Institut für Medizinische Biometrie, Informatik und Epidemiologie

Survival analysis:techniques for censored and truncated data , Survival analysis:techniques for censored and truncated data , کتابخانه مرکزی دانشگاه علوم پزشکی ایران

Insects are the most speciose group of animals, but the phylogenetic relationships of many major lineages remain unresolved. We inferred the phylogeny of insects from 1478 protein-coding genes. Phylogenomic analyses of nucleotide and amino acid sequences, with site-specific nucleotide or domain-specific amino acid substitution models, produced statistically robust and congruent results resolving previously controversial phylogenetic relations hips. We dated the origin of insects to the Early Ordovician [~479 million years ago (Ma)], of insect flight to the Early Devonian (~406 Ma), of major extant lineages to the Mississippian (~345 Ma), and the major diversification of holometabolous insects to the Early Cretaceous. Our phylogenomic study provides a comprehensive reliable scaffold for future comparative analyses of evolutionary innovations among insects.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often, initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

We describe a broad class of family-based association tests that are adjusted for admixture; use either dichotomous or measured phenotypes; accommodate phenotype-unknown subjects; use nuclear families, sibships or a combination of the two, permit multiple nuclear families from a single pedigree; incorporate di- or multi-allelic marker data; allow additive, dominant or recessive models; and permit adjustment for covariates and gene-by-environment interactions. The test statistic is basically the covariance between a user-specified function of the genotype and a user-specified function of the trait. The distribution of the statistic is computed using the appropriate conditional distribution of offspring genotypes that adjusts for admixture.

Abstract Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine 1,2 . Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes 3 . However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation 4,5 . Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning—a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine.

Unlike numerous pore-forming amphiphilic peptide antibiotics, the lantibiotic nisin is active in nanomolar concentrations, which results from its ability to use the lipid-bound cell wall precursor lipid II as a docking molecule for subsequent pore formation. Here we use genetically engineered nisin variants to identify the structural requirements for the interaction of the peptide with lipid II. Mutations affecting the conformation of the N-terminal part of nisin comprising rings A through C, e.g. [S3T]nisin, led to reduced binding and increased the peptide concentration necessary for pore formation. The binding constant for the S3T mutant was 0.043 10 7 M 1 compared with 2 10 7 M 1 for the wildtype peptide, and the minimum concentration for pore formation increased from the 1 nM to the 50 nM range. In contrast, peptides mutated in the flexible hinge region, e.g. [N20/M21]nisin, were completely inactive in the pore formation assay, but were reduced to some extent in their in vivo activity. We found the remaining in vivo activity to result from the unaltered capacity of the mutated peptide to bind to lipid II and thus to inhibit its incorporation into the peptidoglycan network. Therefore, through interaction with the membrane-bound cell wall precursor lipid II, nisin inhibits peptidoglycan synthesis and forms highly specific pores. The combination of two killing mechanisms in one molecule potentiates antibiotic activity and results in nanomolar MIC values, a strategy that may well be worth considering for the construction of novel antibiotics.

Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.

Cardis, E., Vrijheid, M., Blettner, M., Gilbert, E., Hakama, M., Hill, C., Howe, G., Kaldor, J., Muirhead, C. R., Schubauer-Berigan, M., Yoshimura, T., Bermann, F., Cowper, G., Fix, J., Hacker, C., Heinmiller, B., Marshall, M., Thierry-Chef, I., Utterback, D., Ahn, Y-O., Amoros, E., Ashmore, P., Auvinen, A., Bae, J-M., Bernar, J. S., Biau, A., Combalot, E., Deboodt, P., Diez Sacristan, A., Eklöf, M., Engels, H., Engholm, G., Gulis, G., Habib, R. R., Holan, K., Hyvonen, H., Kerekes, A., Kurtinaitis, J., Malker, H., Martuzzi, M., Mastauskas, A., Monnet, A., Moser, M., Pearce, M. S., Richardson, D. B., Rodriguez-Artalejo, F., Rogel, A., Tardy, H., Telle-Lamberton, M., Turai, I., Usel, M. and Veress, K. The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: Estimates of Radiation-Related Cancer Risks. Radiat. Res. 167, 396– 416 (2007).A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI −0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

