American Cancer Society guideline for the early detection of prostate cancer: update 2010.

In 2009, the American Cancer Society (ACS) Prostate Cancer Advisory Committee began the process of a complete update of recommendations for early prostate cancer detection. A series of systematic evidence reviews was conducted focusing on evidence related to the early detection of prostate cancer, test performance, harms of therapy for localized prostate cancer, and shared and informed decision making in prostate cancer screening. The results of the systematic reviews were evaluated by the ACS Prostate Cancer Advisory Committee, and deliberations about the evidence occurred at committee meetings and during conference calls. On the basis of the evidence and a consensus process, the Prostate Cancer Advisory Committee developed the guideline, and a writing committee drafted a guideline document that was circulated to the entire committee for review and revision. The document was then circulated to peer reviewers for feedback, and finally to the ACS Mission Outcomes Committee and the ACS Board of Directors for approval. The ACS recommends that asymptomatic men who have at least a 10-year life expectancy have an opportunity to make an informed decision with their health care provider about screening for prostate cancer after they receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening. Prostate cancer screening should not occur without an informed decision-making process. Men at average risk should receive this information beginning at age 50 years. Men in higher risk groups should receive this information before age 50 years. Men should either receive this information directly from their health care providers or be referred to reliable and culturally appropriate sources. Patient decision aids are helpful in preparing men to make a decision whether to be tested.

Psychophysiological responses to affective pictures in younger and older adults

Despite the central role that emotional reactivity plays in adaptation, few studies have examined age differences in this capacity under well-controlled laboratory conditions, on the basis of standardized emotion-evoking stimuli and assessing experiential, expressive, and physiological measures. 212 adults ranging in age from 20 to 81 years were exposed to 14 picture series, each lasting 60 s and of a different valence and arousal. We assessed valence and arousal ratings, cardiovascular, respiratory and electrodermalmeasures, facial muscle activity and gaze activity. Here, we present findings for 22 younger (mean age=24.0) and 22 older (mean age=72.1) adults for valence and arousal ratings, systolic bloodpressure (SBP) andheart rate (HR).Compared to younger adults, older adults rated unpleasant seriesmore negatively and showed a smaller range in arousal for pleasant series. SBP linearly increased with increasing appetitive activation. HR showed the expected deceleration from the pleasant to the unpleasant series.However, this effect was clearer for the younger adults than the older adults. For older adults, if something is pleasant, it is also judged to be generally lower in arousal, whereas, if something is unpleasant, it is also judged to be generally higher in arousal. The results for SBP indicate that the association between arousal and sympathetic outflow to the cardiovascular system might be similar in younger and older adults. The results for HR suggest that the parasympathetic activation might be attenuated in older adults as compared to younger adults.

Determination of picogram levels of midazolam, and 1- and 4-hydroxymidazolam in human plasma by gas chromatography-negative chemical ionization-mass spectrometry.

Midazolam is a widely accepted probe for phenotyping cytochrome P4503A. A gas chromatography-mass spectrometry (GC-MS)-negative chemical ionization method is presented which allows measuring very low levels of midazolam (MID), 1-OH midazolam (1OHMID) and 4-OH midazolam (4OHMID), in plasma, after derivatization with the reagent N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide. The standard curves were linear over a working range of 20 pg/ml to 5 ng/ml for the three compounds, with the mean coefficients of correlation of the calibration curves (n = 6) being 0.999 for MID and 1OHMID, and 1.0 for 4OHMID. The mean recoveries measured at 100 pg/ml, 500 pg/ml, and 2 ng/ml, ranged from 76 to 87% for MID, from 76 to 99% for 1OHMID, from 68 to 84% for 4OHMID, and from 82 to 109% for N-ethyloxazepam (internal standard). Intra- (n = 7) and inter-day (n = 8) coefficients of variation determined at three concentrations ranged from 1 to 8% for MID, from 2 to 13% for 1OHMID and from 1 to 14% for 4OHMID. The percent theoretical concentrations (accuracy) were within +/-8% for MID and 1OHMID, within +/-9% for 4OHMID at 500 pg/ml and 2 ng/ml, and within +/-28% for 4OHMID at 100 pg/ml. The limits of quantitation were found to be 10 pg/ml for the three compounds. This method can be used for phenotyping cytochrome P4503A in humans following the administration of a very low oral dose of midazolam (75 microg), without central nervous system side-effects.

