lunes, 30 de septiembre de 2013

Breast Cancer Awareness

Breast Cancer Awareness

Centers for Disease Control and Prevention

Breast Cancer Awareness

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Photo of a technician preparing a woman to get a mammogram
The best way to find breast cancer early is with a mammogram. If you are a woman age 50 years or older, be sure to have a screening mammogram every two years.

What are the symptoms of breast cancer?

When breast cancer starts out, it is too small to feel and does not cause signs and symptoms. As it grows, breast cancer can cause changes in how the breast looks or feels. Symptoms may include—
  • New lump in the breast or underarm (armpit).
  • Thickening or swelling of part of the breast.
  • Irritation or dimpling of breast skin.
  • Redness or flaky skin in the nipple area or the breast.
  • Pulling in of the nipple or pain in the nipple area.
  • Nipple discharge other than breast milk, including blood.
  • Any change in the size or the shape of the breast.
  • Pain in any area of the breast.

What is a mammogram?

A mammogram is an X-ray of the breast. Doctors use a mammogram to look for early signs of breast cancer. Having mammograms regularly can lower your risk of dying from breast cancer. If you are 50 to 74 years old, be sure to have a screening mammogram every two years. If you are 40 to 49 years old, talk to your doctor about when and how often you should have a screening mammogram.
Regular mammograms are the best way to find breast cancer early, sometimes up to three years before it can be felt. When their breast cancer is found early, many women go on to live long and healthy lives.

Are you worried about the cost? CDC's National Breast and Cervical Cancer Early Detection Program (NBCCEDP) offers free or low-cost mammograms. Find out if you qualify.

Can men get breast cancer?


Men can also get breast cancer, but it is not very common. For every 100 cases of breast cancer, less than 1 is in men

CDC-Authored Genomics Publications

CDC-Authored Genomics Publications



ScienceclipsCDC
CDC authors are indicated in bold
Collaborative cancer epidemiology in the 21st century: the model of cancer consortia.External Web Site Icon
Burgio MR Jr, Ioannidis JP, Kaminski BM, Derycke E, Rogers S, Khoury MJ, Seminara D.
Cancer Epidemiol Biomarkers Prev. 2013 Sep 19.
Factors affecting maternal participation in the genetic component of the National Birth Defects Prevention Study—United States, 1997–2007External Web Site Icon
Jill Glidewell MSN, MPH, Jennita Reefhuis PhD, Sonja A. Rasmussen MD, MS, Alison Woomert PhD, Charlotte Hobbs MD, PhD, Paul A. Romitti PhD & Krista S. Crider PhD
Application of real time RT-PCR for the genetic homogeneity and stability tests of the seed candidates for live attenuated influenza vaccine production.External Web Site Icon
Shcherbik S, Sergent SB, Davis WG, Shu B, Barnes J, Kiseleva I, Larionova N, Klimov A, Bousse T. J Virol Methods. 2013 Sep 18.
Genetic testing strategies in newly diagnosed endometrial cancer patients aimed at reducing morbidity or mortality from Lynch syndrome in the index case or her relatives.External Web Site Icon
Stewart A Phd. PLoS Curr. 2013 Sep 16;5.

A systematic approach to assessing the clinical s... [Clin Genet. 2013] - PubMed - NCBI

A systematic approach to assessing the clinical s... [Clin Genet. 2013] - PubMed - NCBI

2013 Sep 4. doi: 10.1111/cge.12257. [Epub ahead of print]

A systematic approach to assessing the clinical significance of genetic variants.

Source

Harvard Medical School Genetics Training Program, Boston, MA; Laboratory for Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine, Cambridge, MA.

