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Could Teleradiology contribute to “cross-borders” standardization of imaging protocols in cancer management?

June 16, 2013 by Dror Nir

Could Teleradiology contribute to “cross-borders” standardization of imaging protocols in cancer management?

Writer: Dror Nir, PhD

Teleradiology is accepted as a legitimate medical service for several years now.  It has many clinical utilities worldwide, ranging from services for expert or second opinions to comprehensive remote management of radiology departments in hospitals. Rapid advances in web-technologies infrastructure eliminated the barriers related to the transfer, reading and reporting of radiology images from remote locations. Today’s main controversies are related to issues that are relevant also to “in-house” radiology departments; e.g. clinical governance, quality assessment, work-flow and medico-legal issues.

The concept of Teleradiology is as simple as plotted in this chart.

Images are automatically uploaded from the imaging system itself or from the institution’s PACS. Reports are sent to the “client” within few hours.

The value for the users goes well beyond mere image interpretation, for example:

• On-site physicians have more time to spend with patients.
• Offering of additional subspecialty/multidisciplinary expertise.
• Comprehensive image-interpretation and reporting service at reduced time-span and reduced cost
• Sharing images and reports with referring physicians and patients with no effort.

As an example for “cross-border” standardization of a major existing radiology service, let’s consider the use-case of centralized review of mammography images. I know, quite ambitious! And; politically very challenging!

But; seem to be technologically and clinically feasible, at least according to the below quoted publication:

Teleradiology with uncompressed digital mammograms: Clinical assessment

Julia Fruehwald-Pallamar, Marion Jantsch, Katja Pinker, Ricarda Hofmeister, Friedrich Semturs, Kathrin Piegler, Daniel Staribacher, Michael Weber, Thomas H. Helbich

published online 13 April 2012.

Abstract 

Purpose

The purpose of our study was to demonstrate the feasibility of sending uncompressed digital mammograms in a teleradiologic setting without loss of information by comparing image quality, lesion detection, and BI-RADS assessment.

Materials and methods

CDMAM phantoms were sent bidirectionally to two hospitals via the network. For the clinical aspect of the study, 200 patients were selected based on the BI-RAD system: 50% BI-RADS I and II; and 50% BI-RADS IV and V. Two hundred digital mammograms (800 views) were sent to two different institutions via a teleradiology network. Three readers evaluated those 200 mammography studies at institution 1 where the images originated, and in the two other institutions (institutions 2 and 3) where the images were sent. The readers assessed image quality, lesion detection, and BI-RADS classification.

Results

Automatic readout showed that CDMAM image quality was identical before and after transmission. The image quality of the 200 studies (total 600 mammograms) was rated as very good or good in 90–97% before and after transmission. Depending on the institution and the reader, only 2.5–9.5% of all studies were rated as poor. The congruence of the readers with respect to the final BI-RADS assessment ranged from 90% and 91% at institution 1 vs. institution 2, and from 86% to 92% at institution 1 vs. institution 3. The agreement was even higher for conformity of content (BI-RADS I or II and BI-RADS IV or V). Reader agreement in the three different institutions with regard to the detection of masses and calcifications, as well as BI-RADS classification, was very good (κ: 0.775–0.884). Results for interreader agreement were similar.

Conclusion

Uncompressed digital mammograms can be transmitted to different institutions with different workstations, without loss of information. The transmission process does not significantly influence image quality, lesion detection, or BI-RADS rating.

Keywords: Breast cancer, Imaging, Digital mammography, Teleradiology, Comparative studies

 

What could be the benefits from centralizing mammography interpretation through Teleradiology?

• A baseline protocol that could enable pulling together large number of cases from different populations without having to worry about differences in practice and experience of reporters. This will enable better epidemiology studies of this disease.
• Quantified measure, in real-time, of the relative quality of imaging between institutions could contribute to bringing all screening services to a maximal level.
• Development of comprehensive training program for radiologists involved in mammography based screening of breast cancer.
• Better information sharing between all players involved in the pathway of each individual patient could improve clinical decision making and patient’s support.
• Lower costs of screening programs, disease treatment and follow-up.

Who could organize and carry out such an operation?

There are many reputable large university hospitals already offering Teleradiology services. They are already supported by government’s funds in addition to the fact that the service itself is carrying profits. I’m not listing any of these for obvious reasons, but; google “teleradiology” will bring you many results.

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Posted in Health Economics and Outcomes Research, HealthCare IT, Imaging-based Cancer Patient Management, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound | Tagged Cancer - General, mammography, Medical imaging, Medical Specialties, Teleradiology | 4 Comments »

High-Sensitivity Cardiac Troponin Assays

June 13, 2013 by larryhbern

Preparing the United States for High-Sensitivity Cardiac Troponin Assays

Curator: Larry Bernstein, MD, FCAP

 

UPDATED on 12/12/2017

Evidence Mounts for Myocardial Injury After Noncardiac Surgery

Patrice Wendling

December 11, 2017

Based on an absolute rise of high-sensitivity cardiac troponin T (hs-cTnT) of >14 ng/L from presurgery to postsurgery levels, perioperative myocardial injury (PMI) occurred in one out of seven surgeries (16%) in the prospective BASEL-PMI study.

Despite being at increased CV risk, 82% of patients did not show any ischemic symptoms and only 6% had chest pain. Overall, only 29% of patients fulfilled any of the additional criteria required for spontaneous acute MI such as loss of viable myocardium on imaging or ECG findings suggestive of myocardial ischemia.

Senior author and long-time proponent of hs-cTnT, Dr Christian Mueller (University Hospital of Basel), said in an email, “The current evidence may justify different conclusions on which patients undergoing noncardiac operations should receive hs-cTnT screening. Likely Dr Puelacher’s is the more precise one.

“On the other hand, the criteria to receive screening in our study are such that not all physicians (and patients) would consider these patients ‘high-risk patients’ (eg, all patients above the age of 65 years [until 85 years]).”

Patients with PMI had more CV comorbidities at baseline and a higher rate of nonelective surgery than those without.

Patients with PMI had six times the 30-day mortality of those without PMI (9.8% vs 1.6%), with the excess mortality persisting up to 1 year (22.5% vs 9.3%; both P<0.001).

Of special note, 30-day and 1-year mortality was comparable in PMI patients not fulfilling any additional criteria required for spontaneous AMI vs those fulfilling at least one additional criteria (10.4% vs 8.7%, P=0.684; and 22.1% vs 29.1%, P=0.47).

Although the use of hs-cTnT testing was approved in the US in 2017, he’s aware of only three hospitals that do routine troponin testing in noncardiac surgery patients—two in Switzerland and one in Brazil.

“We have a very close cooperation with anesthesiology and also with the surgical department, and that’s a prerequisite for actually doing this; maybe we need to look outside of our own realm to actually find this cooperation,” he added.

