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Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. Participants aged 40–69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4–7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10–1.19; P ≤.001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05–2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02–1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46–39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61–3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15–1.96) in the first 4 rounds. Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. ClinicalTrials.gov , Number: NCT00102011. Fecal-based colorectal cancer screening is effective when there is adherence to the program of sequential (annual) testing. In circumstances when the uptake of fecal-based tests is suboptimal, colonoscopy should be considered in order to obtain maximum benefit. [ABSTRACT FROM AUTHOR]

Multidisciplinary team (MDT) meetings have emerged as a promising approach for the treatment of cancer patients. These meetings involve a team of healthcare professionals from different disciplines working together to develop a holistic, patient-centered treatment. Although MDT meetings are well established in oncology, they play a minor role in other diseases. Recent evidence suggests that the implementation of MDT meetings can improve patient outcomes in musculoskeletal infections. The aim of this retrospective, observational study was to present the agenda of our multidisciplinary limb board including live microscopy with a special focus on the pathologist's role. The descriptive analysis of the limb board included 66 cases receiving live microscopy at the meeting and a total of 124 histopathological findings and 181 stainings. We could elucidate that pathologists seem to play an important role especially in clarifying the correct diagnosis. In 80.3 % of the findings, the pathologist specified the clinical diagnosis of the requesting physician leading to a consensus-based treatment plan for each patient. The implementation of MDT meetings including live microscopy in patients with musculoskeletal infections holds potential benefits, such as improved communication, scientific collaboration, and raising clinicians' awareness and understanding of histopathology findings. However, potential challenges, such as organizational effort and technical prerequisites should be considered. • MDTs and digital pathology effectively expand beyond oncology for diverse diseases. • MDT meetings enhance decision-making in musculoskeletal infections. • Live microscopy in MDTs improves diagnosis accuracy in musculoskeletal infections. • Pathologists in MDTs significantly shape therapy plans. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jeem.2007.10.001 Byline: Erin T. Mansur (a), Robert Mendelsohn (b), Wendy Morrison (c) Keywords: Climate change; Adaptation; Energy demand; Discrete-continuous model Abstract: Using cross-sectional data, this paper estimates a national energy model of fuel choice by both households and firms. Consumers in warmer locations rely relatively more heavily on electricity rather than natural gas, oil, and other fuels. They also use more energy. Climate change will likely increase electricity consumption on cooling but reduce the use of other fuels for heating. On net, American energy expenditures will likely increase, resulting in welfare damages that increase as temperatures rise. For example, if the US warms by 5[degrees]C by 2100, we predict annual welfare losses of $57 billion. Author Affiliation: (a) Yale School of Management and NBER, 135 Prospect Street, P.O. Box 208200, New Haven, CT 065208200, USA (b) Yale School of Forestry and Environmental Studies, 230 Prospect Street, New Haven, CT 06511, USA (c) Texas A&M, El Paso Agricultural Research Center, USA Article History: Received 15 November 2005

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.04.029 Byline: John M. Gansner (a), Bryce A. Mendelsohn (a), Keith A. Hultman (b), Stephen L. Johnson (b), Jonathan D. Gitlin (a)(b) Keywords: Zebrafish; Notochord; Lysyl oxidase; Copper; Nutrition; Disease model; col2a1 Abstract: Recent studies reveal a critical role for copper in the development of the zebrafish notochord, suggesting that specific cuproenzymes are required for the structural integrity of the notochord sheath. We now demonstrate that [beta]-aminopropionitrile, a known inhibitor of the copper-dependent lysyl oxidases, causes notochord distortion in the zebrafish embryo identical to that seen in copper deficiency. Characterization of the zebrafish lysyl oxidase genes reveals eight unique sequences, several of which are expressed in the developing notochord. Specific gene knockdown demonstrates that loss of loxl1 results in notochord distortion, and that loxl1 and loxl5b have overlapping roles in notochord formation. Interestingly, while notochord abnormalities are not observed following partial knockdown of loxl1 or loxl5b alone, in each case this markedly sensitizes developing embryos to notochord distortion if copper availability is diminished. Likewise, partial knockdown of the lysyl oxidase substrate col2a1 results in notochord distortion when combined with reduced copper availability or partial knockdown of loxl1 or loxl5b. These data reveal a complex interplay of gene expression and nutrient availability critical to notochord development. They also provide insight into specific genetic and nutritional factors that may play a role in the pathogenesis of structural birth defects of the axial skeleton. Author Affiliation: (a) Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA (b) Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA Article History: Received 9 December 2006; Revised 24 April 2007; Accepted 24 April 2007

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jeem.2006.12.002 Byline: Nicholas Z. Muller, Robert Mendelsohn Abstract: This paper measures the damages due to emissions of air pollution in the United States. An integrated assessment model is used to calculate the marginal damage associated with emitting an additional ton of pollution from nearly 10,000 sources in the U.S. The total damage produced by a source is the marginal damage of an emission, its shadow price, times the total tons emitted from a specific source. Adding total damages across all sources yields gross annual damages (GAD) which is a green accounting parallel to gross domestic product (GDP). GAD in 2002 varies between $71 billion and $277 billion (0.7-2.8% of GDP). The range of values depends largely on the value of health and the concentration-response function relating exposures to fine particulate matter (PM.sub.2.5) to adult mortality rates. Source location also matters. Urban emissions constitute 52% of total emissions by weight yet they cause nearly three-quarters of the GAD. Author Affiliation: School of Forestry and Environmental Studies, Yale University, 230 Prospect Street, New Haven, CT 06611, USA Article History: Received 26 July 2006