Deccan volcanism linked to the Cretaceous-Tertiary boundary mass extinction: New evidence from ONGC wells in the Krishna-Godavari basin

A scientific challenge is to assess the role of Deccan volcanism in the Cretaceous-Tertiary boundary (KTB) mass extinction. Here we report on the stratigraphy and biologic effects of Deccan volcanism in eleven deep wells from the Krishna-Godavari (K-G) Basin, Andhra Pradesh, India. In these wells, two phases of Deccan volcanism record the world's largest and longest lava mega-flows interbedded in marine sediments in the K-G Basin about 1500 km from the main Deccan volcanic province. The main phase-2 eruptions (similar to 80% of total Deccan Traps) began in C29r and ended at or near the KTB, an interval that spans planktic foraminiferal zones CF1-CF2 and most of the nannofossil Micula prinsii zone, and is correlative with the rapid global warming and subsequent cooling near the end of the Maastrichtian. The mass extinction began in phase-2 preceding the first of four mega-flows. Planktic foraminifera suffered a 50% drop in species richness. Survivors suffered another 50% drop after the first mega-flow, leaving just 7 to 8 survivor species. No recovery occurred between the next three mega-flows and the mass extinction was complete with the last phase-2 mega-flow at the KTB. The mass extinction was likely the consequence of rapid and massive volcanic CO(2) and SO(2) gas emissions, leading to high continental weathering rates, global warming, cooling, acid rains, ocean acidification and a carbon crisis in the marine environment. Deccan volcanism phase-3 began in the early Danian near the C29R/C29n boundary correlative with the planktic foraminiferal zone P1a/P1b boundary and accounts for similar to 14% of the total volume of Deccan eruptions, including four of Earth's longest and largest mega-flows. No major faunal changes are observed in the intertrappeans of zone P1b, which suggests that environmental conditions remained tolerable, volcanic eruptions were less intense and/or separated by longer time intervals thus preventing runaway effects. Alternatively, early Danian assemblages evolved in adaptation to high-stress conditions in the aftermath of the mass extinction and therefore survived phase-3 volcanism. Full marine biotic recovery did not occur until after Deccan phase-3. These data suggest that the catastrophic effects of phase-2 Deccan volcanism upon the Cretaceous planktic foraminifera were a function of both the rapid and massive volcanic eruptions and the highly specialized faunal assemblages prone to extinction in a changing environment. Data from the K-G Basin indicates that Deccan phase-2 alone could have caused the KTB mass extinction and that impacts may have had secondary effects.

Compliance with the Swiss Society for Nutrition's dietary recommendations in the population of Geneva, Switzerland: a 10-year trend study (1999-2009).

The trends in compliance with the dietary recommendations of the Swiss Society for Nutrition in the Geneva population were assessed for the period from 1999 to 2009 using 10 cross-sectional, population-based surveys (Bus Santé study) with a total of 9,320 participants aged 35 to 75 years (50% women). Dietary intake was assessed using a self-administered, validated, semi-quantitative food frequency questionnaire. Trends were assessed by logistic regression adjusting for age, smoking status, education, and nationality using survey year as the independent variable. After excluding participants with extreme intakes, the percentage of participants with a cholesterol intake of <300 mg/day increased from 40.8% in 1999 to 43.6% in 2009 for men (multivariate-adjusted P for trend=0.04) and from 57.8% to 61.4% in women (multivariate-adjusted P for trend=0.06). Calcium intake >1 g/day decreased from 53.3% to 46% in men and from 47.6% to 40.7% in women (multivariate-adjusted P for trend<0.001). Adequate iron intake decreased from 68.3% to 65.3% in men and from 13.3% to 8.4% in women (multivariate-adjusted P for trend<0.001). Conversely, no significant changes were observed for carbohydrates, protein, total fat (including saturated, monounsaturated, and polyunsaturated fatty acids), fiber, and vitamins D and A. We conclude that the quality of the Swiss diet did not improve between 1999 and 2009 and that intakes deviate substantially from expert recommendations for health promotion and chronic disease risk reduction.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes.