For those wanting to screen, the researchers caution that preoperative troponin measurements are needed to reliably distinguish PMI from chronic hs-cTnT elevations. In BASEL-PMI, 51% of patients already had preoperative hs-cTnT levels at or above 14 ng/L, while 13.8% patients in VISION had their peak value before surgery.

SOURCE

https://www.medscape.com/viewarticle/889852?nlid=119520_3866&src=WNL_mdplsfeat_171212_mscpedit_card&uac=93761AJ&spon=2&impID=1506822&faf=1

Frederick K. Korley, MD, Allan S. Jaffe, MD
Journal of the American College of Cardiology
J Am Coll Cardiol. 2013;61(17):1753-1758.

It is only a matter of time before the use of high-sensitivity cardiac troponin assays (hs-cTn) becomes common throughout the United States. In preparation for this inevitability, this article raises a number of important issues regarding these assays that deserve consideration. These include:

the need for the adoption of a universal nomenclature;

the importance of defining uniform criteria for reference populations;

the challenge of discriminating between acute and nonacute causes of hs-cTn elevations, and between type 1 and type 2 acute myocardial infarction (AMI);

factors influencing the analytical precision of hs-cTn;

ascertaining the optimal duration of the rule-out period for AMI;

the need for further evaluation to determine the causes of a positive hs-cTn in non-AMI patients; and

the use of hs-cTn to risk-stratify patients with disease conditions other than AMI.

This review elaborates on these critical issues as a means of educating clinicians and researchers about them.

Highlights:

Need for a Universally Accepted Nomenclature

Defining Uniform Criteria for Reference Populations

Discriminating Between Acute and Nonacute Causes of hs-cTn Elevations

Distinguishing Between Type 1 and Type 2 AMI

Analytical Imprecision in Cardiac Troponin Assays

Ruling Out AMI

Investigating the Causes of Positive Troponin Values in Non-AMI Patients

Risk Stratifying Patients With Nonacute Coronary Syndrome Conditions

Conclusions

Related articles

• Dealing with the Use of the hs cTn Assays (pharmaceuticalintelligence.com)
• MediPoint: Diagnostic Cardiac Biomarkers for Acute Coronary Syndromes – Current and Future Players (sacbee.com)
• MediPoint: Diagnostic Cardiac Biomarkers for Acute Coronary Syndromes – Current and Future Players (sys-con.com)
• Decision Aids for Low-Risk Chest Pain. (zedie.wordpress.com)
• TTR-Related Cardiac Amyloidosis Inherited Condition (23andme.com)

typical changes in CK-MB and cardiac troponin in Acute Myocardial Infarction (Photo credit: Wikipedia)

Troponin activation. Troponin C (red) binds Ca2+, which stabilizes the activated state, where troponin I (yellow) is no longer bound to actin. Troponin T (blue) anchors the complex on tropomyosin. (Photo credit: Wikipedia)

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Posted in Biomarkers & Medical Diagnostics | Tagged biomarker assays, chronic heart disease, CRF, hs-cTn, non-acute elevation, plaque rupture, troponins, types of AMI | 5 Comments »

Combining Nanotube Technology and Genetically Engineered Antibodies to Detect Prostate Cancer Biomarkers

June 13, 2013 by sjwilliamspa

Combining Nanotube Technology and Genetically Engineered Antibodies to Detect Prostate Cancer Biomarkers

Writer, Curator: Stephen J. Williams, Ph.D.

WordCloud Image Produced by Adam Tubman

Figure of  Carbon Nanotube Transistor design with functionalized antibodies for biomarker detection.  From paper of A.T. Johnson; used with permission from A.T. Johnson)

In a literature review of the current status of the breast cancer biomarker field[2], author Dr. Michael Duffy, from University College Dublin, pondered the clinical utility of breast cancer serum markers and suggested that due to lack of sensitivity and specificity none of available markers is of value for detection of early breast cancer however these biomarkers have been shown useful in monitoring patients with advanced disease. For instance high preoperative CA15-3 is indicative of adverse patient outcome.  According to American Society of Clinical Oncology Expert Panel, however CA 15-3 may lack the sensitivity and disease specificity for breast cancer as a prognostic marker.  For panel suggestions please click on the link below:

http://www.asco.org/sites/www.asco.org/files/breast_tm_2007_changes-final.pdf

The same panel also concurred on the lack of prognostic value of other markers (for example CEA for colon cancer) but did agree that 66-73% of patients with advanced disease, who responded to therapy, showed reduction in these serum markers.  Indeed, CA125, long associated as a biomarker for ovarian cancer, does not have the sensitivity and especially the disease specificity to be a stand-alone prognostic marker[3].  Therefore, although “omics” strategies have suggested multiple possible biomarkers  for various cancers, a major issue in translating a putative biomarker to either:

1)      a clinically validated (panel) of disease-relevant biomarkers or

2)      biomarkers useful for therapeutic monitoring

is obtaining the specificity and sensitivity for detection in bio-specimens.   As discussed below, this is being achieved with the merger of nanotechnology-based sensors and bioengineering of biomolecule.

For ASCO panel suggestions of biomarkers useful in Prostate cancer please see the link below:

http://jco.ascopubs.org/site/misc/specialarticles.xhtml#GENITOURINARY_CANCER

As a side note, since 2010, ASCO has focused on reviewing and producing new guidelines for cancer biomarkers including genome sequencing:

http://www.medscape.com/viewarticle/723349

Osteopontin (OPN) and prostate cancer

Osteopontin is a phosphorylated glycoprotein secreted by activated macrophages, leukocytes, activated T lymphocytes and is present at sites of inflammation (for a review of OPN see [4]).  Osteopontin interacts with several integrins and CD44 (a putative cancer stem cell marker).  Binding of OPN to cell integrins mediates cell-matrix and cell-cell communication, stimulating adhesion, migration (through interaction with urokinase plasminogen activator {uPA}) and cell signaling pathways such as the HGF-Met pathway.  Overexpression is found on a variety of cancers including breast, lung, colorectal, ovarian and melanoma[5].  And although OPN is detected in normal tissue, it is known that OPN over-expression can alter the malignant potential of tumor cells.

Roles of osteopontin in cancer include:

• Binding to CD44
• Increase in growth factor signaling (HGF/Met pathway)
• Increase uPA activity- increase invasiveness
• Angiogenesis thru binding with α_vβ₃ integrin and increased VEGF expression
• Protection against apoptosis: OPN activates nuclear factor Κβ

Some researchers have suggested it could be a prognostic marker for breast and lung cancer while there have been conflicting reports as to whether OPN expression is correlated to malignant potential in prostate cancer[6].  Osteopontin is found on tumor infiltrating macrophages, which may contribute to OPN as a prognostic marker. Breast cancer patients (disseminated carcinomas) have 4-10 times higher serum levels of OPN than found in healthy patients, although there is no difference in pre- or post-menopausal women[7].

