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PubMed2001

Phytotoxic protein PcF, purification, characterization, and cDNA sequencing of a novel hydroxyproline-containing factor secreted by the strawberry pathogen Phytophthora cactorum.

A novel protein factor, named PcF, has been isolated from the culture filtrate of Phytophthora cactorum strain P381 using a highly sensitive leaf necrosis bioassay with tomato seedlings. Isolated PcF protein alone induced leaf necrosis on its host strawberry plant. The primary structure and cDNA sequence of this novel phytotoxic protein was determined, and BLAST searches of Swiss-Prot, EMBL, and GenBank(TM)/EBI data banks showed that PcF shared no significant homology with other known sequences. The 52-residue PcF protein, which contains a 4-hydroxyproline residue along with three S-S bridges, exhibits a high content of acidic sidechains, accounting for its isoelectric point of 4.4. The molecular mass of isolated PcF is 5,622 +/- 0.5 Da as determined by mass spectrometry and matches that calculated from the deduced amino acid sequence with cDNA sequencing. The cDNA sequence indicates that PcF is first produced as a larger precursor, comprising an additional N-terminal, 21-residue secretory signal peptide. Maturation of this protein involves the hydroxylation of proline 49, a feature that is unique among other known secreted fungal phytopathogenic proteins.

Amino Acid Sequence↗
PubMed2004

Comparison of TFII-I gene family members deleted in Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is a neurological disorder resulting from a microdeletion, typically 1.5 megabases in size, at 7q11.23. Atypical patients implicate genes at the telomeric end of this multigene deletion as the main candidates for the pathology of WBS in particular the unequal cognitive profile associated with the condition. We recently identified a gene (GTF2IRD2) that shares homology with other members of a unique family of transcription factors (TFII-I family), which reside in the critical telomeric region. Using bioinformatics tools this study focuses on the detailed assessment of this gene family, concentrating on their characteristic structural components such as the leucine zipper (LZ) and I-repeat elements, in an attempt to identify features that could aid functional predictions. Phylogenetic analysis identified distinct I-repeat clades shared between family members. Linking functional data to one such clade has implicated them in DNA binding. The identification of PEST, synergy control motifs, and sumoylation sites common to all family members suggest a shared mechanism regulating the stability and transcriptional activity of these factors. In addition, the identification/isolation of short truncated isoforms for each TFII-I family member implies a mode of self-regulation. The exceptionally high identity shared between GTF2I and GTF2IRD2, suggests that heterodimers as well as homodimers are possible, and indicates overlapping functions between their respective short isoforms. Such cross-reactivity between GTF2I and GTF2IRD2 short isoforms might have been the evolutionary driving force for the 7q11.23 chromosomal rearrangement not present in the syntenic region in mice.

Amino Acid Motifs↗
PubMed1994

Identification of an immunoreactive Brucella abortus HtrA stress response protein homolog.

An 11-kb fragment of Brucella abortus genomic DNA cloned into the BamHI site of pUC9 expressed a 60-kDa protein in Escherichia coli DH5-alpha. Antibodies reactive with this 60-kDa protein were detected by Western blot (immunoblot) analysis in sera from mice, cattle, and goats experimentally infected with B. abortus, in sera from mice experimentally infected with Brucella melitensis, and in serum from a dog experimentally infected with Brucella canis. Similar results were seen with sera obtained from cattle and dogs with naturally acquired brucellosis. The gene encoding the 60-kDa Brucella protein was localized to a 2-kb EcoRI fragment which was also reactive in Southern blots with genomic DNA from other strains of B. abortus as well as with genomic DNA from B. melitensis and B. canis. Nucleotide sequence analysis of the cloned EcoRI fragment revealed an open reading frame encoding a protein with a predicted molecular mass of 51,847 Da and an isoelectric point of 5.15. Comparison of the deduced amino acid sequence of the immunoreactive Brucella protein with the SWISS-PROT protein sequence data base revealed that it shares > 40% amino acid sequence identity with the E. coli and Salmonella typhimurium HtrA stress response proteins. Computer-assisted analysis of this amino acid sequence also predicted that the putative Brucella HtrA homolog contains an export signal sequence and a serine protease active site, two structural features characteristic of previously described HtrA proteins. A potential sigma E type heat shock promoter sequence was detected upstream of the cloned Brucella htrA gene, and Northern (RNA) blot analysis demonstrated that exposure of B. abortus 2308 to heat shock conditions resulted in a transient elevation of htrA transcription. These results strongly suggest that the immunoreactive 60-kDa Brucella protein is a member of the HtrA class of stress response proteins.

