Alcohol and the death of Ludwig van Beethoven: comparison of general biographies to the medical literature.

Beethoven's autopsy findings of cirrhosis may have been due to alcoholism. This condition may have been underemphasized historically, given its stigma and the incongruence with the often heroic portrayal of Beethoven. We therefore aimed to compare how medical experts and biographers writing for a non-medical audience describe his final illness in the context of alcoholism. English-language biographies were identified using a survey of biographies of Beethoven and supplemented by the authors. English-language medical publications were identified by searching for "Beethoven" in the PubMed® MEDLINE database. We included studies that mentioned Beethoven's final illness and death. We recorded statements regarding alcohol consumption, alcoholism, or alcohol use disorder, and the role of alcohol in Beethoven's death. The most commonly cited final illness was liver disease. Alcohol use was more frequently mentioned in biographies, but alcoholism less so. Alcohol use was invoked as a possible cause of final illness more frequently by medical publications.

Genomic analyses of hair from Ludwig van Beethoven.

Ludwig van Beethoven (1770-1827) remains among the most influential and popular classical music composers. Health problems significantly impacted his career as a composer and pianist, including progressive hearing loss, recurring gastrointestinal complaints, and liver disease. In 1802, Beethoven requested that following his death, his disease be described and made public. Medical biographers have since proposed numerous hypotheses, including many substantially heritable conditions. Here we attempt a genomic analysis of Beethoven in order to elucidate potential underlying genetic and infectious causes of his illnesses. We incorporated improvements in ancient DNA methods into existing protocols for ancient hair samples, enabling the sequencing of high-coverage genomes from small quantities of historical hair. We analyzed eight independently sourced locks of hair attributed to Beethoven, five of which originated from a single European male. We deemed these matching samples to be almost certainly authentic and sequenced Beethoven's genome to 24-fold genomic coverage. Although we could not identify a genetic explanation for Beethoven's hearing disorder or gastrointestinal problems, we found that Beethoven had a genetic predisposition for liver disease. Metagenomic analyses revealed furthermore that Beethoven had a hepatitis B infection during at least the months prior to his death. Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven's severe liver disease, which culminated in his death. Unexpectedly, an analysis of Y chromosomes sequenced from five living members of the Van Beethoven patrilineage revealed the occurrence of an extra-pair paternity event in Ludwig van Beethoven's patrilineal ancestry.

Diagnostic challenges, best sources, and future paths for diagnoses of Beethoven's physical and mental illnesses.

Significant problems have plagued medical and musicological researchers who wish to understand the complexities of Beethoven's physical and mental health. The most significant is a lack of detailed information on the composer's medical and mental conditions as they appeared and progressed. Though he consistently saw well-regarded doctors from around 1800 to his death, only one wrote a detailed description and only a few left information in the conversation books. Other problems are the limited medical knowledge about certain diseases at the time (such as the causes of deafness) and treatments with no or limited effectiveness (both for deafness and liver disease, for instance). Two additional problems are the focus of this essay. The first is the fact that studying the composer's health and diseases is a cross-disciplinary endeavor that requires specialized knowledge both of medical science and of musicological expertise into every corner of Beethoven's biography. The second concerns acquiring a knowledge of all the available sources that have survived to document the composer's health and a critical assessment of their value.

Preservation and Distributions of Covalently Bound Polyaromatic Hydrocarbons in Ancient Biogenic Kerogens and Insoluble Organic Macromolecules.

The likelihood of finding pristine molecular biosignatures preserved in Earth's oldest rocks or on other planetary bodies is low, and new approaches are needed to assess the origins of highly altered and recalcitrant organic matter. In this study, we aim to understand the distributions and systematics of preservation of ancient polycyclic aromatic hydrocarbons (PAHs), as both free hydrocarbons and bound within insoluble macromolecules. We report the distributions of bound PAHs generated by catalytic hydropyrolysis from ancient biogenic kerogens and from insoluble organic matter (IOM) in high-temperature carbonaceous residues from pyrobitumens and synthetic coke. For biogenic kerogens, the degree of thermal maturity exerts the primary control on the preservation and distributions of the major five-ring and six-ring PAH compounds. This holds for both Precambrian and Phanerozoic rocks, thus source variation in primary biogenic organic matter inputs does not exert the major control on bound PAH. The IOM samples, predominantly residues from hydrocarbon cracking at high temperatures, preserve a bound PAH profile significantly distinct from ancient biogenic kerogens and characterized by an absence of perylene and higher abundance of large-ring condensed PAHs. Covalently bound PAH profiles offer promise as "last resort" molecular biosignatures for aiding the astrobiological search for ancient life.