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.

Accuracy profile validation of a new analytical method for propane measurement using headspace-gas chromatography-mass spectrometry

Propane can be responsible for several types of lethal intoxication and explosions. Quantifying it would be very helpful to determine in some cases the cause of death. Some gas chromatography-mass spectrometry (GC-MS) methods of propane measurements do already exist. The main drawback of these GC-MS methods described in the literature is the absence of a specific propane internal standard necessary for accurate quantitative analysis. The main outcome of the following study was to provide an innovative Headspace-GC-MS method (HS-GC-MS) applicable to the routine determination of propane concentration in forensic toxicology laboratories. To date, no stable isotope of propane is commercially available. The development of an in situ generation of standards is thus presented. An internal-labeled standard gas (C3DH7) is generated in situ by the stoichiometric formation of propane by the reaction of deuterated water (D2O) with Grignard reagent propylmagnesium chloride (C3H7MgCl). The method aims to use this internal standard to quantify propane concentrations and, therefore, to obtain precise measurements. Consequently, a complete validation with an accuracy profile according to two different guidelines, the French Society of Pharmaceutical Sciences and Techniques (SFSTP) and the Gesellschaft für toxikologische und Forensische Chemie (GTFCh), is presented.

An evaluation of the inorganic and organic geochemistry of the San Vicente Mississippi Valley-type zinc-lead district, central Peru: Implications for ore fluid composition, mixing processes, and sulfate reduction

Mississippi Tialley-type zinc-lead deposits and ore occurrences in the San Vicente belt are hosted in dolostones of the eastern Upper Triassic to Lower Jurassic Pucara basin, central Peru. Combined inorganic and organic geochemical data from 22 sites, including the main San Vicente deposit, minor ore occurrences, and barren localities, provide better understanding of fluid pathways and composition, ore precipitation mechanisms, Eh-pH changes during mineralization, and relationships between organic matter and ore formation. Ore-stage dark replacement dolomite and white sparry dolomite are Fe and rare earth element (REE) depleted, and Mn enriched, compared to the host dolomite. In the main deposit, they display significant negative Ce and probably Eu anomalies. Mixing of an incoming hot, slightly oxidizing, acidic brine (H2CO3 being the dominant dissolved carbon species), probably poor in REE and Fe, with local intraformational, alkaline, reducing waters explains the overall carbon and oxygen isotope variation and the distributions of REE and other trace elements in the different hydrothermal carbonate generations. The incoming ore fluid flowed through major aquifers, probably basal basin detrital units, with limited interaction with the carbonate host rocks. The hydrothermal carbonates show a strong regional chemical homogeneity, indicating access of the ore fluids by interconnected channelways near the ore occurrences. Negative Ce anomalies in the main deposit, that are absent at the district scale, indicate local ore-fluid chemical differences. Oxidation of both migrated and indigenous hydrocarbons by the incoming fluid provided the local reducing conditions necessary for sulfate reduction to H2S, pyrobitumen precipitation, and reduction of Eu3+ to Eu2+. Fe-Mn covariations, combined with the REE contents of the hydrothermal carbonates, are consistent with the mineralizing system shifting from reducing/rock-dominated to oxidizing/fluid-dominated conditions following ore deposition. Sulfate and sulfide sulfur isotopes support sulfide origin from evaporite-derived sulfate by thermochemical organic reduction; further evidence includes the presence of C-13-depleted calcite cements (similar to-12 parts per thousand delta(13)C) as sulfate pseudomorphs, elemental sulfur, altered organic matter in the host dolomite, and isotopically heavier, late, solid bitumen. Significant alteration of the indigenous and extrinsic hydrocarbons, with absent bacterial membrane biomarkers (hopanes) is observed. The light delta(34)S of sulfides from small mines and occurrences compared to the main deposit reflect a local contribution of isotopically light sulfur, evidence of local differences in the ore-fluid chemistry.

