Solution chemistry impacts on the seawater neutralisation process: Benefits of nanofiltered seawater and reverse osmosis brine

It is well known that the neutralisation of Bayer liquor with seawater causes the precipitation of stable alkaline products and a reduction in pH and dissolved metal concentrations in the effluent. However, there is limited information available on solution chemistry effects on the stability and reaction kinetics of these precipitates. This investigation shows the influence of reactive species (magnesium and calcium) in seawater on precipitate stabilities and volumetric efficiencies during the neutralisation of bauxite refinery residues. Correlations between synthetic seawater solutions and real samples of seawater (filtered seawater, nanofiltered seawater and reverse osmosis brine) have been made. These investigations have been used to confirm that alternative seawater sources can be used to increase the productivity potential of the neutralisation process with minimal implications on the composition and stability of precipitates formed. The volume efficiency of the neutralisation process using synthetic analogues has been shown to be almost directly proportional with the concentration of magnesium. This was further confirmed in the nanofiltered seawater and reverse osmosis brine that showed increases in the efficiency of neutralisation by factors of 3 and 2 compared to seawater, which corresponds with relatively the same increase in the concentration of magnesium in these alternative seawater sources. An assessment of the chemical stability of the precipitates, volumetric efficiency, and discharge water quality have been determined using numerous techniques that include pH, conductivity, inductively coupled plasma optical emission spectroscopy, infrared spectroscopy, thermogravimetric analysis coupled to mass spectrometry and X-ray diffraction. Correlations between synthetic solution compositions and alternative seawater sources have been used to determine if alternative seawater sources are potential substitutes for seawater based on improvements in productivity, implementation costs, savings to operations and environmental benefits.

Feasibility of perflutren microsphere contrast transthoracic echocardiography in the visualization of ventricular endocardium during venovenous extracorporeal membrane oxygenation in a validated ovine model

Background: Transthoracic echocardiography (TTE) during extra corporeal membrane oxygenation (ECMO) is important but can be technically challenging. Contrast-specific TTE can improve imaging in suboptimal studies. These contrast microspheres are hydrodynamically labile structures. This study assessed the feasibility of contrast echocardiography (CE) during venovenous (VV) ECMO in a validated ovine model. Method: Twenty-four sheep were commenced on VV ECMO. Parasternal long-axis (Plax) and short-axis (Psax) views were obtained pre- and postcontrast while on VV ECMO. Endocardial definition scores (EDS) per segment were graded: 1 = good, 2 = suboptimal 3 = not seen. Endocardial border definition score index (EBDSI) was calculated for each view. Endocardial length (EL) in the Plax view for the left ventricle (LV) and right ventricle (RV) was measured. Results: Summation EDS data for the LV and RV for unenhanced TTE (UE) versus CE TTE imaging: EDS 1 = 289 versus 346, EDS 2 = 38 versus 10, EDS 3 = 33 versus 4, respectively. Wilcoxon matched-pairs rank-sign tests showed a significant ranking difference (improvement) pre- and postcontrast for the LV (P < 0.0001), RV (P < 0.0001) and combined ventricular data (P < 0.0001). EBDSI for CE TTE was significantly lower than UE TTE for the LV (1.05 ± 0.17 vs. 1.22 ± 0.38, P = 0.0004) and RV (1.06 ± 0.22 vs. 1.42 ± 0.47, P = 0.0.0006) respectively. Visualized EL was significantly longer in CE versus UE for both the LV (58.6 ± 11.0 mm vs. 47.4 ± 11.7 mm, P < 0.0001) and the RV (52.3 ± 8.6 mm vs. 36.0 ± 13.1 mm, P < 0.0001), respectively. Conclusions: Despite exposure to destructive hydrodynamic forces, CE is a feasible technique in an ovine ECMO model. CE results in significantly improved EDS and increased EL.

