tbuckley/cabot-search huggingface dataset:
Fostering Healthy Mental, Emotional, and Behavioral Development in Child Health Care
Authors: Thomas F. Boat, Kelly J. Kelleher
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Household Fuel Use and the Risk of Gastrointestinal Cancers: The Golestan Cohort Study
Authors: Mahdi Sheikh, Hossein Poustchi, Akram Pourshams, Masoud Khoshnia, Abdolsamad Gharavi, Mahdi Zahedi, Gholamreza Roshandel, Sadaf G. Sepanlou, Abdolreza Fazel, Maryam Hashemian, Behrooz Abaei, Masoud Sotoudeh, Arash Nikmanesh, Shahin Merat, Arash Etemadi, Siavosh Nasseri Moghaddam, Farhad Islami, Farin Kamangar, Paul D. Pharoah, Sanford M. Dawsey, Christian C. Abnet, Paolo Boffetta, Paul Brennan, Reza Malekzadeh
Journal: Environmental Health Perspectives (2020)

Background: Three billion people burn nonclean fuels for household purposes. Limited evidence suggests a link between household fuel use and gastrointestinal (GI) cancers. Objectives: We investigated the relationship between indoor burning of biomass, kerosene, and natural gas with the subsequent risk of GI cancers. Methods: During the period 2004–2008, a total of 50,045 Iranian individuals 40–75 years of age were recruited to this prospective population-based cohort. Upon enrollment, validated data were collected on demographics, lifestyle, and exposures, including detailed data on lifetime household use of different fuels and stoves. The participants were followed through August 2018 with <1% loss. Results: During the follow-up, 962 participants developed GI cancers. In comparison with using predominantly gas in the recent 20-y period, using predominantly biomass was associated with higher risks of esophageal [hazard ratio (HR): 1.89; 95% confidence interval (CI): 1.02, 3.50], and gastric HR: 1.83; 95% CI: 1.01, 3.31) cancers, whereas using predominantly kerosene was associated with higher risk of esophageal cancer (HR: 1.84; 95% CI: 1.10, 3.10). Lifetime duration of biomass burning for both cooking and house heating (exclusive biomass usage) using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.14; 95% CI: 1.07, 1.21), esophageal (10-y HR: 1.19; 95% CI: 1.08, 1.30), gastric (10-y HR: 1.11; 95% CI: 1.00, 1.23), and colon (10-y HR: 1.26; 95% CI: 1.03, 1.54) cancers. The risks of GI cancers combined, esophageal cancer, and gastric cancer were lower when biomass was burned using chimney-equipped heating-stoves (strata difference p-values=0.001, 0.003, and 0.094, respectively). Duration of exclusive kerosene burning using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.05; 95% CI: 1.00, 1.11), and esophageal cancer (10-y HR: 1.14; 95% CI: 1.04, 1.26). Discussion: Household burning of biomass or kerosene, especially without a chimney, was associated with higher risk of some digestive cancers. Using chimney-equipped stoves and replacing these fuels with natural gas may be useful interventions to reduce the burden of GI cancers worldwide. https://doi.org/10.1289/EHP5907
Covid-19 in Peru: from supervised walks for children to the first case of Kawasaki-like syndrome
Authors: Jaime A Yáñez, Aldo Alvarez-Risco, Jaime Delgado-Zegarra
Journal: BMJ (2020)

