To examine the link between bone material properties and skeletal fragility, we analyzed the mechanical, histological, biochemical, and spectroscopic properties of bones from a murine model of ...skeletal fragility (SAMP6). Intact bones from SAMP6 mice are weak and brittle compared with SAMR1 controls, a defect attributed to reduced strength of the bone matrix. The matrix weakness is attributed primarily to poorer organization of collagen fibers and reduced collagen content.
Introduction: The contribution of age‐related changes in tissue material properties to skeletal fragility is poorly understood. We previously reported that bones from SAMP6 mice are weak and brittle versus age‐matched controls. Our present objectives were to use the SAMP6 mouse to assess bone material properties in a model of skeletal fragility and to relate defects in the mechanical properties of bone to the properties of demineralized bone and to the structure and organization of collagen and mineral.
Materials and Methods: Femora from 4‐ and 12‐month‐old SAMR1 (control) and SAMP6 mice were analyzed using bending and torsional mechanical testing of intact bones, tensile testing of demineralized bone, quantitative histology (including collagen fiber orientation), collagen cross‐links biochemistry, and Raman spectroscopic analysis of mineral and collagen.
Results: Intact bones from SAMP6 mice have normal elastic properties but inferior failure properties, with 60% lower fracture energy versus SAMR1 controls. The strength defect in SAMP6 bones was associated with a 23% reduction in demineralized bone strength, which in turn was associated with poorer collagen fiber organization, lower collagen content, and higher hydroxylysine levels. However, SAMP6 have normal levels of collagen cross‐links and normal apatite mineral structure.
Conclusions: Bones from SAMP6 osteoporotic mice are weak and brittle because of a defect in the strength of the bone matrix. This defect is attributed primarily to poorer organization of collagen fibers and reduced collagen content. These findings highlight the role of the collagen component of the bone matrix in influencing skeletal fragility.
Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the ...specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established. The KTB is, to our knowledge, the only biorepository in the world prospectively established to collect normal, healthy breast tissue from volunteer donors. As a first initiative toward a molecular understanding of the biology and developmental genetics of the normal mammary gland, the effect of the menstrual cycle and hormonal contraceptives on DNA expression in the normal breast epithelium was examined.
Using normal breast tissue from 20 premenopausal donors to KTB, the changes in the mRNA of the normal breast epithelium as a function of phase of the menstrual cycle and hormonal contraception were assayed using next-generation whole transcriptome sequencing (RNA-Seq).
In total, 255 genes representing 1.4% of all genes were deemed to have statistically significant differential expression between the two phases of the menstrual cycle. The overwhelming majority (221; 87%) of the genes have higher expression during the luteal phase. These data provide important insights into the processes occurring during each phase of the menstrual cycle. There was only a single gene significantly differentially expressed when comparing the epithelium of women using hormonal contraception to those in the luteal phase.
We have taken advantage of a unique research resource, the KTB, to complete the first-ever next-generation transcriptome sequencing of the epithelial compartment of 20 normal human breast specimens. This work has produced a comprehensive catalog of the differences in the expression of protein-coding genes as a function of the phase of the menstrual cycle. These data constitute the beginning of a reference data set of the normal mammary gland, which can be consulted for comparison with data developed from malignant specimens, or to mine the effects of the hormonal flux that occurs during the menstrual cycle.
Infineon said it couldn't predict the full financial impact of the investigations and lawsuits. Its new charge, which follows a previous 28 million euros provision for the case, adds to a long list ...of woes plaguing the company. Infineon has been rudderless since a boardroom coup in March prompted the ouster of longtime Chief Executive Ulrich Schumacher. Infineon also is a defendant in an antitrust suit brought by Rambus Inc., a Silicon Valley company, accusing the German chip maker and others of conspiring to hinder adoption of its memory-chip technology. In the past three years, Infineon, Munich-based and a former subsidiary of Siemens AG, lost more than 2 billion euros amid the chip industry's worst downturn. Despite a recent recovery, driven by stronger demand for handsets, digital cameras and other advanced gadgets, Infineon's shares have fallen 14% this year.
