Proceedings of the American Chemical Society.

Photolithograph reproduction by permission of the American Chemical Society.

Revue des ëtudes historiques

Publication suspended, 1945-

Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas

TSLC1 (tumor suppressor in lung cancer-1, IGSF4) encodes a member of the immunoglobulin superfamily molecules, which is involved in cell-cell adhesion. TSLC1 is connected to the actin cytoskeleton by DAL-1 (differentially expressed in adenocarcinoma of the lung-1, EPB41L3) and it directly associates with MPP3, one of the human homologues of a Drosophila tumor suppressor gene, Discs large. Recent data suggest that aberrant promoter methylation is important for TSLC1 inactivation in lung carcinomas. However, little is known about the other two genes in this cascade, DAL-1 and MPP3. Thus, we investigated the expression and methylation patterns of these genes in lung cancer cell lines, primary lung carcinomas and nonmalignant lung tissue samples. By reverse transcription-polymerase chain reaction, loss of TSLC1 expression was observed in seven of 16 (44%) non-small-cell lung cancer (NSCLC) cell lines and in one of 11 (9%) small-cell lung cancer (SCLC) cell lines, while loss of DAL- 1 expression was seen in 14 of 16 (87%) NSCLC cell lines and in four of 11 (36%) SCLC cell lines. By contrast, MPP3 expression was found in all tumor cell lines analysed. Similar results were obtained by microarray analysis. TSLC1 methylation was seen in 13 of 39 (33%) NSC LC cell lines, in one of 11 (9%) SCLC cell lines and in 100 of 268 (37%) primary NSCLCs. DAL-1 methylation was observed in 17 of 39 (44%) NSCLC cell lines, in three of 11 (27%) SCLC cell lines and in 147 of 268 (55%) primary NSCLCs. In tumors of NSCLC patients with stage II-III disease, DAL-1 methylation was seen at a statistically significant higher frequency compared to tumors of patients with stage I disease. A significant correlation between loss of expression and methylation of the genes in lung cancer cell lines was found. Overall, 65% of primary NSCLCs had either TSLC1 or DAL-1 methylated. Methylation of one of these genes was detected in 59% of NSCLC cell lines; however, in SCLC cell lines, methylation was much less frequently observed. The majority of nonmalignant lung tissue samples was not TSLC1 and DAL-1 methylated. Re-expression of TSLC1 and DAL-1 was seen after treatment of lung cancer cell lines with 5-aza-2$-deoxy-cytidine. Our results suggest that methylation of TSLC1 and/or DAL-1, leading to loss of their expression, is an important event in the pathogenesis of NSCLC.

Severe visual impairment due to diabetes mellitus:can this be influenced by community & hospital retinal screening and formal hospital diabetic annual review?

Purpose: Diabetes is a leading cause of visual impairment in working age population in the UK. This study looked at the causes of Severe Visual Impairment(SVI) in the patients attending diabetic eye clinic and influence on the rate of SVI, over a 12 year period, after introducing retinal screening programmes in the hospital and the community in 1993 (review in 1992, 1998 & 2004). Methods: Medical records of all the patients attending the diabetic eye clinic over a period of 5months(April to August) in 1992, 1998 and 2004 were reviewed. The data collected for each patient included age, sex, ethnic origin, diabetes (type,duration &treatment), the best corrected visual acuity (present and at time of presentation), type and duration of retinopathy and attendance record to both diabetic clinic and diabetic eye clinic. In this study, SVI is defined as a visual acuity of 6/36 or worse in at least one eye. Results: In 1992, of a total 245 patients, 58patients(23.6%) had SVI {38 (15.5% of total) due to diabetic retinopathy [31(12.6%) maculopathy, 2(0.8%) vitreous haemorrhage and 5(2%) retinal detachment] and 20(8.1%) due to non–diabetic retinopathy causes}. In 1998, of a total 297, 77patients(25.9%) had SVI {33(11.1% of total) due to diabetic retinopathy [19(6.4%) maculopathy, 9(3%) proliferative retinopathy, 8(2.7%) vitreous haemorrhage and 3(1%) retinal detachment]and 44(14.8%)due to non–diabetic retinopathy}. In 2004, of a total 471, 72patients(15.2%) had SVI{46(9.7%of total) due to diabetic retinopathy [37(7.8%) maculopathy, 1(0.2%) proliferative retinopathy, 6(1.8%) vitreous haemorrhage and 2(0.4%) retinal detachment]and 26(5.5%) due to non– diabetic retinopathy causes}. Conclusions: Introduction of formalised annual diabetic review including retinal screening and a community retinal screening programme has reduced the rate of severe visual impairment due to diabetic retinopathy, in patients attending diabetic eye clinic, from 15.5% in1992 to 9.7% in2004. Keywords: diabetic retinopathy