<h3>Background</h3> Tobacco companies claim that higher taxes will force smokers into buying illicit tobacco, but if they were truly concerned about increasing illicit sales with higher prices they would only increase retail prices in line with changes in taxation. In this paper, we explore UK pricing of both factory-made cigarettes (FM) and roll-your-own tobacco (RYO) to explore the extent to which price increases were due to government tax rises or industry strategies to increase profit per pack. <h3>Method</h3> Nielsen commercial data on UK tobacco sales data (2010–2015) were combined with official UK data on inflation and tax rates, to identify the source of real price increases. <h3>Results</h3> Between 2010 and 2012, when there were unexpected large tax increases, industry driven price changes were small (16% of the price rise in FM and 20% in RYO), and changes were similar between market segments. Between 2013 and 2015, when tax increases were smaller and expected, industry behaviour generally accounted for a larger share of price rises (33% FM, 48% RYO), but changes varied considerably by segment. <h3>Conclusion</h3> The industry has increased its prices beyond that required by tax changes, even when tax rises were larger and unexpected, although were notably smaller in such conditions. This suggests (1) that the industry is not actually concerned by the threat of illicit, especially since RYO had the highest levels of industry driven price increases despite higher levels of illicit, and (2) there remains scope for further tax increases, which should be relatively large and unexpected.
Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity
Authors: Ursula Smole, Naina Gour, Jordan Phelan, Gerhard Hofer, Cordula Köhler, Bernhard Kratzer, Peter A. Tauber, Xiao Xiao, Nu Yao, Jan Dvorak, Luis Caraballo, Leonardo Puerta, Sandra Rosskopf, Jamila Chakir, Ernst Malle, Andrew P. Lane, Winfried F. Pickl, Stephane Lajoie, Marsha Wills-Karp
Journal: Nature Immunology (2020)
Harnessing the power of health taxes
Authors: Vageesh Jain, Peter Baker, Kalipso Chalkidou
Journal: BMJ (2020)

Health taxes are a cost effective opportunity for progress in public health. Yet decision making processes on such policies lack the diligence routinely used in appraising other health interventions, and this limits their use, say <b>Vageesh Jain and colleagues</b>
Nivolumab-induced synovitis is characterized by florid T cell infiltration and rapid resolution with synovial biopsy-guided therapy
Authors: William Murray-Brown, Tom D Wilsdon, Helen Weedon, Susanna Proudman, Shawgi Sukumaran, Sonja Klebe, Jennifer G Walker, Malcolm D Smith, Mihir D Wechalekar
Journal: Journal for ImmunoTherapy of Cancer (2020)

Immune checkpoint inhibitors (ICIs) are associated with rheumatic and musculoskeletal immune-related adverse events (irAEs) in 5%-20% of patients. Currently, patients refractory to corticosteroids and conventional disease-modifying antirheumatic drugs (cDMARD) are treated with biological DMARDs (bDMARDs) targeting tumor necrosis factor α (TNFα) and interleukin-6, although without a clear biological rationale. Synovial tissue (ST) biopsy presents a valuable opportunity to investigate irAE pathogenesis and appropriately stratify bDMARD use in refractory irAE patients.We provide the first report of comparative, parallel ST and synovial fluid (SF) analyses of severe, cDMARD-refractory, seronegative polyarthritis, classified as a grade 3 irAE occurring in response to nivolumab treatment for metastatic squamous cell lung cancer, in comparison with ST and SF from patients with untreated rheumatoid arthritis (RA). We investigated immunohistochemical labeling of ST cytokine expression as a biological rationale for selecting therapy. Flow cytometric analysis of lymphocytes from ST, SF and blood collected before and after synovial biopsy-guided therapy, in comparison with RA, were evaluated for insights into the immunopathogenesis of irAE. Immunolabeling of ST demonstrated an excess of TNFα cytokine expression. Subsequent treatment with infliximab resulted in resolution of inflammatory symptoms and a significant reduction in C reactive protein levels. Flow cytometric analysis of synovial infiltrates indicated absence of programmed cell death protein-1 (PD-1) receptor positivity despite cessation of nivolumab approximately 200 days prior to the analyzes.A deeper understanding of the immunopathogenetic basis of immune activation in irAEs is required in order to select therapy that is likely to be the most effective. This is the first report investigating parallel blood, ST and SF in ICI-induced severe rheumatic irAE. Use of a bDMARD directed by the dominant inflammatory cytokine achieved resolution of synovitis while maintaining cancer remission.
リボソームタンパク質L17,RpL17は,血管平滑筋の成長および頸動脈内膜形成の阻害物質である | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: M Smolock Elaine, A Korshunov Vyacheslav, Glazko Galina, Qiu Xing, Gerloff Janice, C Berk Bradford
Journal: Circulation (2012)
HDAC11 Is a Candidate Therapeutic Target in Multiple Myeloma
Authors: Jason B. Brayer, Allison Distler, Mark B. Meads, Eva Sahakian, John J. Powers, Tuan Nguyen, Melissa Alsina, Taiga Nishihori, Rachid Baz, Javier Pinilla-Ibarz, Eduardo Martin Sotomayor, Ken H Shain
Journal: Blood (2017)
Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer
Authors: G. Serna, F. Ruiz-Pace, J. Hernando, L. Alonso, R. Fasani, S. Landolfi, R. Comas, J. Jimenez, E. Elez, S. Bullman, J. Tabernero, J. Capdevila, R. Dienstmann, P. Nuciforo
Journal: Annals of Oncology (2020)

