A hybrid deconvolution approach for estimation of in vivo non-displaceable binding for brain PET targets without a reference region

Background and aim Estimation of a PET tracer’s non-displaceable distribution volume (VND) is required for quantification of specific binding to its target of interest. VND is generally assumed to be comparable brain-wide and is determined either from a reference region devoid of the target, often not available for many tracers and targets, or by imaging each subject before and after blocking the target with another molecule that has high affinity for the target, which is cumbersome and involves additional radiation exposure. Here we propose, and validate for the tracers [11C]DASB and [11C]CUMI-101, a new data-driven hybrid deconvolution approach (HYDECA) that determines VND at the individual level without requiring either a reference region or a blocking study. Methods HYDECA requires the tracer metabolite-corrected concentration curve in blood plasma and uses a singular value decomposition to estimate the impulse response function across several brain regions from measured time activity curves. HYDECA decomposes each region’s impulse response function into the sum of a parametric non-displaceable component, which is a function of VND, assumed common across regions, and a nonparametric specific component. These two components differentially contribute to each impulse response function. Different regions show different contributions of the two components, and HYDECA examines data across regions to find a suitable common VND. HYDECA implementation requires determination of two tuning parameters, and we propose two strategies for objectively selecting these parameters for a given tracer: using data from blocking studies, and realistic simulations of the tracer. Using available test-retest data, we compare HYDECA estimates of VND and binding potentials to those obtained based on VND estimated using a purported reference region. Results For [11C]DASB and [11C]CUMI-101, we find that regardless of the strategy used to optimize the tuning parameters, HYDECA provides considerably less biased estimates of VND than those obtained, as is commonly done, using a non-ideal reference region. HYDECA test-retest reproducibility is comparable to that obtained using a VND determined from a non-ideal reference region, when considering the binding potentials BPP and BPND. Conclusions HYDECA can provide subject-specific estimates of VND without requiring a blocking study for tracers and targets for which a valid reference region does not exist

Development and characterization of a long‐acting recombinant hFSH agonist

Background: Fusion of the carboxyterminal peptide (CTP) of hCG to FSH results in a follitropin agonist with an extended half-life, presumably due to the four O-oligosaccharides on the CTP. Alternatively, an rhFSH analogue containing additional N-linked carbohydrate is described in this report. Methods: A DNA sequence containing two N-oligosaccharide signal sequences was ligated into a vector containing hFSHβ- and α-subunit encoding cDNA, and expressed in CHO-K1 cells. In-vitro bioactivity of the single-chain hormone was assessed in CHO cells expressing the hFSH receptor. Pharmacokinetic values were derived from serial serum assays of the analogue in immature female rats following a single i.v. injection. In-vivo bioactivity was assessed by measuring ovarian weight gain 3 days post-injection. Results: rhFSH-N2 and native rhFSH induced comparable levels of cAMP in vitro. t1/2 for native rhFSH, rhFSH-CTP and rhFSH-N2 were 3.7, 7.1 and 7.3 h respectively. Rats receiving rhFSH-N2 had a mean ± SD ovarian weight 3 days post-i.v. injection (22 ± 3.6 mg) significantly greater than rats receiving rhFSH and saline (16.7 ± 1.5 and 15.3 ± 0.47 mg respectively, P < 0.05). Conclusions: rhFSH-N2 has prolonged half-life and increased bioactivity compared with native rhFSH. This rhFSH agonist, and other analogues containing additional N-oligosaccharides may have important clinical applications

The publics' understanding of daily caloric recommendations and their perceptions of calorie posting in chain restaurants

<p>Abstract</p> <p>Background</p> <p>Calorie posting in chain restaurants has received increasing attention as a policy lever to reduce energy intake. Little research has assessed consumer understanding of overall daily energy requirements or perceived effectiveness of calorie posting.</p> <p>Methods</p> <p>A phone survey was conducted from May 1 through 17, 2009 with 663 randomly selected, nationally-representative adults aged 18 and older, including an oversample of Blacks and Hispanics in the United States. To examine differences in responses by race and ethnicity (White, Black, and Hispanic) and gender, we compared responses by conducting chi-squared tests for differences in proportions.</p> <p>Results</p> <p>We found that most Americans were knowledgeable about energy requirements for moderately active men (78%) and women (69%), but underestimated energy requirements for inactive adults (60%). Whites had significantly higher caloric literacy and confidence about their caloric knowledge than Blacks and Hispanics (p < 0.05). As compared to their counterparts, Blacks, Hispanics and women reported a significantly higher likelihood of eating at a chain restaurant and of selecting lower calorie foods where caloric information was posted. Most Americans favored the government requiring chain restaurants to post calorie information on menus at the point of purchase (68%). Support for government mandated calorie posting in chain restaurants was significantly higher among Blacks, Hispanics and women as compared to their counterparts. The public was divided about the mode of caloric information that would best help them make a lower calorie decision; a third favored number of calories (35%) which is the current standard mode of presenting caloric information in chain restaurants, a third favored a physical activity equivalent (26%), and a third favored percentage of total energy intake (39%).</p> <p>Conclusion</p> <p>Mandating calorie posting in chain restaurants may be a useful policy tool for promoting energy balance, particularly among Blacks, Hispanics and women who have higher obesity risk.</p

