“Loose” RNA Stimulates Regeneration of Skin

MedicalResearch.com Interview with:

Luis Garza, M.D., Ph.D. Associate Professor of Dermatology Johns Hopkins University School of Medicine.

Dr. Garza

Luis Garza, M.D., Ph.D.
Associate Professor of Dermatology
Johns Hopkins University School of Medicine.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We wanted to find out what might stimulate regeneration in mice and humans. We find that in both species during wounding, released “loose” dsRNA induces production of retinoic acid that stimulates regeneration. Continue reading

Does Genetic Information Encourage Doctors to Switch Anticoagulation Medications?

MedicalResearch.com Interview with:

Thomas J. Povsic, MD, PhDInterventional CardiologistDuke Clinical Research InstituteDuke University School of MedicineDurham, North Carolina 

Dr. Povsic

Thomas J. Povsic, MD, PhD
Interventional Cardiologist
Duke Clinical Research Institute
Duke University School of Medicine
Durham, North Carolina 

MedicalResearch.com: What is the background for this study? 

Response: The background for this study is that it is unknown how mandatory reporting of CYP2C19 metabolizer status affects how doctors treat patients or to what degree provision of this information would affect choice of a P2Y12 inhibitor within a clinical trial.

As part of the GEMINI-ACS trial, all patients underwent CYP2C19 metabolizer testing.  This trial enrolled patients with a recent acute coronary syndrome and randomized them to aspirin or a low dose of rivaroxaban.  All patients were also to be treated with ticagrelor or clopidogrel, which was at the discretion of the investigator.  Investigators were given information regarding the CYP2C19 metabolizer status about a week after randomization.  Importantly prior to randomization, all investigators were asked how they expected to use this information, and then we followed what they actually did.

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Cesarean Section: Multimodal Program Using Non-Opioid EXPAREL Reduced Pain and Need for Opioids After Surgery

MedicalResearch.com Interview with:
Ashraf Habib, MDChief of the Division of Women’s Anesthesia and Professor of AnesthesiologyDuke University Ashraf Habib, MD
Chief of the Division of Women’s Anesthesia
Professor of Anesthesiology
Duke University 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This was a multicenter study conducted in 13 clinical sites in the United States enrolling patients undergoing elective Cesarean-section and receiving spinal anesthesia. 186 patients were enrolled and randomized to receive EXPAREL, a long-acting, non-opioid option to manage postsurgical pain, administered via transversus abdominis plane (TAP) field block, mixed with plain bupivacaine or TAP block with plain bupivacaine alone. A TAP block numbs the nerves that supply the abdominal wall. We presented the data at the 51st Annual Meeting of the Society of Obstetric Anesthesia and Perinatology (SOAP) in Phoenix, AZ.

We aimed to collect clinical evidence that a multimodal postsurgical pain regimen using a TAP block with EXPAREL (bupivacaine liposome injectable suspension) together with regularly scheduled acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce opioid consumption more so than a standard multimodal pain control approach that combines TAP block with standard bupivacaine, regularly scheduled acetaminophen, and NSAIDs.

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Chemicals in Household Dust May Promote Fat-Cell Development

MedicalResearch.com Interview with:

Christopher D. Kassotis, Ph.D.NRSA Postdoctoral Research ScholarStapleton LabDuke UniversityNicholas School of the EnvironmentDurham, NC 27708 

Dr. Kassotis

Christopher D. Kassotis, Ph.D.
NRSA Postdoctoral Research Scholar
Stapleton Lab
Duke University
Nicholas School of the Environment
Durham, NC 27708 

MedicalResearch.com: What is the background for this study? What are the main findings?