Accumulating evidence has identified Fusobacterium as an important pathogenic gut bacterium associated with colorectal cancer. Nevertheless, only limited data exist about the role of this bacterium in locally advanced rectal cancer (LARC). In this study, we quantified Fusobacterium nucleatum in untreated and post-neoadjuvant chemoradiotherapy (nCRT) samples from LARC patients and investigated its association with therapy response and survival.
Are Electroencephalogram-Derived Predictors of Antidepressant Efficacy Closer to Clinical Usefulness?
Authors: Dan V. Iosifescu
Journal: JAMA Network Open (2020)

Pranav Rajpurkar, MS; Jingbo Yang, BS; Nathan Dass, MS; Vinjai Vale; Arielle S. Keller, MS; Jeremy Irvin, MS; Zachary Taylor, BS; Sanjay Basu, MD, PhD; Andrew Ng, PhD; Leanne M. Williams, PhD
Multidisciplinary research priorities for the COVID-19 pandemic – Authors' reply
Authors: Rory C O'Connor, Matthew Hotopf, Carol M Worthman, V Hugh Perry, Irene Tracey, Simon Wessely, Louise Arseneault, Clive Ballard, Helen Christensen, Roxane Cohen Silver, Tamsin Ford, Ann John, Thomas Kabir, Kate King, Alan Simpson, Ira Madan, Katherine Cowan, Ed Bullmore, Emily A Holmes
Journal: The Lancet Psychiatry (2020)
Role of antimalarials in COVID-19: observational data from a cohort of rheumatic patients
Authors: Ennio Giulio Favalli, Orazio De Lucia, Martina Biggioggero, Nicoletta Del Papa, Roberto Caporali
Journal: Annals of the Rheumatic Diseases (2020)

The potential role of chloroquine (CQ) and hydroxychloroquine (HCQ) in the management of COVID-19 is certainly of relevance in this health emergency scenario. For this reason, we read with great interest the letter published by Romao and colleagues highlighting the need for more definite evidence on the role of antimalarial drugs in both preventing severe acute respiratory syndrome coronavirus-2 infection and making COVID-19 clinical course milder.1 While several ongoing clinical trials are progressively providing controversial data about the real efficacy and safety of antimalarials in the treatment of overt COVID-19,2–4 rheumatological patients already taking CQ or HCQ for the treatment of chronic inflammatory diseases are an excellent bench for testing the potential effect in preventing the contagion.5 Being operative in the Research Center for Adult and Paediatric Rheumatic Diseases of the ASST Gaetano Pini-CTO in Milan (Lombardy), we had the opportunity to deal with …
Mindfulness for those with COPD, Asthma, Lung Cancer and Lung Transplantation
Authors: Ni-Cheng Liang, Tania Von Visger, Asha Devereaux
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Mindfulness for those with COPD, Asthma, Lung Cancer and Lung Transplantation." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Plastic surgeons lambasted by coroner for failing to admit mistakes over death of woman who had hyperkalaemia
Authors: Clare Dyer
Journal: BMJ (2020)

