Ctenosaura palearis

Number of Pages: 3Integrative BiologyGeological Science

Stemming the Global Trade in Falsified and Substandard Medicines

Drug safety and quality is an essential assumption of clinical medicine, but there is growing concern that this assumption is not always correct. Poor manufacturing and deliberate fraud occasionally compromises the drug supply in the United States, and the problem is far more common and serious in low- and middle-income countries with weak drug regulatory systems. An Institute of Medicine consensus committee report identified the causes and possible solutions to the problem of falsified and substandard drugs around the world. The vocabulary people use to discuss the problem is itself a concern. The word counterfeit is often used innocuously to describe any drug that is not what it seems, but some NGOs and emerging manufacturing nations object to this term. These groups see hostility to generic pharmaceuticals in a discussion of counterfeit medicines. These groups see hostility to generic pharmaceuticals in a discussion of counterfeit medicines. Precisely speaking, a counterfeit drug infringes on a registered trademark, and trademark infringement in not necessarily a problem of public health consequence. Instead of talking broadly about counterfeit drugs, the WHO and other stakeholders should consider two main categories of drug quality problems. Falsified medicines misrepresent the product’s identity or source or both. Substandard drugs fail to meet the national specifications given in an accepted pharmacopeia or the manufacturer’s dossier. In practice, there is often considerable overlap between categories. There is considerable uncertainty about the size of the falsified and substandard drug market. Improved pharmacovigilance, especially in developing countries, give a better picture of the scope of the problem. In the United States, tighter regulatory controls on the wholesale market and a mandatory drug tracking system would improve drug safety. In developing countries, development finance organizations should invest in small- and medium-sized pharmaceutical manufacturers, and governments should use tools such as franchising, accreditation, low-interest loans, and task shifting to encourage private sector investment in drug retail. Finally, the WHO should work with stakeholders such as the UNODC and the WCO to develop an international code of practice on falsified and substandard drugs

Spread Supersymmetry

In the multiverse the scale of SUSY breaking, \tilde{m} = F_X/M_*, may scan and environmental constraints on the dark matter density may exclude a large range of \tilde{m} from the reheating temperature after inflation down to values that yield a LSP mass of order a TeV. After selection effects, the distribution for \tilde{m} may prefer larger values. A single environmental constraint from dark matter can then lead to multi-component dark matter, including both axions and the LSP, giving a TeV-scale LSP lighter than the corresponding value for single-component LSP dark matter. If SUSY breaking is mediated to the SM sector at order X^* X, only squarks, sleptons and one Higgs doublet acquire masses of order \tilde{m}. The gravitino mass is lighter by a factor of M_*/M_Pl and the gaugino masses are suppressed by a further loop factor. This Spread SUSY spectrum has two versions; the Higgsino masses are generated in one from supergravity giving a wino LSP and in the other radiatively giving a Higgsino LSP. The environmental restriction on dark matter fixes the LSP mass to the TeV domain, so that the squark and slepton masses are order 10^3 TeV and 10^6 TeV in these two schemes. We study the spectrum, dark matter and collider signals of these two versions of Spread SUSY. The Higgs is SM-like and lighter than 145 GeV; monochromatic photons in cosmic rays arise from dark matter annihilations in the halo; exotic short charged tracks occur at the LHC, at least for the wino LSP; and there are the eventual possibilities of direct detection of dark matter and detailed exploration of the TeV-scale states at a future linear collider. Gauge coupling unification is as in minimal SUSY theories. If SUSY breaking is mediated at order X, a much less hierarchical spectrum results---similar to that of the MSSM, but with the superpartner masses 1--2 orders of magnitude larger than in natural theories.Comment: 20 pages, 5 figure

Substrate and catalyst effects in the enantioselective copper catalysed C–H insertion reactions of α-diazo-β-oxo sulfones

Excellent enantioselectivities of up to 98% ee are achieved employing the copper‐bis(oxazoline)‐NaBARF catalyst system in the C‐H insertion reactions of α‐diazo‐β‐oxo sulfones. The influence of variation of the bis(oxazoline) ligand, copper salt, additive and substrate on both the efficiency and the enantioselectivities of these intramolecular C‐H insertion reactions has been explored. Optimum enantioselectivities are achieved with the phenyl and diphenyl ligands across the substrate series