Piezoelectric sensors have been used by the same group at Fox Chase Cancer Center to detect serum levels of the HER2 protein in breast cancer patients, for the purpose of therapeutic monitoring after anti-HER2 antibody trastuzumab (Herceptin™) therapy.  Lina Loo, in the laboratory of Dr. Gregory Adams showed the utility of using (scFv) to trastuzumab (anti-HER2) with pizo-electric nanotubes to accurately and reproducibly determine levels of serum HER2[8].  This method improved the sensitivity of serum HER2 detection over other methods such as:

• ELISA {enzyme-linked immunoassay}
• Luminex platforms

Please watch the following video interview concerning genetically engineered scFV antibody fragments and their use in cancer detection and treatment (with Dr. Matt Robinson and Dr. Greg Adams, from Fox Chase Cancer Center)

PLEASE WATCH VIDEO

However the advent of nanotechnology-based detection system combined with engineered affinity-based biomolecules has increased both the sensitivity and specificity of biomarker detection from complex fluids such as plasma and urine.  The advent of multiple types of biosensors, including

has given the ability to measure, with enhanced sensitivity and specificity,  putative biomarkers of disease in minute volumes of precious bio-samples.

The basic design of a biosensor is made of three components:

1. A recognition element (I.e. antibodies, nucleic acids, enzymes)
2. A signal transducer (electrochemical, optical, piezoelectric)
3. Signal processor (relays and displays)

In the journal ACS Nano Mitchel Lerner from Dr. Charlie Johnson’s laboratory at University of Pennsylvania in collaboration with Fox Chase Cancer researchers in the laboratory of Dr. Matthew Robinson, describe a piezoelectric detection system for quantifying levels of osteopontin (OPN), a putative biomarker for prostate cancer[1].  In this paper Dr. Robinson’s group at Fox Chase, genetically engineered a single chain variable fragment (scFv) protein {the binding portion of the antibody} which had high affinity for OPN.  This scFv was attached to a carbon nanotube field-effect transistor (NT-FET), designed by Dr. Johnson’s group, using a chemical process called chemical functionalization {a process using diazonium salts to covalently attach scFV to NT-FET.

Figure. Functionalization scheme for OPN attachment to carbon nanotubes. As figure 1 legend in paper states: “First, sp8 hybridized-sites are created o the nanotube sidewall by incubation in a diazonium salt solution.  The carboxylic acid group is then activated by EDC and stabilized with NHS.ScFv antibody displaces the NHS and forms an amide bond.  OPN epitope is shown in yellow and the C and N-terminuses are in orange and green respectively.” (used by permision for A.T. Charlie Johnson)

This system was then used to determine the selectivity and sensitivity of OPN from complex solutions.

Methods: 

Nanotube (NT) design

• Grown by catalytic vapor deposition
• Electrical contacts patterned using photo-lithography
• Atomic Force microscopy was used to verify structure of nanotube

Chemical Linking of scFv to nanotube

• Diazonium treatment resulted in activation and subsequent stabilization of amino (NHS) side chain
• Amine group on lysine of scFV displaced NHS group => covalent attachment of scFV to NT
• Atomic Force Spectroscopy used to verify linkage of scFv to nanotube

Results showed there was

• minimal non-specific binding of OPN to the scFv
• system allowed for detection limit of 1 pg/ml OPN (pictogram/milliliter) or 30 fM (fentomolar) in a phosphate buffered saline solution.
•  Only a minute volume (10 µl) of sample is needed
• Sensor able to measure million-fold  range of OPN concentrations ( from 10^-3 to 10³ ng/mL OPN)

Two experiments were conducted to determine the specificity of OPN to the antibody-detection system.

1^st experiment

–          scFv functionalized  sensor was incubated in a solution of high concentration of BSA (450 mg/ml) to approximate nonspecific proteins in patient samples

–           minimal signal was detected

        2^nd experiment

–          Functionalized NT-FET devices with a scFv based on the HER2 therapeutic antibody trastuzumab

–          There was no binding of OPN to anti-HER2 devices

–          Therefore anti OPN (23C3) scFv-functionalized carbon nanotube sensors exhibit high levels of specificity to OPN

The authors conclude “the functionalization procedure described here is expected to be generalizable to any antibody containing an accessible amine group, and to result in biosensors appropriate for detection of corresponding complementary proteins at fM concentrations”.

I had the opportunity to speak with co-author Dr. Matthew Robinson, Assistant Professor in the Developmental Therapeutics Program at Fox Chase Cancer Center about the next steps for this work.  Dr. Robinson mentioned that “at this point we have not looked in patient samples yet but our plan is to move in that direction. We need to establish sensitivity/specificity in increasingly complex samples (e.g. spiked normal serum and retrospectively in patient serum with known levels of biomarkers).” 

Cancer patients often present a complex metabolic profile.  The paper notes that OPN has a pI (isoelectric point) of 4.2, which would result in a negative charge at physiologically normal pH of 7.6. I asked Dr. Robinson about if changes in metabolic profile could hinder OPN binding to the NT-FET system would require some preprocessing of blood samples.  Dr. Robinson  agreed “that confounding variables such as additional diseases but even things like diet (i.e. is fasting necessary) need to be addressed before this platform is ready for use in clinical setting.
It is likely that sample prep will be needed to remove albumin, lower salt concentrations, etc. This could end up being problematic for biomarkers that are unstable and would degrade over the time necessary for sample prep. It is also possible that sample prep to remove albumin and other background factors could result in loss of biomarkers. This will need to be determined on a case-by-case basis with validated testing methods.”
One useful advantage of this system is the possibility of measuring multiple biomarkers, clinically important as studies has suggested that

multiple markers result in the higher sensitivity/specificity for many infrequent cancers, such as ovarian. Dr. Robinson agrees “that panels of biomarkers are likely to be better at early detection and diagnosis. In principle the platform that we describe can be set up to allow for detection of  multiple biomarkers at a time. From the biology end of things we have built antibodies against 3 different prostate cancer biomarkers for that purpose.”

Dr. Johnson  commented on the ability of the platform allowed for the simultaneous detection of multiple biomarkers, noting that ”the platform is compatible with the measurement of multiple biomarkers through the use of multiple devices, each functionalized with their own antibody.”