The Arctic Summer Cloud Ocean Study (ASCOS): overview and experimental design

The climate in the Arctic is changing faster than anywhere else on earth. Poorly understood feedback processes relating to Arctic clouds and aerosol–cloud interactions contribute to a poor understanding of the present changes in the Arctic climate system, and also to a large spread in projections of future climate in the Arctic. The problem is exacerbated by the paucity of research-quality observations in the central Arctic. Improved formulations in climate models require such observations, which can only come from measurements in situ in this difficult-to-reach region with logistically demanding environmental conditions. The Arctic Summer Cloud Ocean Study (ASCOS) was the most extensive central Arctic Ocean expedition with an atmospheric focus during the International Polar Year (IPY) 2007–2008. ASCOS focused on the study of the formation and life cycle of low-level Arctic clouds. ASCOS departed from Longyearbyen on Svalbard on 2 August and returned on 9 September 2008. In transit into and out of the pack ice, four short research stations were undertaken in the Fram Strait: two in open water and two in the marginal ice zone. After traversing the pack ice northward, an ice camp was set up on 12 August at 87°21' N, 01°29' W and remained in operation through 1 September, drifting with the ice. During this time, extensive measurements were taken of atmospheric gas and particle chemistry and physics, mesoscale and boundary-layer meteorology, marine biology and chemistry, and upper ocean physics. ASCOS provides a unique interdisciplinary data set for development and testing of new hypotheses on cloud processes, their interactions with the sea ice and ocean and associated physical, chemical, and biological processes and interactions. For example, the first-ever quantitative observation of bubbles in Arctic leads, combined with the unique discovery of marine organic material, polymer gels with an origin in the ocean, inside cloud droplets suggests the possibility of primary marine organically derived cloud condensation nuclei in Arctic stratocumulus clouds. Direct observations of surface fluxes of aerosols could, however, not explain observed variability in aerosol concentrations, and the balance between local and remote aerosols sources remains open. Lack of cloud condensation nuclei (CCN) was at times a controlling factor in low-level cloud formation, and hence for the impact of clouds on the surface energy budget. ASCOS provided detailed measurements of the surface energy balance from late summer melt into the initial autumn freeze-up, and documented the effects of clouds and storms on the surface energy balance during this transition. In addition to such process-level studies, the unique, independent ASCOS data set can and is being used for validation of satellite retrievals, operational models, and reanalysis data sets.

Metrological assessment of a portable analyzer for monitoring the particle size distribution of ultrafine particles

Adverse health effects caused by worker exposure to ultrafine particles have been detected in recent years. The scientific community focuses on the assessment of ultrafine aerosols in different microenvironments in order to determine the related worker exposure/dose levels. To this end, particle size distribution measurements have to be taken along with total particle number concentrations. The latter are obtainable through hand-held monitors. A portable particle size distribution analyzer (Nanoscan SMPS 3910, TSI Inc.) was recently commercialized, but so far no metrological assessment has been performed to characterize its performance with respect to well-established laboratory- based instruments such as the scanning mobility particle sizer (SMPS) spectrometer. The present paper compares the aerosol monitoring capability of the Nanoscan SMPS to the laboratory SMPS in order to evaluate whether the Nanoscan SMPS is suitable for field experiments designed to characterize particle exposure in different microenvironments. Tests were performed both in a Marple calm air chamber, where fresh diesel particulate matter and atomized dioctyl phthalate particles were monitored, and in microenvironments, where outdoor, urban, indoor aged, and indoor fresh aerosols were measured. Results show that the Nanoscan SMPS is able to properly measure the particle size distribution for each type of aerosol investigated, but it overestimates the total particle number concentration in the case of fresh aerosols. In particular, the test performed in the Marple chamber showed total concentrations up to twice those measured by the laboratory SMPS—likely because of the inability of the Nanoscan SMPS unipolar charger to properly charge aerosols made up of aggregated particles. Based on these findings, when field test exposure studies are conducted, the Nanoscan SMPS should be used in tandem

Optimal management of the critically Ill: Anaesthesia, monitoring, data capture, and point-of-care technological practices in ovine models of critical care