Effect of char addition on anaerobic digestion of animal by-products: evaluating biogas production and process performance.

The effect of char addition on the digestion of animal by-products was evaluated as a way for enhancing the performance of the process. Two different types of carbonaceous materials were tested as carbon conductive elements to improve biological treatment. One was derived from a torrefaction process intended for increasing the energy density of lignocellulosic biomass, and the other was obtained from a hydrothermal carbonisation process. In this research, batch digestion systems of animal waste samples were evaluated at a volatile solid (VS) ratio of 1:1 inoculum-substrate (where the content of the substrate in the system was 1.69 ± 0.2 g). The system reported a baseline methane yield of 380 L CH4 kg VS-1 which increased on average to 470 L CH4 kg VS-1 following to the addition of char. The presence of char allowed a faster degradation of the lipid and protein material, reducing inhibitory interactions. The use of Fourier transformed infrared spectroscopy was applied for elucidating the predetermination of the degradation process and bring an insight into the greater degradation potential attained when carbon materials are used for enhancing microbial performance.

Methane transport in agricultural soil after injection of isotopically-enriched methane in the sub-surface.

Small quantities of radioactive methane (14CH4) may be released over prolonged periods from geological disposal facilities for radioactive waste. The impact of this release depends on the capacity of soil to oxidise 14CH4 to 14CO2 during transport from the sub-surface to the atmosphere. We investigated this capacity by pulse-injecting isotopically-enriched methane 50 cm below the surface of an agricultural soil in central England. Three sequential injections were made during growth of a spring wheat crop. Samples of gas were taken from the pore space throughout the soil profile at predetermined time points after injection, accompanied by samples of the atmosphere above the soil collected in sampling chambers, deployed at scheduled intervals. Methane and CO2 were measured in soil and above-ground gas using gas chromatography; the isotopic composition of CH4 and CO2 was determined using gas chromatography with isotopic ratio mass spectrometry. Supporting measurements of environmental variables were made during the experiment. The data can be used to test mathematical models describing CH4 and CO2 transport and fate in temperate agricultural soils.

Evaluating the effect of biochar addition on the anaerobic digestion of swine manure: application of Py-GC/MS.

The anaerobic digestion process of swine manure was studied when char was used as supplement for improving performance. The use of pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was proposed for assessing the organic matter degradation. The assessment on biogas production was carried out using samples of swine manure (SM) supplemented with char in one case and pre-treated by microwave irradiation in the other. This experimental set-up allows for the comparison of the biological degradation observed under these two different configurations and therefore aids in understanding the effect of char particles on the process. Results showed similar performance for both systems, with an average improvement of 39% being obtained in methane production when compared to the single digestion of SM. The analysis of digestate samples by Fourier transform infrared (FTIR) spectroscopy and Py-GC/MS showed improved degradation of proteins, with the Py-GC/MS technique also capable of identifying an increase in microbial-derived material when char was added, therefore highlighting the relevant role of carbon conductive particles on biological systems. Py-GC/MS along with the use of FTIR spectroscopy has proven to be useful tools when evaluating anaerobic digestion.

Cryogenian evolution of stigmasteroid biosynthesis.