  • So this was something that Heather Stapleton had been curious about for years, as she’s been one of several researchers characterizing the hundreds of chemicals that have been measured in indoor house dust. Before I came to Duke, one of her PhD students had measured the ability of many common indoor contaminants to activate the peroxisome proliferator activated receptor gamma (PPARg). The majority of these chemicals did, often quite well, which led to them testing indoor house dust extracts, also finding that the majority of dust extracts were also able to do so at very low levels. As PPARg is often considered the master regulator of fat cell development, the next obvious question was whether these common contaminants (and house dust) could promote fat cell development in cell models. My first work at Duke evaluated a suite of common indoor contaminants, finding that many of these chemicals could promote fat cell development, and that low levels of house dust extracts did as well.
  • We next explored this more systematically in a group of adults involved in a thyroid cancer cohort (this was just recently published in Science of the Total Environment:
    https://www.sciencedirect.com/science/article/pii/S0048969719307715?dgcid=author
  • In this study we evaluated the extent to which house dust extracts could promote fat cell development in a common cell model, and associated this with the metabolic health of adults living in these homes. We found that the greater extent of fat cell development was associated with significantly greater thyroid stimulating hormone concentrations (control residents only, with no evidence of thyroid dysfunction) and lower free triiodothyronine (T3) and thyroxine (T4). We further found a significant and positive association between extent of fat cell development and the body mass index (BMI) of all adults in the study. So this suggested that the indoor environment might play a role in the BMI and metabolic health of residents, and we next wondered if this would be more pronounced in children, who may be exposed to these contaminants during a critical window of development.
  • The next step, for our current work, was to substantiate these effects in a larger group of households, each with children.
  • Our major conclusions thus far have been that ~80% of house dust extracts promote significant fat cell development in a cell model – either via development from precursor cells into mature fat cells, measured via accumulation of lipids into the cells, or via the proliferation of those precursor fat cells. We also reported positive correlations of fat cell development with the concentrations of 70 different contaminants in the dust from these homes, suggesting that mixtures of contaminants are likely all acting weakly to produce these effects in combination. We’ve also begun to assess the other chemicals present in dust – chemistry can be either targeted (measuring concentrations of specific known chemicals in a sample), or non-targeted, where you try and determine the identity of the other chemicals in a sample. This has greater utility for identifying many more chemicals, though you will often not get chemical concentrations from this, nor absolute confirmed identification – just varying degrees of certainty based on evidence.

    Thus far we report approximately 35,000 chemicals in house dust samples across this study, and differential analyses have begun to pick out the few (less than 10 in each case) chemicals most differentially expressed between samples that exhibit high degrees of fat cell development in the lab vs inactive samples, for example, or which are differentially present in the homes of children categorized as obese or overweight. We are now working to confirm identity of these select contaminants that are more likely to be causative factors in the results we have observed.

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Atrial Fibrillation: Antithrombotic Therapy after Acute Coronary Syndrome or PCI

MedicalResearch.com Interview with:

Renato D. Lopes MD, MHS, PhD Duke University Medical Center Duke Clinical Research Institute Durham, NC 27705

Dr. Renato Lopes

Renato D. Lopes MD, MHS, PhD
Professor of Medicine
Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In patients with acute coronary syndromes (ACS), approximately 20% to 30% of those with nonvalvular atrial fibrillation (NVAF) have concomitant coronary artery disease (CAD), and 5 to 10% of patients who undergo PCI have NVAF. These patients often receive both antiplatelet therapy and oral anticoagulants; and how best to combine these agents to minimize bleeding risk without compromising protection against thrombosis is an important unanswered question.

Analysis of results for bleeding indicated no significant interaction between the two randomization factors permitting independent analysis of results for the two key comparisons. The first showed that apixaban was both non-inferior and significantly superior to VKA for the primary outcome with a 31% reduction in the relative risk for bleeding. Aspirin significantly increased the relative risk for bleeding versus placebo by 89%.

Results for the composite of death and hospitalization showed that apixaban resulted in a relative risk reduction of 17%, primarily driven by a reduction in all cause hospitalization. There was no significant difference between results for aspirin versus placebo for this outcome.

Analysis of the composite of death and ischemic events indicated no significant differences in results for apixaban versus VKA or aspirin versus placebo.

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Most Cardiovascular Guidelines Not Supported By Randomized Clinical Trials

MedicalResearch.com Interview with:
Renato D. Lopes MD, MHS, PhD
Professor of Medicine
Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute

Alexander C. Fanaroff, MD, MHS
Division of Cardiology and Duke Clinical Research Institute
Duke University, Durham, North Carolina

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: About ten years ago, a group of researchers examined the evidence supporting guideline recommendations in cardiology for the first time. Quite surprisingly, they found that only 11% of recommendations in American College of Cardiology/American Heart Association (ACC/AHA) guidelines were supported by evidence from randomized controlled trials, the highest level of evidence. The researchers called for greater collaboration among investigators and funders in identifying key research questions, development of streamlined clinical trial methods, and expansion of funding for clinical research. Over the past 10 years, some of these steps have been taken, but it is unclear how the evidence supporting guideline recommendations has changed.

We therefore analyzed the 51 current cardiovascular guideline documents — 26 from the ACC/AHA and 25 from the European Society of Cardiology (ESC) — including 6,329 recommendations.

Overall, 8.5% of recommendations in ACC/AHA guidelines and 14.3% of recommendations in ESC guidelines were supported by evidence from randomized controlled trials. When looking specifically at guidelines that have been updated, we found no significant changes in the proportion of recommendations supported by evidence from randomized controlled trials.