Abstract

Molecular genetic testing informs diagnosis, prognosis, and risk assessment for patients and their family members. Recent advances in low-cost, high-throughput DNA sequencing and computing technologies have enabled the rapid expansion of genetic test content, resulting in dramatically increased numbers of DNA variants identified per test. To address this challenge, our laboratory has developed a systematic approach to thorough and efficient assessments of variants for pathogenicity determination. We first search for existing data in publications and databases including internal, collaborative and public resources. We then perform full evidence-based assessments through statistical analyses of observations in the general population and disease cohorts, evaluation of experimental data from in vivo or in vitro studies, and computational predictions of potential impacts of each variant. Finally, we weigh all evidence to reach an overall conclusion on the potential for each variant to be disease-causing. In this report, we highlight the principles of variant assessment, address the caveats and pitfalls, and provide examples to illustrate the process. By sharing our experience and providing a framework for variant assessment, including access to a freely available customizable tool, we hope to help move towards standardized and consistent approaches to variant assessment.
This article is protected by copyright. All rights reserved.

KEYWORDS:

(4-9): Clinical Interpretation, Gain of Function (GOF), Genetic Variant, Loss of Function (LOF), Next-Generation Sequencing (NGS), Sequence Analysis, Variant Assessment, Variant of Uncertain Significance (VUS)

PMID:
24033266
[PubMed - as supplied by publisher]

Distinguishing between viral and bacterial infections using genomic test

Distinguishing between viral and bacterial infections using genomic test

Distinguishing between viral and bacterial infections using genomic test

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Respiratory / Asthma; Genetics
Article Date: 20 Sep 2013 - 1:00 PDT

A blood test developed by researchers at Duke Medicine showed more than 90-percent accuracy in distinguishing between viral and bacterial infections when tested in people with respiratory illnesses.

The test, which detects a specific genetic "signature" that the sick person's immune system expresses as a response to the virus, demonstrates a potential new method for diagnosing the source of illnesses that have long been tough to pinpoint.

Reported in the journal Science Translational Medicine, the finding moves the technology closer to clinical use, where it could help patients get quicker diagnoses and treatments, while curbing the unnecessary use of antibiotics that don't work on viral infections.

"In instances such as pandemic flu or the corona-virus that has erupted in the Middle East, it's extremely important to diagnose a viral illness far more accurately and speedier than can be done using traditional diagnostics," said co-senior author Geoffrey S. Ginsburg, M.D., Ph.D., director of Genomic Medicine and professor of medicine at Duke University School of Medicine. "Current tests require knowledge of the pathogen to confirm infection, because they are strain-specific. But our test could be used right away when a new, unknown pathogen emerges."

When infected by a virus, a person's immune system responds differently than when fighting a bacterial infection. These differences are evident at the genetic level, where certain genes are switched on during a viral attack, creating a fingerprint that broadly identifies the culpable pathogen.

In previous work, the Duke team described the development of a blood test, using a special assay, to identify some 30 genes involved in the immune response to viral infection among volunteers who had agreed to be infected with a series of common upper respiratory viruses.

Unlike current tests that rely on evidence of the pathogen in the blood stream - requiring knowledge of that particular bug to detect it - the new approach could be used to detect unknown emerging diseases, including potential bioterrorism threats.

"This is important not only in viral pandemics where infection may be caused by unknown viruses but also in routine care where the decision to treat or not with antibiotics is paramount," said lead author Aimee K. Zaas, M.D., MHS, associate professor of infectious diseases and international health at Duke.

The current study was a trial run of the blood test in a "real-world" setting. Among 102 people arriving at a hospital's emergency department with fever, 28 had a viral infection, 39 had a bacterial infection and 35 were healthy controls. Using the test, the Duke researchers were able to accurately classify more than 90 percent of the patients as having viral infection or not.

The assay provided true positive identifications of viral infection in 89 percent of the cases, and correctly ruled out the negative cases 94 percent of the time.

"This work opens new approaches to diagnosis of infectious diseases," said Geoffrey S.F. Ling, M.D., Ph.D., deputy director of the Defense Sciences Office for the Defense Advanced Research Projects Agency (DARPA).

