Climate and human impact during the past 2000 years as recorded in the Lagunas de Yala, Jujuy, northwestern Argentina

210Pb, 137Cs and 14C dated sediments of two late Holocene landslide lakes in the Provincial Park Lagunas de Yala (Laguna Rodeo, Laguna Comedero, 24°06′S, 65°30′W, 2100 m asl, northwestern Argentina) reveal a high-resolution multi-proxy data set of climate change and human impact for the past ca. 2000 years. Comparison of the lake sediment data set for the 20th century (sediment mass accumulation rates MARs, pollen spectra, nutrient and charcoal fluxes) with independent dendroecological data from the catchment (fire scars, tree growth) and long regional precipitation series (from 1934 onwards) show that (1) the lake sediment data set is internally highly consistent and compares well with independent data sets, (2) the chronology of the sediment is reliable, (3) large fires (1940s, 1983/1984–1989) as documented in the local fire scar frequency are recorded in the charcoal flux to the lake sediments and coincide with low wet-season precipitation rates (e.g., 1940s, 1983/1984) and/or high interannual precipitation variability (late 1940s), and (4) the regional increase in precipitation after 1970 is recorded in an increase in the MARs (L. Rodeo from 100 to 390 mg cm−2 yr−1) and in an increase in fern spores reflecting wet vegetation. The most significant change in MARs and nutrient fluxes (Corg and P) of the past 2000 years is observed with the transition from the Inca Empire to the Spanish Conquest around 1600 AD. Compared with the pre-17th century conditions, MARs increased by a factor of ca. 5 to >8 (to 800 +130, −280 mg cm−2 yr−1), PO4 fluxes increased by a factor of 7, and Corg fluxes by a factor of 10.5 for the time between 1640 and 1930 AD. 17th to 19th century MARs and nutrient fluxes also exceed 20th century values. Excess Pb deposition as indicated by a significant increase in Pb/Zr and Pb/Rb ratios in the sediments after the 1950s coincides with a rapid expansion of the regional mining industry. Excess Pb is interpreted as atmospheric deposition and direct human impact due to Pb smelting.

Meta-analysis: chondroitin for osteoarthritis of the knee or hip

BACKGROUND: Previous meta-analyses described moderate to large benefits of chondroitin in patients with osteoarthritis. However, recent large-scale trials did not find evidence of an effect. PURPOSE: To determine the effects of chondroitin on pain in patients with osteoarthritis. DATA SOURCES: The authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and conference proceedings; checked reference lists; and contacted authors. The last update of searches was performed on 30 November 2006. STUDY SELECTION: Studies were included if they were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip. There were no language restrictions. DATA EXTRACTION: The authors extracted data in duplicate. Effect sizes were calculated from the differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled SD. Trials were combined by using random-effects meta-analysis. DATA SYNTHESIS: 20 trials (3846 patients) contributed to the meta-analysis, which revealed a high degree of heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials. When the authors restricted the analysis to the 3 trials with large sample sizes and an intention-to-treat analysis, 40% of patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13 to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of 0.99 (CI, 0.76 to 1.31) for any adverse event. LIMITATIONS: For 9 trials, the authors had to use approximations to calculate effect sizes. Trial quality was generally low, heterogeneity among the trials made initial interpretation of results difficult, and exploring sources of heterogeneity in meta-regression and stratified analyses may be unreliable. CONCLUSIONS: Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.

Large genomic fibrillin-1 (FBN1) gene deletions provide evidence for true haploinsufficiency in Marfan syndrome

Mutations in the FBN1 gene are the major cause of Marfan syndrome (MFS), an autosomal dominant connective tissue disorder, which displays variable manifestations in the cardiovascular, ocular, and skeletal systems. Current molecular genetic testing of FBN1 may miss mutations in the promoter region or in other noncoding sequences as well as partial or complete gene deletions and duplications. In this study, we tested for copy number variations by successively applying multiplex ligation-dependent probe amplification (MLPA) and the Affymetrix Human Mapping 500 K Array Set, which contains probes for approximately 500,000 single-nucleotide polymorphisms (SNPs) across the genome. By analyzing genomic DNA of 101 unrelated individuals with MFS or related phenotypes in whom standard genetic testing detected no mutation, we identified FBN1 deletions in two patients with MFS. Our high-resolution approach narrowed down the deletion breakpoints. Subsequent sequencing of the junctional fragments revealed the deletion sizes of 26,887 and 302,580 bp, respectively. Surprisingly, both deletions affect the putative regulatory and promoter region of the FBN1 gene, strongly indicating that they abolish transcription of the deleted allele. This expectation of complete loss of function of one allele, i.e. true haploinsufficiency, was confirmed by transcript analyses. Our findings not only emphasize the importance of screening for large genomic rearrangements in comprehensive genetic testing of FBN1 but, importantly, also extend the molecular etiology of MFS by providing hitherto unreported evidence that true haploinsufficiency is sufficient to cause MFS.