Sedimentary hydrocarbon remnants of eukaryotic C26-C30 sterols can be used to reconstruct early algal evolution. Enhanced C29 sterol abundances provide algal cell membranes a density advantage in large temperature fluctuations. Here, we combined a literature review with new analyses to generate a comprehensive inventory of unambiguously syngenetic steranes in Neoproterozoic rocks. Our results show that the capacity for C29 24-ethyl-sterol biosynthesis emerged in the Cryogenian, that is, between 720 and 635 million years ago during the Neoproterozoic Snowball Earth glaciations, which were an evolutionary stimulant, not a bottleneck. This biochemical innovation heralded the rise of green algae to global dominance of marine ecosystems and highlights the environmental drivers for the evolution of sterol biosynthesis. The Cryogenian emergence of C29 sterol biosynthesis places a benchmark for verifying older sterane signatures and sets a new framework for our understanding of early algal evolution.

Multiple Cosmic Sources for Meteorite Macromolecules?

The major organic component in carbonaceous meteorites is an organic macromolecular material. The Murchison macromolecular material comprises aromatic units connected by aliphatic and heteroatom-containing linkages or occluded within the wider structure. The macromolecular material source environment remains elusive. Traditionally, attempts to determine source have strived to identify a single environment. Here, we apply a highly efficient hydrogenolysis method to liberate units from the macromolecular material and use mass spectrometric techniques to determine their chemical structures and individual stable carbon isotope ratios. We confirm that the macromolecular material comprises a labile fraction with small aromatic units enriched in (13)C and a refractory fraction made up of large aromatic units depleted in (13)C. Our findings suggest that the macromolecular material may be derived from at least two separate environments. Compound-specific carbon isotope trends for aromatic compounds with carbon number may reflect mixing of the two sources. The story of the quantitatively dominant macromolecular material in meteorites appears to be made up of more than one chapter.

Epidemiology of West Nile virus: a silent epiornitic in Northern Delaware in 2007 without associated human cases.

ABSTRACT. We performed a 2-year longitudinal study (2006-2007) of West Nile virus (WNV) infections in wild birds, mosquitoes, and sentinel chickens at 6 WNV-endemic sites in northern Delaware. We determined virus infection rates of Culex pipiens and other mosquito vectors as well as seroprevalence and antibody titers of amplifying hosts. Endemicity status varied widely among the 6 sites based on 3 criteria-mosquito infections, sentinel chicken seropositivity, and wild bird seropositivity. A highly endemic site would display at least 2 of the 3 criteria during each year of the study, while a site with just 1 positive criterion was considered to have low endemicity. Culex pipiens was the principal vector detected at 2 highly endemic sites in 2006 vs. 1 site in 2007. However, in 2006, we also found 2 other WNV-positive vector species as well as an unidentifiable Culex species at 1 highly endemic site, suggesting increased activity at the end of the 1st year of the study. Wild birds were early indicators of WNV at highly endemic sites in mid-July to early August of both 2006-2007. Mosquitoes were positive in mid- to late August, appearing concurrently with seroconverted sentinel chickens, with wild resident birds appearing approximately 4 wk prior to those indicators. Of birds tested with n > or = 9, Northern cardinals had the highest seropositivity rates (47%) followed by Carolina wrens (19%), house sparrows (13%), American robins (13%), tufted titmice (11%), and gray catbirds (9%). The overall seropositive rates in trapped birds increased from 5.0% in 2006 to 20.0% in 2007, while the geometric mean titers of all positive birds increased from 1:34 to 1:47 during the comparable periods. Based on these results, we suggest that an epiornitic in birds occurred in 2007, but that greatly reduced abundance of mosquito vectors caused by an extreme drought largely precluded human infection.

Near-isogenic cotton germplasm lines that differ in fiber-bundle strength have temporal differences in fiber gene expression patterns as revealed by comparative high-throughput profiling.