Animal models of critical illness are vital in biomedical research. They provide possibilities for the investigation of pathophysiological processes that may not otherwise be possible in humans. In order to be clinically applicable, the model should simulate the critical care situation realistically, including anaesthesia, monitoring, sampling, utilising appropriate personnel skill mix, and therapeutic interventions. There are limited data documenting the constitution of ideal technologically advanced large animal critical care practices and all the processes of the animal model. In this paper, we describe the procedure of animal preparation, anaesthesia induction and maintenance, physiologic monitoring, data capture, point-of-care technology, and animal aftercare that has been successfully used to study several novel ovine models of critical illness. The relevant investigations are on respiratory failure due to smoke inhalation, transfusion related acute lung injury, endotoxin-induced proteogenomic alterations, haemorrhagic shock, septic shock, brain death, cerebral microcirculation, and artificial heart studies. We have demonstrated the functionality of monitoring practices during anaesthesia required to provide a platform for undertaking systematic investigations in complex ovine models of critical illness.

Evaluation of electrocoagulation for the pre-treatment of coal seam water

This work explored the applicability of electrocoagulation (EC) using aluminium electrodes for the removal of contaminants which can scale and foul reverse osmosis membranes from a coal seam (CS) water sample, predominantly comprising sodium chloride, and sodium bicarbonate. In general, the removal efficiency of species responsible for scaling and fouling was enhanced by increasing the applied current density/voltage and contact times (30–60 s) in the EC chamber. High removal efficiencies of species potentially responsible for scale formation in reverse osmosis units such as calcium (100%), magnesium (87.9%), strontium (99.3%), barium (100%) and silicates (98.3%) were achieved. Boron was more difficult to eliminate (13.3%) and this was postulated to be due to the elevated solution pH. Similarly, fluoride removal from solution (44%) was also inhibited by the presence of hydroxide ions in the pH range 9–10. Analysis of produced flocs suggested the dominant presence of relatively amorphous boehmite (AlOOH), albeit the formation of Al(OH)3 was not ruled out as the drying process employed may have converted aluminium hydroxide to aluminium oxyhydroxide species. Evidence for adsorption of contaminants on floc surface sites was determined from FTIR studies. The quantity of aluminium released during the electrocoagulation process was higher than the Faradaic amount which suggested that the high salt concentrations in the coal seam water had chemically reacted with the aluminium electrodes.

Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide

The objective of this study was to compare the short-term respiratory effects due to the inhalation of electronic and conventional tobacco cigarette-generated mainstream aerosols through the measurement of the exhaled nitric oxide (eNO). To this purpose, twenty-five smokers were asked to smoke a conventional cigarette and to vape an electronic cigarette (with and without nicotine), and an electronic cigarette without liquid (control session). Electronic and tobacco cigarette mainstream aerosols were characterized in terms of total particle number concentrations and size distributions. On the basis of the measured total particle number concentrations and size distributions, the average particle doses deposited in alveolar and tracheobronchial regions of the lungs for a single 2-s puff were also estimated considering a subject performing resting (sitting) activity. Total particle number concentrations in the mainstream resulted equal to 3.5 ± 0.4 × 109, 5.1 ± 0.1 × 109, and 3.1 ± 0.6 × 109 part. cm− 3 for electronic cigarettes without nicotine, with nicotine, and for conventional cigarettes, respectively. The corresponding alveolar doses for a resting subject were estimated equal to 3.8 × 1010, 5.2 × 1010 and 2.3 × 1010 particles. The mean eNO variations measured after each smoking/vaping session were equal to 3.2 ppb, 2.7 ppb and 2.8 ppb for electronic cigarettes without nicotine, with nicotine, and for conventional cigarettes, respectively; whereas, negligible eNO changes were measured in the control session. Statistical tests performed on eNO data showed statistically significant differences between smoking/vaping sessions and the control session, thus confirming a similar effect on human airways whatever the cigarette smoked/vaped, the nicotine content, and the particle dose received.

