Predicting Puget Sound\u27s organic carbon—and why we need enhanced monitoring

How much has the total organic carbon deposited into the water column and sediments of Puget Sound increased due to human activity? How has that increase impacted sediment flux rates, hypoxia and the carbonate system balance? These are two important questions with answers that are still elusive. To date, both marine and freshwater organic carbon measurements in Puget Sound are relatively sparse. In the long-term, inadequate temporal and spatial organic carbon data may lead to an incomplete and incoherent understanding of carbon cycling in the Puget Sound. The Salish Sea Model, developed by PNNL in collaboration with Department of Ecology, provides insights into the extent of organic carbon loading and concentrations in the Puget Sound. Model scenario runs indicate that autochtonous organic detritus derived from increased productivity related to human nitrogen loading, combined with allochthonous carbon from direct loading due to human activity, has resulted in an increased loading of non-algal organic carbon ranging from 20 and 25% in a significant portion of the Puget Sound’s main basin, as well as in multiple inlets. This increase in organic carbon is expected to have an impact in heterotrophic respiration rates and eutrophication. This presentation will focus on loading rates and predicted organic carbon concentrations throughout the Puget Sound using the Salish Sea Model. It will point to the need for enhanced dissolved and particulate organic carbon measurements in our region, as well as basin-scale measurements of respiration rates, to optimize the alignment of on-going, long term monitoring and modeling efforts

Prognostic value of prostate circulating cells detection in prostate cancer patients: a prospective study

In clinically organ-confined prostate cancer patients, bloodstream tumour cell dissemination generally occurs, and may be enhanced by surgical prostate manipulation. To evaluate cancer-cell seeding impact upon patient recurrence-free survival, 155 patients were prospectively enrolled then followed. Here, 57 patients presented blood prostate cell shedding preoperatively and intraoperatively (group I). Of the 98 preoperatively negative patients, 53 (54%) remained negative (group II) and 45 (46%) became intraoperatively positive (group III). Median biological and clinical recurrence-free time was far shorter in group I (36.2 months, P<0.0001) than in group II (69.6 months) but did not significantly differ in group II and III (69.6 months vs 65.0). Such 5-year follow-up data show that preoperative circulating prostate cells are an independent prognosis factor of recurrence. Moreover, tumour handling induces cancer-cell seeding but surgical blood dissemination does not accelerate cancer evolution

Diagnostic Accuracy of Magnetic Resonance Imaging Measures of Brain Atrophy Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Degeneration

The accurate diagnosis of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) is hampered by imperfect clinical-pathological correlations.To assess and compare the diagnostic value of the magnetic resonance parkinsonism index (MRPI) and other magnetic resonance imaging-based measures of cerebral atrophy to differentiate between PSP, CBD, and other neurodegenerative diseases.This prospective diagnostic study included participants with 4-repeat tauopathies (4RT), PSP, CBD, other neurodegenerative diseases and available MRI who appeared in the University of California, San Francisco, Memory and Aging Center database. Data were collected from October 27, 1994, to September 29, 2019. Data were analyzed from March 1 to September 14, 2021.The main outcome of this study was the neuropathological diagnosis of PSP or CBD. The clinical diagnosis at the time of the MRI acquisition was noted. The imaging measures included the MRPI, cortical thickness, subcortical volumes, including the midbrain, pons, and superior cerebellar peduncle volumes. Multinomial logistic regression models (MLRM) combining different cortical and subcortical regions were defined to discriminate between PSP, CBD, and other pathologies. The areas under the receiver operating characteristic curves (AUROC) and cutoffs were calculated to differentiate between PSP, CBD, and other diseases.Of the 326 included participants, 176 (54%) were male, and the mean (SD) age at MRI was 64.1 (8.0) years. The MRPI showed good diagnostic accuracy for the differentiation between PSP and all other pathologies (accuracy, 87%; AUROC, 0.90; 95% CI, 0.86-0.95) and between 4RT and other pathologies (accuracy, 80%; AUROC, 0.82; 95% CI, 0.76-0.87), but did not allow the discrimination of participants with CBD. Its diagnostic accuracy was lower in the subgroup of patients without the canonical PSP-Richardson syndrome (PSP-RS) or probable corticobasal syndrome (CBS) at MRI. MLRM combining cortical and subcortical measurements showed the highest accuracy for the differentiation between PSP and other pathologies (accuracy, 95%; AUROC, 0.98; 95% CI, 0.97-0.99), CBD and other pathologies (accuracy, 83%; AUROC, 0.86; 95% CI, 0.81-0.91), 4RT and other pathologies (accuracy, 89%; AUROC, 0.94; 95% CI, 0.92-0.97), and PSP and CBD (accuracy, 91%; AUROC, 0.95; 95% CI, 0.91-0.99), even in participants without PSP-RS or CBS at MRI.In this study, the combination of widely available cortical and subcortical measures of atrophy on MRI discriminated between PSP, CBD, and other pathologies and could be used to support the diagnosis of 4RT in clinical practice