A coroner has lambasted the plastic surgery department at Southmead Hospital in Bristol for having been “serially unwilling to acknowledge, respond to, investigate, be open about, or admit to its mistakes.”1

Robert Sowersby, assistant coroner for Avon, delivered the rebuke in an unusually detailed and strongly worded report to prevent future deaths sent to the chief executive of North Bristol NHS Trust and to its head of clinical governance. The trust has until 24 July to respond.

Sowersby conducted the inquest into the death of Lesley Brass, 58, who died from a cardiac arrest after developing severe hyperkalaemia. Under the trust’s own standard operating procedure, the condition is a life threatening emergency which must be treated within 30 minutes with intravenous calcium.

Brass was on the plastic surgery ward in October 2018 after a wound she sustained …
Identification of Somatically Acquired<i>BRCA1/2</i>Mutations by cfDNA Analysis in Patients with Metastatic Breast Cancer
Authors: Neelima Vidula, Taronish Dubash, Michael S. Lawrence, Antoine Simoneau, Andrzej Niemierko, Erica Blouch, Becky Nagy, Whijae Roh, Brian Chirn, Brittany A. Reeves, Giuliana Malvarosa, Jochen Lennerz, Steven J. Isakoff, Dejan Juric, Douglas Micalizzi, Seth Wander, Laura Spring, Beverly Moy, Kristen Shannon, Jerry Younger, Richard Lanman, Mehmet Toner, A. John Iafrate, Gad Getz, Lee Zou, Leif W. Ellisen, Shyamala Maheswaran, Daniel A. Haber, Aditya Bardia
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Plasma genotyping may identify mutations in potentially “actionable” cancer genes, such as BRCA1/2, but their clinical significance is not well-defined. We evaluated the characteristics of somatically acquired BRCA1/2 mutations in patients with metastatic breast cancer (MBC). Experimental Design: Patients with MBC undergoing routine cell-free DNA (cfDNA) next-generation sequencing (73-gene panel) before starting a new therapy were included. Somatic BRCA1/2 mutations were classified as known germline pathogenic mutations or novel variants, and linked to clinicopathologic characteristics. The effect of the PARP inhibitor, olaparib, was assessed in vitro, using cultured circulating tumor cells (CTCs) from a patient with a somatically acquired BRCA1 mutation and a second patient with an acquired BRCA2 mutation. Results: Among 215 patients with MBC, 29 (13.5%) had somatic cfDNA BRCA1/2 mutations [nine (4%) known germline pathogenic and rest (9%) novel variants]. Known germline pathogenic BRCA1/2 mutations were common in younger patients (P = 0.008), those with triple-negative disease (P = 0.022), and they were more likely to be protein-truncating alterations and be associated with TP53 mutations. Functional analysis of a CTC culture harboring a somatic BRCA1 mutation demonstrated high sensitivity to PARP inhibition, while another CTC culture harboring a somatic BRCA2 mutation showed no differential sensitivity. Across the entire cohort, APOBEC mutational signatures (COSMIC Signatures 2 and 13) and the “BRCA” mutational signature (COSMIC Signature 3) were present in BRCA1/2-mutant and wild-type cases, demonstrating the high mutational burden associated with advanced MBC. Conclusions: Somatic BRCA1/2 mutations are readily detectable in MBC by cfDNA analysis, and may be present as both known germline pathogenic and novel variants.
Use of the prevented fraction for the population to determine deaths averted by existing prevalence of physical activity: a descriptive study
Authors: Tessa Strain, Søren Brage, Stephen J Sharp, Justin Richards, Marko Tainio, Ding Ding, Jacques Benichou, Paul Kelly
Journal: The Lancet Global Health (2020)