Collision Mortality Has No Discernible Effect on Population Trends of North American Birds

Avian biodiversity is threatened by numerous anthropogenic factors and migratory species are especially at risk. Migrating birds frequently collide with manmade structures and such losses are believed to represent the majority of anthropogenic mortality for North American birds. However, estimates of total collision mortality range across several orders of magnitude and effects on population dynamics remain unknown. Herein, we develop a novel method to assess relative vulnerability to anthropogenic threats, which we demonstrate using 243,103 collision records from 188 species of eastern North American landbirds. After correcting mortality estimates for variation attributable to population size and geographic overlap with potential collision structures, we found that per capita vulnerability to collision with buildings and towers varied over more than four orders of magnitude among species. Species that migrate long distances or at night were much more likely to be killed by collisions than year-round residents or diurnal migrants. However, there was no correlation between relative collision mortality and long-term population trends for these same species. Thus, although millions of North American birds are killed annually by collisions with manmade structures, this source of mortality has no discernible effect on populations

Chronic Maternal Depression Is Associated with Reduced Weight Gain in Latino Infants from Birth to 2 Years of Age

BACKGROUND: Latino children are at increased risk for mirconutrient deficiencies and problems of overweight and obesity. Exposures in pregnancy and early postpartum may impact future growth trajectories. OBJECTIVES: To evaluate the relationship between prenatal and postnatal maternal depressive symptoms experienced in pregnancy and infant growth from birth to 2 years of age in a cohort of Latino infants. METHODS: We recruited pregnant Latina mothers at two San Francisco hospitals and followed their healthy infants to 24 months of age. At 6, 12 and 24 months of age, infants were weighed and measured. Maternal depressive symptoms were assessed prenatally and at 4-6 weeks postpartum. Women who had high depressive symptoms at both time periods were defined as having chronic depression. Logistic mixed models were applied to compare growth curves and risk for overweight and underweight based on exposure to maternal depression. RESULTS: We followed 181 infants to 24 months. At 12 and 24 months, respectively, 27.4% and 40.5% were overweight, and 5.6% and 2.2% were underweight. Exposure to chronic maternal depression was associated with underweight (OR = 12.12, 95%CI 1.86-78.78) and with reduced weight gain in the first 2 years of life (Coef = -0.48, 95% CI -0.94-0.01) compared with unexposed infants or infants exposed to episodic depression (depression at one time point). Exposure to chronic depression was also associated with reduced risk for overweight in the first 2 years of life (OR 0.28, 95%CI 0.03-0.92). CONCLUSIONS: Exposure to chronic maternal depression in the pre- and postnatal period was associated with reduced weight gain in the first two years of life and greater risk for failure to thrive, in comparison with unexposed infants or those exposed episodically. The infants of mothers with chronic depression may need additional nutritional monitoring and intervention

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

BACKGROUND: Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure. METHODS AND RESULTS: MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3. CONCLUSIONS: This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation

The vertebral body growth plate in scoliosis: a primary disturbance of growth?

Study Design and Aims: This was an observational pilot study of the vertebral body growth plates in scoliosis involving high-resolution coronal plane magnetic resonance (MR) imaging and histological examination. One aim of this study was to determine whether vertebral body growth plates in scoliosis demonstrated abnormalities on MR imaging. A second aim was to determine if a relationship existed between MR and histological abnormalities in these vertebral body growth plates. Methods: MR imaging sequences of 18 patients demonstrated the vertebralbody growth plates well enough to detect gross abnormalities/ deficient areas/zones. Histological examination of ten vertebral body growth plates removed during routine scoliosis surgery was performed. Observational histological comparison with MR images was possible in four cases. Results: Four of the 18 MR images demonstrated spines with normal curvature and normal vertebral body growth plates. In 13 scoliotic spines, convex and concave side growth plate deficiencies were observed most frequently at or near the apex of the curve. One MR image demonstrated a 55° kyphosis and no convex or concave side deficiencies. The degree of vertebral body wedging was independent of the presence of vertebral body growth plate deficiency. Histological abnormalities of the vertebral body growth plates were demonstrated in four with MR imaging abnormalities. Conclusion: This study demonstrated MR image abnormalities of scoliotic vertebral body growth plates compared to controls. A qualitative relationship was demonstrated between MR imaging and histological abnormalities. The finding that vertebral body growth plate deficiencies occurred both on the convex and concave sides of the spine, closest to the apical vertebra of the scoliosis curve, implied that they are less likely to be the result of adaptive changes to the physical forces involved in the scoliotic deformity. One explanation is that they represent a primary disturbance of growth