Failure to Achieve PSA Level ≤I ng/ml Following Neo-Adjuvant LHRHa Therapy Predicts for a Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated with Radiotherapy

PURPOSE: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to /=2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. METHODS AND MATERIALS: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was 1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of 1 ng/mL at the beginning of external beam radiotherapy after >/=2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of

Level of renal function and serum erythropoietin levels independently predict anaemia post-renal transplantation

Background. Post-renal transplant anaemia is a potentially reversible cardiovascular risk factor. Graft function, immunosuppressive agents and inhibition of the renin-angiotensin system have been implicated in its aetiology. The evaluation of erythropoietin (EPO) levels may contribute to understanding the relative contributions of these factors. Methods. Two-hundred and seven renal transplant recipients attending the Belfast City Hospital were studied. Clinical and laboratory data were extracted from the medical records and laboratory systems. Results. Of the 207 patients (126 male), 47 (22.7%) were found to be anaemic (males, haemoglobin (Hb) <12 g/dl, females Hb <11g/dl). The anaemic group had a significantly higher mean serum creatinine level (162.8 µmol/l vs 131.0 µmol/l, P <0.001) and lower mean estimated glomerular filtration rate (eGFR) (41.5 ml/min vs 54.9 ml/min, P <0.001) than the non-anaemic group. Individual immunosuppressive regimens were comparable between those with and those without anaemia. Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) administration was not more prevalent in those with anaemia compared with those without (36.2 vs 38.8, P = 0.88). There was a significant inverse correlation between Hb levels and serum EPO levels (R = -0.29, P <0.001), but not between EPO levels and eGFR (R = 0.02, P = 0.74). Higher EPO levels were predictive of anaemia, independent of eGFR in multivariate analysis. Conclusion. Anaemia is common in post-renal transplant patients. The levels of renal function and serum EPO and not immunosuppressive regimens or ACE-I/ARB use, are strong and independent predictors of anaemia. © The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Effects of environment and an introduced invertebrate species on the structure of benthic macroinvertebrate species at the catchment level

Biotic interactions such as predation and competition can influence aquatic communities at small spatial scales, but they are expected to be overridden by environmental factors at large scales. The continuing threat to freshwater biodiversity of biological invasions indicates that biotic factors do, however, have important structuring roles. In Irish rivers, the native amphipod Gammarus duebeni celticus has become locally extinct, ostensibly through differential predation by the more aggressive and introduced G. pulex. This mechanism explains impacts of G. pulex at within-river spatial scales on native macroinvertebrate community diversity, including declines in ephemeropterans, plecopterans, dipterans and oligochaetes. To determine if these patterns are predictable at larger spatial scales, we assessed patterns in native macroinvertebrate communities across river sites of the Erne catchment in 1998 and 1999, in conjunction with the distribution of G. pulex and G. d. celticus. In both years, G. pulex dominated invaded sites, whereas G. d. celticus occurred at low abundance in uninvaded sites. In both years, invaded sites had lower diversity and fewer pollution sensitive invertebrate species than un-invaded sites. Community ordination in 1998 showed that invaded sites had higher conductivity, smaller substrate particle size and comprised a lower proportion of pollution sensitive taxa including Ephemeroptera and Plecoptera. In contrast, in 1999, conductivity was the only variable explaining site ordination along axis 1, but was unable to separate sites with respect to invasion status. A second explanatory axis separated sites with respect to invasion status, with invaded sites having fewer taxa, including lower abundance of ephemeropterans, dipterans and plecopterans. Laboratory experiments examined the potential role of differential predation between the two Gammarus species in explaining these taxon specific patterns in the field. Survival of the ephemeropterans, Ephemerella ignita and Ecdyonurus venosus and the isopod, Asellus aquaticus, was lower when interacting with G. pulex than with G. d. celticus. This study indicates that G. putex may alter invertebrate community structure at scales beyond those detected within individual rivers. However, effects may be influenced by gradients in physico-chemistry, which may be temporal or depend on catchment characteristics. Invasions by amphipods have increased globally, thus comprehensive assessments of their impacts and of other aquatic invaders, may only be apparent when studies are conducted at a range of spatio-temporal scales.