1962

Turf on the Launching Pad (page 1) Turf management Club News (3) Education, Experience and Attitude (4) A Blade of Grass (5) Picture - Professor Lawrence S. Dickinson (6) Picture - Thomas Mascaro - Banquet Speaker (7) Planting Trees on the Golf Course (8) Two-Way Radios (8) Greens Mowing Procedure (9) Watering and Topdressing as Related to Poa annua Infestations (10) Picture - Stockbridge Majors in Turf Management (12) Picture - Graduates of Winter School for Turf Managers - 1962 (13) Review of Season\u27s Pests by Joseph Troll (A-1) Today\u27s Trends in Golf Course Development by Col. Harry C. Eckoff (A-3) Breeding and Selection of Fine Turf Grasses by Dr. B. R. Anderson Penncross Bentgrass by J. Dutch(A-13) Poa annua by Alexander Radko (A-16) Velvet Bent by Jesse DeFrance (A-19) Vegetative Creeping Bentgrasses by Fred Grau (A-21) Modification of SOils for Green Construction & Top Dressing by Prof. H. B. Musser (A-27) Soil COmpaction by Donald Waddington (A-32) Irrigation Practices and the Need of Basic Research by Prof. Edward PIra (A-36) Water Sources by Z. Mills (A-39) Athletic Field Maintenance by Thomas Mascaro (A-41) Planning the Landscape Around the House by Prof. Harold Mosher (A-43

The Impact of the Physical Environment on Intrapartum Maternity Care: Identification of Eight Crucial Building Spaces.

OBJECTIVES, PURPOSE, OR AIM: This article investigates whether the physical environment in which childbirth occurs impacts the intrapartum intervention rates and how this might happen. The study explores the spatial physical characteristics that can support the design of spaces to promote the health and well-being of women, their supporters, and maternity care professionals. BACKGROUND: Medical interventions during childbirth have consequences for the health of women and babies in the immediate and long term. The increase in interventions is multifactorial and may be influenced by the model of care adopted, the relationships between caregivers and the organizational culture, which is made up of many factors, including the built environment. In the field of birth architecture research, there is a gap in the description of the physical characteristics of birth environments that impact users' health. METHOD: A scoping review on the topic was performed to understand the direct and indirect impacts of the physical environment on birth intervention rates. RESULTS AND DISCUSSION: The findings are organized into three tables reporting the influence that the physical characteristics of a space might have on people's behaviors, experiences, practices and birth health outcomes. Eight building spaces that require further investigation and research were highlighted: unit layout configuration, midwives' hub/desk, social room, birth philosophy vectors, configuration of the birth room, size and shape of the birth room, filter, and sensory elements. CONCLUSIONS: The findings show the importance of considering the physical environment in maternity care and that further interdisciplinary studies focused on architectural design are needed to enrich the knowledge and evidence on this topic and to develop accurate recommendations for designers

Extragalactic Background Light Inferred from AEGIS Galaxy SED-type Fractions

The extragalactic background light (EBL) is of fundamental importance both for understanding the entire process of galaxy evolution and for gamma-ray astronomy, but the overall spectrum of the EBL between 0.1-1000 microns has never been determined directly from galaxy spectral energy distribution (SED) observations over a wide redshift range. The evolving, overall spectrum of the EBL is derived here utilizing a novel method based on observations only. This is achieved from the observed evolution of the rest-frame K-band galaxy luminosity function up to redshift 4 (Cirasuolo et al. 2010), combined with a determination of galaxy SED-type fractions. These are based on fitting SWIRE templates to a multiwavelength sample of about 6000 galaxies in the redshift range from 0.2 to 1 from the All-wavelength Extended Groth Strip International Survey (AEGIS). The changing fractions of quiescent galaxies, star-forming galaxies, starburst galaxies and AGN galaxies in that redshift range are estimated, and two alternative extrapolations of SED-types to higher redshifts are considered. This allows calculation of the evolution of the luminosity densities from the UV to the IR, the evolving star formation rate density of the universe, the evolving contribution to the bolometric EBL from the different galaxy populations including AGN galaxies and the buildup of the EBL. Our EBL calculations are compared with those from a semi-analytic model, from another observationally-based model and observational data. The EBL uncertainties in our modeling based directly on the data are quantified, and their consequences for attenuation of very high energy gamma-rays due to pair production on the EBL are discussed. It is concluded that the EBL is well constrained from the UV to the mid-IR, but independent efforts from infrared and gamma-ray astronomy are needed in order to reduce the uncertainties in the far-IR.Comment: 25 pages, 18 figures, 4 tables; accepted for publication in MNRAS on September 3, 2010. Online material available at http://side.iaa.es/EB