Gene expression profiles of developing cotton (Gossypium hirsutum L.) fibers from two near-isogenic lines (NILs) that differ in fiber-bundle strength, short-fiber content, and in fewer than two genetic loci were compared using an oligonucleotide microarray. Fiber gene expression was compared at five time points spanning fiber elongation and secondary cell wall (SCW) biosynthesis. Fiber samples were collected from field plots in a randomized, complete block design, with three spatially distinct biological replications for each NIL at each time point. Microarray hybridizations were performed in a loop experimental design that allowed comparisons of fiber gene expression profiles as a function of time between the two NILs. Overall, developmental expression patterns revealed by the microarray experiment agreed with previously reported cotton fiber gene expression patterns for specific genes. Additionally, genes expressed coordinately with the onset of SCW biosynthesis in cotton fiber correlated with gene expression patterns of other SCW-producing plant tissues. Functional classification and enrichment analysis of differentially expressed genes between the two NILs revealed that genes associated with SCW biosynthesis were significantly up-regulated in fibers of the high-fiber quality line at the transition stage of cotton fiber development. For independent corroboration of the microarray results, 15 genes were selected for quantitative reverse transcription PCR analysis of fiber gene expression. These analyses, conducted over multiple field years, confirmed the temporal difference in fiber gene expression between the two NILs. We hypothesize that the loci conferring temporal differences in fiber gene expression between the NILs are important regulatory sequences that offer the potential for more targeted manipulation of cotton fiber quality.

Modeling life-span growth curves of cognition using longitudinal data with multiple samples and changing scales of measurement.

The authors use multiple-sample longitudinal data from different test batteries to examine propositions about changes in constructs over the life span. The data come from 3 classic studies on intellectual abilities in which, in combination, 441 persons were repeatedly measured as many as 16 times over 70 years. They measured cognitive constructs of vocabulary and memory using 8 age-appropriate intelligence test batteries and explore possible linkage of these scales using item response theory (IRT). They simultaneously estimated the parameters of both IRT and latent curve models based on a joint model likelihood approach (i.e., NLMIXED and WINBUGS). They included group differences in the model to examine potential interindividual differences in levels and change. The resulting longitudinal invariant Rasch test analyses lead to a few new methodological suggestions for dealing with repeated constructs based on changing measurements in developmental studies.

Identification of associations between SSR markers and fiber traits in an exotic germplasm derived from multiple crosses among Gossypium tetraploid species.

Genetic improvement in yield and fiber quality is needed for worldwide cotton production. Identification of molecular markers associated with fiber-related traits can facilitate selection for these traits in breeding. This study was designed to identify associations between SSR markers and fiber traits using an exotic germplasm population, species polycross (SP), derived from multiple crosses among Gossypium tetraploid species. The SP population underwent 11 generations of mixed random mating and selfing followed by 12 generations of selfing. A total of 260 lines were evaluated for fiber-related traits under three environments in 2005 and 2006. Large genotypic variance components in traits were identified relative to components of genotype x environment. Eighty-six primer pairs amplified a total of 314 polymorphic fragments among 260 lines. A total of 202 fragments with above 6% allele frequency were analyzed for associations. Fifty-nine markers were found to have a significant (P < 0.05, 0.01, or 0.001) association with six fiber traits. There were six groups identified within the population using structure analysis. Allele frequency divergence among six groups ranged from 0.11 to 0.27. Of the 59 marker-trait associations, 39 remained significant after correction for population structure and kinship using a mixed linear model. The effect of population sub-structure on associations was most significant in boll weight among the traits analyzed. The sub-structure among the SP lines may be caused by natural selection, the breeding method applied during development of inbred lines, and unknown factors. The identified marker-trait associations can be useful in breeding and help determine genetic mechanisms underlying interrelationships among fiber traits.

Evaluating scholarship productivity in COAMFTE-accredited PhD programs.

Due to an increasing trend among states to cut higher education funds, many universities are relying more on private donations and federal funding to keep programs afloat. Scholarship productivity in general has become an integral factor in terms of universities granting tenure to faculty, allocating resources, and supporting program goals due to the fact that more research in a particular area tends to increase the likelihood that one will obtain funding from federal, state, and private sources. In the past, ranking systems have also been used to evaluate programs. However, most ranking systems use methodologies that do not quantify research productivity or evaluate factors that match current university trends. The purpose of this article is to explore current scholarship productivity trends among COAMFTE-accredited doctoral programs through the use of several evaluation methods. Specifically, productivity was examined in regard to the following areas: (a) family therapy journal publications; (b) family science journal publications; (c) historic journal publication trends; and (d) recent journal publication trends.

Fossil steroids record the appearance of Demospongiae during the Cryogenian period.