Official Positions for FRAX® clinical regarding falls and frailty: can falls and frailty be used in FRAX®? From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Risk factors for fracture can be purely skeletal, e.g., bone mass, microarchitecture or geometry, or a combination of bone and falls risk related factors such as age and functional status. The remit of this Task Force was to review the evidence and consider if falls should be incorporated into the FRAX® model or, alternatively, to provide guidance to assist clinicians in clinical decision-making for patients with a falls history. It is clear that falls are a risk factor for fracture. Fracture probability may be underestimated by FRAX® in individuals with a history of frequent falls. The substantial evidence that various interventions are effective in reducing falls risk was reviewed. Targeting falls risk reduction strategies towards frail older people at high risk for indoor falls is appropriate. This Task Force believes that further fracture reduction requires measures to reduce falls risk in addition to bone directed therapy. Clinicians should recognize that patients with frequent falls are at higher fracture risk than currently estimated by FRAX® and include this in decision-making. However, quantitative adjustment of the FRAX® estimated risk based on falls history is not currently possible. In the long term, incorporation of falls as a risk factor in the FRAX® model would be ideal.

Quantify this! Report on a round table discussion on quantitative mass spectrometry in proteomics.

Following the success of the first round table in 2001, the Swiss Proteomic Society has organized two additional specific events during its last two meetings: a proteomic application exercise in 2002 and a round table in 2003. Such events have as their main objective to bring together, around a challenging topic in mass spectrometry, two groups of specialists, those who develop and commercialize mass spectrometry equipment and software, and expert MS users for peptidomics and proteomics studies. The first round table (Geneva, 2001) entitled "Challenges in Mass Spectrometry" was supported by brief oral presentations that stressed critical questions in the field of MS development or applications (Stöcklin and Binz, Proteomics 2002, 2, 825-827). Topics such as (i) direct analysis of complex biological samples, (ii) status and perspectives for MS investigations of noncovalent peptide-ligant interactions; (iii) is it more appropriate to have complementary instruments rather than a universal equipment, (iv) standardization and improvement of the MS signals for protein identification, (v) what would be the new generation of equipment and finally (vi) how to keep hardware and software adapted to MS up-to-date and accessible to all. For the SPS'02 meeting (Lausanne, 2002), a full session alternative event "Proteomic Application Exercise" was proposed. Two different samples were prepared and sent to the different participants: 100 micro g of snake venom (a complex mixture of peptides and proteins) and 10-20 micro g of almost pure recombinant polypeptide derived from the shrimp Penaeus vannamei carrying an heterogeneous post-translational modification (PTM). Among the 15 participants that received the samples blind, eight returned results and most of them were asked to present their results emphasizing the strategy, the manpower and the instrumentation used during the congress (Binz et. al., Proteomics 2003, 3, 1562-1566). It appeared that for the snake venom extract, the quality of the results was not particularly dependant on the strategy used, as all approaches allowed Lication of identification of a certain number of protein families. The genus of the snake was identified in most cases, but the species was ambiguous. Surprisingly, the precise identification of the recombinant almost pure polypeptides appeared to be much more complicated than expected as only one group reported the full sequence. Finally the SPS'03 meeting reported here included a round table on the difficult and challenging task of "Quantification by Mass Spectrometry", a discussion sustained by four selected oral presentations on the use of stable isotopes, electrospray ionization versus matrix-assisted laser desorption/ionization approaches to quantify peptides and proteins in biological fluids, the handling of differential two-dimensional liquid chromatography tandem mass spectrometry data resulting from high throughput experiments, and the quantitative analysis of PTMs. During these three events at the SPS meetings, the impressive quality and quantity of exchanges between the developers and providers of mass spectrometry equipment and software, expert users and the audience, were a key element for the success of these fruitful events and will have definitively paved the way for future round tables and challenging exercises at SPS meetings.

Central control of glucose homeostasis: the brain--endocrine pancreas axis.

