The influence of chronic conditions and the environment on pubertal development. An example from medieval England

Adolescence is a unique period in human development encompassing sexual maturation (puberty) and the physical and psychological transition into adulthood. It is a crucial time for healthy development and any adverse environmental conditions, poor nutrition, or chronic infection can alter the timing of these physical changes; delaying menarche in girls or the age of peak height velocity in boys. This study explores the impact of chronic illness on the tempo of puberty in 607 adolescent skeletons from medieval England (AD 900-1550). A total of 135 (22.2%) adolescents showed some delay in their pubertal development, and this lag increased with age. Of those with a chronic condition, 40.0% (n=24/60) showed delay compared to only 20.3% (n=111/547) of the non-pathology group. This difference was statistically significant. A binary logistic regression model demonstrated a significant association between increasing delay in pubertal stage attainment with age in the pathology group. This is the first time that chronic conditions have been directly associated with a delay in maturation in the osteological record, using a new method to assess stages of puberty in skeletal remains.

Loss of Methylation at H19 DMD Is Associated with Biallelic Expression and Reduced Development in Cattle Derived by Somatic Cell Nuclear Transfer

Although cloning of mammals has been achieved successfully, the percentage of live offspring is very low because of reduced fetal size and fewer implantation sites. Recent studies have attributed such pathological conditions to abnormal reprogramming of the donor cell used for cloning. The inability of the oocyte to fully restore the differentiated status of a somatic cell to its pluripotent and undifferentiated state is normally evidenced by aberrant DNA methylation patterns established throughout the genome during development to blastocyst. These aberrant methylation patterns are associated with abnormal expression of imprinted genes, which among other genes are essential for normal embryo development and gestation. We hypothesized that embryo loss and low implantation rates in cattle derived by somatic cell nuclear transfer (SCNT) are caused by abnormal epigenetic reprogramming of imprinted genes. To verify our hypothesis, we analyzed the parental expression and the differentially methylated domain (DMD) methylation status of the H19 gene. Using a parental-specific analysis, we confirmed for the first time that H19 biallelic expression is tightly associated with a severe demethylation of the paternal H19 DMD in SCNT embryos, suggesting that these epigenetic anomalies to the H19 locus could be directly responsible for the reduced size and low implantation rates of cloned embryos in cattle.

Financing for sustainable development: visions and proposals for action from a Latin American and Caribbean perspective

Foreword Throughout the preparatory process for the World Summit on Sustainable Development and at the Summit itself, which was held in Johannesburg, South Africa, from 26 August to 4 September 2002, discussions were dominated by one central concern: the need to define and reach consensus on concrete, quantitative goals, with fixed deadlines for implementation, which were to supplement the Millennium Development Goals and facilitate progress towards an effective transition to sustainable development. Participants at the Summit explicitly affirmed the need, as a matter of urgency, to identify the financial and technical resources whereby sustainable development would become a reality and benefit directly and particularly rural and urban communities in the developing countries. The document we are now presenting is the outcome of extensive discussions held at a high-level forum during the Johannesburg Summit. Led by representatives of the Government of Mexico, the Economic Commission for Latin America and the Caribbean (ECLAC), the United Nations Development Programme (UNDP) and the Andean Development Corporation, those discussions were based on the ECLAC/UNDP study entitled Financing for sustainable development in Latin America and the Caribbean: from Monterrey to Johannesburg, which considers the opportunities and challenges for improving prospects for investment and financing for sustainable development and underscores the need to establish a new balance between the market economy and public interest through joint public/private initiatives that combine market innovation, social responsibility and appropriate regulations. Other eminent persons attending the event included heads of State, such as Gustavo Noboa, then President of Ecuador; Enrique V. Iglesias, President of the Inter-American Development Bank (IDB); José María Figueres, Managing Director of the Global Agenda of the World Economic Forum and former President of Costa Rica; and Gro Harlem Brundtland, the legendary figure who pioneered sustainable development. Valuable contributions to the discussions were made by Yolanda Kakabadse, President of the World Conservation Union; Xóchitl Gálvez Ruiz, head of the Unit for the Development of Indigenous Peoples of the Office of the President of Mexico; Cecilia López, former Minister for the Environment of Colombia; and Juan Carlos Maqueda, then Vice President of Argentina. The views emerging from the forum as set forth in this document are designed to facilitate and promote application of the Plan of Implementation of the World Summit on Sustainable Development within the framework of the Millennium Development Goals and the commitments assumed at the International Conference on Financing for Development, which was held in Monterrey, Mexico. We also aspire to continue moving forward with the adoption of measures and policies to increase investment and financing for sustainable development as well as to foster partnerships between the public and private sectors and nongovernmental organizations. We recognize, in this context, the importance of strengthening and improving public and private institutions in order to meet the operational needs associated with the effort to achieve the Millennium Development Goals and pursue the Plan of Implementation formulated in Johannesburg. We trust that this document will contribute to in-depth discussions on the application of the Plan of Implementation in the relevant forums, in particular the United Nations Commission on Sustainable Development. The Plan of Implementation of the World Summit on Sustainable Development opens up new opportunities for Latin America and the Caribbean to renew and revive their own regional agenda -with emphasis on global and especially regional public goods- and to interweave it more cohesively with the global agenda in order to promote the common interests of Latin America and the Caribbean more forcefully in international development forums. The regional agenda and the global agenda cannot be separated in a contrived manner; indeed, to an increasing degree, what we are witnessing are global environmental processes which call for action at the local level. The achievement of sustainable development in Latin America and the Caribbean, where the necessary economic, social, environmental and geopolitical conditions are combined, requires a subtle balance between the market economy, the State and the citizen. Such a balance will result in the consolidation of democratic governance in the service of human development. VICENTE FOX President of Mexico JOSÉ ANTONIO OCAMPO Executive Secretary, Economic Commission for Latin America and the Caribbean (ECLAC) ELENA MARTÍNEZ Assistant Aministrator and Regional Director for Latin America and the Caribbean of the United Nations Development Programme (UNDP) ENRIQUE GARCÍA Executive President, Andean Development Corporation (ADC)""