The researchers said larger studies are planned, and additional work is ongoing to trim the amount of time it takes for the test results to be reported. Ginsburg said the test currently takes 12 hours, and analyzes about 30 genes. He said both the time and the number of genes could be pared.

"We were very pleased that the assay could pick out those with viral infection with a high degree of accuracy," Zaas said. "This is perhaps the most important aspect of this effort - the accuracy of the new test in a real-world setting. It is a major step forward in the test becoming a useful diagnostic to help physicians and patients."

Co-senior author Christopher W. Woods, M.D., MPH, associate professor of medicine, pathology and global health at Duke and the Durham VA Medical Center, said the new test, if proven successful in additional studies, could help resolve some of the most pressing issues around infectious diseases.

"One of the big global threats at the moment is the emergence of bacterial resistance, and that is largely driven by overuse of antibiotics," Woods said. "This is a growing public health threat, creating infections that are increasingly difficult to manage. A tool that enables us to accurately identify viral infections could curb the indiscriminate use of antibiotics and reduce the development of resistant pathogens."

A host-based rt-PCR gene expression signature... [Sci Transl Med. 2013] - PubMed - NCBI

A host-based rt-PCR gene expression signature... [Sci Transl Med. 2013] - PubMed - NCBI

2013 Sep 18;5(203):203ra126. doi: 10.1126/scitranslmed.3006280.

A host-based rt-PCR gene expression signature to identify acute respiratory viral infection.

Source

Institute for Genome Sciences and Policy, Duke University School of Medicine, Durham, NC 27710, USA.

Abstract

Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to pathogen-based diagnostic testing and may improve diagnostic accuracy. We have developed a host-based assay with a reverse transcription polymerase chain reaction (RT-PCR) TaqMan low-density array (TLDA) platform for classifying respiratory viral infection. We developed the assay using two cohorts experimentally infected with influenza A H3N2/Wisconsin or influenza A H1N1/Brisbane, and validated the assay in a sample of adults presenting to the emergency department with fever (n = 102) and in healthy volunteers (n = 41). Peripheral blood RNA samples were obtained from individuals who underwent experimental viral challenge or who presented to the emergency department and had microbiologically proven viral respiratory infection or systemic bacterial infection. The selected gene set on the RT-PCR TLDA assay classified participants with experimentally induced influenza H3N2 and H1N1 infection with 100 and 87% accuracy, respectively. We validated this host gene expression signature in a cohort of 102 individuals arriving at the emergency department. The sensitivity of the RT-PCR test was 89% [95% confidence interval (CI), 72 to 98%], and the specificity was 94% (95% CI, 86 to 99%). These results show that RT-PCR-based detection of a host gene expression signature can classify individuals with respiratory viral infection and sets the stage for prospective evaluation of this diagnostic approach in a clinical setting.

PMID:
24048524
[PubMed - in process]

The emergence of commercial genomics: analysis of... [Genome Med. 2013] - PubMed - NCBI

The emergence of commercial genomics: analysis of... [Genome Med. 2013] - PubMed - NCBI

2013 Sep 20;5(9):83. [Epub ahead of print]

The emergence of commercial genomics: analysis of the rise of a biotechnology subsector during the Human Genome Project, 1990-2004.

Abstract

BACKGROUND:

Development of the commercial genomics sector within the biotechnology industry relied heavily on the scientific commons, public funding, and technology transfer between academic and industrial research. This study tracks financial and intellectual property data on genomics firms from 1990 through 2004, thus following these firms as they emerged in the era of the Human Genome Project and through the 2000--2001 market bubble.

METHODS:

A database was created based on an early survey of genomics firms, which was expanded using three web-based biotechnology services, scientific journals, and biotechnology trade and technical publications. Financial data for publicly traded firms was collected through the use of four databases specializing in firm financials. Patent searches were conducted using firm names in the U.S. Patent and Trademark Office website search engine and the DNA Patent Database.