A panel of genes methylated with high frequency in colorectal cancer

Background: The development of colorectal cancer (CRC) is accompanied by extensive epigenetic changes, including frequent regional hypermethylation particularly of gene promoter regions. Specific genes, including SEPT9, VIM1 and TMEFF2 become methylated in a high fraction of cancers and diagnostic assays for detection of cancer-derived methylated DNA sequences in blood and/or fecal samples are being developed. There is considerable potential for the development of new DNA methylation biomarkers or panels to improve the sensitivity and specificity of current cancer detection tests. Methods: Combined epigenomic methods - activation of gene expression in CRC cell lines following DNA demethylating treatment, and two novel methods of genome-wide methylation assessment - were used to identify candidate genes methylated in a high fraction of CRCs. Multiplexed amplicon sequencing of PCR products from bisulfite-treated DNA of matched CRC and non-neoplastic tissue as well as healthy donor peripheral blood was performed using Roche 454 sequencing. Levels of DNA methylation in colorectal tissues and blood were determined by quantitative methylation specific PCR (qMSP). Results: Combined analyses identified 42 candidate genes for evaluation as DNA methylation biomarkers. DNA methylation profiles of 24 of these genes were characterised by multiplexed bisulfite-sequencing in ten matched tumor/normal tissue samples; differential methylation in CRC was confirmed for 23 of these genes. qMSP assays were developed for 32 genes, including 15 of the sequenced genes, and used to quantify methylation in tumor, adenoma and non-neoplastic colorectal tissue and from healthy donor peripheral blood. 24 of the 32 genes were methylated in \u3e50% of neoplastic samples, including 11 genes that were methylated in 80% or more CRCs and a similar fraction of adenomas. Conclusions: This study has characterised a panel of 23 genes that show elevated DNA methylation in \u3e50% of CRC tissue relative to non-neoplastic tissue. Six of these genes (SOX21, SLC6A15, NPY, GRASP, ST8SIA1 and ZSCAN18) show very low methylation in non-neoplastic colorectal tissue and are candidate biomarkers for stool-based assays, while 11 genes (BCAT1, COL4A2, DLX5, FGF5, FOXF1, FOXI2, GRASP, IKZF1, IRF4, SDC2 and SOX21) have very low methylation in peripheral blood DNA and are suitable for further evaluation as blood-based diagnostic markers

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Introduction Mechanical injury can greatly influence articular cartilage, propagating inflammation, cell injury and death – risk factors for the development of osteoarthritis. Melanocortin peptides and their receptors mediate anti-inflammatory and pro-resolving mechanisms in chondrocytes. This study aimed to investigate the potential chondroprotective properties of α-MSH and [DTRP8]-γ-MSH in mechanically injured cartilage explants, their ability to inhibit pro-inflammatory and stimulate anti-inflammatory cytokines in in situ and in freshly isolated articular chondrocytes. Methods The effect of melanocortins on in situ chondrocyte viability was investigated using confocal laser scanning microscopy of bovine articular cartilage explants, subjected to a single blunt impact (1.14 N, 6.47 kPa) delivered by a drop tower. Chondroprotective effects of α-MSH, [DTRP8]-γ-MSH and dexamethasone on cytokine release by TNF-α-activated freshly isolated articular chondrocytes/mechanically injured cartilage explants were investigated by ELISA. Results A single impact to cartilage caused discreet areas of chondrocyte death, accompanied by pro-inflammatory cytokine release; both parameters were modulated by α-MSH, [DTRP8]-γ-MSH and dexamethasone. Melanocortin pre-treatment of TNF-α-stimulated freshly isolated chondrocytes resulted in a bell-shaped inhibition in IL-1β, IL-6 and IL-8, and elevation of IL-10 production. The MC3/4 antagonist, SHU9119, abrogated the effect of [DTRP8]-γ-MSH but not α-MSH on cytokine release. Conclusion Melanocortin peptide pre-treatment prevented chondrocyte death following mechanical impact to cartilage and led to a marked reduction of pro-inflammatory cytokines, whilst prompting the production of anti-inflammatory/pro-resolving cytokine IL-10. Development of small molecule agonists towards melanocortin receptors could thus be a viable approach for preventing chondrocyte inflammation and death within cartilage and represent an alternative approach for the treatment of osteoarthritis