Equity, development and citizenship: abridged edition

Includes bibliography

Contribution of energy services to the Millennium Development Goals and to poverty alleviation in Latin America and the Caribbean: executive summary

Includes bibliography

Contribution of energy services to the millennium development goals and to poverty alleviation in Latin America and the Caribbean

Includes bibliography

Caribbean forum: Shaping a sustainable development agenda to address the Caribbean reality in the twenty-first century

Includes bibliography.

The Caribbean and the post-2015 development agenda

This paper will contend that the post-2015 development agenda presents a major opportunity for Caribbean countries to reverse decades of lagging economic performance and make the transition to balanced, holistic, and people-centred growth and development. The MDGs, while valuable in promoting gains in poverty reduction, health, education, nutrition, and maternal well-being were not tailored to the growth and development needs of the region. This can now be changed by a post-2015 development agenda which goes beyond improving the welfare of citizens by meeting basic needs and enhancing access to primary services. The necessary scaling-up of the MDG framework will require that the sustainable development goals, which will anchor the post- 2015 development agenda, are capable of promoting structural change, competitiveness and output gains while advancing social development and meeting environmental concerns. They must also address the unfinished business of the millennium development goals, primarily in the area of human development.

Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative

Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a "roadmap" for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH.

Identifying indicators of sustainable development using the global sustainability quadrant approach

Advances in information technology and global data availability have opened the door for assessments of sustainable development at a truly macro scale. It is now fairly easy to conduct a study of sustainability using the entire planet as the unit of analysis; this is precisely what this work set out to accomplish. The study began by examining some of the best known composite indicator frameworks developed to measure sustainability at the country level today. Most of these were found to value human development factors and a clean local environment, but to gravely overlook consumption of (remote) resources in relation to nature’s capacity to renew them, a basic requirement for a sustainable state. Thus, a new measuring standard is proposed, based on the Global Sustainability Quadrant approach. In a two‐dimensional plot of nations’ Human Development Index (HDI) vs. their Ecological Footprint (EF) per capita, the Sustainability Quadrant is defined by the area where both dimensions satisfy the minimum conditions of sustainable development: an HDI score above 0.8 (considered ‘high’ human development), and an EF below the fair Earth‐share of 2.063 global hectares per person. After developing methods to identify those countries that are closest to the Quadrant in the present‐day and, most importantly, those that are moving towards it over time, the study tackled the question: what indicators of performance set these countries apart? To answer this, an analysis of raw data, covering a wide array of environmental, social, economic, and governance performance metrics, was undertaken. The analysis used country rank lists for each individual metric and compared them, using the Pearson Product Moment Correlation function, to the rank lists generated by the proximity/movement relative to the Quadrant measuring methods. The analysis yielded a list of metrics which are, with a high degree of statistical significance, associated with proximity to – and movement towards – the Quadrant; most notably: Favorable for sustainable development: use of contraception, high life expectancy, high literacy rate, and urbanization. Unfavorable for sustainable development: high GDP per capita, high language diversity, high energy consumption, and high meat consumption. A momentary gain, but a burden in the long‐run: high carbon footprint and debt. These results could serve as a solid stepping stone for the development of more reliable composite index frameworks for assessing countries’ sustainability.