The Neoproterozoic era (1,000-542 Myr ago) was an era of climatic extremes and biological evolutionary developments culminating in the emergence of animals (Metazoa) and new ecosystems. Here we show that abundant sedimentary 24-isopropylcholestanes, the hydrocarbon remains of C(30) sterols produced by marine demosponges, record the presence of Metazoa in the geological record before the end of the Marinoan glaciation ( approximately 635 Myr ago). These sterane biomarkers are abundant in all formations of the Huqf Supergroup, South Oman Salt Basin, and, based on a new high-precision geochronology, constitute a continuous 100-Myr-long chemical fossil record of demosponges through the terminal Neoproterozoic and into the Early Cambrian epoch. The demosponge steranes occur in strata that underlie the Marinoan cap carbonate (>635 Myr ago). They currently represent the oldest evidence for animals in the fossil record, and are evidence for animals pre-dating the termination of the Marinoan glaciation. This suggests that shallow shelf waters in some late Cryogenian ocean basins (>635 Myr ago) contained dissolved oxygen in concentrations sufficient to support basal metazoan life at least 100 Myr before the rapid diversification of bilaterians during the Cambrian explosion. Biomarker analysis has yet to reveal any convincing evidence for ancient sponges pre-dating the first globally extensive Neoproterozoic glacial episode (the Sturtian, approximately 713 Myr ago in Oman).

Production of mRNA from the cry1Ac transgene differs among Bollgard lines which correlates to the level of subsequent protein.

Commercial cultivars of Bollgard cotton, Gossypium hirsutum L., differ in the amount of expressed Cry1Ac protein. However, the plant-mechanism for which this occurs is still unknown. Using quantitative real-time polymerase chain reaction (qPCR), we developed a method to determine if differences in the overall level of Cry1Ac among Bollgard lines could be correlated to the mRNA transcripts. Our data shows that the cry1Ac mRNA transcript differs among Bollgard lines and are correlated with corresponding Cry1Ac protein levels. In addition, qPCR based methods can efficiently be employed to quantify Cry1Ac protein expression levels in transgenic cotton cultivars. We postulate that qPCR based methods could be successfully employed for quantifying expression levels of transgenes in plants carrying different Bt toxins.

An essay on measurement and factorial invariance.

BACKGROUND: Analysis of subgroups such as different ethnic, language, or education groups selected from among a parent population is common in health disparities research. One goal of such analyses is to examine measurement equivalence, which includes both qualitative review of the meaning of items as well as quantitative examination of different levels of factorial invariance and differential item functioning. OBJECTIVES: The purpose of this essay is to review the definitions and assumptions associated with factorial invariance, placing this formulation in the context of bias, fairness, and equity. The connection between the concepts of factorial invariance and item bias (differential item functioning) using a variant of item response theory is discussed. The situations under which different forms of invariance (weak, strong, and strict) are required are discussed. METHODS: Establishing factorial invariance involves a hierarchy of levels that include tests of weak, strong, and strict invariance. Pattern (metric or weak) factorial invariance implies that the regression slopes are invariant across groups. Pattern invariance requires only invariant factor loadings. Strong factorial invariance implies that the conditional expectation of the response, given the common and specific factors, is invariant across groups. Strong factorial invariance requires that specific factor means (represented as invariant intercepts) also be identical across groups. Strict factorial invariance implies that, in addition, the conditional variance of the response, given the common and specific factors, is invariant across groups. Strict factorial invariance requires that, in addition to equal factor loadings and intercepts, the residual (specific factor plus error variable) variances are equivalent across groups. The concept of measurement invariance that is most closely aligned to that of item response theory considers the latent variable as a common factor measured by manifest variables; the specific factors can be characterized as nuisance variables. CONCLUSIONS: Invariance of factor loadings across studied groups is required for valid comparisons of scale score or latent variable means. Strong and strict invariance may be less important in the context of basic research in which group differences in specific factors are indicative of individual differences that are important for scientific exploration. However, for most applications in which the aim is to ensure fairness and equity, strict factorial invariance is required. Health disparities research often focuses on self-reported clinical outcomes such as quality of life that are not observed directly. Latent variable models such as factor analyses are central to establishing valid assessment of such outcomes.