A large body of data gathered over the last decades has delineated the neuronal pathways that link the central nervous system with the autonomic innervation of the endocrine pancreas, which controls alpha- and beta-cell secretion activity and mass. These are important regulatory functions that are certainly keys for preserving the capacity of the endocrine pancreas to control glucose homeostasis over a lifetime. Identifying the cells involved in controlling the autonomic innervation of the endocrine pancreas, in response to nutrient, hormonal and environmental cues and how these cues are detected to activate neuronal activity are important goals of current research. Elucidation of these questions may possibly lead to new means for preserving or restoring defects in insulin and glucagon secretion associated with type 2 diabetes.

Sharing data between LSDBs and central repositories.

Several Locus-Specific DataBases (LSDBs) have recently been approached by larger, more general data repositories (including NCBI and UCSC) with the request to share the DNA variant data they have collected. Within the Human Genome Variation Society (HGVS) a document was generated summarizing the issues related to these requests. The document has been circulated in the HGVS/LSDB community and was discussed extensively. Here we summarize these discussions and present the concluded recommendations for LSDB data sharing with central repositories.

Tectonomagmatic evolution of Western Amazonia: Geochemical characterization and zircon U-Pb geochronologic constraints from the Peruvian Eastern Cordilleran granitoids

The results of a coupled, in situ laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) U-Pb study on zircon and geochemical characterization of the Eastern Cordilleran intrusives of Peru reveal 1.15 Ga of intermittent magmatism along central Western Amazonia, the Earth's oldest active open continental margin. The eastern Peruvian batholiths are volumetrically dominated by plutonism related to the assembly and breakup of Pangea during the Paleozoic-Mesozoic transition. A Carboniferous-Permian (340-285 Ma) continental arc is identified along the regional orogenic strike from the Ecuadorian border (6 degrees S) to the inferred inboard extension of the Arequipa-Antofalla terrane in southern Peru (14 degrees S). Widespread crustal extension and thinning, which affected western Gondwana throughout the Permian and Triassic resulted in the intrusion of the late- to post-tectonic La Merced-San Ramon-type anatectites dated between 275 and 220 Ma, while the emplacement of the southern Cordillera de Carabaya peraluminous granitoids in the Late Triassic to Early Jurassic (220-190 Ma) represents, temporally and regionally, a separate tectonomagmatic event likely related to resuturing of the Arequipa-Antofalla block. Volcano-plutonic complexes and stocks associated with the onset of the present Andean cycle define a compositionally bimodal alkaline suite and cluster between 180 and 170 Ma. A volumetrically minor intrusive pulse of Oligocene age (ca. 30 Ma) is detected near the southwestern Cordilleran border with the Altiplano. Both post-Gondwanide (30-170 Ma), and Precambrian plutonism (691-1123 Ma) are restricted to isolated occurrences spatially comprising less than 15% of the Eastern Cordillera intrusives. Only one remnant of a Late Ordovician intrusive belt is recognized in the Cuzco batholith (446.5 +/- 9.7 Ma) indicating that the Famatinian arc system previously identified in Peru along the north-central Eastern Cordillera and the coastal Arequipa-Antofalla terrane also existed inboard of this parautochthonous crustal fragment. Hitherto unknown occurrences of late Mesoproterozoic and middle Neoproterozoic granitoids from the south-central cordilleran segment define magmatic events at 691 +/- 13 Ma, 751 +/- 8 Ma, 985 +/- 14 Ma, and 1071-1123 +/- 23 Ma that are broadly coeval with the Braziliano and Grenville-Sunsas orogenies, respectively. Our data suggest the existence of a continuous orogenic belt in excess of 3500 km along Western Amazonia during the formation of Rodinia, its ``early'' fragmentation prior to 690 Ma, and support a model of reaccretion of the Paracas-Arequipa-Antofalla terrane to western Gondwana in the Early Ordovician with subsequent detachment of the Paracas segment in form of the Mexican Oaxaquia microcontinent in Middle Ordovician. A tectonomagmatic model involving slab detachment, followed by underplating of cratonic margin by asthenospheric mantle is proposed for the genesis of the volumetrically dominant Late Paleozoic to early Mesozoic Peruvian Cordilleran batholiths.