Gazdasági kórkép alulnézetből 2. rész (Syndrome of Hungarian Economy from Bottom-view - part 2.)

A magyar gazdaság új növekedési pályára állása a kilencvenes évek végére tehető, s ebben meghatározó szerepe volt a pótlólagos erőforrásként szolgáló külföldi működőtőke-befektetéseknek. A nemzetközi tőkeáramlás ezredfordulót követő módosulása (csökkenő volumen, változó irányultság) kedvezőtlenül érintette a hazai gazdaságot, aminek egyik következménye a beruházások csökkenése és a növekedési ütem lassulása, másik következménye viszont – a jövedelemkiáramlást semlegesítő hatás elmaradása miatt – a fizetési mérleg romlása. Ebben a helyzetben halaszthatatlanná vált az államháztartási egyensúlyromlás megállítása, illetve a gazdasági fejlődés új alapokra helyezése. A szerző elemzésében – a hazai versenyszektor eredményességi és vagyoni jellemzőinek értékelésével – azt szeretné jelezni, hogy az egyensúlytalansági állapot megszüntetése nem szorítkozhat az államháztartási rendszerre, vagyis az ország helyzetének stabilizálása, majd új növekedési pályára állás nem képzelhető el a gazdaság átfogó modernizációja nélkül. Vizsgálata a ténylegesen működő (343 ezer) hazai társas vállalkozás 2000–2008. évi pénzügyi beszámolóinak adataira épül. Álláspontja szerint a mintavétel nagysága ellensúlyozza az esetleges torzító hatásokat (lásd: helyenként előforduló kreatív beszámolók), így a vállalkozások mennyiségi gyarapodása, méret szerinti megoszlása, a gazdasági tevékenység jellege, a teljesítmények és eredmények alakulása, a vállalkozói vagyon módosulása megbízhatóan értékelhető, illetve a tapasztalatok alapján a korrekciós intézkedések igénye és azok tartalma is jól körvonalazható. Tanulmányát így ajánljuk a téma iránt érdeklődőknek, a versenyszektor szereplőinek, de leginkább a gazdaságpolitika formálóinak. _________ The economic performance during the transition period was characterized by the alternations of fulfilled hopes and unrealized expectations. The economic restructuring and changes in market relations took place during the first decade, while new – mostly foreign – investment groups entered on the new market. As a result the economy was stabilized and was put to a new growth path. But after the millennium the foreign investment based economy development strategy was no more adequate. The new engine for the growth should have been the domestic small and medium enterprise sector (SsME), but despite the subsidies this sector was not strengthened to take this role. The author – the researcher of BCE, and the ex-president of APpEH – analyses the characteristics of the domestic business demography, performance and effectiveness, based on the 2000–2008 annual financial statements of the business sector. In the author’s analysis – with assessment of the domestic business sector and financial performance characteristicst - he would like to point out that the imbalance can not be confined to the elimination of state government system, that is, the country’s situation to stabilize, and then post a new growth path is not conceivable without the modernization of the economy overall. In his view, the sample size outweighed the possible distortionary effects (see occurring in places of creative accounts), so the growth of business volume, size distribution, the nature of economic activity, the evolution of performance and results, a reliable assessment of changes in the business of property and the experience on the basis of the need for corrective action, and its contents are also well delineated. Sstudy it is recommended for those interested in the topic, the business sector actors, but most of the economic policy makers.