ASCO guidelines Expert Panel on Tumor Biomarkers 2007 Update for Breast Cancer:

http://www.asco.org/sites/www.asco.org/files/breast_tm_2007_changes-final.pdf 

ASCO Guidelines for Genitourinary Cancer:

Screening for Prostate Cancer With Prostate-Specific Antigen Testing: American Society of Clinical Oncology Provisional Clinical Opinion

Published in JCO, Vol. 30, Issue 24 (August 20), 2012: 3020-3025

American Society of Clinical Oncology Clinical Practice Guideline on Uses of Serum Tumor Markers in Adult Males With Germ Cell Tumors

Published in JCO, Vol 28, Issue 20 (July 10), 2010: 3388-3404

American Society of Clinical Oncology Endorsement of the Cancer Care Ontario Practice Guideline on Nonhormonal Therapy for Men With Metastatic Hormone-Refractory (castration-resistant) Prostate Cancer

Published in JCO, Vol 25, Issue 33 (November 20), 2007: 5313-5318

Initial Hormonal Management of Androgen-Sensitive Metastatic, Recurrent, or Progressive Prostate Cancer: 2006 Update of an American Society of Clinical Oncology Practice Guideline

Published in JCO, Vol. 25, Issue 12 (April 20), 2007: 1596-1605

References:

1.            Lerner MB, D’Souza J, Pazina T, Dailey J, Goldsmith BR, Robinson MK, Johnson AT: Hybrids of a genetically engineered antibody and a carbon nanotube transistor for detection of prostate cancer biomarkers. ACS nano 2012, 6(6):5143-5149.

2.            Duffy MJ: Serum tumor markers in breast cancer: are they of clinical value? Clinical chemistry 2006, 52(3):345-351.

3.            Meyer T, Rustin GJ: Role of tumour markers in monitoring epithelial ovarian cancer. British journal of cancer 2000, 82(9):1535-1538.

4.            Rodrigues LR, Teixeira JA, Schmitt FL, Paulsson M, Lindmark-Mansson H: The role of osteopontin in tumor progression and metastasis in breast cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2007, 16(6):1087-1097.

5.            Brown LF, Berse B, Van de Water L, Papadopoulos-Sergiou A, Perruzzi CA, Manseau EJ, Dvorak HF, Senger DR: Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces. Molecular biology of the cell 1992, 3(10):1169-1180.

6.            Thoms JW, Dal Pra A, Anborgh PH, Christensen E, Fleshner N, Menard C, Chadwick K, Milosevic M, Catton C, Pintilie M et al: Plasma osteopontin as a biomarker of prostate cancer aggression: relationship to risk category and treatment response. British journal of cancer 2012, 107(5):840-846.

7.            Brown LF, Papadopoulos-Sergiou A, Berse B, Manseau EJ, Tognazzi K, Perruzzi CA, Dvorak HF, Senger DR: Osteopontin expression and distribution in human carcinomas. The American journal of pathology 1994, 145(3):610-623.

8.            Loo L, Capobianco JA, Wu W, Gao X, Shih WY, Shih WH, Pourrezaei K, Robinson MK, Adams GP: Highly sensitive detection of HER2 extracellular domain in the serum of breast cancer patients by piezoelectric microcantilevers. Analytical chemistry 2011, 83(9):3392-3397.

Other posts from this site on Biomarkers, Cancer, and Nanotechnology include:

Stanniocalcin: A Cancer Biomarker.

Mesothelin: An early detection biomarker for cancer (By Jack Andraka)

Squeezing Ovarian Cancer Cells to Predict Metastatic Potential: Cell Stiffness as Possible Biomarker

PIK3CA mutation in Colorectal Cancer may serve as a Predictive Molecular Biomarker for adjuvant Aspirin therapy

Biomarker tool development for Early Diagnosis of Pancreatic Cancer: Van Andel Institute and Emory University

Early Biomarker for Pancreatic Cancer Identified

In Search of Clarity on Prostate Cancer Screening, Post-Surgical Followup, and Prediction of Long Term Remission

Prostate Cancer Molecular Diagnostic Market – the Players are: SRI Int’l, Genomic Health w/Cleveland Clinic, Myriad Genetics w/UCSF, GenomeDx and BioTheranostics

Early Detection of Prostate Cancer: American Urological Association (AUA) Guideline

A Blood Test to Identify Aggressive Prostate Cancer: a Discovery @ SRI International, Menlo Park, CA

Prostate Cancer Cells: Histone Deacetylase Inhibitors Induce Epithelial-to-Mesenchymal Transition

Prostate Cancer and Nanotecnology

 

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Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, BioSimilars, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Prevention: Research & Programs, Disease Biology, Small Molecules in Development of Therapeutic Drugs, FDA Regulatory Affairs, Health Economics and Outcomes Research, Human Immune System in Health and in Disease, Interviews with Scientific Leaders, ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics, Medical Devices R&D Investment | Tagged Antibody, bioengineering, Biosensors, breast cancer, Cancer - General, health, HER2, nanotechnology, osteopontin, Prostate cancer, Trastuzumab | 4 Comments »

Preeclampsia: Pregnency Induced-Hypertension – Potential New Treatment in Development

June 12, 2013 by 2012pharmaceutical

Reporter: Aviva Lev-Ari, PhD, RN

PRE-ECLAMPSIA

Preeclampsia is a disorder that occurs only during pregnancy and the postpartum period and affects both the mother and the unborn baby. Affecting at least 5-8% of all pregnancies, it is a rapidly progressive condition characterized by high blood pressure and the presence of protein in the urine. Swelling, sudden weight gain, headaches and changes in vision are important symptoms; however, some women with rapidly advancing disease report few symptoms.

Typically, preeclampsia occurs after 20 weeks gestation (in the late 2nd or 3rd trimesters or middle to late pregnancy) and up to six weeks postpartum, though in rare cases it can occur earlier than 20 weeks. Proper prenatal care is essential to diagnose and manage preeclampsia. Pregnancy Induced Hypertension (PIH) and toxemia are outdated terms for preeclampsia. HELLP syndrome and eclampsia (seizures) are other variants of preeclampsia.

Globally, preeclampsia and other hypertensive disorders of pregnancy are a leading cause of maternal and infant illness and death. By conservative estimates, these disorders are responsible for 76,000 maternal and 500,000 infant deaths each year.

http://www.preeclampsia.org/health-information/about-preeclampsia?gclid=CNeVjpG537cCFUYaOgodC0QASg

VIEW VIDEO – SIX Sections, Pauses in between

http://on.aol.com/video/preeclampsia-vs–pregnancy-induced-hypertension-484063856

• Preeclampsia vs. Pregnency -Induced Hypertension
• When Preeclampsia Occur
• Preeclampsia – Effects on Fetus Health
• Preeclampsia – Effects on the Baby

Genetic Aspects of Pre-eclampsia

The genetics of pre-eclampsia and other hypertensive disorders of pregnancy

Paula J. Williams and Fiona Broughton Pipkin

Human Genetics Research Group, School of Molecular and Medical Sciences, University of Nottingham, A Floor West Block, Queen’s Medical Centre, Nottingham NG7 2UH, UK

Paula J. Williams: Paula.Williams@nottingham.ac.uk

Corresponding author. Tel.: +44 (0) 115 8230758; Fax: +44 (0) 115 8230759. Email: Paula.Williams@nottingham.ac.uk

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145161/

Epidemiological studies clearly confirm a genetic component to pre-eclampsia. Numerous candidate genes have been studied that fall into groups based on their proposed pathological mechanism, including

• thrombophilia,
• endothelial function,
• vasoactive proteins,
• oxidative stress and
• lipid metabolism and
• immunogenetics.