Amino Acid Sequence↗
PubMed1997

Large hierarchical Bayesian analysis of multivariate survival data.

Failure times that are grouped according to shared environments arise commonly in statistical practice. That is, multiple responses may be observed for each of many units. For instance, the units might be patients or centers in a clinical trial setting. Bayesian hierarchical models are appropriate for data analysis in this context. At the first stage of the model, survival times can be modelled via the Cox partial likelihood, using a justification due to Kalbfleisch (1978, Journal of the Royal Statistical Society, Series B 40, 214-221). Thus, questionable parametric assumptions are avoided. Conventional wisdom dictates that it is comparatively safe to make parametric assumptions at subsequent stages. Thus, unit-specific parameters are modelled parametrically. The posterior distribution of parameters given observed data is examined using Markov chain Monte Carlo methods. Specifically, the hybrid Monte Carlo method, as described by Neal (1993a, in Advances in Neural Information Processing 5, 475-482; 1993b, Probabilistic inference using Markov chain Monte Carlo methods), is utilized.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Calcyclin in the mouse decidua: expression and effects on placental lactogen secretion.

Placental lactogens are protein hormones produced by the placentas of many mammals. These hormones have diverse reproductive functions and are structurally similar to the pituitary hormones growth hormone and prolactin. Isolated decidual cells were previously shown to release a protein that stimulates mouse placental lactogen (mPL)-II release from mouse trophoblast cells in culture. Partial amino acid sequence data suggested that this protein shared sequence identity with mouse calcyclin. In the present study the sequence identity of this protein was determined by sequencing reverse transcription-polymerase chain reaction (RT-PCR) products. The sequence matched that of mouse calcyclin. The distribution of calcyclin message was determined in the conceptus by in situ hybridization, and a gestational profile of calcyclin mRNA was determined by Northern blot analysis. Calcyclin was localized primarily to cells that exhibited a uterine natural killer cell morphology within the decidua and to glycogen cells of the labyrinth and junctional zone. Although calcyclin was detectable by RT-PCR in midterm placentas, isolated trophoblast cells in culture did not contain detectable quantities of calcyclin by RT-PCR. Calcyclin stimulated secretion of mPL-II from isolated trophoblast cells in vitro but did not affect mPL-I secretion.

Amino Acid Sequence↗
PubMed2025

DigiNet: Optimizing personalized care for patients with stage IV non-small cell lung cancer (NSCLC) through a digitally connected provider network-analysis plan of a prospective multicenter cohort trial.

PURPOSE: The German sector-based healthcare system poses a major challenge to continuous patient monitoring and long-term follow-up, both essential for generating high-quality, longitudinal real-world data. The national Network for Genomic Medicine (nNGM) bridges the inpatient and outpatient care sectors to provide comprehensive molecular diagnostics and personalized treatment for non-small cell lung cancer (NSCLC) patients in Germany. Building on the established nNGM infrastructure, the DigiNet study aims to evaluate the impact of digitally integrated, personalized care on overall survival (OS) and the optimization of treatment pathways, compared to routine care. METHODS: DigiNet is a prospective, controlled, non-randomized multicenter cohort study including patients with stage IV NSCLC in two study regions (East and West) in Germany. The results of molecular diagnostics and clinical information, along with the entire treatment data are documented in a shared database. A board of lung cancer specialists monitors critical events. Patients digitally complete quality of life questionnaires, with results visualized for physicians. To assess the impact of this personalized digital care, a population-based control group will be identified by matching cohorts within the involved cancer registries. The primary endpoint is OS, and secondary endpoints comprise time on first-line treatment and hospitalization rates. Furthermore, a health economic and business economic evaluation will be conducted. Qualitative interviews with patients and physicians will be performed to assess barriers and facilitating factors for implementing the DigiNet intervention. ETHICS: The study protocol was reviewed and approved by the Ethics Committee of the University Hospital of Cologne (21-1521). TRIAL REGISTRATION: NCT05818449, registered retrospectively on December 12, 2022.