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Psychiatric Problems Related to Lead Exposure Detected As Early As Age 11

MedicalResearch.com Interview with:
Aaron Reuben, MEM
Department of Psychology and Neuroscience
Duke University, Durham, North Carolina

MedicalResearch.com: What is the background for this study? What are the main findings?

(1)  Study members with greater lead exposure in childhood tended to endorse more psychiatric symptoms when assessed for psychiatric disorders in adulthood (between 18 and 38 years of age).

  1. These individuals tended to report more internalizing (e.g., depression, anxiety) and thought disorder (e.g., OCD, schizophrenia, mania) symptoms.
  2. Compared to other findings from this sample, the associations reported in this article are similar to those reported for lead and IQ, and are stronger than those reported for lead and criminal offending.
    1. Informants who knew Study members well reported higher levels of difficult adult personality traits among Study members with greater lead exposure in childhood.
    2. Specifically, Study members with greater blood lead levels at age 11 were rated as more neurotic, less agreeable, and less conscientious by 38 years of age.
    3. These personality traits have been previously linked to a number of poor life outcomes, including greater psychopathology, worse physical health, less job satisfaction, and troubled interpersonal relationships
  3. Psychiatric problems related to lead exposure could be detected as early as 11 years of age. In the 1980’s, parents and teachers of children with higher blood-lead levels had described them as displaying more antisocial behavior, hyperactivity, and negative emotions (e.g., sadness, anxiety).

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RAS Inhibitor Linked to Reduced Heart Failure and Mortality After TAVR

MedicalResearch.com Interview with:

Taku Inohara MD, PhD Duke Clinical Research Institute,  Duke University Medical Center, Durham, North Carolina Department of Cardiology  Keio University School of Medicine, Tokyo, Japan

Dr. Inohara

Taku Inohara MD, PhD
Duke Clinical Research Institute,
Duke University Medical Center,
Durham, North Carolina
Department of Cardiology
Keio University School of Medicine, Tokyo, Japan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Transcatheter aortic valve replacement (TAVR) has been increasingly used for treating patients with severe aortic stenosis.

Owing to the advancement of TAVR technology, the mortality and heart failure (HF) readmission after TAVR is decreasing over time, but 4.3% experienced readmission due to HF and 23.7% died within 1 year after TAVR. Inhibition of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin-receptor blockers (ARBs) is known to improve clinical outcomes in patients with heart failure, but there remains unknown whether a RAS inhibitor is associated with a reduction in mortality and heart failure readmission after TAVR.

Using the STS/ACC TVT Registry, a nationwide TAVR Registry in the US, we analyzed 15896 propensity-matched patients who underwent TAVR and found that receiving a prescription for a RAS inhibitor at discharge, compared with no prescription, was associated with a reduced risk for mortality ( 12.5% vs 14.9%) and HF readmission (12.0% vs 13.8%).

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Untreated Hearing Loss: Higher Health Care Costs, More ER Visits and Readmissions

MedicalResearch.com Interview with:

Nicholas S. Reed, AuD Assistant Professor | Department of Otolaryngology-Head/Neck Surgery Core Faculty  | Cochlear Center for Hearing and Public Health Johns Hopkins University School of Medicine Johns Hopkins University Bloomberg School of Public Health

Nicholas Reed AuD

Nicholas S. Reed, AuD
Assistant Professor | Department of Otolaryngology-Head/Neck Surgery
Core Faculty | Cochlear Center for Hearing and Public Health
Johns Hopkins University School of Medicine
Johns Hopkins University Bloomberg School of Public Health

MedicalResearch.com: What is the background for this study?

Response: This study was a true team effort. It was funded by AARP and AARP Services, INC and the research was a collaboration of representatives from Johns Hopkins University, OptumLabs, University of California – San Francisco, and AARP Services, INC. Given all of the resent research on downstream effects of hearing loss on important health outcomes such as cognitive decline, falls, and dementia, the aim was to explore how persons with hearing loss interacted with the healthcare system in terms of cost and utilization.

MedicalResearch.com: What are the main findings?

Response: Over a 10 year period, untreated hearing loss (hearing aid users were excluded from this study as they are difficult to capture in the claims database) was associated with higher healthcare spending and utilization. Specifically, over 10 years, persons with untreated hearing loss spent 46.5% more, on average, on healthcare (to the tune of approximately $22000 more) than those without evidence of hearing loss. Furthermore, persons with untreated hearing loss had 44% and 17% higher risk for 30-day readmission and emergency department visit, respectively.