It is expected that no one gene will be identified as the sole risk factor for pre-eclampsia, as in the general population pre-eclampsia represents a complex genetic disorder. Interactions between numerous SNP either alone or with combination with predisposing environmental factors, are most likely underpin the genetic component of this disorder. We must be cautious in our approach to genetics and acknowledge that we are still in the infancy of this research. Following on from GWAS, further fine mapping studies to delineate SNP that are causal from those that are in linkage disequilibrium, followed by functional laboratory studies will be required. Only when we have a better understanding of how the environment interacts with genes will we be in a better position to target treatment for women, for example knowing that women with a certain genotype will benefit from losing weight, enabling us to yield clinical benefit.

At present no genetic test is available to predict pre-eclampsia. The lack of a predictive test can be overcome by careful monitoring and assessment of women, especially those in high-risk groups, including:

Those at either end of the reproductive age spectrum•Obesity•Black ethnicity•Primiparity•Previous history of pre-eclampsia•Multiple pregnancy•Pre-existing medical conditions: renal disease, insulin-dependent diabetes, autoimmune disease, antiphospholipid syndrom

Genetic aspects of pre-eclampsia

Clustering of cases of pre-eclampsia within families has been recognised since the 19th century, suggesting a genetic component to the disorder.2 Deciphering the genetic involvement in pre-eclampsia is challenging, not least because the phenotype is expressed only in parous women. Furthermore, in complex disorders of pregnancy, it is necessary to consider two genotypes, that of the mother and that of the fetus, which includes genes inherited from both mother and father. Maternal and fetal genes may have independent or interactive effects on the risk of pre-eclampsia. Finally, the heterogeneous nature of the disorder, with a sliding scale of severity, has resulted in differences in the definition of pre-eclampsia used within studies (see above), often with overlap of non-proteinuric gestational hypertension.

Twin studies investigating the relative contribution of genetic versus environmental factors to pre-eclampsia risk, initially yielded disappointing results. They showed that discordance for pre-eclampsia between monozygotic twin sisters was common, suggesting that heritability caused by maternal genes was low.3 These early studies were small. More recent investigations, however, using the large Swedish Twin, Medical Birth and Multigeneration Registries have estimated the heritability of pre-eclampsia to be about 55%, with contributions from both maternal and fetal genes. A further study in monozygotic twins4 found concordance of pre-eclampsia to be as common as discordance. Evidence from the largest published twin study, which correlated the Swedish Twin Register with the Swedish Medical Register, revealed pre-eclampsia penetrance to be less than 50%, suggesting diversity within models of inheritance.5–7

Pre-eclampsia: a complex genetic disorder

For a small number of families, pre-eclampsia seems to follow Mendelian patterns of disease inheritance,8 consistent with a rare deleterious monogenic variant or mutation with high penetrance. For most of the population, however, pre-eclampsia seems to represent a complex genetic disorder, and occurs as the result of numerous common variants at different loci which, individually, have small effects but collectively contribute to an individual’s susceptibility to disease. Environmental exposures, including age and weight, also determine whether these low penetrant variants result in phenotypic manifestation of the disease. It is likely that no single cause or genetic variant will account for all cases of pre-eclampsia, although it is possible that different variants are associated with various subsets of disease (e.g. pre-eclampsia combined with intrauterine growth restriction). Complex genetic disorders affect a high proportion of the population, representing a large burden to public health. New approaches to susceptibility gene discovery have emerged to address this challenge. Unfortunately, early diagnosis would only permit closer focus on routine antenatal care, as at present no intervention other than delivery has been shown to alter the course of pre-eclampsia.

Determining susceptibility to pre-eclampsia

The need to assess both the maternal and the fetal genotype is clear. The role of the placenta in the primary pathogenesis of the disorder indisputably indicates a fetal contribution to susceptibility to the disorder.9 Reports of severe, very early-onset pre-eclampsia in cases of fetal chromosomal abnormalities such as diandric hydatifidiform moles of entirely paternal genetic origin10 are consistent with a role for paternally inherited fetal genes in the determination of clinical phenotype. This is supported by epidemiological studies reporting a higher rate of pre-eclampsia in pregnancies fathered by men who were themselves born of pre-eclamptic pregnancies.11 The occurrence of pre-eclampsia in daughters-in-law of index women9 further supports a genetic contribution from both parents. The genetic conflict hypothesis states that fetal (paternal) genes will be selected to increase the transfer of nutrients to the fetus, whereas maternal genes will be selected to limit transfer in excess of a specific maternal optimum.12 Fetal genes are predicted to raise maternal blood pressure in order to enhance the uteroplacental blood flow, whereas maternal genes act the opposite way. Endothelial dysfunction in mothers with pre-eclampsia could, therefore, be interpreted as a fetal attempt to compensate for an inadequate uteroplacental nutrient supply.

As the phenotype is apparently only expressed during pregnancy, identification of ‘susceptible’ men is impossible. Most genetic studies of pre-eclampsia have focused on maternal genotypes only. The Genetics of Pre-eclampsia consortium highlighted the need to include analysis of all contributing genotypes, and carried out transmission disequilibrium testing in maternal and fetal triads.13 Understanding the contribution of the fetal genotype will require large sample sizes, with the development of algorithms to determine the relative contribution from mother and fetus. Furthermore, the decreased incidence of pre-eclampsia in second and subsequent pregnancies hampers analysis of the contribution of the fetal genotype.