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.07.026 Byline: Kai M. Schmidt-Ott (a), Xia Chen (a), Neal Paragas (a), Randy S. Levinson (b), Cathy L. Mendelsohn (b), Jonathan Barasch (a) Keywords: Aorta-gonad-mesonephros region; c-kit; Flk-1; Kidney development; Metanephros; Stem cell factor; Stroma; Ureteric bud Abbreviations: AGM, aorta-gonad-mesonephros; Cl, cloaca; DA, dorsal aorta; DMEM, Dulbecco's modified Eagle's medium; DNA, desoxyribonucleic acid; GDNF, glial derived neuronotrophic factor; Gn, gonad; HM, hindgut-associated mesenchyme; MM, metanephric mesenchyme; ND, nephric duct; PBS, phosphate buffered saline; PCR, polymerase chain reaction; Podxl, podocalyxin-like protein; Raldh2, retinaldehyde dehydrogenase 2; SCF, stem cell factor; sFRP1, secreted frizzled-related protein 1; UB, ureteric bud; UR, urogenital ridge; W, white spotting Abstract: Early inductive events in mammalian nephrogenesis depend on an interaction between the ureteric bud and the metanephric mesenchyme. However, mounting evidence points towards an involvement of additional cell types - such as stromal cells and angioblasts - in growth and patterning of the nephron. In this study, through analysis of the stem cell factor (SCF)/c-kit ligand receptor pair, we describe an additional distinct cell population in the early developing kidney. While SCF is restricted to the ureteric bud, c-kit-positive cells are located within the renal interstitium, but are negative for Foxd1, an established marker of stromal cells. In fact, the c-kit-positive domain is continuous with a central mesodermal cell mass ventral and lateral to the dorsal aorta, while Foxd1-expressing stromal cells are continuous with a dorsal perisomitic cell population suggesting distinct intraembryonic origins for these cell types. A subset of c-kit-positive cells expresses Flk-1 and podocalyxin, suggesting that this cell population includes angioblasts and their progenitors. c-kit activation is not required for the survival of these cells in vivo, because white spotting (c-kit.sup.W/W) mice, carrying a natural inactivating mutation of c-kit, display normal intrarenal distribution of the c-kit-positive cells at E13.5. In addition, early kidney development in these mutants is preserved up to the stage when anemia compromises global embryonic development. In contrast, under defined conditions in organ cultures of metanephric kidneys, c-kit-positive cells, including the Flk-1-positive subset, undergo apoptosis after treatment with STI-571, an inhibitor of c-kit tyrosine phosphorylation. This is associated with reductions in ureteric bud branching and nephron number. Conversely, exogenous SCF expands the c-kit-positive population, including Flk-1-positive angioblasts, and accelerates kidney development in vitro. These data suggest that ureteric bud-derived SCF elicits growth-promoting effects in the metanephric kidney by expanding one or more components of the interstitial c-kit-positive progenitor pool. Author Affiliation: (a) Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA (b) Department of Urology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA Article History: Received 16 February 2006; Revised 1 July 2006; Accepted 25 July 2006

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.06.035 Byline: Stavros Lomvardas (1), Gilad Barnea (1), David J. Pisapia (1), Monica Mendelsohn (1), Jennifer Kirkland (1), Richard Axel (1) Abstract: The expression of a single odorant receptor (OR) gene from a large gene family in individual sensory neurons is an essential feature of the organization and function of the olfactory system. We have used chromosome conformation capture to demonstrate the specific association of an enhancer element, H, on chromosome 14 with multiple OR gene promoters on different chromosomes. DNA and RNA fluorescence in situ hybridization (FISH) experiments allow us to visualize the colocalization of the H enhancer with the single OR allele that is transcribed in a sensory neuron. In transgenic mice bearing additional H elements, sensory neurons that express OR pseudogenes also express a second functional receptor. These data suggest a model of receptor choice in which a single trans-acting enhancer element may allow the stochastic activation of only one OR allele in an olfactory sensory neuron. Author Affiliation: (1) Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA Article History: Received 9 January 2006; Revised 28 April 2006; Accepted 22 June 2006 Article Note: (miscellaneous) Published: July 27, 2006

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2005.05.003 Byline: David H. Fitchett (a)(b), Anatoly Langer (a)(b), Paul W. Armstrong (c), Mary Tan (a), Aurora Mendelsohn (a), Shaun G. Goodman (a)(b) Abstract: Patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) benefit from the early administration of aspirin, a small molecule glycoprotein IIb/IIIa inhibitor such as eptifibatide, and heparin. The INTERACT trial demonstrated that in high-risk patients with ACS receiving aspirin and eptifibatide, the use of enoxaparin compared with unfractionated heparin (UFH) was associated with less bleeding, less early myocardial ischemia, and improved 30-day outcomes. Author Affiliation: (a) Canadian Heart Research Centre, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (b) Division of Cardiology, Terrence Donnelly Heart Centre, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (c) Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Article History: Received 23 February 2005; Accepted 2 May 2005 Article Note: (footnote) Conflicts of interest: Drs Fitchett, Langer, Armstrong, and Goodman have received research grant support, speaker honoraria, or consultant fees from Aventis Canada, Key Pharmaceuticals, Division of Schering Canada Inc, and Millenium Pharmaceuticals.