Similar relationships were seen across other measures where persons with untreated hearing loss were more likely to be hospitalized and spent longer in the hospital compared to those without evidence of hearing loss. Continue reading

Young Adults with Hypertension at Higher Risk of Stroke and Heart Failure

MedicalResearch.com Interview with:

Yuichiro Yano MD PhD Assistant Professor in Community and Family Medicine Duke University

Dr. Yano

Yuichiro Yano MD PhD
Assistant Professor in Community and Family Medicine
Duke University

MedicalResearch.com: What is the background for this study?

Response: New blood pressure guidelines, issued in 2017 in the US, lowered the blood pressure thresholds for hypertension from systolic blood pressure/diastolic ≥140/90 mm Hg to systolic/diastolic ≥130/80 mm Hg. This change increased the prevalence of hypertension two- to three-fold among young adults. The guidelines also newly defined elevated blood pressure as, 120-129 mmHg systolic blood pressure over 80 mmHg diastolic or less. However, no study investigated that high blood pressure, as defined by the new criteria, is something that younger people should be concerned about as a potential precursor to serious problems.

Our study is among the first to report that people younger than age 40 who have elevated blood pressure or hypertension are at increased risk of heart failure, strokes and blood vessel blockages as they age. Continue reading

PITS Gene Linked To Rare Neurologic Disorders

MedicalResearch.com Interview with: 

Paul C Marcogliese, Ph.D. Postdoctoral Associate, Laboratory of Dr. Hugo Bellen Department of Molecular and Human Genetics Baylor College of Medicine Houston, Texas 77030

Dr. Marcogliese

Paul C Marcogliese, Ph.D.
Postdoctoral Associate,
Laboratory of Dr. Hugo Bellen
Department of Molecular and Human Genetics
Baylor College of Medicine
Houston, Texas 77030

Loren D. Pena, MD PhD Pediatric Medical Genetics Specialist Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine, Durham, NC

Dr. Peña


Loren D. Pena, MD PhD
Division of Human Genetics
Cincinnati Children’s Hospital Medical Center
Department of Pediatrics
University of Cincinnati
Cincinnati, OH 45229


MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Undiagnosed Diseases Network (UDN) is a multi-site collaboration across the US that seeks to help diagnose patients with rare disorders that are ill-defined.

Dr. Loren D.M. Pena and Dr. Vandana Shashi at the Duke-Columbia clinical site of the UDN had seen a patient with a severe neurological disorder. While the patient had no symptoms at birth, the patient began falling at about 3 years of age, eventually losing motor coordination and developing seizures. In the interim, the regression has progressed to a severely debilitating state. Re-analysis of the participant’s exome data by our site bioinformatician at Columbia (Nicholas Stong) in Dr. David Goldstein’s laboratory revealed a truncating variant in the single exon gene IRF2BPL that could be the candidate disease-causing gene. The UDN clinicians at Duke then contacted the UDN Model Organism Screening Center (MOSC) led by Dr. Hugo Bellen at Baylor College of Medicine and the Howard Hughes Medical Institute for functional analysis. In parallel, four more patients were found with truncating mutations causing a similar disorder though the UDN and GeneMatcher.org. Additionally, two patients with missense variants in IRF2BPL were identified that displayed seizures and some developmental delay or autism spectrum disorder but no motor regression.

Work in MOSC by Dr. Paul Marcogliese using fruit flies revealed that the IRF2BPL truncating variants are severe loss of function mutations and one of the missense variants was a partial loss of function. Additionally, it was found that the fruit fly IRF2BPL gene, called pits, is expressed in the neurons of the adult fly brain. Lowering the levels of pits by about 50% in fly neurons leads to progressive behavioural abnormalities and neurodegeneration. By combining the human genetics, bioinformatics and model organism data, IRF2BPL was found to be a novel disease-causing gene in humans.

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Cognitive Changes Mapped Over Time in Young Persons at Risk for Psychosis

MedicalResearch.com Interview with:

Richard Keefe PhD Professor in Psychiatry and Behavioral Sciences Duke Institute for Brains Sciences

Dr. Keefe

Richard Keefe PhD
Professor in Psychiatry and Behavioral Sciences
Duke Institute for Brains Sciences

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A lot of studies have shown that cognitive deficits are present in young people at risk for psychosis. There have been calls for investigations of the idea that cognition declines over time in the young people who are at highest risk, but longitudinal studies are hard to conduct so not much work has been done to address this question.