Candidate gene approach

The candidate gene approach has been widely used in pre-eclampsia, and largely focuses on the maternal genotype. In this method, a single gene is chosen as the candidate for investigation based on prior biological knowledge of the pathophysiology of pre-eclampsia. The choice is strengthened if the gene lies within a region identified by linkage studies. A case-control design is usually used, comparing the frequencies of allelic variants in women with pre-eclampsia and normotensive pregnancies. Such studies need careful definition of inclusion criteria for cases and controls, and subtle ethnic stratification of groups must be avoided. Such performance characteristics of the genotyping assays as the rate of mis-genotyping, and the quality assurance methods used, should be clearly stated, but this is rarely done. Over 70 biological candidate genes have been examined, representing pathways involved in various pathophysiological processes, including vasoactive proteins, thrombophilia and hypofibrinolysis, oxidative stress and lipid metabolism, endothelial injury and immunogenetics.14 In common with the experience in other genetically complex disorders, results from candidate gene studies have been inconsistent, and no universally accepted susceptibility gene has been identified. Although this may, in part, be attributed to variation within populations, a more important factor is the small size of most of the candidate studies, which have been underpowered to detect variants with small effects. As there are more than 20,000 genes and 10 million single nucleotide polymorphisms (SNP) available, multiple testing will inevitably result in numerous results that achieve P values of less than 0.05. The development of robust statistical techniques for the minimisation of both false positive and false negative results is an important area.15,16 Only in recent years, as susceptibility genes for other complex disorders have been reported, has the small effect size of individual genetic variants become apparent, the majority increasing the risk of disease by less than 50%. A further limitation of the candidate gene approach is its reliance on the generation of an a-priori hypothesis based on our current incomplete knowledge of the pathophysiology of the disorder. The candidate genes studied belong to different groups according to their functional properties and plausible role in the pathophysiology (Table 2).

Thrombophilia

A successful pregnancy requires the development of adequate placental circulation. It is hypothesised that thrombophilias may increase the risk of placental insufficiency because of placental micro-vascular thrombosis, macro-vascular thrombosis, or both, as well as effects on trophoblast growth and differentiation.17 Abnormalities of the clotting cascade are well documented in women with pre-eclampsia.18 The endothelial damage of pre-eclampsia is associated with an altered phenotype from anticoagulant to procoagulant and decreased endothelially mediated vasorelaxation. It is possible that this phenotype is present before pre-eclampsia in pregnancy, or it may develop as a consequence of damage initiated during placentation. Furthermore, a subset of women develop frank thrombocytopaenia, often in association with haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome. Association of the three most widely studied thrombophilic factors, factor V Leiden (F5), methylenetetrahydrofolate (MTHFR) and prothrombin (F2), with pre-eclampsia has been shown; however, several studies have also shown contradictory results.14 A recent meta-analysis indicated a two-fold increase in risk for pre-eclampsia associated with 1691G>A mutation in F5, but no associations were found for MTHFR or F2.19 To date, the number of studies showing no association with pre-eclampsia for these three genes is much higher than the number confirming association. Association with the inhibitor of fibrinolysis plasminogen activator factor-1 gene has also been reported; however, replication attempts have failed.20–22

Haemodynamics and endothelial function

The renin-angiotensin system (RAS) is important for regulating the cardiovascular and renal changes that occur in pregnancy. Several studies have implicated the RAS in the pathophysiology of pre-eclampsia.23 As such, genes in the RAS have been considered as plausible candidates for pre-eclampsia. Angiotensin-converting enzyme (ACE), angiotensin II type 1 and type 2 receptor (AGTR1, AGTR2), and angiotensinogen (AGT) have all been studied extensively in pre-eclampsia. Recent meta-analyses have identified the T allele of AGT M235T as increasing the risk of developing pre-eclampsia by 1.62 times and similar increases in disease risk have been found in AGT and the angiotensin-converting enzyme I/D polymorphism.24 A rare functional polymorphism in AGT, which results in replacement of leucine by phenylalanine at the site of renin cleavage, has been reported in association with severe pre-eclampsia.25

Endothelial nitric oxide synthase 3 (eNOS3), which is involved in vascular remodelling and vasodilation, has been shown to have reduced activity in pre-eclampsia26 Association studies in different ethnic populations, however, have yielded both positive and negative findings. A meta-analysis investigating the E298D polymorphism, which had initially been associated with pre-eclampsia in Colombian women, failed to find increased risk.24 Vascular endothelial growth factor (VEGF) is important for endothelial cell proliferation, migration, survival and regulation of vascular permeability. The number of studies that have investigated SNP in the genes involved in the VEGF system is small. Two polymorphisms in VEGF, 405G>C and 936C>T, were found to be associated with the severe form of pre-eclampsia in two small studies, but cannot at present be considered as major risk factors.27,28

Oxidative stress and lipid metabolism

Oxidative stress plays a central role in the pathogenesis of pre-eclampsia. Maternal perfusion of the placenta does not occur until towards the end of the first trimester,29 when a rapid increase in local oxygen tension takes place, and the probable occurrence of a period of hypoxia–reperfusion until stability is reached. This is accompanied by increased expression and activity of such antioxidants as glutathione peroxidase, catalase and the various forms of superoxide dismutase.30 If this antioxidant response were reduced, then the cascade of events leading to impaired placentation could be initiated. Evidence for reduced antioxidant activity in pre-eclampsia has recently been reviewed.31 Genes involved in the generation or inactivation of reactive oxygen species, if defective, could increase endothelial dysfunction via lipid peroxidation, which has been a candidate causative agent for the endothelial damage of pre-eclampsia for more than 20 years.32 Despite the strong correlation between oxidative stress and pre-eclampsia, only a small handful of genes have been investigated. Functional polymorphisms in the gene for microsomal epoxide hydrolase (EPHX) that catalyses the hydrolysis of certain oxides and may produce toxic intermediates that could be involved in pre-eclampsia, and glutathione S-transferase (GST), an antioxidant capable of inactivating reactive oxygen species, have shown associations. Conflicting results, however, have also been reported.33–36

Abnormal lipid profiles associated with the lipid peroxidation caused by oxidative stress are also characteristic of pre-eclampsia. Lipoprotein lipase (LPL) and apolipoprotein E (ApoE) are the two major regulators of lipid metabolism, abundantly expressed in placenta, and have therefore been proposed as possible candidate genes.37,38 A recent study using bioinformatic analysis identified altered glycosylation of circulating ApoE isoforms in pre-eclampsia.39 A deglycosylated basic ApoE isoform was increased in pre-eclampsia, and an acidic ApoE sialyated isoform was decreased. Functionally, this might increase the risk of developing placental atherotic changes. The most promising genetic variant in this context is a mis-sense mutation, Asn291Ser, in LPL which correlates with lowered LPL activity and increased dyslipidaemia in two separate studies. Again, others have failed to replicate these findings.38,40,41 The fetal genotype of these two genes has also been reported to contribute to the metabolism of the maternal lipoproteins.37

Immune system

The maternal immune response to pregnancy is crucial in determining pregnancy outcome and success. The increased incidence of pre-eclampsia in primiparous women, especially those at either end of the childbearing age range, indicates a strong association between immune factors and pre-eclampsia.42 However, the protective effect of multiparity is lost with change of partner. Advances in assisted reproductive technology are also posing new challenges to the maternal immune system. The use of donated sperm or eggs increases the risk of pre-eclampsia three-fold.43