Humans↗
PubMed2003

The role of teaching and research hospitals in improving global health (in a globalized world).

Globalization is impacting on Hong Kong and Australia in different ways, but the experience of the public healthcare systems in both jurisdictions suggests a need for teaching and research hospitals to refocus from the management of international patients to better meet the needs for global health. Traditional globalization suggests a stockpiling of capital--a focus on improving global health suggests dismantling the stockpiles and sharing access to the necessary data, information, knowledge and discoveries to further develop local health expertise. Consistent with its position as a leading healthcare provider, the University Health Network (UHN) has been reflecting on the impact of increasing globalization on hospitals. The goals of the UHN paper on globalization are threefold--to suggest how the external and internal environments of hospitals will change as a result of globalization; to suggest a role for hospitals in a globalized world; and to stimulate discussion and debate. Given our perspective, from the other side of the world, we are pleased to contribute to the discussion and debate but will limit our comments to the future role of teaching and research hospitals based on some of the experiences of Australia and Hong Kong. The citizens of Hong Kong have been acutely aware of the issue of globalization--the excellent deep-water harbour has ensured the position of Hong Kong as a major trading hub. Hong Kong has also had a continually evolving role as a financial centre and gateway to China, and with China's accession to the World Trade Organization the impact of globalization will be even greater. On the other hand, the citizens of Australia have lived with geographic isolation, relatively limited natural resources and a small population, all of which have limited their role in global trade and financial markets. However, both Hong Kong and Australia have seen recent benefits from the increasing speed of communication and information transfer and exchange. While it may still take close to a month for Australian practitioners to receive the hard copy of the journal in the mail, a electronic transfer is instantaneous. The globalization of knowledge and practice is one of the largest impacts of the Internet. With one of the most connected populations in the world, Hong Kong is very active in the sharing of knowledge with international experts.

Academic Medical Centers↗
PubMed1991

Cloning, sequence and overexpression of NADH peroxidase from Streptococcus faecalis 10C1. Structural relationship with the flavoprotein disulfide reductases.

DNA fragments encoding streptococcal NADH peroxidase (NPXase) have been amplified, cloned and sequenced from the genome of Streptococcus (Enterococcus) faecalis 10C1 (ATCC 11700). The NPXase gene (npr) comprises 1341 base-pairs and is preceded by a typical ribosome binding site. Upstream from the structural gene, putative -10 and -35 promoter regions have been identified, as has a possible factor-independent terminator that occurs in 3'-flanking sequences. The deduced relative molecular mass (Mr = 49,551), amino acid composition and isoelectric point of NPXase are in good agreement with previous values obtained with the purified enzyme. In addition, three sequenced peptides totaling approximately 20% of the protein were located in the npr gene product. From the sequencing data the deduced NPXase sequence shares low but significant homology with the flavoprotein disulfide reductase class of enzymes ranging from 21% for glutathione reductase (GRase) to 28% for thioredoxin reductase. Alignment of NPXase to Escherichia coli GRase allowed the identification of three previously reported fingerprints for the FAD, NADP+ and central domains of GRase, in the peroxidase sequence. In addition, Cys42 of NPXase, which is present as an unusual stabilized cysteine-sulfenic acid in the oxidized enzyme, aligns favorably with the charge-transfer cysteine in E. coli GRase, and both residues closely follow FAD-binding folds found near their respective amino termini. Such sequence characteristics can also be seen in mercuric reductase, lipoamide dehydrogenase and trypanothione reductase, suggesting that all these enzymes may have originally diverged from a common ancestor. Sequences that are on average 50% identical with three previously reported peptides of the related streptococcal NADH oxidase were also identified in the NPXase primary structure, suggesting a strong similarity between these flavoenzymes. Using the E. coli phage T7 expression system the npr gene has now been overexpressed in an E. coli genetic background. The resultant overexpressing clone produced a recombinant NPXase that was catalytically active and immunoreactive to NPXase antisera.