This study describes a computer-based technique for classifying and identifying bacterial samples using Fourier-transform infrared spectroscopy (FT-IR) patterns. Classification schemes were tested for selected series of bacterial strains and species from a variety of different genera. Dissimilarities between bacterial IR spectra were calculated using modified correlation coefficients. Dissimilarity matrices were used for cluster analysis, which yielded dendrograms broadly equated with conventional taxonomic classification schemes. Analyses were performed with selected strains of the taxa Staphylococcus, Streptococcus, Clostridium, Legionella and Escherichia coli in particular, and with a database containing 139 bacterial reference spectra. The latter covered a wide range of Gram-negative and Gram-positive bacteria. Unknown specimens could be identified when included in an established cluster analysis. Thirty-six clinical isolates of Staphylococcus aureus and 24 of Streptococcus faecalis were tested and all were assigned to the correct species cluster. It is concluded that: (1) FT-IR patterns can be used to type bacteria; (2) FT-IR provides data which can be treated such that classifications are similar and/or complementary to conventional classification schemes; and (3) FT-IR can be used as an easy and safe method for the rapid identification of clinical isolates.

Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the genetic factors predisposing to idiopathic generalized epilepsies remain elusive. Studies of structural genomic variations have revealed a significant excess of recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability and schizophrenia. Microdeletions at 15q13.3 have recently been shown to constitute a strong genetic risk factor for common idiopathic generalized epilepsy syndromes, implicating that other recurrent microdeletions may also be involved in epileptogenesis. This study aimed to investigate the impact of five microdeletions at the genomic hotspot regions 1q21.1, 15q11.2, 16p11.2, 16p13.11 and 22q11.2 on the genetic risk to common idiopathic generalized epilepsy syndromes. The candidate microdeletions were assessed by high-density single nucleotide polymorphism arrays in 1234 patients with idiopathic generalized epilepsy from North-western Europe and 3022 controls from the German population. Microdeletions were validated by quantitative polymerase chain reaction and their breakpoints refined by array comparative genomic hybridization. In total, 22 patients with idiopathic generalized epilepsy (1.8%) carried one of the five novel microdeletions compared with nine controls (0.3%) (odds ratio = 6.1; 95% confidence interval 2.8-13.2; chi(2) = 26.7; 1 degree of freedom; P = 2.4 x 10(-7)). Microdeletions were observed at 1q21.1 [Idiopathic generalized epilepsy (IGE)/control: 1/1], 15q11.2 (IGE/control: 12/6), 16p11.2 IGE/control: 1/0, 16p13.11 (IGE/control: 6/2) and 22q11.2 (IGE/control: 2/0). Significant associations with IGEs were found for the microdeletions at 15q11.2 (odds ratio = 4.9; 95% confidence interval 1.8-13.2; P = 4.2 x 10(-4)) and 16p13.11 (odds ratio = 7.4; 95% confidence interval 1.3-74.7; P = 0.009). Including nine patients with idiopathic generalized epilepsy in this cohort with known 15q13.3 microdeletions (IGE/control: 9/0), parental transmission could be examined in 14 families. While 10 microdeletions were inherited (seven maternal and three paternal transmissions), four microdeletions occurred de novo at 15q13.3 (n = 1), 16p13.11 (n = 2) and 22q11.2 (n = 1). Eight of the transmitting parents were clinically unaffected, suggesting that the microdeletion itself is not sufficient to cause the epilepsy phenotype. Although the microdeletions investigated are individually rare (<1%) in patients with idiopathic generalized epilepsy, they collectively seem to account for a significant fraction of the genetic variance in common idiopathic generalized epilepsy syndromes. The present results indicate an involvement of microdeletions at 15q11.2 and 16p13.11 in epileptogenesis and strengthen the evidence that recurrent microdeletions at 15q11.2, 15q13.3 and 16p13.11 confer a pleiotropic susceptibility effect to a broad range of neuropsychiatric disorders.