Disease and mortality burdens of unhealthy lifestyle behaviours are often reported. In contrast, the positive narrative around the burdens that an existing behaviour have averted is rarely acknowledged. We aimed to estimate the prevented fraction for the population (PFP) for premature mortality averted by physical activity on a global scale.
Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients
Authors: Daniel Spakowicz, Shaoke Lou, Brian Barron, Jose L. Gomez, Tianxiao Li, Qing Liu, Nicole Grant, Xiting Yan, Rebecca Hoyd, George Weinstock, Geoffrey L. Chupp, Mark Gerstein
Journal: Genome biology (2020)

Sputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heterogeneous mixtures of human cells and exogenous (microbial) material. In this study, we develop a pipeline that integrates dimensionality reduction and statistical modeling to grapple with the heterogeneity. LDA(Latent Dirichlet allocation)-link connects microbes to genes using reduced-dimensionality LDA topics. We validate our method with single-cell RNA-seq and microscopy and then apply it to the sputum of asthmatic patients to find known and novel relationships between microbes and genes.
How Will Genetics Inform the Clinical Care of Atrial Fibrillation?
Authors: M. Benjamin Shoemaker, Rajan L. Shah, Dan M. Roden, Marco V. Perez
Journal: Circulation Research (2020)

Susceptibility to atrial fibrillation (AF) is determined by well-recognized risk factors such as diabetes mellitus or hypertension, emerging risk factors such as sleep apnea or inflammation, and increasingly well-defined genetic variants. As discussed in detail in a companion article in this series, studies in families and in large populations have identified multiple genetic loci, specific genes, and specific variants increasing susceptibility to AF. Since it is becoming increasingly inexpensive to obtain genotype data and indeed whole genome sequence data, the question then becomes to define whether using emerging new genetics knowledge can improve care for patients both before and after development of AF. Examples of improvements in care could include identifying patients at increased risk for AF (and thus deploying increased surveillance or even low-risk preventive therapies should these be available), identifying patient subsets in whom specific therapies are likely to be effective or ineffective or in whom the driving biology could motivate the development of new mechanism-based therapies or identifying an underlying susceptibility to comorbid cardiovascular disease. While current guidelines for the care of patients with AF do not recommend routine genetic testing, this rapidly increasing knowledge base suggests that testing may now or soon have a place in the management of select patients. The opportunity is to generate, validate, and deploy clinical predictors (including family history) of AF risk, to assess the utility of incorporating genomic variants into those predictors, and to identify and validate interventions such as wearable or implantable device-based monitoring ultimately to intervene in patients with AF before they present with catastrophic complications like heart failure or stroke.
A phase I dose-escalation and pharmacokinetic study of a micellar nanoparticle with entrapped docetaxel (CPC634) in patients with advanced solid tumours
Authors: Florence Atrafi, Herlinde Dumez, Ron H.J. Mathijssen, Catharine W Menke van der Houven van Oordt, Cristianne J.F. Rijcken, Rob Hanssen, Ferry A.L.M. Eskens, Patrick Schöffski
Journal: Journal of Controlled Release (2020)