Vertical profiles of environmental parameters measured from physical, optical and imaging sensors during station TARA_007 of the Tara Oceans expedition 2009-2013

The Tara Oceans Expedition (2009-2013) sampled the world oceans on board a 36 m long schooner, collecting environmental data and organisms from viruses to planktonic metazoans for later analyses using modern sequencing and state-of-the-art imaging technologies. Tara Oceans Data are particularly suited to study the genetic, morphological and functional diversity of plankton. The present data set includes properties of seawater, particulate matter and dissolved matter from physical, optical and imaging sensors mounted on a vertical sampling system (Rosette) used during the 2009-2013 tara Oceans Expedition. It comprised 2 pairs of conductivity and temperature sensors (SEABIRD components), and a complete set of WEtLabs optical sensors, including chrorophyll and CDOM fluorometers, a 25 cm transmissiometer, and a one-wavelength backscatter meter. In addition, a SATLANTIC ISUS nitrate sensor and a Hydroptic Underwater Vision Profiler (UVP) were mounted on the rosette. In the Arctic Ocean and Arctic Seas (2013), a second oxygen sensor (SBE43) and a four frequency Aquascat acoustic profiler were added. The system was powered on specific Li-Ion batteries and data were self-recorded at 24HZ. Sensors have all been factory calibrated before, during and after the four year program. Oxygen was validated using climatologies (WOA09). Nitrate and Fluorescence data were adjusted with discrete measurements from Niskin bottles mounted on the Rosette, and optical darks were performed monthly on board. A total of 839 quality checked vertical profiles were made during the tara Oceans expedition 2009-2013.

Vertical profiles of environmental parameters measured on discrete water samples collected with Niskin bottles at station TARA_007 during the Tara Oceans expedition 2009-2013

The Tara Oceans Expedition (2009-2013) was a global survey of ocean ecosystems aboard the Sailing Vessel Tara. It carried out extensive measurements of evironmental conditions and collected plankton (viruses, bacteria, protists and metazoans) for later analysis using modern sequencing and state-of-the-art imaging technologies. Tara Oceans Data are particularly suited to study the genetic, morphological and functional diversity of plankton. The present data set includes properties of seawater, particulate matter and dissolved matter that were measured from discrete water samples collected with Niskin bottles during the 2009-2013 Tara Oceans expedition. Properties include pigment concentrations from HPLC analysis (10 depths per vertical profile, 25 pigments per depth), the carbonate system (Surface and 400m; pH (total scale), CO2, pCO2, fCO2, HCO3, CO3, Total alkalinity, Total carbon, OmegaAragonite, OmegaCalcite, and dosage Flags), nutrients (10 depths per vertical profile; NO2, PO4, N02/NO3, SI, quality Flags), DOC, CDOM, and dissolved oxygen isotopes. The Service National d'Analyse des Paramètres Océaniques du CO2, at the Université Pierre et Marie Curie, determined CT and AT potentiometrically. More than 200 vertical profiles of these properties were made across the world ocean. DOC, CDOM and dissolved oxygen isotopes are available only for the Arctic Ocean and Arctic Seas (2013).

Last glacial maximum sediment record of the southern Weddell Sea shelf

Abstract: The history of grounded ice-sheet extent on the southern Weddell Sea shelf during the Last Glacial Maximum (LGM) and the timing of post-LGM ice-sheet retreat are poorly constrained. Several glaciological models reconstructed widespread grounding and major thickening of the Antarctic Ice Sheet in the Weddell Sea sector at the LGM. In contrast, recently published onshore data and modelling results concluded only very limited LGM-thickening of glaciers and ice streams feeding into the modern Filchner and Ronne ice shelves. These studies concluded that during the LGM ice shelves rather than grounded ice covered the Filchner and Ronne troughs, two deep palaeo-ice stream troughs eroded into the southern Weddell Sea shelf. Here we review previously published and unpublished marine geophysical and geological data from the southern Weddell Sea shelf. The stratigraphy and geometry of reflectors in acoustic sub-bottom profiles are similar to those from other West Antarctic palaeo-ice stream troughs, where grounded ice had advanced to the shelf break at the LGM. Numerous cores from the southern Weddell Sea shelf recovered sequences with properties typical for subglacially deposited tills or subglacially compacted sediments. These data sets give evidence that grounded ice had advanced across the shelf during the past, thereby grounding in even the deepest parts of the Filchner and Ronne troughs. Radiocarbon dates from glaciomarine sediments overlying the subglacial deposits are limited, but indicate that the ice grounding occurred at the LGM and that ice retreat started before ~15.1 corrected 14C kyrs before present (BP) on the outer shelf and before ~7.7 corrected 14C kyrs BP on the inner shelf, which is broadly synchronous with ice retreat in other Antarctic sectors. The apparent mismatch between the ice-sheet reconstructions from marine and terrestrial data can be attributed to ice streams with very low surface profiles (similar to those of "ice plains") that had advanced through Filchner Trough and Ronne Trough at the LGM. Considering the global sea-level lowstand of ~130 metres below present, a low surface slope of the expanded LGM-ice sheet in the southern Weddell Sea can reconcile grounding-line advance to the shelf break with limited thickening of glaciers and ice streams in the hinterland. This scenario implies that ice-sheet growth in the Weddell Sea sector during the LGM and ice-sheet drawdown throughout the last deglaciation could only have made minor contributions to the major global sea-level fluctuations during these times.