The main finding from our study is that the cognitive architecture – the way the various aspects of cognitive functioning appear to be organized in each individual’s brain based upon their pattern of performance – changes over time in those young people who are in the midst of developing psychosis. Interestingly, cognitive architecture also becomes more disorganized in those whose high-risk symptoms do not remit over a two year period, and is related to the functional difficulties they may be having. The young people whose high risk symptoms were present at the beginning of the study but remitted later actually improved cognitively over the two year period of the study. Continue reading

Recombinant Polio Vaccine Improved Survival Rate Among Some With Aggressive Recurrent Brain Tumor

MedicalResearch.com Interview with:

Dr. Annick Desjardins, Assistant Professor of Medicine, photographed on October 2, 2013.

Dr. Desjardins

Annick Desjardins, M.D., F.R.C.P.C.
Associate Professor of Neurology
Associate Professor of Neurosurgery
Director of Clinical Research
The Preston Robert Tisch Brain Tumor Center at Duke
Duke University School of Medicine
Durham, NC 27710

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The poliovirus receptor (CD155) is an onco-fetal cell adhesion molecule with widespread expression in all solid tumors and particularly in primary CNS tumors (adult and pediatric).

Recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO) was generated by replacing a critical piece of the genetic information from the Sabin type 1 polio vaccine, making PVSRIPO incapable of harming or killing normal brain cells, but toxic/lethal in cancer cells. In preclinical models, it has been demonstrated that the infection of tumor cells, leads to the release of danger signals, which triggers a recruitment of dendritic/CD4/CD8 T cells and a destruction of tumor cells by anti-tumor T cells.

The manuscript reports the results of the phase 1 trial of PVSRSIPO in recurrent WHO grade IV malignant glioma patients. Adult patients with recurrence of a single glioblastoma lesion, 1-5.5cm in dimension, in a non-eloquent area of the brain, were enrolled on study. PVSRIPO is injected slowly over 6.5 hours directly into the tumor via a small catheter inserted via a small bur hole. Once intratumoral injection is completed, the catheter is removed and patients are observed for localized tumor inflammation, followed by tumor contraction. A total of 61 patients were treated on study, 9 patients in a dose escalation phase and 52 in a dose expansion phase. Side effects observed were in relation to the localized inflammation of the tumor and depending on the cerebral functions in close proximity to the tumor: headaches, visual field changes, hemiparesis, etc.

One patient experienced a brain hemorrhage at the time of catheter removal, which triggered right sided weakness and aphasia. The patient remained alive 57.5 months after PVSRIPO infusion at data cutoff of March 20th, 2018. Two on-study death were observed, a patient died from cerebral edema and seizures, which was later found to be due to tumor progression, and one patient died from the complications of an intracranial hemorrhage while receiving anticoagulation and bevacizumab.

The median overall survival among all 61 patients who received PVSRIPO was 12.5 months (95% CI, 9.9 to 15.2), comparatively to 11.3 months (95% CI, 9.8 to 12.5) in a historical control group of patients treated at Duke and who would have met eligibility on trial, would have the trial been available to them.

At 24 months, the survival plateaued in patients treated with PVSRIPO with an overall survival rate of 21% (95% CI, 11 to 33) at 24 months and 36 months in PVSRIPO treated patients, while overall survival in the historical control group continued to decline, with an overall survival rates of 14% (95% CI, 8 to 21) at 24 months and 4% (95% CI, 1 to 9) at 36 months in the historical control group.  Continue reading

African Americans Less Likely To Be Treated With Statins

MedicalResearch.com Interview with:

Michael G. Nanna, MD Fellow, Division of Cardiology Duke University Medical Center Durham, NC

Dr. Nanna

Michael G. Nanna, MD
Fellow, Division of Cardiology
Duke University Medical Center
Durham, NC

MedicalResearch.com: What is the background for this study?

Response: We know that African Americans are at higher risk for cardiovascular disease than white patients. We also know that African American individuals have been less likely to receive statin therapy compared to white individuals in the past. However, the reasons underlying these racial differences in statin treatment are poorly understood. We set out to determine if African American individuals in contemporary practice are treated less aggressively than whites and, if so, we wanted to investigate potential reasons why this might be the case.

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Female Residents Do Not Perceive Cardiology As Conducive To Work-Family Balance

MedicalResearch.com Interview with:

Pamela S. Douglas, MD, MACC, FASE, FAHA Ursula Geller Professor of Research in Cardiovascular Disease Duke University School of Medicine  Durham, NC 27715   

Dr. Douglas

Pamela S. Douglas, MD, MACC, FASE, FAHA
Ursula Geller Professor of Research in Cardiovascular Disease
Duke University School of Medicine
Durham, NC 27715    

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: For any profession to succeed, it needs to attract top talent. We surveyed internal medicine residents to find out what they valued most in their professional development, how they perceived cardiology as field and how these two areas are associated with  their choosing a career in cardiology or another specialty.