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Regression applied to protein binding site prediction and comparison with classification

<p>Abstract</p> <p>Background</p> <p>The structural genomics centers provide hundreds of protein structures of unknown function. Therefore, developing methods enabling the determination of a protein function automatically is imperative. The determination of a protein function can be achieved by studying the network of its physical interactions. In this context, identifying a potential binding site between proteins is of primary interest. In the literature, methods for predicting a potential binding site location generally are based on classification tools. The aim of this paper is to show that regression tools are more efficient than classification tools for patches based binding site predictors. For this purpose, we developed a patches based binding site localization method usable with either regression or classification tools.</p> <p>Results</p> <p>We compared predictive performances of regression tools with performances of machine learning classifiers. Using leave-one-out cross-validation, we showed that regression tools provide better predictions than classification ones. Among regression tools, Multilayer Perceptron ranked highest in the quality of predictions. We compared also the predictive performance of our patches based method using Multilayer Perceptron with the performance of three other methods usable through a web server. Our method performed similarly to the other methods.</p> <p>Conclusion</p> <p>Regression is more efficient than classification when applied to our binding site localization method. When it is possible, using regression instead of classification for other existing binding site predictors will probably improve results. Furthermore, the method presented in this work is flexible because the size of the predicted binding site is adjustable. This adaptability is useful when either false positive or negative rates have to be limited.</p

HIV-1 Tat mimetic of VEGF correlates with increased microvessels density in AIDS-related diffuse large B-cell and Burkitt lymphomas

Angiogenic switch marks the beginning of tumor’s strategy to acquire independent blood supply. In some subtypes of non-Hodgkin’s lymphomas, higher local vascular endothelial growth factor (VEGF) expression correlates with increased microvessel density. However, this local VEGF expression is higher only in tumors with elevated expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. Several studies have indicated that VEGF receptors are also targeted by Tat protein from the HIV-1-infected cells. Given the similarity of the basic region of Tat to the angiogenic factors (basic fibroblast growth factor, VEGF), Tat mimics these proteins and binds to their receptors. We evaluated the role of HIV-1 Tat in regulating the level of VEGF expression and microvessel density in the AIDS-related diffuse large B-cell (DLBCL) and Burkitt lymphomas (BL). By luciferase assay, we showed that VEGF promoter activity was downregulated in vitro in cells transfected with Tat. Reduced VEGF protein expression in primary HIV-1 positive BL and DLBCL, compared to the negative cases, supported the findings of promoter downregulation from the cell lines. Microvascular density assessed by CD34 expression was, however, higher in HIV-1 positive than in HIV-1 negative tumors. These results suggest that Tat has a wider angiogenic role, besides the regulation of VEGF expression. Thus, targeting Tat protein itself and stabilizing transient silencing of VEGF expression or use of monoclonal antibodies against their receptors in the AIDS-associated tumors will open a window for future explorable pathways in the management of angiogenic phenotypes in the AIDS-associated non-Hodgkin’s lymphomas

The macroeconomics of a financial Dutch disease

We describe the medium-run macroeconomic effects and long-run development consequences of a financial Dutch disease that may take place in a small developing country with abundant natural resources. The first move is in financial markets. An initial surge in foreign direct investment targeting natural resources sets in motion a perverse cycle between exchange rate appreciation and mounting short- and medium-term capital flows. Such a spiral easily leads to exchange rate volatility, capital reversals, and sharp macroeconomic instability. In the long run, macroeconomic instability and overdependence on natural resource exports dampen the development of nontraditional tradable goods sectors and curtail labor productivity dynamics. We advise the introduction of constraints to short- and medium-term capital flows to tame exchange rate/capital flows boom-and-bust cycles. We support the implementation of a developmentalist monetary policy targeting competitive nominal and real exchange rates in order to encourage product and export diversification

Diagnostische Bedeutung der Proteinbindung von Plasmacortisol, bestimmt durch Dextrangelfiltration