Human leucocyte antigen

Trophoblast cells express an unusual repertoire of histocompatibility antigens, comprising human leucocyte C, E and G class antigens (HLA-C, HLA-E, HLA-E), of which only HLA-C displays marked polymorphism. The expression of HLA on the invading cytotrophoblast is important, as these interact with killer immunoglobulin, such as receptors (KIR) expressed on maternal uNKs and cytotoxic T-lymphocytes, down-regulating their cytolytic activity and stimulating the production of cytokines needed for successful placentation. Multiple highly homologous KIR genes map to chromosome 19q, probably arising from ancestral gene duplications, and the two main resulting gene clusters have been classified as haplotypes A and B. The A group codes mainly for KIR, which inhibit natural killer cells, whereas the B group has additional stimulatory genes.44 Pre-eclampsia is more frequent in women who are homozygous for the inhibitory A haplotypes (AA) than in women homozygous for the stimulatory B haplotypes (BB). The effect is strongest if the fetus is homozygous for the HLA-C2 haplotype.45 Alteration in KIR interaction on uNK cells with HLA-C on interstitial trophoblast alters the decidual immune response, resulting in impaired extravillous trophoblast invasion and deficient spiral artery remodelling, associated with pre-eclampsia.

An association of HLA-G, which displays limited polymorphism, with pre-eclampsia, has also been reported. A possible association between the presence of the HLA-G allele G*0106 in the placenta and an increased risk of pre-eclampsia has been identified in two small studies.46,47 these were underpowered, however, and further studies using larger cohorts of mothers and babies are needed to replicate these results. HLA-G variants foreign to the mother may lead to histo-incompatibility between mother and child. A maternal rejection response to the semi-allogeneic fetus may represent one of the pathways involved in the development of pre-eclampsia.

A number of pro-inflammatory cytokines have also been investigated for possible associations with pre-eclampsia. Excessive release of tumour necrosis factor alpha (TNFα) has been implicated owing to its contribution to endothelial activation, which in turn could contribute to maternal symptoms.48 Interestingly, in pregnant rats, TNF induces hypertension, a response not seen in non-pregnant rats.49 Furthermore, plasma levels of TNFα are significantly higher in women with pre-eclampsia than matched controls.50 TNFα is also involved in the production of reactive oxygen species and subsequently oxidant mediated endothelial damage. The most frequently studied variant in pre-eclampsia is the –308G>A transition in the promoter region, which is associated with increased levels of TNFα production and an increased risk for pre-eclampsia linked disorders, including type 2 diabetes, coronary artery disease and dyslipidaemia.51,52 However, a meta-analysis from 2008 combined 16 studies investigating this promoter SNP, but failed to detect a significant association to pre-eclampsia.53

Interleukin-10 (IL-10) has also been implicated in the pathogenesis of pre-eclampsia by enhancing the inflammatory response towards trophoblast cells resulting in reduced invasion and remodelling of the spiral arteries.54 Expression of IL-10 is reduced in pre-eclamptic placentae.55 Studies investigating associations of variants of the gene and pre-eclampsia, however, have yielded conflicting results.56–58 Associations have also been detected for two additional inflammatory genes, interleukin-1α (IL-1α) and the interleukin 1 receptor anatagonist (IL1Ra) in relatively small studies, but few studies have addressed the role of polymorphisms in these genes so far.59,60

Antioxidant enzymes

A large family of cytosolic glutathione-s-transferases (GST) exists, and the P class is highly expressed in the human placenta. Several relatively small case-control studies of polymorphisms in this family in relation to pre-eclampsia have failed to identify any significant effect of several GST polymorphisms studied individually. However, a cumulative effect of the number of polymorphisms in various biotransformation enzymes, including GST, which would result in decreased antioxidant capacity, has been reported.61 Intriguingly, the use of semi-quantitative polymerase chain reaction on a small data set identified using serial analysis of gene expression profiles, seems to identify a specific molecular signature for HELLP, which includes decreased expression of GST P1.62

Remarkably, few studies of possible functional polymorphisms in antioxidant enzyme systems have been reported. The 242C>T polymorphism in exon 4 of the gene for the p22phox subunit of NADPH/NADH oxidase (CYBA), which is part of the cascade of superoxide generation, has been reported as showing no evidence of an association with either pre-eclampsia or HELLP and pre-eclampsa.63 A small preliminary study of the Ala40Thr polymorphism of the superoxide dismutase 3 gene (SOD3), which has been associated with insulin resistance, reported a significant excess of the mutant allele in women with severe intrauterine growth restriction.64

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145161/?report=printable

High blood pressure in pregnancy: What’s your story?

By Mary M. Murry, R.N., C.N.M.

Blood pressure tends to fluctuate during pregnancy.

For example, it’s normal to experience a drop in blood pressure during the second trimester. In fact, your blood pressure might be lower than it’s ever been. During the third trimester, a gradual increase in blood pressure is common.

Sometimes, though, blood pressure changes more dramatically — or sustained high blood pressure becomes a concern.

By definition, there are various types of high blood pressure during pregnancy:

• Chronic hypertension. If high blood pressure develops before pregnancy or during pregnancy but before 20 weeks, it’s known as chronic hypertension. High blood pressure that lasts more than 12 weeks after delivery is also considered chronic hypertension.
• Gestational hypertension. If high blood pressure develops after 20 weeks of pregnancy, it’s known as gestational hypertension. Gestational hypertension usually goes away after delivery.
• Preeclampsia. Sometimes chronic hypertension or gestational hypertension leads to preeclampsia. This is a serious condition characterized by high blood pressure and protein in the urine after 20 weeks of pregnancy.

All of these conditions can be dangerous for you and your baby. If your pregnancy has been normal until now, a diagnosis of high blood pressure can be especially jarring.

Depending on the circumstances, your health care provider might recommend close monitoring or, in some cases, an early delivery.

Count on your health care provider to help you understand what’s happening and what you can do to promote a healthy outcome. Above all, don’t hesitate to ask questions. Being fully informed can help you make the best decisions for you and your baby.

http://www.mayoclinic.com/health/high-blood-pressure-in-pregnancy/MY02263

Texas A&M Researcher Uncovers New Data for the Treatment of Preeclampsia

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Posted Thursday , June 06,2013

A Researcher From Texas A&M Has Uncovered New Data for the Treatment of Preeclampsia: Preclinical Research Shows PLX Cells May Be Effective in Treating Preeclampsia.

Preliminary research led by Brett Mitchell, PhD, an Associate Professor of Internal Medicine in the Cardiovascular Research Institute (CVRI) at Texas A&M University College of Medicine, is demonstrating that administrating placental stem cells may aid in reversing symptoms linked with preeclampsia within days after dosing with no apparent harmful effects to fetus or mother.