RESULTS:

A biotechnology subsector of genomics firms emerged in parallel to the publicly funded Human Genome Project. Trends among top firms show that hiring, capital improvement, and research and development expenditures continued to grow after a 2000--2001 bubble. The majority of firms are small businesses with great diversity in type of research and development, products, and services provided. Over half the public firms holding patents have the majority of their intellectual property portfolio in DNA-based patents.

CONCLUSIONS:

These data allow estimates of investment, research and development expenditures, and jobs that paralleled the rise of genomics as a sector within biotechnology between 1990 and 2004.

PMID:
24050173
[PubMed - as supplied by publisher]

Diverse Sources of C. difficile Infection Identified on Whole-Genome Sequencing — NEJM

Diverse Sources of C. difficile Infection Identified on Whole-Genome Sequencing — NEJM

Diverse Sources of C. difficile Infection Identified on Whole-Genome Sequencing

David W. Eyre, B.M., B.Ch., Madeleine L. Cule, Ph.D., Daniel J. Wilson, D.Phil., David Griffiths, B.Sc., Alison Vaughan, B.Sc., Lily O'Connor, B.Sc., Camilla L.C. Ip, Ph.D., Tanya Golubchik, Ph.D., Elizabeth M. Batty, Ph.D., John M. Finney, B.Sc., David H. Wyllie, Ph.D., Xavier Didelot, D.Phil., Paolo Piazza, Ph.D., Rory Bowden, Ph.D., Kate E. Dingle, Ph.D., Rosalind M. Harding, Ph.D., Derrick W. Crook, M.B., B.Ch., Mark H. Wilcox, M.D., Tim E.A. Peto, D.Phil., and A. Sarah Walker, Ph.D.
N Engl J Med 2013; 369:1195-1205September 26, 2013DOI: 10.1056/NEJMoa1216064
Comments open through October 2, 2013

Abstract
Article
References
Citing Articles (1)
Comments

Background

It has been thought that Clostridium difficile infection is transmitted predominantly within health care settings. However, endemic spread has hampered identification of precise sources of infection and the assessment of the efficacy of interventions.

Methods

From September 2007 through March 2011, we performed whole-genome sequencing on isolates obtained from all symptomatic patients with C. difficile infection identified in health care settings or in the community in Oxfordshire, United Kingdom. We compared single-nucleotide variants (SNVs) between the isolates, using C. difficile evolution rates estimated on the basis of the first and last samples obtained from each of 145 patients, with 0 to 2 SNVs expected between transmitted isolates obtained less than 124 days apart, on the basis of a 95% prediction interval. We then identified plausible epidemiologic links among genetically related cases from data on hospital admissions and community location.

Results

Of 1250 C. difficile cases that were evaluated, 1223 (98%) were successfully sequenced. In a comparison of 957 samples obtained from April 2008 through March 2011 with those obtained from September 2007 onward, a total of 333 isolates (35%) had no more than 2 SNVs from at least 1 earlier case, and 428 isolates (45%) had more than 10 SNVs from all previous cases. Reductions in incidence over time were similar in the two groups, a finding that suggests an effect of interventions targeting the transition from exposure to disease. Of the 333 patients with no more than 2 SNVs (consistent with transmission), 126 patients (38%) had close hospital contact with another patient, and 120 patients (36%) had no hospital or community contact with another patient. Distinct subtypes of infection continued to be identified throughout the study, which suggests a considerable reservoir of C. difficile.

Conclusions

Over a 3-year period, 45% of C. difficile cases in Oxfordshire were genetically distinct from all previous cases. Genetically diverse sources, in addition to symptomatic patients, play a major part in C. difficile transmission. (Funded by the U.K. Clinical Research Collaboration Translational Infection Research Initiative and others.)

Impact of CYP3A4*22 Allele on Tacrolimus Pha... [Ther Drug Monit. 2013] - PubMed - NCBI

Impact of CYP3A4*22 Allele on Tacrolimus Pha... [Ther Drug Monit. 2013] - PubMed - NCBI

2013 Oct;35(5):608-16. doi: 10.1097/FTD.0b013e318296045b.

Impact of CYP3A4*22 Allele on Tacrolimus Pharmacokinetics in Early Period After Renal Transplantation: Toward Updated Genotype-Based Dosage Guidelines.