1. Mittels Dextrangelfiltration wurde nach Inkubation von markiertem Cortisol und Plasma der proteingebundene und der sog. freie Anteil (%) des endogenen Plasmacortisols ermittelt und bei gleichzeitiger fluorimetrischer Bestimmung der 11-OHCS auch die Menge proteingebundenen, bzw. sog. freien Cortisols (µg-%) berechnet. 2. Die diagnostische Brauchbarkeit der Methode wurde bei Patienten mit Nebennierenrindeninsuffizienz, mit Hypophysentumoren, nach Hypophysektomie, mit Cushing-Syndrom mit der fluorimetrischen Bestimmung der 11-OHCS verglichen. Die einfache Bestimmung der Cortisolbindung war bei hypophysektomierten Patienten der Bestimmung der 11-OHCS überlegen und entsprach der aufwendigeren ACTH-Belastung. 3. Falsch hohe fluorimetrische 11-OHCS-Spiegel im Plasma unter Spirolacton- oder Oestrogenbehandlung und in der Gravidität lassen sich durch Bestimmung der Cortisolbindung klären. Bei Schilddrüsenüberfunktion war das sog. freie Cortisol im Plasma relativ und absolut vermehrt, bei Schilddrüsenunterfunktion fand sich eine Zunahme des plasmaproteingebundenen Cortisols.1. Following incubation of labeled cortisol and plasma the percentages of protein bound and socalled free endogenous cortisol were determined by means of dextran gel filtration. 2. The diagnostic value of this method was compared with fluorimetric determinations of 11-OHCS for patients with adrenal insufficiency, Cushing-Syndrome, pituitary tumors and after hypophysectomy. In hypophysectomized patients the simple determination of protein bound cortisol was found to correlate well with diagnostic ACTH-infusion tests and to be more sensitive than fluorimetric determinations of 11-OHCS in 9 a.m. plasma. 3. Falsely elevated fluorimetric values of plasma 11-OHCS in patients treated with spirolactone or estrogens, resp. during pregnancy may be recognized through determination of cortisol binding. — In thyrotoxicosis socalled free cortisol was elevated, both relatively and absolutely; in hypothyroidism an increase of protein bound cortisol was found

Improving women’s diet quality pre-conceptionally and during gestation: effects on birth weight and prevalence of low birth weight; a randomized controlled efficacy trial in India (Mumbai Maternal Nutrition Project)

BACKGROUND: Low birth weight (LBW) is an important public health problem in undernourished populations.OBJECTIVE: We tested whether improving women's dietary micronutrient quality before conception and throughout pregnancy increases birth weight in a high-risk Indian population.DESIGN: The study was a nonblinded, individually randomized controlled trial. The intervention was a daily snack made from green leafy vegetables, fruit, and milk (treatment group) or low-micronutrient vegetables (potato and onion) (control group) from ? 90 d before pregnancy until delivery in addition to the usual diet. Treatment snacks contained 0.69 MJ of energy (controls: 0.37 MJ) and 10-23% of WHO Reference Nutrient Intakes of ?-carotene, riboflavin, folate, vitamin B-12, calcium, and iron (controls: 0-7%). The primary outcome was birth weight.RESULTS: Of 6513 women randomly assigned, 2291 women became pregnant, 1962 women delivered live singleton newborns, and 1360 newborns were measured. In an intention-to-treat analysis, there was no overall increase in birth weight in the treatment group (+26 g; 95% CI: -15, 68 g; P = 0.22). There was an interaction (P &lt; 0.001) between the allocation group and maternal prepregnant body mass index (BMI; in kg/m(2)) [birth-weight effect: -23, +34, and +96 g in lowest (&lt;18.6), middle (18.6-21.8), and highest (&gt;21.8) thirds of BMI, respectively]. In 1094 newborns whose mothers started supplementation ? 90 d before pregnancy (per-protocol analysis), birth weight was higher in the treatment group (+48 g; 95% CI: 1, 96 g; P = 0.046). Again, the effect increased with maternal BMI (-8, +79, and +113 g; P-interaction = 0.001). There were similar results for LBW (intention-to-treat OR: 0.83; 95% CI: 0.66, 1.05; P = 0.10; per-protocol OR = 0.76; 95% CI: 0.59, 0.98; P = 0.03) but no effect on gestational age in either analysis.CONCLUSIONS: A daily snack providing additional green leafy vegetables, fruit, and milk before conception and throughout pregnancy had no overall effect on birth weight. Per-protocol and subgroup analyses indicated a possible increase in birth weight if the mother was supplemented ? 3 mo before conception and was not underweight. This trial was registered at www.controlled-trials.com/isrctn/ as ISRCTN62811278<br/