We found that trainees were seeking careers that had stable hours, were family friendly and female friendly, while they perceived cardiology to  have adverse work conditions, interfere with family life and to not be diverse. We were able to predict career choice with 89-97% accuracy from these responses; the predictors are mix of things that attract to cardiology and those that are deterrents.

For men, the attractors outnumber the deterrents, for women its just the opposite.

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Higher Connectivity of Brain Networks Linked to Increased Risk of Psychopathology

MedicalResearch.com Interview with:

Maxwell Elliott Clinical psychology PhD student Working with Ahmad Hariri and the Moffitt & Caspi lab Duke University

Maxwell Elliott

Maxwell Elliott
Clinical psychology PhD student
Working with Ahmad Hariri and the Moffitt & Caspi lab
Duke University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The traditional clinical science model identifies individuals who meet specific criteria for mental illness diagnoses (e.g. Depression, Anxiety) and compares them to “healthy” controls to find brain correlates of mental illness.  However, this approach often overlooks the high rates of comorbidity and shared symptamatology across mental illnesses. Emerging research has identified a general factor of psychopathology that accounts for shared risk among internalizing, externalizing, and thought disorders across diverse samples.

This general factor of psychopathology has been called the p-factor. In our study we investigate the brain correlates of the p-factor using a data-driven analysis of resting state functional connectivity. We find that higher p-factor scores and associated risk for common mental illness maps onto hyper-connectivity between visual association cortex and both frontoparietal and default mode networks.

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Cardiovascular Trials Need Better Characterization of Heart Failure in Diabetics

MedicalResearch.com Interview with:

Stephen J. Greene, MD Division of Cardiology Duke University Medical Center Durham, NC

Dr. Greene

Stephen J. Greene, MD
Division of Cardiology
Duke University Medical Center
Durham, NC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In 2008, the United States FDA issued an industry guidance specifying that diabetes drugs should routinely be tested in large cardiovascular outcome trials to confirm cardiovascular safety. The guidance specifically mentioned cardiovascular safety in terms of MACE, or major adverse cardiac events, including cardiovascular death, myocardial infarction, and stroke.  Largely because of this, these trials have traditionally had a focus on cardiovascular disease in terms of atherosclerotic events. Heart failure was not mentioned in the FDA document and these trials have had a lesser focus on it.

As the years have gone by, we have learned more and more about the connection between diabetes and heart failure. There is tremendous overlap between the two patient populations. Also, as more and more of the large cardiovascular outcome trials have been completed, we have seen multiple examples of various glucose lowering therapies either increasing or decreasing risk of heart failure events. Given all these data on heart failure/ diabetes interactions, the goal of our research was to carefully examine all of the completed large cardiovascular outcome trials of diabetes therapies to systematically describe the type of heart failure-related data they capture. As an initial step in improving heart failure characterization in these trials, we wanted to first describe what trials have already been doing and where the gaps in understanding heart failure in these trials exist.

Overall, we found major gaps in the amount and quality of the heart failure data capture in these trials. We looked at 21 large trials, including over 150,000 patients. Rates of patients with baseline heart failure were inconsistently provided, and among those trials that did provide it, heart failure patients tended to be underrepresented compared to the general population. Patients with baseline heart failure were also poorly characterized, with minimal data on functional status, ejection fraction, or heart failure medications. Only 6 trials reported rates of new-onset heart failure and the definitions used were non-specific. Most trials tended to report rates of heart failure hospitalization, but did not include data on fatal or other types of heart failure events. Only 2 trials included heart failure events within the primary study endpoint. More details are included in our full manuscript, which was published in the Journal of the American College of Cardiology to coincide with our presentation at the ACC conference.

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Should Digoxin Still Be Used in Patients With Atrial Fibrillation?

MedicalResearch.com Interview with:

Renato D. Lopes MD, MHS, PhD Duke University Medical Center Duke Clinical Research Institute Durham, NC 27705

Dr. Renato Lopes

Renato D. Lopes MD, MHS, PhD
Professor of Medicine, Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute
Terrace Level, Durham, NC 27705

MedicalResearch.com: What is the background for this study?