IMPORTANCE: As the field of medicine strives for equity in care, research showing the association of social determinants of health (SDOH) with poorer health care outcomes is needed to better inform ...quality improvement strategies. OBJECTIVE: To evaluate the association of SDOH with prostate cancer–specific mortality (PCSM) and overall survival (OS) among Black and White patients with prostate cancer. DATA SOURCES: A MEDLINE search was performed of prostate cancer comparative effectiveness research from January 1, 1960, to June 5, 2020. STUDY SELECTION: Two authors independently selected studies conducted among patients within the United States and performed comparative outcome analysis between Black and White patients. Studies were required to report time-to-event outcomes. A total of 251 studies were identified for review. DATA EXTRACTION AND SYNTHESIS: Three authors independently screened and extracted data. End point meta-analyses were performed using both fixed-effects and random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed, and 2 authors independently reviewed all steps. All conflicts were resolved by consensus. MAIN OUTCOMES AND MEASURES: The primary outcome was PCSM, and the secondary outcome was OS. With the US Department of Health and Human Services Healthy People 2030 initiative, an SDOH scoring system was incorporated to evaluate the association of SDOH with the predefined end points. The covariables included in the scoring system were age, comorbidities, insurance status, income status, extent of disease, geography, standardized treatment, and equitable and harmonized insurance benefits. The scoring system was discretized into 3 categories: high (≥10 points), intermediate (5-9 points), and low (<5 points). RESULTS: The 47 studies identified comprised 1 019 908 patients (176 028 Black men and 843 880 White men; median age, 66.4 years IQR, 64.8-69.0 years). The median follow-up was 66.0 months (IQR, 41.5-91.4 months). Pooled estimates found no statistically significant difference in PCSM for Black patients compared with White patients (hazard ratio HR, 1.08 95% CI, 0.99-1.19; P = .08); results were similar for OS (HR, 1.01 95% CI, 0.95-1.07; P = .68). There was a significant race-SDOH interaction for both PCSM (regression coefficient, −0.041 95% CI, –0.059 to 0.023; P < .001) and OS (meta-regression coefficient, −0.017 95% CI, –0.033 to –0.002; P = .03). In studies with minimal accounting for SDOH (<5-point score), Black patients had significantly higher PCSM compared with White patients (HR, 1.29; 95% CI, 1.17-1.41; P < .001). In studies with greater accounting for SDOH variables (≥10-point score), PCSM was significantly lower among Black patients compared with White patients (HR, 0.86; 95% CI, 0.77-0.96; P = .02). CONCLUSIONS AND RELEVANCE: The findings of this meta-analysis suggest that there is a significant interaction between race and SDOH with respect to PCSM and OS among men with prostate cancer. Incorporating SDOH variables into data collection and analyses are vital to developing strategies for achieving equity.
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour, with few available therapies providing significant improvements in mortality. Biomarkers, which are defined by ...the National Institutes of Health as 'characteristics that are objectively measured and evaluated as indicators of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention', have the potential to play valuable roles in the diagnosis and treatment of GBM. Although GBM biomarker research is still in its early stages because of the tumour's complex pathophysiology, a number of potential markers have been identified which can be measured in either brain tissue or blood serum. In conjunction with other clinical data, particularly neuroimaging modalities such as MRI, these proteins could contribute to the clinical management of GBM by helping to classify tumours, predict prognosis and assess treatment response. In this article, we review the current understanding of GBM pathophysiology and recent advances in GBM biomarker research, and discuss the potential clinical implications of promising biomarkers. A better understanding of GBM pathophysiology will allow researchers and clinicians to identify optimal biomarkers and methods of interpretation, leading to advances in tumour classification, prognosis prediction and treatment assessment.
Banks Shoulder Too Much of LDC Burden MATTHEW W. BARRETT, President and CEO, Bank of Montreal
The American banker,
12/1989, Letnik:
154, Številka:
238
Newspaper Article
Unfortunately, the Nicholas Brady plan has not worked this way. Resources from G-7 governments for credit enhancement of residual debt have been inadequate and have been applied with insufficient ...flexibility. Debtor countries have formed unrealistic expectations about the extent of debt reduction likely to be acceptable to the banks. Certain debtor countries, including some that are demonstrably able to service their debts, have allowed interest arrears to increase significantly. Finally, G-7 governments should help debtor countries' efforts toward integration in a stable and growing world economy. This means fewer barriers, tariff and nontariff, to international trade. Also, while demanding reforms in debtor economies, industrialized nations need to look to reforms in their own. As has often been said, the only long-term solution to LDC debt is for the debtor countries to achieve sustained growth. The development potential of several of the LDCs is huge. Many are rich in natural resources and have significant industrial sectors and well-trained work forces. But they cannot achieve their potential if they remain isolated and starved of technology, investment, and foreign exchange.