Mineralogy of selected geological deposits from the United Kingdom and the Republic of Ireland as possible capping materials for low-level radioactive waste disposal facilities

Solid low-level radioactive waste (LLW) is currently being disposed at a number of facilities in the United Kingdom (UK). The safety of these facilities relies to some extent on the use of engineered barriers, such as a cap, to isolate the waste and protect the environment. Generally, the material used as the barrier layer within such a cap should be of low permeability and it should retain this property over long timescales (beyond a few decades normally required for facilities containing non-radioactive wastes). The objective of this research is to determine the mineralogy of selected geological deposits from the UK and Ireland as part of a larger project to examine their suitability as a capping material, particularly on LLW sites. Mineral transformations, as a result of future climate change, may impact on the long-term performance of the cap and even the disposal facility. X-ray diffraction (XRD) was carried-out on the sand, silt and clay fractions of the London Clay, Belfast Upper Boulder Clay, Irish Glacial Till, Belfast Sleech, and Ampthill Clay geological deposits. Minerals were present that could pose both positive and negative effects on the long-term performance of the cap. Smectite, which has a high shrink swell potential, may produce cracks in London Clay, Belfast Upper Boulder Clay and Ampthill Clay capping material during dry, hotter periods as a possible consequence of future climate change; thus, resulting in higher permeability. Ampthill Clay and Belfast Sleech had elevated amounts of organic matter (OM) at 5.93% and 5.88%, respectively, which may also contribute to cracking. Over time, this OM may decompose and result in increased permeability. Gypsum (CaSO4) in the silt and sand fractions of Ampthill Clay may reduce the impact of erosion during wetter periods if it is incorporated into the upper portion of the cap. There are potential negative effects from the acidity created by the weathering of pyrite (FeS2) present in the silt and sand fractions of Belfast Sleech and Ampthill Clay that could impede the growth of grasses used to stabilize the surface of the capping material if this material is used as part of the vegetative soil layer. Additionally, acidic waters generated from pyrite weathering could negatively impact the lower lying capping layers and the disposal facility in general. However, the calcium carbonate (CaCO3) present in the silt and sand fractions of these deposits, and dolomite (CaMg(CO3)2) in Belfast Sleech, may counter act the acidity.

Temperature Dependence of the Primary Relaxation in 1-Hexyl-3-methylimidazolium bis{(trifluoromethyl)sulfonyl}imide

We present results from complementary characterizations of the primary relaxation rate of a room temperature ionic liquid (RTIL), 1-hexyl-3-methylimidazolium bis{(trifluoromethyl)sulfonyl} imide, [C(6)mim][Tf2N], over a wide temperature range. This extensive data set is successfully merged with existing literature data for conductivity, viscosity, and NMR diffusion coefficients thus providing, for the case of RTILs, a unique description of the primary process relaxation map over more than 12 decades in relaxation rate and between 185 and 430 K. This unique data set allows a detailed characterization of the VTF parameters for the primary process, that are: B = 890 K, T-0 = 155.2 K, leading to a fragility index m = 71, corresponding to an intermediate fragility. For the first time neutron spin echo data from a fully deuteriated sample of RTIL at the two main interference peaks, Q = 0.76 and 1.4 angstrom(-1) are presented. At high temperature (T > 250 K), the collective structural relaxation rate follows the viscosity behavior; however at lower temperatures it deviates from the viscosity behavior, indicating the existence of a faster process.

High density mangrove plantation enhances surface accretion, surface elevation change, and tree survival in coastal areas susceptible to sea-level rise

Survival, growth, above ground biomass accumulation, soil surface elevation dynamics and nitrogen accumulation in accreted sediments were studied in experimental treatments planted with four different densities (6.96, 3.26, 1.93 and 0.95 seedlings m-2) of the mangrove Rhizophora mucronata in Puttalam Lagoon, Sri Lanka. Measurements were taken over a period of 1171 days and were compared with those from unplanted controls. Trees at the lowest density showed significantly reduced survival, whilst measures of individual tree growth did not differ significantly among treatments. Rates of surface sediment accretion (means ± S.E.) were 13.0 (±1.3), 10.5 (±0.9), 8.4 (±0.3), 6.9 (±0.5) and 5.7 (±0.3) mm yr-1 at planting densities of 6.96, 3.26, 1.93, 0.95, and 0 (unplanted control) seedlings m-2, respectively, showing highly significant differences among treatments. Mean (± S.E.) rates of surface elevation change were much lower than rates of accretion at 2.8 (±0.2), 1.6 (±0.1), 1.1 (±0.2), 0.6 (±0.2) and -0.3 (±0.1) mm yr-1 for 6.96, 3.26, 1.93, 0.95, and 0 seedlings m-2, respectively. All planted treatments appeared to accumulate greater nitrogen concentrations in the sediment compared to the unplanted control, and suggests one potential causal mechanism for the facilitatory effects observed; high densities of plants potentially contribute to the accretion of greater amounts of nutrient rich sediment. While this potential process needs further study, this study demonstrated how higher densities of mangroves enhance rates of sediment accretion and surface elevation, processes that may be crucial in mangrove ecosystem adaptation to sea level rise. There was no evidence that increasing plant density evoked a trade-off with growth and survival of the planted trees. Rather facilitatory effects enhanced survival at high densities, suggesting that local land managers may be able to take advantage of plantation densities to help mitigate sea-level rise effects by encouraging positive soil surface elevation increment, and perhaps even greater nutrient retention to promote mangrove growth and ameliorate nearshore eutrophication in tropical island environments.