Involvement of heparin-like glycosaminoglycans and expression of a novel heparan sulfate binding protein (p24) during human placentation and in a model for human implantation

Previous studies in our laboratory have indicated that heparan sulfate proteoglycans (HSPGs) play an important role in murine embryo implantation. To investigate the potential function of HSPGs in human implantation, two human cell lines (RL95 and JAR) were selected to model uterine epithelium and embryonal trophectoderm, respectively. A heterologous cell-cell adhesion assay showed that initial binding between JAR and RL95 cells is mediated by cell surface glycosaminoglycans (GAG) with heparin-like properties, i.e., heparan sulfate and dermatan sulfate. Furthermore, a single class of highly specific, protease-sensitive heparin/heparan sulfate binding sites exist on the surface of RL95 cells. Three heparin binding, tryptic peptide fragments were isolated from RL95 cell surfaces and their amino termini partially sequenced. Reverse transcription-polymerase chain reaction (RT-PCR) generated 1 to 4 PCR products per tryptic peptide. Northern blot analysis of RNA from RL95 cells using one of these RT-PCR products identified a 1.2 Kb mRNA species (p24). The amino acid sequence predicted from the cDNA sequence contains a putative heparin-binding domain. A synthetic peptide representing this putative heparin binding domain was used to generate a rabbit polyclonal antibody (anti-p24). Indirect immunofluorescence studies on RL95 and JAR cells as well as binding studies of anti-p24 to intact RL95 cells demonstrate that p24 is distributed on the cell surface. Western blots of RL95 membrane preparations identify a 24 kDa protein (p24) highly enriched in the 100,000 g pellet plasma membrane-enriched fraction. p24 eluted from membranes with 0.8 M NaCl, but not 0.6 M NaCl, suggesting that it is a peripheral membrane component. Solubilized p24 binds heparin by heparin affinity chromatography and $\sp{125}$I-heparin binding assays. Furthermore, indirect immunofluorescence studies indicate that cytotrophoblast of floating and attached villi of the human fetal-maternal interface are recognized by anti-p24. The study also indicates that the HSPG, perlecan, accumulates where chorionic villi are attached to uterine stroma and where p24-expressing cytotrophoblast penetrate the stroma. Collectively, these data indicate that p24 is a cell surface membrane-associated heparin/heparan sulfate binding protein found in cytotrophoblast, but not many other cell types of the fetal-maternal interface. Furthermore, p24 colocalizes with HSPGs in regions of cytotrophoblast invasion. These observations are consistent with a role for HSPGs and HSPG binding proteins in human trophoblast-uterine cell interactions. ^

Regulation and function of {\it Xparaxis\/} during the development of paraxial mesoderm in {\it Xenopus laevis\/}

Genes of the basic helix-loop-helix transcription factor family have been implicated in many different developmental processes from neurogenesis to myogenesis. The recently cloned bHLH transcription factor, paraxis, has been found to be expressed in the paraxial mesoderm of the mouse suggesting a role for paraxis in the development of this mesodermal subtype which gives rise to the axial muscle, skeleton, and dermis of the embryo. In order to perform in vivo gain of function assays and obtain a better understanding of the possible roles of paraxis in mesodermal and somitic development, we have successfully identified homologues of paraxis in the frog, Xenopus laevis, where the process of mesodermal induction and development is best understood. The two homologues, Xparaxis-a and Xparaxis-b, are conserved with respect to their murine homologue in structure and expression within the embryo. Xparaxis genes are expressed immediately after gastrulation in the paraxial mesoderm of Xenopus embryos and are down regulated in the myotome of the mature somite with continued expression in the undifferentiated dermatome. Overexpression of Xparaxis-b in Xenopus embryos caused defects in the organization and morphology of the somites. This effect was not dependent on DNA binding of Xparaxis but is likely due to its dimerization with other bHLH factors. Co-injections with XE12 did not diminish the effects indicating that the defects were not the result of limiting amounts of XE12. We also demonstrated that Xparaxis does not cause obvious defects in the cell adhesions and movements required for proper mesoderm patterning during gastrulation. The paraxis proteins also lacked the ability to activate transcription as GAL4 fusion proteins in a GAL4 reporter assay, indicating that the genes may function more as modulators of the activity of dimerization partners than as positively acting cell determination factors. In agreement with this, Xparaxis is regulated in response to other pathways of bHLH gene action, in that XE12 can activate Xparaxis-b, in vivo. In addition we show regulation of Xparaxis in response to mMyoD induced myogenesis pathways, again suggesting Xparaxis plays an important role in the patterning and organization of the paraxial mesoderm. ^