Amino Acid Sequence↗
PubMed2004

A genomic scan for habitual smoking in families of alcoholics: common and specific genetic factors in substance dependence.

Smoking is a highly heritable, addictive disorder that commonly co-occurs with alcohol dependence. The purpose of this study is to perform a genomic screen for habitual smoking and comorbid habitual smoking and alcohol dependence in families from the Collaborative Study on the Genetics of Alcoholism (COGA). Subjects were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) to evaluate alcohol dependence and habitual smoking (smoking one pack per day or more for at least 6 months). Sixty seven multi-generational families with 154 independent sibling pairs affected with habitual smoking were genotyped in a screening sample. Analyses on 79 multi-generational families with 173 independent sibling pairs were repeated in a replication sample. Sibpair analyses were performed using ASPEX. Four chromosomal regions in the screening sample had increased allele sharing among sibling pairs for habitual smoking with a LOD score greater than 1 (chromosomes 5, 9, 11, and 21). The highest LOD score was on chromosome 9 (LOD = 2.02; allele sharing 58.9%). Four chromosomal regions also had modest evidence for linkage to the comorbid phenotype habitual smoking and alcohol dependence (chromosomes 1, 2, 11, 15); and the strongest finding was on chromosome 2 (LOD = 3.30; allele sharing 69.1%). Previously identified areas (chromosomes 1 and 7) implicated in the development of alcohol dependence in this same data set did not provide evidence for linkage to habitual smoking in the screening sample. In the replication data set, there continued to be increased allele sharing near peaks identified in the screening sample on chromosomes 2 and 9, but the results were modest. An area on chromosome 7, approximately 60 cM from a location previously identified in linkage analysis with alcohol dependence, had increased allele sharing for the comorbid habitual smoking and alcohol dependence. These data provide evidence of specific genetic regions involved in the development of habitual smoking and not alcohol dependence. Conversely, genetic regions that influence the development of alcohol dependence do not appear to contribute to the development of habitual smoking. Finally, there is also evidence of an area on chromosome 2 that may reflect a common genetic vulnerability locus to both habitual smoking and alcohol dependence.

Adolescent↗
PubMed2006

Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma.

Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The orchestrated processes of regeneration, involving cell proliferation and immune response, were reflected in the concordant genes. The discordant gene signature revealed processes (e.g., morphogenesis and glycolysis) and pathways (e.g., hypoxia-inducible factor and insulin-like growth factor-I) that reflect the intrinsic pathologic nature of RCC. This is the first study that compares gene expression patterns in RCC and RRR. It does so, in particular, with relation to the hypothesis that RCC resembles the wound healing processes seen in RRR. However, careful attention to the genes that are regulated in the discordant direction provides new insights into the critical differences between renal carcinogenesis and wound healing. The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia.

Animals↗
PubMed2005

The MammoGrid Virtual Organisation - Federating Distributed Mammograms.

The MammoGrid project aims to deliver a prototype which enables the effective collaboration between radiologists using grid, service-orientation and database solutions. The grid technologies and service-based database management solution provide the platform for integrating diverse and distributed resources, creating what is called a 'virtual organisation'. The MammoGrid Virtual Organisation facilitates the sharing and coordinated access to mammography data, medical imaging software and computing resources of participating hospitals. Hospitals manage their local database of mammograms, but in addition, radiologists who are part of this organisation can share mammograms, reports, results and image analysis software. The MammoGrid Virtual Organisation is a federation of autonomous multi-centres sites which transcends national boundaries. This paper outlines the service-based approach in the creation and management of the federated distributed mammography database and discusses the role of virtual organisations in distributed image analysis.

Computer Communication Networks↗
PubMed1982

Homocystine uptake in isolated rat renal cortical tubules.