1-      Digoxin is used in ≈ 30% of patients with atrial fibrillation (AF) worldwide, despite the lack of randomized clinical trials to assess its efficacy and safety in this setting.
2-      Current AF guidelines recommend digoxin for rate control in patients with AF with and without heart failure (HF).
3-      There are no specific recommendations about serum digoxin concentration monitoring in the atrial fibrillation guidelines.

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Despite Promise, EMRs Have Not Reduced Administrative or Billing Expenses

Barak Richman JD, PhD Bartlett Professor of Law and Business Administration Duke University

Prof. Barak Richman

MedicalResearch.com Interview with:
Barak Richman JD, PhD
Bartlett Professor of Law and Business Administration
Duke University 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The US not only has the highest health care costs in the world, we have the highest administrative costs in the world. If we can reduce non-value added costs like the ones we document, we can make substantial changes in the affordability of health care without having to resort to more draconian policy solutions.

Our paper finds that administrative costs remain high, even after the adoption of electronic health records.  Billing costs, for example, constituted 25.2% of professional revenue for ED departments and 14.5% of revenue for primary care visits.  The other numbers are captured below.

Administrative Costs Still High With EHRs

Administrative Costs Still High With EHRs

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Stem Cell Transplantation Offers Hope For Severe Scleroderma

MedicalResearch.com Interview with:

“Breastfeeding welcome here” by Newtown grafitti is licensed under CC BY 2.0

Picture of a female patient’s left arm, showing skin lesions caused by Scleroderma
Wikipedia image

Keith M. Sullivan, M.D.
James B. Wyngaarden Professor Of Medicine
Division of Cellular Therapy
Duke University Medical Center
Durham, North Carolina 27710, USA 

MedicalResearch.com: What is the background for this study? What are the main findings?

  • Scleroderma with internal organ involvement is a devastating  autoimmune disorder with considerable morbidity and high mortality which have not changed in 40 years of reporting. Effective new therapies are needed.
  • Despite 2 prior randomized trials showing benefit for reduced-intensity stem cell transplant vs. conventional cyclophosphamide immune suppression, clinical practice in the US did not change due in part due to concern about patient safety and durability of response (attached).
  • The current randomized trial compares 12 monthly infusions of cyclophosphamide with high-dose chemotherapy plus whole-body irradiation designed to wipe-out (myeloablate) the defective, self-reactive immune system and replace with the patients own stem cells which had been treated to remove self-reacting lymphocytes. This was the first study to test if myeloablative autologous could re-establish a normal functioning immune system in patients with scleroderma.

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Financial Distress Common Among Cancer Patients, Especially Underinsured

MedicalResearch.com Interview with:

Dr. Fumiko Chino, MD Duke Radiation Oncology Duke School of Medicine

Dr. Chino

Dr. Fumiko Chino, MD
Duke Radiation Oncology
Duke School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The financial burden of cancer treatment is a growing concern. Out-of-pocket expenses are higher for patients with cancer than for those who have other chronic illnesses. Fifty percent of elderly cancer patients spend at least 10% of their income on treatment-related out-of-pocket expenses. Additionally, high financial burden is associated with both increased risk of poor psychological well-being and worse health-related quality of life. A cancer diagnosis has been shown to be an independent risk factor for declaring personal bankruptcy, and cancer patients who declare personal bankruptcy are at greater risk for mortality. These potentially harmful outcomes resulting from financial burden have been recognized as the financial toxicity of cancer therapy, analogous to the more commonly considered physical toxicity.

We conducted an IRB approved study of financial distress and cost expectations among patients with cancer presenting for anti-cancer therapy. In this cross-sectional, survey based study of 300 patients, over one third of patients reported higher than expected financial burden. Cancer patients with highest financial distress are underinsured, paying nearly 1/3 of income in cancer-related costs. In adjusted analysis, experiencing higher than expected financial burden was associated with high/overwhelming financial distress (OR 4.78; 95% CI 2.02-11.32; p<0.01) and with decreased willingness to pay for cancer care (OR 0.48, 95% CI 0.25-0.95, p=0.03).

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Survival Benefit from Primary Prevention Implantable Cardioverter Defibrillators

MedicalResearch.com Interview with:

Daniel J. Friedman, MD Duke University Hospital Duke Clinical Research Institute Durham, NC

Dr. Friedman

Daniel J. Friedman, MD
Duke University Hospital
Duke Clinical Research Institute
Durham, NC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although primary prevention ICDs have saved countless lives among patients with heart failure and a reduced ejection fraction, the use of primary prevention ICDs in patients with more advanced heart failure [defined by New York Heart Association Class (NYHA)] is controversial.