Background: CPC634 is docetaxel entrapped in core-cross linked polymeric micelles. In preclinical studies, CPC634 demonstrated enhanced pharmacokinetics and improved therapeutic index. This phase I dose escalation study is the first-in-human study with CPC634. Methods: adult patients with advanced solid tumours received CPC634 intravenously either 3-weekly (Q3W) (part 1, dose range 15–100 mg/m2), 2-weekly (Q2W) (part 2, 45 mg/m2) or Q3W with dexamethasone premedication (part 3, 60 mg/m2). Results: thirty-three patients were enrolled. Skin toxicity was dose limiting (DLT) at ≥60 mg/m2 in part 1 and at 45 mg/m2 in part 2 and was the most common CPC634 related grade ≥ 3 adverse event (24%). With dexamethasone premedication no DLTs were observed at 60 mg/m2 Q3W. CPC634 exhibited a dose-proportional pharmacokinetic profile. At 60 mg/m2, the plasma area under the curve was 4067.5 ± 2974.0 ng/h/mL and the peak plasma level 217.3 ± 91.9 ng/mL with a half-life of 39.7 ± 9.4 h for released docetaxel. Conclusion: CPC634 could be administered safely upon pretreatment with dexamethasone. Cumulative skin toxicity was the main DLT. The recommended phase 2 dose was determined at 60 mg/m2 Q3W with dexamethasone premedication.
A Clinical Tool to Identify Candidates for Stress-First Myocardial Perfusion Imaging
Authors: Soroush Rouhani, Ali Al Shahrani, Alomgir Hossain, Yeung Yam, R. Glenn Wells, Robert A. deKemp, Rob S. Beanlands, Terrence D. Ruddy, Marcelo F. Di Carli, Michael E. Merhige, Brent A. Williams, Emir Veledar, Daniel S. Berman, Sharmila Dorbala, Benjamin J.W. Chow
Journal: JACC. Cardiovascular imaging (2020)
Cardiac Magnetic Resonance Characterization of Myocarditis-Like Acute Cardiac Syndrome in COVID-19
Authors: Antonio Esposito, Anna Palmisano, Luigi Natale, Guido Ligabue, Giovanni Peretto, Luigi Lovato, Davide Vignale, Federica Fiocchi, Riccardo Marano, Vincenzo Russo
Journal: JACC. Cardiovascular imaging (2020)
177Lu-/68Ga-PSMA Theranostics in Recurrent Glioblastoma Multiforme
Authors: Arunav Kumar, Sanjana Ballal, Madhav Prasad Yadav, S.T. ArunRaj, K.P. Haresh, Subhash Gupta, Nishikant Avinash Damle, Ajay Garg, Madhavi Tripathi, Chandrasekhar Bal
Journal: Clinical Nuclear Medicine (2020)

A 37-year-old man, treated case of left temporal glioblastoma presented with headache, seizures, and progressive right-sided weakness with MRI evidence of recurrence. Exploratory Ga-PSMA PET/CT demonstrated PSMA expression in the recurrent lesion; it was decided to treat this patient with Lu-PSMA-617. After 3 cycles of Lu-PSMA-617, Ga-PSMA PET/CT showed significant reduction in PSMA uptake and regression in size of lesion on MRI with improvement in patient's symptoms and performance status. Lu-/Ga-PSMA theranostics has potential in patients with recurrent glioblastoma multiforme when other therapeutic options are not feasible.
Neurocysticercosis-related seizures in the post-partum period: two cases and a review of the literature
Authors: Tamara Ursini, Roberta Di Giacomo, Sara Caldrer, Andrea Angheben, Lorenzo Zammarchi, Stefania Filipponi, Nicola Renato Pizio, Zeno Bisoffi, Dora Buonfrate
Journal: The Lancet Infectious Diseases (2020)
Omics-Driven Systems Interrogation of Metabolic Dysregulation in COVID-19 Pathogenesis
Authors: Jin-Wen Song, Sin Man Lam, Xing Fan, Wen-Jing Cao, Si-Yu Wang, He Tian, Gek Huey Chua, Chao Zhang, Fan-Ping Meng, Zhe Xu, Jun-Liang Fu, Lei Huang, Peng Xia, Tao Yang, Shaohua Zhang, Bowen Li, Tian-Jun Jiang, Raoxu Wang, Zehua Wang, Ming Shi, Ji-Yuan Zhang, Fu-Sheng Wang, Guanghou Shui
Journal: Cell Metabolism (2020)
内因子-ビタミンB 12 受容体,キュビリンをコードするCUBNの変異は遺伝性巨赤芽球性貧血を生じる
Authors: Aminoff M, Carter J E, Graesbeck R, Abdelaal M A, Broch H, Jenner L B, Verroust P J, Moestrup S K, Krahe R
Journal: Nature Genetics (1999)