Rapid changes in the level of Kluane Lake in Yukon Territory over the last millennium

The level of Kluane Lake, the largest lake in Yukon Territory, was lower than at present during most of the Holocene. The lake rose rapidly in the late seventeenth century to a level 12 m above present, drowning forest and stranding driftwood on a conspicuous high-stand beach, remnants of which are preserved at the south end of the lake. Kluane Lake fell back to near its present level by the end of the eighteenth century and has fluctuated within a range of about 3 m over the last 50 yr. The primary control on historic fluctuations in lake level is the discharge of Slims River, the largest source of water to the lake. We use tree ring and radiocarbon ages, stratigraphy and sub-bottom acoustic data to evaluate two explanations for the dramatic changes in the level of Kluane Lake. Our data support the hypothesis of Hugh Bostock, who suggested in 1969 that the maximum Little Ice Age advance of Kaskawulsh Glacier deposited large amounts of sediment in the Slims River valley and established the present course of Slims River into Kluane Lake. Bostock argued that these events caused the lake to rise and eventually overflow to the north. The overflowing waters incised the Duke River fan at the north end of Kluane Lake and lowered the lake to its present level. This study highlights the potentially dramatic impacts of climate change on regional hydrology during the Little Ice Age in glacierised mountains. © 2006 University of Washington.

Frontal EEG/ERP correlates of attentional processes, cortisol and motivational states in adolescents from lower and higher socioeconomic status

Event-related potentials (ERPs) and other electroencephalographic (EEG) evidence show that frontal brain areas of higher and lower socioeconomic status (SES) children are recruited differently during selective attention tasks. We assessed whether multiple variables related to self-regulation (perceived mental effort) emotional states (e.g., anxiety, stress, etc.) and motivational states (e.g., boredom, engagement, etc.) may co-occur or interact with frontal attentional processing probed in two matched-samples of fourteen lower-SES and higher-SES adolescents. ERP and EEG activation were measured during a task probing selective attention to sequences of tones. Pre- and post-task salivary cortisol and self-reported emotional states were also measured. At similar behavioural performance level, the higher-SES group showed a greater ERP differentiation between attended (relevant) and unattended (irrelevant) tones than the lower-SES group. EEG power analysis revealed a cross-over interaction, specifically, lower-SES adolescents showed significantly higher theta power when ignoring rather than attending to tones, whereas, higher-SES adolescents showed the opposite pattern. Significant theta asymmetry differences were also found at midfrontal electrodes indicating left hypo-activity in lower-SES adolescents. The attended vs. unattended difference in right midfrontal theta increased with individual SES rank, and (independently from SES) with lower cortisol task reactivity and higher boredom. Results suggest lower-SES children used additional compensatory resources to monitor/control response inhibition to distracters, perceiving also more mental effort, as compared to higher-SES counterparts. Nevertheless, stress, boredom and other task-related perceived states were unrelated to SES. Ruling out presumed confounds, this study confirms the midfrontal mechanisms responsible for the SES effects on selective attention reported previously and here reflect genuine cognitive differences.

Does flexibility in secondary level mathematics curriculum affect degree performance?

The authors have much experience in developing mathematics skills of first-year engineering students and attempting to ensure a smooth transition from secondary school to university. Concerns exist due to there being flexibility in the choice of modules needed to obtain a secondary level (A-level) mathematics qualification. This qualification is based on some core (pure maths) modules and a selection from mechanics and statistics modules. A survey of aerospace and mechanical engineering students in Queen’s University Belfast revealed that a combination of both mechanics and statistics (the basic module in both) was by far the most popular choice and therefore only about one quarter of this cohort had studied mechanics beyond the basic module within school maths. Those students who studied the extra mechanics and who achieved top grades at school subsequently did better in two core, first-year engineering courses. However, students with a lower grade from school did not seem to gain any significant advantage in the first-year engineering courses despite having the extra mechanics background. This investigation ties in with ongoing and wider concerns with secondary level mathematics provision in the UK.

Multi-level wordline driver for robust SRAM design in nano-scale CMOS technology

In this paper, a multi-level wordline driver scheme is presented to improve 6T-SRAM read and write stability. The proposed wordline driver generates a shaped pulse during the read mode and a boosted wordline during the write mode. During read, the shaped pulse is tuned at nominal voltage for a short period of time, whereas for the remaining access time, the wordline voltage is reduced to save the power consumption of the cell. This shaped wordline pulse results in improved read noise margin without any degradation in access time for small wordline load. The improvement is explained by examining the dynamic and nonlinear behavior of the SRAM cell. Furthermore, during the hold mode, for a short time (depending on the size of boosting capacitance), wordline voltage becomes negative and charges up to zero after a specific time that results in a lower leakage current compared to conventional SRAM. The proposed technique results in at least 2× improvement in read noise margin while it improves write margin by 3× for lower supply voltages than 0.7 V. The leakage power for the proposed SRAM is reduced by 2% while the total power is improved by 3% in the worst case scenario for an SRAM array. The main advantage of the proposed wordline driver is the improvement of dynamic noise margin with less than 2.5% penalty in area. TSMC 65 nm technology models are used for simulations.