Isolated rat renal cortical tubules were used to study the nature of homocystine entry into the tubule cell and its transport interactions with cystine and the dibasic amino acids. The uptake of homocystine with time was progressive, reaching a steady state after 60 min. of incubation. Analysis of the intracellular pool after 5 and 30 min. of incubation revealed that virtually all of the transported homocystine had been converted to other metabolites of the transsulfuration pathway. The major metabolite was cystathionine with a somewhat lesser, but still significant amount as S-adenosylhomocysteine. A kinetic analysis showed that two systems for cellular entry of homocysteine existed with a Km1 of 0.17 mM and a Km2 of 7.65 mM. Arginine and lysine inhibited homocystine uptake via the low Km, high affinity system, but appeared not to inhibit the high Km, low affinity system. Cystine inhibited the low Km, high affinity system, but had an indeterminate effect on the high Km, low affinity system. Homocystine inhibited the uptake of cystine, lysine and arginine by isolated rat renal cortical tubules. The inhibition of homocystine on cystine uptake appeared to occur on both the high and low Km system for tubule cell entry of cystine. The data suggest that the low Km system for homocystine transport is shared with cystine and the dibasic amino acids. These data extend the knowledge of homocystine metabolism and provide a rational basis for new approaches to the treatment of homocystinuria.

Amino Acids↗
PubMed1996

Interspecific variation at the Y-linked RPS4Y locus in hominoids: implications for phylogeny.

Within- and between-species variation in restriction endonuclease recognition sites was examined at the Y-linked RPS4Y locus of six hominoid species: human (Homo sapiens), gorilla (Gorilla gorilla), chimpanzee (Pan troglodytes), bonobo (Pan paniscus), orangutan (Pongo pygmaeus), and gibbon (Hylobates lar). RPS4Y is an expressed gene that maps to the non-recombining region of the Y chromosome. An approximately 1,490 base pair fragment of the RPS4Y gene, including all of intron 3, was amplified by PCR from DNA extracted from each of the six species. Forty-seven restriction sites were identified on the six-species composite map derived from double-digest restriction analyses of the amplified fragment. As expected, maximum parsimony analysis indicated that chimpanzee and bonobo are the two most closely related living hominoids. The same analysis suggested that the closest living relative of Homo is Gorilla, not Pan, although support for this relationship was relatively weak. These results disagree with recently published phylogenies based on analyses of mtDNA sequences (Horai et al. [1995] Proc. Natl. Acad. Sci. U.S.A. 88:7401-7404) and the Y-linked ZFY locus (Dorit et al. [1995] Science 268:1183-1185). A combined data set derived from three distinct Y-linked loci-RPS4Y, SRY, and ZFY-was also analyzed. The maximum parsimony topology for the combined data provided only weak support for a shared common ancestor for Homo and Pan subsequent to divergence from the Gorilla lineage. Taken together, the data from the Y chromosome do not provide unequivocal support for any single, dichotomously branching species tree linking Homo, Pan, and Gorilla.

Animals↗
PubMed2002

Preparation of name and address data for record linkage using hidden Markov models.

BACKGROUND: Record linkage refers to the process of joining records that relate to the same entity or event in one or more data collections. In the absence of a shared, unique key, record linkage involves the comparison of ensembles of partially-identifying, non-unique data items between pairs of records. Data items with variable formats, such as names and addresses, need to be transformed and normalised in order to validly carry out these comparisons. Traditionally, deterministic rule-based data processing systems have been used to carry out this pre-processing, which is commonly referred to as "standardisation". This paper describes an alternative approach to standardisation, using a combination of lexicon-based tokenisation and probabilistic hidden Markov models (HMMs). METHODS: HMMs were trained to standardise typical Australian name and address data drawn from a range of health data collections. The accuracy of the results was compared to that produced by rule-based systems. RESULTS: Training of HMMs was found to be quick and did not require any specialised skills. For addresses, HMMs produced equal or better standardisation accuracy than a widely-used rule-based system. However, accuracy was worse when used with simpler name data. Possible reasons for this poorer performance are discussed. CONCLUSION: Lexicon-based tokenisation and HMMs provide a viable and effort-effective alternative to rule-based systems for pre-processing more complex variably formatted data such as addresses. Further work is required to improve the performance of this approach with simpler data such as names. Software which implements the methods described in this paper is freely available under an open source license for other researchers to use and improve.

Data Collection↗
PubMed1999

Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q.