Silent screen: book review.

Book Review. Kevin Rockett, Irish film censorship: a cultural journey from silent cinema to internet pornography (Dublin, 2004) and Mary Corcoran and Mark O'Brien (eds), Political censorship and the democratic state: the Irish broadcasting ban (Dublin, 2005)

Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials

Objective: To assess the effects of selective cyclo-oxygenase-2 (COX 2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of vascular events. Design: Meta-analysis of published and unpublished tabular data from randomised trials, with indirect estimation of the effects of traditional NSAIDs. Data sources: Medline and Embase (January 1966 to April 2005); Food and Drug Administration records; and data on file from Novartis, Pfizer, and Merck. Review methods: Eligible studies were randomised trials that included a comparison of a selective COX 2 inhibitor versus placebo or a selective COX 2 inhibitor versus a traditional NSAID, of at least four weeks' duration, with information on serious vascular events (defined as myocardial infarction, stroke, or vascular death). Individual investigators and manufacturers provided information on the number of patients randomised, numbers of vascular events, and the person time of follow-up for each randomised group. Results: In placebo comparisons, allocation to a selective COX 2 inhibitor was associated with a 42% relative increase in the incidence of serious vascular events (1.2%/year v 0.9%/year; rate ratio 1.42, 95% confidence interval 1.13 to 1.78; P = 0.003), with no significant heterogeneity among the different selective COX 2 inhibitors. This was chiefly attributable to an increased risk of myocardial infarction (0.6%/year v 0.3%/year; 1.86, 1.33 to 2.59; P = 0.0003), with little apparent difference in other vascular outcomes. Among trials of at least one year's duration (mean 2.7 years), the rate ratio for vascular events was 1.45 (1.12 to 1.89; P = 0.005). Overall, the incidence of serious vascular events was similar between a selective COX 2 inhibitor and any traditional NSAID (1.0%/year v 0.9/%year; 1.16, 0.97 to 1.38; P = 0.1). However, statistical heterogeneity (P = 0.001) was found between trials of a selective COX 2 inhibitor versus naproxen (1.57, 1.21 to 2.03) and of a selective COX 2 inhibitor versus non-naproxen NSAIDs (0.88, 0.69 to 1.12). The summary rate ratio for vascular events, compared with placebo, was 0.92 (0.67 to 1.26) for naproxen, 1.51 (0.96 to 2.37) for ibuprofen, and 1.63 (1.12 to 2.37) for diclofenac. Conclusions: Selective COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen and diclofenac, but high dose naproxen is not associated with such an excess.

Personalized absolute benefit of statin treatment for primary or secondary prevention of vascular disease in individual elderly patients