It is generally assumed that type A lantibiotics primarily kill bacteria by permeabilization of the cytoplasmic membrane. As previous studies had demonstrated that nisin interacts with the membrane-bound peptidoglycan precursors lipid I and lipid II, we presumed that this interaction could play a role in the pore formation process of lantibiotics. Using a thin-layer chromatography system, we found that only nisin and epidermin, but not Pep5, can form a complex with [14C]-lipid II. Lipid II was then purified from Micrococcus luteus and incorporated into carboxyfluorescein-loaded liposomes made of phosphatidylcholine and cholesterol (1:1). Liposomes supplemented with 0.05 or 0.1 mol% of lipid II did not release any marker when treated with Pep5 or epilancin K7 (peptide concentrations of up to 5 mol% were tested). In contrast, as little as 0.01 mol% of epidermin and 0.1 mol% of nisin were sufficient to induce rapid marker release; phosphatidylglycerol-containing liposomes were even more susceptible. Controls with moenomycin-, undecaprenol- or dodecaprenolphosphate-doped liposomes demonstrated the specificity of the lantibiotics for lipid II. These results were correlated with intact cells in an in vivo model. M. luteus and Staphylococcus simulans were depleted of lipid II by preincubation with the lipopeptide ramoplanin and then tested for pore formation. When applied in concentrations below the minimal inhibitory concentration (MIC) and up to 5-10 times the MIC, the pore formation by nisin and epidermin was blocked; at higher concentrations of the lantibiotics the protective effect of ramoplanin disappeared. These results demonstrate that, in vitro and in vivo, lipid II serves as a docking molecule for nisin and epidermin, but not for Pep5 and epilancin K7, and thereby facilitates the formation of pores in the cytoplasmic membrane.

Summary Background: The concept of boosting emerged from the field of machine learning. The basic idea is to boost the accuracy of a weak classifying tool by combining various instances into a more accurate prediction. This general concept was later adapted to the field of statistical modelling. Nowadays, boosting algorithms are often applied to estimate and select predictor effects in statistical regression models. Objectives: This review article attempts to highlight the evolution of boosting algorithms from machine learning to statistical modelling. Methods: We describe the AdaBoost algorithm for classification as well as the two most prominent statistical boosting approaches, gradient boosting and likelihood-based boosting for statistical modelling. We highlight the methodological background and present the most common software implementations. Results: Although gradient boosting and likelihood-based boosting are typically treated separately in the literature, they share the same methodological roots and follow the same fundamental concepts. Compared to the initial machine learning algorithms, which must be seen as black-box prediction schemes, they result in statistical models with a straight-forward interpretation. Conclusions: Statistical boosting algorithms have gained substantial interest during the last decade and offer a variety of options to address important research questions in modern biomedicine.

Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001), were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

Lantibiotics are biologically active peptides which contain the thioether amino acid lanthionine as well as several other modified amino acids. They can be broadly divided into two groups on the basis of their structures: type-A lantibiotics are elongated, amphiphilic peptides, while type-B lantibiotics are compact and globular. In the last decade there has been a marked increase in research interest in these peptides due both to the novel biosynthetic mechanisms by which they are produced, as well as to their potential applications. Lantibiotics are synthesised on the ribosome as a prepeptide which undergoes several post-translational modification events, including dehydration of specific hydroxyl amino acids to form dehydroamino acids, addition of neighbouring sulfhydryl groups to form thioethers and, in specific cases, other modifications such as introduction of D-alanine residues from L-serine, formation of lysinoalanine bridges, formation of novel N-terminal blocking groups and oxidative decarboxylation of a C-terminal cysteine. The genetic elements responsible for these specific modification reactions encode unique enzymes with hitherto unknown reaction mechanisms. Production of these peptides also requires accessory proteins including processing proteases, translocators of the ATP-binding cassette transporter family, regulatory proteins and dedicated producer self-protection mechanisms. While the principle biological activity of most type-B lantibiotics appears to be directed at the inhibition of enzyme functions, the type-A lantibiotics kill bacterial cells by forming pores in the cytoplasmic membrane.