Source

*Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium; †Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands; and ‡Laboratory of Analytical Biochemistry, §Surgery and Abdominal Transplantation Division, and ¶Laboratory of Immuno-haematology, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium.

Abstract

BACKGROUND:

Tacrolimus (Tac) metabolism is mainly mediated by the cytochrome P450 3A (CYP3A) subfamily. Recently, it has been reported that kidney transplant recipients carrying the CYP3A4*22 decrease-of-function allele require lower Tac doses and are more at risk of Tac overexposure than CYP3A4*1/*1 patients. This effect was shown to be independent of the CYP3A5*3 allelic status. However, the pharmacokinetic (PK) parameters assessed in previous studies were limited on single time point whole blood trough concentrations (C0) during routine follow-up of the patient after transplantation.

METHODS:

Our study investigates the impact of the CYP3A4*22 allele on Tac PK [C0, area under the time vs concentration curve (AUC0-12h), apparent clearance (Cl/F), Cmax, and dose requirement], time to achieve target C0, and creatinine clearance (CrCl) in 96 kidney transplant recipients considering the 2 first weeks after the graft. All patients were genotyped for both the CYP3A4*22 and the CYP3A5*3 polymorphisms.

RESULTS:

CYP3A4*22 carriers had higher Tac C0 during the first week with significant longer exposures to C0 > 15 ng/mL. These patients showed reduced Tac Cl/F but higher dose-adjusted AUC0-12h and Cmax and were at increased risk of C0 > 20 ng/mL. These effects were independent from CYP3A5*3 genotype: clustering patients according to both CYP3A4*22 and CYP3A5*3 allelic status did increase the predictive value of the genotype to explain interindividual differences in Tac PK. During the second week after transplantation, CrCl was on average 9.5 mL/min higher for CYP3A4*22 carriers compared with CYP3A4*1/*1 patients (P = 0.007), suggesting that Tac overexposure in CYP3A4*22 carriers might provide a renal function benefit.

CONCLUSIONS:

Our study confirms the decreased CYP3A4 activity toward Tac for CYP3A4*22 carriers early after transplantation and provides evidence for refining genotype-based dosage by adding the CYP3A4*22 genotype information to the CYP3A5*3 allelic status.

PMID:
24052064
[PubMed - in process]

Gene expression profiling and expanded immunohistochemistry tests for guiding adjuvant chemotherapy decisions in early breast cancer management: MammaPrint, Oncotype DX, IHC4 and Mammostrat

full-text:
Gene expression profiling and expanded immunohistochemistry tests for guiding adjuvant chemotherapy decisions in early breast cancer management: MammaPrint, Oncotype DX, IHC4 and Mammostrat

Guidelines and Recommendations

chess pieces with arrows pointing up
Ensuring the integrity of clinical practice guidelines: a tool for protecting patientsExternal Web Site Icon
Lenzer J, et al. BMJ. 2013 Sep 17;347:f5535.
Gene expression profiling and expanded immunohistochemistry tests for guiding adjuvant chemotherapy decisions in early breast cancer management: MammaPrint, Oncotype DX, IHC4 and Mammostrat (DG10),External Web Site Icon NICE, Sep 20
Medications for risk reduction of primary breast cancer in women: U.S. Preventive Services Task Force recommendation statementExternal Web Site Icon, USPSTF, Sep 24
Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes?External Web Site Icon
Genetics in Medicine 2013 Sep 26
Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus ConferenceExternal Web Site Icon
Northrup H, et al. Pediatric Neurology vol 49 iss 4 pg 243-254 2012 Oct
Testing of CYP2C19 variants and platelet reactivity for guiding antiplatelet treatment,External Web Site Icon AHRQ, Sep 25