Objective: To estimate the absolute treatment effect of statin therapy on major adverse cardiovascular events (MACE; myocardial infarction, stroke and vascular death) for the individual patient aged C70 years. Methods: Prediction models for MACE were derived in patients aged C70 years with (n = 2550) and without (n = 3253) vascular disease from the ‘‘PROspective Study of Pravastatin in Elderly at Risk’’ (PROSPER) trial and validated in the ‘‘Secondary Manifestations of ARTerial disease’’ (SMART) cohort study (n = 1442) and the ‘‘Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm’’ (ASCOT-LLA) trial (n = 1893), respectively, using competing risk analysis. Prespecified predictors were various clinical characteristics including statin treatment. Individual absolute risk reductions (ARRs) for MACE in 5 and 10 years were estimated by subtracting ontreatment from off-treatment risk. Results: Individual ARRs were higher in elderly patients with vascular disease [5-year ARRs: median 5.1 %, interquartile range (IQR) 4.0–6.2 %, 10-year ARRs: median 7.8 %, IQR 6.8–8.6 %] than in patients without vascular disease (5-year ARRs: median 1.7 %, IQR 1.3–2.1 %, 10-year ARRs: 2.9 %, IQR 2.3–3.6 %). Ninetyeight percent of patients with vascular disease had a 5-year ARR C2.0 %, compared to 31 % of patients without vascular disease. Conclusions: With a multivariable prediction model the absolute treatment effect of a statin on MACE for individual elderly patients with and without vascular disease can be quantified. Because of high ARRs, treating all patients is more beneficial than prediction-based treatment for secondary prevention of MACE. For primary prevention of MACE, the prediction model can be used to identify those patients who benefit meaningfully from statin therapy.

Reconstructions of eolian dust accumulation in northwest African margin sediments

Reconstructions of eolian dust accumulation in northwest African margin sediments provide important continuous records of past changes in atmospheric circulation and aridity in the region. Existing records indicate dramatic changes in North African dust emissions over the last 20 ka, but the limited spatial extent of these records and the lack of high-resolution flux data do not allow us to determine whether changes in dust deposition occurred with similar timing, magnitude and abruptness throughout northwest Africa. Here we present new records from a meridional transect of cores stretching from 31°N to 19°N along the northwest African margin. By combining grain size endmember modeling with 230Th-normalized fluxes for the first time, we are able to document spatial and temporal changes in dust deposition under the North African dust plume throughout the last 20 ka. Our results provide quantitative estimates of the magnitude of dust flux changes associated with Heinrich Stadial 1, the Younger Dryas, and the African Humid Period (AHP; ~11.7-5 ka), offering robust targets for model-based estimates of the climatic and biogeochemical impacts of past changes in North African dust emissions. Our data suggest that dust fluxes between 8 and 6 ka were a factor of ~5 lower than average fluxes during the last 2 ka. Using a simple model to estimate the effects of bioturbation on dust input signals, we find that our data are consistent with abrupt, synchronous changes in dust fluxes in all cores at the beginning and end of the AHP. The mean ages of these transitions are 11.8±0.2 ka (1Sigma) and 4.9±0.2 ka, respectively.

A Group-Enhanced Sprint Interval Training Program for Amateur Athletes

Sprint interval training (SIT) can elicit improvements in aerobic and anaerobic capacity. While variations in SIT protocols have been investigated, the influence of social processes cannot be overlooked. As research supports the use of groups to influence individual cognitions and behaviours, the current project assessed the effectiveness of a group-based intervention with participants conducting SIT. Specifically, 53 amateur athletes (age, 21.9 ± 2.9 years; 53% females) took part in a 4-week training program (3 sessions per week, 30-s “all-out” efforts with 4 min active recovery, repeated 4–6 times per session), and were assigned to “true group”, aggregate, or individual conditions. Results indicated no significant differences between groups for the physiological measures. With regards to training improvements from baseline for all participants— regardless of condition — significant main effects for time were identified for maximal oxygen uptake (2.5–2.8 mL·kg−1·min−1, p < 0.001, η2 = 0.03), time-trial performance (14–32 s, p < 0.001, η2 = 0.37), and anaerobic power (1.1–1.7 k·h−1, p < 0.001, η2 = 0.66). With regards to the psychological measures, significant main effects between groups were found for motivation (p = 0.033, η2 = 0.13), task self-efficacy (p = 0.018, η2 = 0.15), and scheduling self-efficacy (p = 0.003, η2 = 0.22). The true group experienced greater improvements in motivation than the individual condition, but the aggregate and individual conditions demonstrated greater increases in task and scheduling self-efficacy. Though the SIT paradigm employed induced training improvements similar to previous work, the group intervention was not able to further these improvements

Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium

AIMS: Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.

METHODS AND RESULTS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination (C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals <6 ng/L of troponin I, whereas the relative risk reduction was similar.

CONCLUSION: In individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.