Evidence for suggestive linkage to schizophrenia with chromosome 6q markers was previously reported from a two-stage approach. Using nonparametric affected sib pairs (ASP) methods, nominal p-values of 0.00018 and 0.00095 were obtained in the screening (81 ASPs; 63 independent) and the replication (109 ASPs; 87 independent) data sets, respectively. Here, we report a follow-up study of this 50cM 6q region using 12 microsatellite markers to test for linkage to schizophrenia. We increased the replication sample size by adding an independent sample of 43 multiplex pedigrees (66 ASPs; 54 independent). Pairwise and multipoint nonparametric linkage analyses conducted in this third data set showed evidence consistent with excess sharing in this 6q region, though the statistical level is weaker (p=0.013). When combining both replication data sets (total of 141 independent ASPs), an overall nominal p-value=0.000014 (LOD=3. 82) was obtained. The sibling recurrence risk (lambdas) attributed to this putative 6q susceptibility locus is estimated to be 1.92. The linkage region could not be narrowed down since LOD score values greater than three were observed within a 13cM region. The length of this region was only slightly reduced (12cM) when using the total sample of independent ASPs (204) obtained from all three data sets. This suggests that very large sample sizes may be needed to narrow down this region by ASP linkage methods. Study of the etiological candidate genes in this region is ongoing.

Chromosomes, Human, Pair 6↗
PubMed1969

Time-shared computing. Implications for medical libraries.

Many library data processing systems are unresponsive to the needs of librarians because of the necessity to batch-process transactions in a computer center. Such systems tend to be reportoriented rather than information-oriented with resultant problems in the timeliness of information. Time-shared computing permits multiple users to process jobs simultaneously through on-line interaction with the computer. Such systems offer to the librarian the advantages of immediate access to information, costs shared with other users, and direct man-machine interaction. This tutorial paper describes time-shared systems with applications in the library. Problems concerning the cost and present state-of-the-art of time-sharing are discussed.

Cataloging↗
PubMed1994

Is age-related maculopathy associated with cataracts?

OBJECTIVE: To evaluate the relationship between three types of cataract or cataract surgery and age-related maculopathy. DESIGN: Population-based prevalence study. PARTICIPANTS: A total of 4926 people participating in The Beaver Dam Eye Study from 1988 through 1990. MAIN OUTCOME MEASURES: Grading of photographs for nuclear sclerosis, cortical cataract, and posterior subcapsular cataract and signs of age-related maculopathy was performed using standardized protocols. RESULTS: After adjusting for other risk factors, nuclear sclerosis was associated with increased odds of early age-related maculopathy (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.28 to 3.01) but not of late age-related maculopathy (OR, 1.38; 95% CI, 0.52 to 3.63). Neither cortical nor posterior subcapsular cataracts were related to age-related maculopathy. There were increased odds of early age-related maculopathy in eyes that had undergone cataract surgery. CONCLUSION: These data suggest a possible commonly shared pathogenesis between nuclear sclerotic cataract and age-related maculopathy.

Adult↗
PubMed1998

Familial correlation of dietary intakes among postmenopausal women.

A positive family history is a risk factor for many chronic diseases, including most cancers, coronary heart disease, and diabetes. Since diet is also associated with most chronic diseases, one possible explanation for non-Mendelian familial clustering is shared eating habits. Food frequency data were obtained on 3,515 sisters in the Iowa Women's Health Study, a prospective cohort of postmenopausal women. Intraclass correlations between sisters were computed on a range of energy-adjusted nutrients to determine whether dietary intakes were more similar among siblings than among unrelated individuals. Two methods were used to calculate correlations: analysis of variance modeling and weighted sibling correlations. F-tests and randomization tests were used to determine statistical significance. The intraclass correlations for all of the nutrients examined were statistically significantly greater than the hypothesized value of zero (P < 0.05). Representative correlations include dietary fiber (0.15), animal fat (0.12), vegetable fat (0.13), calcium (0.14), iron (0.04), cholesterol (0.08), sodium (0.10), vitamin D (0.16), and total energy intake (0.11). When corrected for measurement error, the magnitude of these correlations increased, on average 62%. Although modest in magnitude, these correlations may be high enough to influence familial clustering of complex diseases that are attributed, in part, to diet.

Aged↗