Children in low-income Hispanic families are at high risk of obesity and are more likely to live with grandparents than their non-Hispanic white counterparts. We aimed to determine if grandparent coresidence (prenatal through age 2 years) was associated with: 1) obesogenic feeding practices; and 2) child weight outcomes from birth to three years. We analyzed data from 267 low-income, Hispanic mother-infant pairs in the control group of an obesity prevention trial in New York City. Linear and logistic regression tested differences in obesogenic feeding practices and weight outcomes at 2 and 3 years, dependent upon grandparent coresidence. Multilevel modeling tested associations between grandparent coresidence and WFAz over time. Persistent grandparent coresidence (vs none) was associated with putting cereal in the bottle (adjusted odds ratio [aOR] 3.46; 95% confidence interval [CI] 1.43, 8.40). Persistent grandparent coresidence (vs none) was associated with higher mean WFAz (2 years: B 0.83; 95% CI 0.41, 1.25; 3 years: B 0.79; 95% CI 0.32, 1.25) and higher odds of child overweight/obesity risk (2 years: aOR 4.38; 95% CI 1.64, 11.69; 3 years: aOR 3.15; 95% CI 1.19, 8.36). In multilevel models, more occasions of grandparent coresidence were associated with higher WFAz. Grandparent coresidence may be associated with higher risk of child overweight/obesity in low-income, Hispanic families. Further research is needed to elucidate mechanisms of these associations and to inform obesity prevention strategies in the context of multigenerational families. [ABSTRACT FROM AUTHOR]

Maternal stress has been associated with early child obesity through pathways related to decreased exclusive breastfeeding and increased nonresponsive maternal-infant feeding styles. We sought to gain an in-depth understanding of how maternal stress, sadness, and isolation are perceived to affect feeding, in order to inform modifiable targets of intervention. We conducted semi-structured qualitative interviews with Hispanic mothers living in poverty with young infants between 3 and 7 months old (n = 32) from the intervention group of a randomized controlled trial of an early child obesity prevention intervention (Starting Early Program). Bilingual English-Spanish interviewers conducted the interviews, which were audio recorded, transcribed, and translated. Building on an existing theoretical framework developed by the National Scientific Council on the Developing Child, we used an iterative process of textual analysis to code the transcripts, until thematic saturation was reached. Three key themes were described: 1) maternal stress responses were varied and included positive (brief and mild), tolerable (sustained but limited long-term impacts), or toxic stress (sustained and severe); 2) buffers included support from family, infants, health care providers, social service programs, and community organizations; 3) perceived effects on infant feeding included decreased breastfeeding due to concerns about stress passing directly through breast milk and indirectly through physical closeness, and increased nonresponsive feeding styles. Maternal stress, particularly toxic stress, was perceived to negatively affect infant feeding. Mothers reported disrupting healthy feeding to avoid infant exposure to stress. Interventions to enhance buffering may help to mitigate toxic stress and promote healthy feeding interactions. Maternal stress, including toxic stress, was perceived to adversely affect breastfeeding and maternal-infant feeding interactions. Findings highlight the need for early child obesity prevention to incorporate stress reduction and mental health counseling, and to enhance buffering with increased social support. [ABSTRACT FROM AUTHOR]

A study was conducted to demonstrate that deletions or nonsense mutations in the P2 odorant receptor gene cause the axons of olfactory neurons to wander rather than converge on a specific glomerulus. Receptor substitution experiments that replace the P2 gene with the coding region of the P3 gene result in the projection of P3 to P2 axons to a glomerulus touching the wild-type P3 glomerulus. These data indicate that the odorant receptor plays an instructive role in the establishment of the topographic map of odor quality.

A genetic method of visualizing axons from olfactory sensory neurons expressing a given odorant receptor, as they project to the olfactory bulb, is introduced. Among the 1800 glomeruli in the mouse olfactory bulb, neurons expressing a specific receptor project to only two topographically fixed loci. These results affirm a model wherein a topographic map of receptor activation encodes odor quality in the olfactory bulb. The olfactory receptor is believed to play an instructive role in the guidance process, but is not the sole determinant in axon targeting.

Analysis of mice embryonic motor neuron differentiation revealed the importance of the expression of the LIM homeodomain transcription factor, Isl1. Isl1 is responsible for motor neuron differentiation in the neural tube embryos. The significance of Isl1 expression was confirmed with the findings that motor neurons send signals that initiate differentiation of interneurons.