BACKGROUND: Brain tumors are the most common disease group of solid tumors in childhood, and children with brain tumors have a relatively poor survival rate. Epidemiologic data from a population-based cancer registry provide the necessary information to obtain a full picture of the frequency of this disease, which is a great challenge in pediatric oncology. METHODS: The German Childhood Cancer Registry (GCCR) is a population-based registry. The level of completeness of patient registration is 95%, but it is somewhat lower for patients with brain tumors. More than 300 children with newly diagnosed brain tumors are reported every year. Analyses of GCCR data are performed according to the International Classification of Childhood Cancer and the recently published World Health Organization classification of tumors of the nervous system. In addition, incidence rates of childhood brain tumors in Germany are compared with those of other countries, as published by the International Agency for Research on Cancer. RESULTS: In the years 1990-1999, a total of 3268 brain tumors were observed (excluding intracranial and intraspinal germ cell tumors). The respective incidence rate for children age < 15 years was 2.6 per 100,000 children and lies between the rates from other countries, which range between 1.7 and 4.1 per 100,000 children. The most common brain tumors were astrocytomas (41.7%), medulloblastomas (18.1%), ependymomas (10.4%), supratentorial primative neuroectodermal tumors (PNETs; 6.7%), and craniopharyngiomas (4.4%). They were located mainly in the cerebellum (27.9%) and the cerebrum (21.2%). The 5-year survival rate for all brain tumors was 64%, with the poorest prognosis for children with PNET. CONCLUSIONS: The large data base of the GCCR made it possible to present representative data on patients with childhood tumors of the central nervous system in Germany. The data quality was high, not least because of the strong cooperation with corresponding clinical trials. However, for children with central nervous system tumors, the ascertainment of newly diagnosed patients needs further improvement.

Psychological data from 560 male survivors of acute myocardial infarction (AMI) were documented in the third week after onset of AMI. The psychodiagnostic assessment was designed to detect different forms of depression as well as hyperactive behaviour. A complete follow-up of these patients, which covers a period of 6 months, is available. Our findings indicate that affective disorders play an important role in the post-acute phase after AMI although the extent of myocardial infarction (as defined by an ECG score) and behaviour responses are not significantly related to one another. Different subforms of depression are not influenced by a history of angina pectoris, the degree and location of myocardial infarction, the occurrence of late potentials and age, whereas dyspnoea (P less than 0.001) and the recurrence of myocardial infarction (P less than 0.001) favour depressive mood states. Twelve cardiac deaths and 17 arrhythmic events occurred during the study period; they were significantly predicted by severe forms of post-AMI depression as revealed by univariate analysis. The evidence was stronger for predicting cardiac death (P less than 0.001) than for arrhythmic events (P = less than 0.035). The effect remains of borderline significance for cardiac death if all risk factors with a significant univariate influence are included in a multiple logistic regression model. The effect of depression is illustrated by Kaplan-Meier survival curves separated for patient groups with high as compared to low degrees of depression. Hyperactivity showed no impact on patient survival.

// Hojjat Ahmadzadehfar 1 , Elisabeth Eppard 1 , Stefan K&uuml;rpig 1 , Rolf Fimmers 2 , Anna Yordanova 1 , Carl Diedrich Schlenkhoff 1 , Florian G&auml;rtner 1 , Sebastian Rogenhofer 3 , Markus Essler 1 1 Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany 2 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany 3 Department of Urology, University Hospital Bonn, Bonn, Germany Correspondence to: Hojjat Ahmadzadehfar, e-mail: Hojjat.ahmadzadehfar@ukb.uni-bonn.de , nuclearmedicine@gmail.com Keywords: PSMA, 177 Lu, prostate cancer, radioligand therapy, PSA Received: October 26, 2015&emsp;&emsp;&emsp;&emsp; Accepted: January 27, 2016&emsp;&emsp;&emsp;&emsp; Published: February 08, 2016 ABSTRACT Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with 177 Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64&ndash;82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17&ndash;2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients.

A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment.