cell proliferation or inhibit apoptosis

Investigating the association of rs2910164 with cancer predisposition in an Irish cohort.

IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA-mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.MethodsThe study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.ResultsThe total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98-1.46), P  = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18-2.14), P = 0.002).ConclusionThe rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort

The Impact of Latrine Construction on Densities and Pathogen Infection Rates of Synanthropic Flies and Culex Quinquefasciatus Mosquitoes in Odisha, India

Diarrhoeal disease is one of the leading causes of mortality and morbidity globally. Non-biting synanthropic flies are of public health importance due to their habit of flying between faecal matter and households, potentially transmitting pathogenic bacteria by regurgitation, defecation or mechanical transmission via legs or wings. Lymphatic filariasis (LF), caused by Wuchereria bancofti and transmitted by Culex quinquefasciatus, affects approximately 120 million people in Asia. Controlling the mosquito vector can have a significant impact on LF incidence rates. It is assumed that increasing the coverage of latrines will reduce the amount of open defecation and environmental faecal contamination resulting in a healthier population. However, few studies have measured the impact of building latrines on human health and even fewer have demonstrated its impact on synanthropic fly populations or their bacterial carriage and associated diarrhoeal disease. Similarly, although Cx. quinquefasciatus has long been associated with pit latrines, the resulting impact through the construction of improved pour-flush latrines on population densities has yet to be explored. Initial experiments were conducted to determine the best methodology for trapping both synanthropic flies and Cx. quinquefasciatus, to inform the design of the entomological component of a cluster randomised control trial (cRCT). Thereafter, the focus was on determining the impact of latrine construction on the exposure of households to populations of flies and the bacteria that they carry, and on Cx. quinquefasciatus densities and W. bancofti prevalence. Results indicate that latrine construction had no impact on the density of flies within households or on the carriage of bacteria. There was no statistical difference between control and intervention arms in the population density of synanthropic flies (IRR=0.89; 95%CI=[0.76-1.03]; p=0.131). There was a significant correlation between fly numbers and rainfall. Data were analysed by season for between arm differences; in the monsoon season 40% fewer flies were caught in the intervention arm compared to the control arm (p=<0.001). Most flies caught belonged to the Muscidae family: Musca domestica or M. sorbens. Of the flies tested for bacteria, 60.3% were positive for at least one of either Escherichia coli 0157:H7, Vibrio cholerae, Salmonella spp. or Shigella spp.. Escherichia coli was detected most frequently with 46% testing positive. Numbers of Cx. quinquefasciatus caught (IRR=0.88; 95%CI=[0.74-1.06]; p=0.178). between the control and intervention villages. Less than 1% of Cx. quinquefasciatus tested positive for W. bancrofti, equivalent to an LF prevalence rate of 0.0034% within the vector population. Latrine construction was not associated with a reduction in the densities of vectors and their pathogens, compared to villages without latrines. However, it should not be concluded that latrines have little value in improving public health. Reducing open defecation is one step towards limiting fly population densities and bacterial contamination in the environment, by reducing available larval habitats. However, latrine coverage by itself is not enough to prevent open defecation; construction needs to be supported by behaviour change. These findings reflect that there are multiple pathways for the spread of bacteria in the environment, one of which is fly-borne. In environments with high bacterial transmission reducing fly numbers alone is not enough to impact the transmission of diarrhoeal pathogens