Preeclampsia may occur after the 20^th week of pregnancy when the mother-to-be’s blood pressure has increased and there are signs of excessive protein in the urine. This condition affects somewhere between 6-8 percentage of pregnancies in the US, and can be serious, as there is a shift from protecting mother and fetus as immunologically privileged sites. This brings about vascular issues that involve the inability of blood vessels to dilate or relax.

Dr. Mitchel has been able to look at the immune cells that are responsible for the development of high blood pressure (hypertension) during pregnancy in hopes to develop new therapies that diminish the immune cells that are responsible for this action while maintaining normal immune cell function.

Mitchel and colleagues have taken mice that had preeclampsia and injected placenta-based cells (stem cells) known as PLX (Placentall eXpanded) into leg muscle.  PLX cells are used as a way of delivering drugs and in particular therapeutic proteins in response to inflammatory and ischemic events.  They tested eight groups of 2 separate animal models (preeclampsia models) and found that PLX cells were effective in treating preeclampsia.

They observed a reduction in

• systolic pressure to normal levels within 3 days and a reduction of
• urinary proteins within 4 days.

They also observed an

• increase in endothelial function.  This was measured by acetylcholine-induced relaxation and was effective within 4 days. A
• weight reduction of the spleen was also observed within 4 days.

Pregnant mice who didn’t have preeclampsia were subjected to the same protocol and it was found that muscle injection of PLX cells did not effect a normal pregnancy.  They also found that the number of pups or fetal demise in a litter were not different indicating that PLX cells caused no fetal harm.

Dr. Mitchel presented his findings at the Society for Gynecologic Investigation Summit in Jerusalem on May 30, 2013.  Mitchell suggests that the factors that were secreted from the PLX cells were able to decrease inflammation thereby restoring endothelial function.

Currently, there are no treatments available for preeclampsia, so this therapy looks promising.

http://bionews-tx.com/news/2013/06/06/texas-a-and-m-new-data-for-the-treatment-of-preeclampsia-preclinical-research-shows-plx-cells-may-be-effective-in-treating-preeclampsia/

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145161/?report=printable

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Posted in HTN, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation | Tagged Blood pressure, HELLP syndrome, Hypertension, PLX, Pre-eclampsia, pregnancy, SNP, Texas A&M Health Science Center College of Medicine, University of Nottingham | 1 Comment »

Celebrating One Year Anniversary of PeerJ

June 12, 2013 by 2012pharmaceutical

Celebrating One Year Anniversary of PeerJ

Reporter: Aviva Lev-Ari, PhD, RN

Article ID #60: Celebrating One Year Anniversary of PeerJ. Published on 6/12/2013

WordCloud Image Produced by Adam Tubman

 

READ THE HISTORY OF PeerJ

http://pharmaceuticalintelligence.com/open-access-scientific-journal/peerj-model-for-open-access-online-scientific-journal/

 

From: PeerJ <newsletter@peerj.com>
Date: Wed, 12 Jun 2013 18:10:54 +0000
To: AvivaLev-Ari <Avivalev-ari@alum.Berkeley.edu>
Subject: PeerJ turned One today – help us celebrate by entering our competition

PeerJ
Hi Aviva,
We are very pleased to announce <http://blog.peerj.com/post//celebrating-the-one-year-anniversary-of-peerj>  that this is the one year anniversary of PeerJ – it was on June 12th, 2012 that we first announced ourselves and started the process towards becoming a fully-fledged publishing company. Today, just 12 months later, PeerJ is completely up and running; we are publishing high quality peer-reviewed science; and we are doing our very best to change the world by pushing the boundaries of Open Access!

To briefly overview what has been achieved in the last year – we announced ourselves on June 12th 2012 and opened the PeerJ doors for submissions on December 3rd. We published our first PeerJ articles on Feb 12th 2013, and followed up by launching PeerJ PrePrints on April 3rd 2013. This last year has been spent recruiting an Editorial Board of 800 world renowned researchers; building cutting edge submission, peer-review, publication and pre-print software from scratch; establishing ourselves with all the major organizations who archive, index, list and certify new publications; and building an entirely new type <http://blog.peerj.com/post/46261563342/6-reasons-to-publish-with-peerj>  of publishing company from the ground up.

Some of the highlights have included:

* the fantastic reception <http://svpow.com/2012/08/30/peerj-sorted/>  to our membership model <https://peerj.com/pricing/&gt;  which means that authors now have a way to publish for their lifetime for a single low price payment (starting at just $99);

* the fact that we have been processing submissions with extreme speed and effectiveness <http://blog.peerj.com/post/45340534713/peerj-is-fast> ;

* the fact that our Open Peer Review process has been so well received <http://blog.peerj.com/post/43139131280/the-reception-to-peerjs-open-peer-review>  with over 40% of reviewers now providing their name and almost 80% of authors making their reviews public;

* being named by the Chronicle of Higher Education as one of the “Top 10 Tech Innovators in the Education Sector <http://chronicle.com/article/The-Idea-Makers-Tech/138823/> ” and by Nature as “a significant innovation <http://www.nature.com/news/journal-offers-flat-fee-for-all-you-can-publish-1.10811> ”;

* and of course the fact that the journal has turned out to be so innovative <http://blog.peerj.com/post/42920094844/peerj-functionality> , beautiful and aesthetically pleasing <http://theseamonster.net/2013/05/peerj-awesomeness/> .

The giveaway

We are celebrating this milestone with a new PeerJ Competition. On June 19th, we will give away 12 “complimentary publication” passes (the ability to publish one paper with us at no cost to you or any of your co-authors) + a PeerJ Charlie T-Shirt + a pin + a fridge magnet (!) to a random selection of 12 people (one for each month of our first year) who publicly post some variation of the following message:

“PeerJ just turned one! Open access publishing, for just $99 for life – check them out and submit now!”

Please include a link to us as well (you choose the best one!).

The last year has been an intense journey, and to be honest we have been so busy we almost missed the anniversary! We would like to take this opportunity to thank the many thousands of researchers who have signed up as PeerJ Members; all those who have authored or reviewed articles; all those who have joined our Editorial Board; and anyone who have simply expressed their support – without the involvement and enthusiasm of these people we would not be where we are today. Of course, we must also thank our dedicated staff (Alf Eaton, Patrick McAndrew and Jackie Thai) and Tim O’Reilly, who collectively took a chance on a brand new publishing concept, but who have been irreplaceable in making us what we are today!

Please encourage your colleagues to look into PeerJ, and make sure they consider submitting their next article to us. The future of academic publishing is here, right now <http://blog.peerj.com/post/46261563342/6-reasons-to-publish-with-peerj> .

The PeerJ Founders
and the PeerJ Team

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Posted in Interviews with Scientific Leaders, Scientist: Career considerations | Tagged Academic publishing, Chronicle of Higher Education, Open access | Leave a Comment »

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