Spatial distribution of selected persistent organic pollutants (POPs) in Australia's atmosphere

A nation-wide passive air sampling campaign recorded concentrations of persistent organic pollutants in Australia's atmosphere in 2012. XAD-based passive air samplers were deployed for one year at 15 sampling sites located in remote/background, agricultural and semi-urban and urban areas across the continent. Concentrations of 47 polychlorinated biphenyls ranged from 0.73 to 72 pg m-3 (median of 8.9 pg m-3) and were consistently higher at urban sites. The toxic equivalent concentration for the sum of 12 dioxin-like PCBs was low, ranging from below detection limits to 0.24 fg m-3 (median of 0.0086 fg m-3). Overall, the levels of polychlorinated biphenyls in Australia were among the lowest reported globally to date. Among the organochlorine pesticides, hexachlorobenzene had the highest (median of 41 pg m-3) and most uniform concentration (with a ratio between highest and lowest value [similar]5). Bushfires may be responsible for atmospheric hexachlorobenzene levels in Australia that exceeded Southern Hemispheric baseline levels by a factor of [similar]4. Organochlorine pesticide concentrations generally increased from remote/background and agricultural sites to urban sites, except for high concentrations of [small alpha]-endosulfan and DDTs at specific agricultural sites. Concentrations of heptachlor (0.47-210 pg m-3), dieldrin (ND-160 pg m-3) and trans- and cis-chlordanes (0.83-180 pg m-3, sum of) in Australian air were among the highest reported globally to date, whereas those of DDT and its metabolites (ND-160 pg m-3, sum of), [small alpha]-, [small beta]-, [gamma]- and [small delta]-hexachlorocyclohexane (ND-6.7 pg m-3, sum of) and [small alpha]-endosulfan (ND-27 pg m-3) were among the lowest.

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.

Tumor-associated mutations inO6-methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality

MGMT is the primary vehicle for cellular removal of alkyl lesions from the O-6 position of guanine and the O-4 position of thymine. While key to the maintenance of genomic integrity, MGMT also removes damage induced by alkylating chemotherapies, inhibiting the efficacy of cancer treatment. Germline variants of human MGMT are well-characterized, but somatic variants found in tumors were, prior to this work, uncharacterized. We found that MGMT G132R, from a human esophageal tumor, and MGMT G156C, from a human colorectal cancer cell line, are unable to rescue methyltransferase-deficient Escherichia coli as well as wild type (WT) human MGMT after treatment with a methylating agent. Using pre-steady state kinetics, we biochemically characterized these variants as having a reduced rate constant. G132R binds DNA containing an O6-methylguanine lesion half as tightly as WT MGMT, while G156C has a 40-fold decrease in binding affinity for the same damaged DNA versus WT. Mammalian cells expressing either G132R or G156C are more sensitive to methylating agents than mammalian cells expressing WT MGMT. G132R is slightly resistant to O6-benzylguanine, an inhibitor of MGMT in clinical trials, while G156C is almost completely resistant to this inhibitor. The impared functionality of expressed variants G132R and G156C suggests that the presence of somatic variants of MGMT in a tumor could impact chemotherapeutic outcomes.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Risk analysis of prostate cancer in PRACTICAL, a multinational consortium, using 25 known prostate cancer susceptibility loci

Background Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived agespecific absolute risks of developing prostate cancer by PRS stratum and family history. Results The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact:We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

Investigation of the effect of balconies on natural ventilation of dwellings in high-rise residential buildings in subtropical climate

Balconies, as one of the main architectural features in subtropical climates, are assumed to enhance the ventilation performance of buildings by redirecting the wind. Although there are some studies on the effect of balconies on natural ventilation inside buildings, the majority have been conducted on single zone buildings with simple geometries. The purpose of this study is to explore the effect of balconies on the internal air flow pattern and ventilation performance of multi-storey residential buildings with internal partitions. To this end, a sample residential unit was selected for investigation and three different conditions tested, base case (no balcony), an open balcony and a semi-enclosed balcony. Computational Fluid Dynamics is used as an analysis method due to its accuracy and ability to provide detailed results. The cases are analysed in terms of average velocity, flow uniformity and number of Air Changes per Hour (ACH). The results suggest the introduction of a semi-enclosed balcony into high-rise dwellings improves the average velocity and flow uniformity. Integrating an open balcony results in reduction of the aforementioned parameters at 0° wind incidence.

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.