Development and testing of a procedure for systematically assigning gestational age for clinical and research use

A graphing method was developed and tested to estimate gestational ages pre-and postnatally in a consistent manner for epidemiological research and clinical purposes on feti/infants of women with few consistent prenatal estimators of gestational age. Each patient's available data was plotted on a single page graph to give a comprehensive overview of that patient. A hierarchical classification of gestational age determination was then applied in a systematic manner, and reasonable gestational age estimates were produced. The method was tested for validity and reliability on 50 women who had known dates for their last menstrual period or dates of conception, and multiple ultrasound examinations and other gestational age estimating measures. The feasibility of the procedure was then tested on 1223 low income women with few gestational age estimators. The graphing method proved to have high inter- and intrarater reliability. It was quick, easy to use, inexpensive, and did not require special equipment. The graphing method estimate of gestational age for each infant was tested against the last menstrual period gestational age estimate using paired t-Tests, F tests and the Kolmogorov-Smirnov test of similar populations, producing a 98 percent probability or better that the means and data populations were the same. Less than 5 percent of the infants' gestational ages were misclassified using the graphing method, much lower than the amount of misclassification produced by ultrasound or neonatal examination estimates. ^

myogenin: Human candidate gene and knockout mouse effect

The myogenin gene encodes an evolutionarily conserved basic helix-loop-helix transcription factor that regulates the expression of skeletal muscle-specific genes and its homozygous deletion results in mice who die of respiratory failure at birth. The histology of skeletal muscle in the myogenin null mice is reminiscent of that found in some severe congenital myopathy patients, many of whom also die of respiratory complications and provides the rationale that an aberrant human myogenin (myf4) coding region could be associated with some congenital myopathy conditions.^ With PCR, we found similarly sized amplimers for the three exons of the myogenin gene in 37 patient and 40 control samples. In contrast to the GeneBank sequence for human myogenin, we report several differences in flanking and coding regions plus an additional 659 and 498 bps in the first and second introns, respectively, in all patients and controls. We also find a novel (CA)-dinucleotide repeat in the second intron. No causative mutations were detected in the myogenin coding regions of genomic DNA from patients with severe congenital myopathy.^ Severe congenital myopathies in humans are often associated with respiratory complications and pulmonary hypoplasia. We have employed the myogenin null mouse, which lacks normal development of skeletal muscle fibers as a genetically defined severe congenital myopathy mouse model to evaluate the effect of absent fetal breathing movement on pulmonary development.^ Significant differences are observed at embryonic days E14, E17 and E20 of lung:body weight, total DNA and histologically, suggesting that the myogenin null lungs are hypoplastic. RT-PCR, in-situ immunofluorescence and EM reveal pneumocyte type II differentiation in both null and wild lungs as early as E14. However, at E14, myogenin null lungs have decreased BrdU incorporation while E17 through term, augmented cell death is detected in the myogenin null lungs, not seen in wild littermates. Absent mechanical forces appear to impair normal growth, but not maturation, of the developing lungs in myogenin null mouse.^ These investigations provide the basis for delineating the DNA sequence of the myogenin gene and and highlight the importance of skeletal muscle development in utero for normal lung organogenesis. My observation of no mutations within the coding regions of the human myogenin gene in DNA from patients with severe congenital myopathy do not support any association with this condition. ^

Local environmental knowledge: a key input for the sustainable development of Andean mountain communities

Local knowledge is crucial to both human development and environmental conservation. This is especially the case in mountain regions, where a combination of remoteness, harsh climatic conditions, rich cultural heritage, and high biological diversity has led to the development of complex local environmental knowledge systems. In the Andes for instance, rural populations mainly rely on their own environmental knowledge to ensure their food security and health. Recent studies conducted within Quechua communities in Peru and Bolivia showed that this knowledge was both persistent and dynamic, and that it responded to socio-economic and environmental changes through cultural resistance and adaptation. As this paper argues, combining local knowledge and so-called scientific knowledge – especially in development projects – can lead to innovative solutions to the socio-environmental challenges facing mountain communities in our globalized world. Based on experiences from the Andes, this paper will provide concrete recommendations to policymakers and practitioners for integrating local knowledge into development and natural resource management initiatives.