Authors apart from NCGR and NCMA affiliates, FB and HMW (who performed 18S rRNA gene analyses), are community members who submitted samples for sequencing, including members of the advisory ...committee, but did not receive GBMF funds directly in support of these efforts. The number of people involved in this project at all levels was too great to allow all to be included in the author list, but in recognition of their tremendous efforts and their position as part of this community, we would like to thank Suzanne Strom (WWU), Mark Hildebrand (SIO); David Moreira, Purification Lopez Garcia (Université Paris-Sud); Adrian Reyes-Prieto (UNB); Bryndan P. Durham, Vanessa Varaljay (UGA); Behzad Imanian, Juan Saldarriaga, Jan Janouskovec, Greg Gavelis, Naoji Yabuki, Yingchun Gong (UBC); Charles Bachy, Sebastian Sudek, Hank Yu (MBARI); Chloe Deodato (UW); Chris Brown, Christien Laber, Kim Thamatrakoln, Brittany Schieler (Rutgers); Ida Orefice, Deepak Nanjappa (Stazione Zoologica Anton Dohrn); Roberto Sierra (University of Geneva); Rebecca Gast, Virginia Edgcomb, Sheean Haley, Harriet Alexander, David Beaudoin, Robert J. Olson (WHOI); Hollie M. Putnam, Michael P. Lesser (UH); Sheri Floge, Michael Preston (NCMA); Dreux Chappell, Amanda Burke, Gang Chen, Kelly Canesi, Andrea Drzewianowski, Joselynn Wallace, LeAnn Whitney, Kerry Whittaker, Amanda Montalbano (URI); Karen Pelletreau, Yunyun Zhuang, Huan Zhang, Yunyun Zhuang, (UCONN); Scott Lawrence (VUW); Min Park (LANL); Behzad Imanian, Jan Janouskovec, Juan Saldarriaga, Erick James, Greg Gavelis, Thierry Heger, Yoshihisa Hirakawa (UBC); K. Fraser Clark, Adam Acorn, Richard Cawthorn (UPEI); Raffaela M. Abbriano, Javier Paz Yepes, Christine N. Shulse (SIO); Kimberly deLong, Harry Masters (UNC-CH); Tom Savage (CSUS); Kendra Hayashi, Raphael Kudela (UCSC); Marianne Potvin, André Comeau (U Laval); Ewelina Rubin (SBU); Matthew Ashworth (UT Austin); Miguel Frada (Weizmann Institute of Science); Sandra Pucciarelli (University of Camerino); Dianna L. Berry, Matthew J. Harke, Yoonja Kang (SBU); Julia F. Hopkins, Eunsoo Kim, Naoko T. Onodera, Goro Tanifuji, Tommy Harding, Andrew Roger (Dalhousie University); Wei-Shu Hu (U Minnesota); William Rosado (U Puerto Rico); Jessica Grant, Dan Lahr (Smith College); Robert Molestina (American Type Culture Collection); Fran Van Dolah (NOAA); Anke Stüken, Russell Orr (U. Oslo); Simon Dittami (UiO); Sara Bender, Colleen Durkin, Gwenn Hennon, Julie Koester, Rhonda Morales, Irina Oleinikov, Micaela Parker, Francois Ribalet, Megan Schatz, Helena van Tol (UW); Robert Sanders (Temple); Karla Heidelberg (USC); Ramiro Logares (ICM, Barcelona); Anke Kremp (SYKE, Finland); Frederic Verret (IMBB); Vittorio Boscaro, Michele Castelli, Graziano Di Giuseppe, Fernando Dini, Graziano Di Giuseppe, Roberto Marangoni, Letizia Modeo (University of Pisa); Ian Probert, Priscillia Gourvil, Florence Le Gall (RCC); Marcus V. X. Senra (Federal University of Rio de Janeiro); Federico Buonanno, Claudio Ortenzi (University of Macerata); Susanna Theroux (JGI); Sophie Sanchez-Ferandin (UPMC); Sheree Yau (CNRS); Philipp Assmy, Sára Beszteri, Fabian Kilpert, Christine Klaas, Jan Meyer (AWI); Gurjeet Kohli (UTS); Sarah D'Adamo, Robert Jinkerson, Huiya Gu (CSM).
Development as Leadership-led Change Matt Andrews, Jesse McConnell, Alison Wescott
2010, 06-21-2010, 2010-06-01, 20100601
eBook, Book, Book Chapter
Odprti dostop
Much of the work on reform and development has focused on the identification and diagnosis of problems and on the formulation of technically sound measures to address these problems. But the main ...challenge that often confronts policy makers in attempting to undertake reforms is not in the 'what', what is the problem and what are the remedies for it, but in the 'why', why does the problem persist, which some research has begun to address, and, more critically, in the 'how' given the why, how to manage the often complex process of change that accompanies any attempt at reform. It is in the latter where the rubber hits the road. Development involves change. But many development initiatives produce unimpressive levels of change in the countries, organizations, and outcomes they target and are disappointing in the final results. This is the case in social sector initiatives, core public management reforms, and even macroeconomic adjustment operations. Change is often limited even when countries adopt solutions in their forms, in apparently good faith and on time (or in reasonable time). This research paper aims to (modestly) contribute to such research by exploring what it takes to get change done; and particularly what role leadership plays in effecting change.
Existing climate-economy models use aggregate damage functions to model the effects of climate change. This approach assumes climate change has equal impacts on the productivity of firms that produce ...consumption and investment goods or services. We show the split between damage to consumption and investment productivity matters for the dynamic consequences of climate change. Drawing on the structural transformation literature, we develop a framework that incorporates heterogeneous climate damages. When investment is more vulnerable to climate, we find short-run consumption losses will be smaller than leading models with aggregate damage functions suggest, but long-run consumption losses will be larger. We quantify these effects for the climate damage from heat stress and find that accounting for heterogeneous damages increases the welfare cost of climate change by approximately 4 to 24 percent, depending on the discount factor.
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