Large panel-survey data demonstrated country-level and ethnic minority variation in consent for health record linkage

Objectives
To investigate individual, household and country variation in consent to health record linkage.

Study Design and Setting
Data from 50,994 individuals aged 16-74 years recruited to wave 1 of a large UK general purpose household survey (January 2009 – December 2010) were analysed using multi-level logistic regression models.

Results
Overall, 70.7% of respondents consented to record linkage. Younger age, marriage, tenure, car ownership and education were all significantly associated with consent, though there was little deviation from 70% in subgroups defined by these variables. There were small increases in consent rates in individuals with poor health when defined by self-reported long term limiting illness (adjusted OR 1.11; 95%CIs 1.06, 1.16), less so when defined by General Health Questionnaire score (adjusted OR=1.05; 95%CIs 1.00, 1.10), but the range in absolute consent rates between categories was generally less than 10%. Larger differences were observed for those of non-white ethnicity who were 38% less likely to consent (adjusted OR 0.62; 95%CIs 0.59, 0.66). Consent was higher in Scotland than England (adjusted OR 1.17; 95%CIs 1.06, 1.29) but lower in Northern Ireland (adjusted OR 0.56; 95%CIs 0.50, 0.63).

Conclusion
The modest overall level of systematic bias in consent to record linkage provides reassurance for record linkage potential in general purpose household surveys. However, the low consent rates amongst non-white ethnic minority survey respondents will further compound their low survey participation rates. The reason for the country-level variation requires further study.

Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials

BACKGROUND: The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain.

METHODS: We undertook meta-analyses of individual data on 31 920 postmenopausal women with oestrogen-receptor-positive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen first-event rate ratios (RRs).

FINDINGS: In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0·64, 95% CI 0·52-0·78) and 2-4 (RR 0·80, 0·68-0·93), and non-significantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12·1% vs 14·2%; RR 0·85, 0·75-0·96; 2p=0·009). In the comparison of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0·74, 0·62-0·89) but not while both groups received aromatase inhibitors during years 2-4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0·90, 0·81-0·99; 2p=0·045), though the breast cancer mortality reduction was not significant (RR 0·89, 0·78-1·03; 2p=0·11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 2-4 (RR 0·56, 0·46-0·67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8·7% vs 10·1%; 2p=0·015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments differed (RR 0·70, 0·64-0·77), but not significantly thereafter (RR 0·93, 0·86-1·01; 2p=0·08). Breast cancer mortality was reduced both while treatments differed (RR 0·79, 0·67-0·92), and subsequently (RR 0·89, 0·81-0·99), and for all periods combined (RR 0·86, 0·80-0·94; 2p=0·0005). All-cause mortality was also reduced (RR 0·88, 0·82-0·94; 2p=0·0003). RRs differed little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0·4% vs 1·2%; RR 0·33, 0·21-0·51) but more bone fractures (5-year risk 8·2% vs 5·5%; RR 1·42, 1·28-1·57); non-breast-cancer mortality was similar.

INTERPRETATION: Aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with tamoxifen while treatments differ, but not thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment.

FUNDING: Cancer Research UK, Medical Research Council.

Education, gender, and state-level disparities in the health of older Indians: Evidence from biomarker data

Using new biomarker data from the 2010 pilot round of the Longitudinal Aging Study in India (LASI), we investigate education, gender, and state-level disparities in health. We find that hemoglobin level, a marker for anemia, is lower for respondents with no schooling (0.7 g/dL less in the adjusted model) compared to those with some formal education and is also lower for females than for males (2.0 g/dL less in the adjusted model). In addition, we find that about one third of respondents in our sample aged 45 or older have high C-reaction protein (CRP) levels (>3 mg/L), an indicator of inflammation and a risk factor for cardiovascular disease. We find no evidence of educational or gender differences in CRP, but there are significant state-level disparities, with Kerala residents exhibiting the lowest CRP levels (a mean of 1.96 mg/L compared to 3.28 mg/L in Rajasthan, the state with the highest CRP). We use the Blinder–Oaxaca decomposition approach to explain group-level differences, and find that state-level disparities in CRP are mainly due to heterogeneity in the association of the observed characteristics of respondents with CRP, rather than differences in the distribution of endowments across the sampled state populations.