Specifically, there are conflicting data from the pivotal primary prevention ICD trials regarding whether primary prevention ICDs reduce all-cause mortality among patients with a severely reduced ejection fraction (≤35%) and NYHA III heart failure.

We performed a patient level meta-analysis using data from 4 pivotal primary prevention ICD trials (MADIT-I, MADIT-II, SCD-HeFT, and DEFINITE) to assess whether primary prevention ICD efficacy varied by NYHA class (II vs. III). Overall, the ICD reduced all-cause mortality among the overall population of patients (NYHA II and III). We subsequently assessed ICD efficacy after stratification by NYHA class.

Among NYHA II patients, the ICD significantly reduced all-cause mortality by reducing sudden cardiac death. Although NYHA III patients randomized to an ICD experienced a significantly lower rate of sudden cardiac death, this did not translate into a reduction in all-cause mortality, due to competing causes of non-sudden death (which an ICD cannot treat). Based on relatively wide confidence intervals associated with the estimate for ICD effect in NYHA III patients, there appears to be substantial heterogeneity in outcomes among these patients. This suggests that many NYHA III patients can benefit from a primary prevention ICD, but further study is necessary to determine which NYHA III patients are poised to benefit.

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Metformin Associated With Lower Mortality in CKD, CHF and Chronic Liver Disease

MedicalResearch.com Interview with:

Matthew J. Crowley, MD, MHS Assistant Professor of Medicine Member in the Duke Clinical Research Institute Duke University Medical Center

Dr. Matthew Crowley

Matthew J. Crowley, MD, MHS
Assistant Professor of Medicine
Member in the Duke Clinical Research Institute
Duke University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although metformin is widely considered to be the first-line drug for type 2 diabetes, concerns about lactic acidosis have traditionally limited its use in some populations. However, FDA now indicates that metformin may be used safely for patients with mild-moderate chronic kidney disease and other historical contraindications like congestive heart failure. With the lactic acidosis question addressed for these groups, this review asked “what do we know about how metformin affects mortality and other outcomes for patients with historical contraindications and precautions?”

The main take-home message is that metformin appears associated with lower mortality in patients with mild-moderate chronic kidney disease, congestive heart failure, and chronic liver disease.

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Marital History Linked to Survival After Stroke

MedicalResearch.com Interview with:

Matthew E. Dupre, Ph.D. Associate Professor Department of Community and Family Medicine & Duke Clinical Research Institute (DCRI) Duke University

Dr. Mathew Dupre

Matthew E. Dupre, Ph.D.
Associate Professor
Department of Community and Family Medicine &
Duke Clinical Research Institute (DCRI)
Duke University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There have been a handful of recent studies showing how divorce and widowhood increase one’s risk of suffering a serious health event such as a heart attack or stroke. Our research is the first to show that an individual’s marital history can have significant consequences for their prognosis after having a stroke.

We found that people who never married and those with a history of marital loss were significantly more likely to die after suffering a stroke than those who were stably married. We also found that adults who experienced more than one divorce or widowhood in their lifetime were about 50% more likely to die after having a stroke than those in a long-term stable marriage. We were also somewhat surprised to find that remarriage did not seem to reduce the risks from past marital losses.

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Hearing Loss Linked To Increased Depression and Dementia Risk

MedicalResearch.com Interview with:

Dr-Frank-Lin.jpg

Dr. Lin

Frank Robert Lin, M.D., Ph.D.
Associate Professor of Geriatric Medicine, Head and Neck Surgery
Johns Hopkins Medicine

MedicalResearch.com Editor’s note: Dr. Lin discussed his research during Cochlear’s Global Research Symposium, which brought together international experts from the audiology community.

MedicalResearch.com: Is there a link between hearing loss and the risk of developing dementia?

Response: In the last few years, we have investigated the link between hearing loss and dementia in large studies of older adults who have been followed for many years. In these studies, we and others have found that those with greater hearing loss have a higher risk of developing dementia even after we account for factors like age, education, medical comorbidities, etc. We think this is because there are some pathways through which hearing loss can directly affect our thinking and memory abilities

MedicalResearch.com: Is there an association between hearing loss and cognitive decline or premature death?

Response: There is a link between hearing loss and accelerated cognitive decline. There is also external research that links hearing loss and premature death (Friburg 2014, Contrera 2015). Hearing loss can also increase a person’s chance of using medical and social services

MedicalResearch.com: How is hearing loss linked to increased social isolation and depression in the elderly?

Response: Older people with hearing loss are at a greater risk of social isolation due to their difficulty communicating with people. These individuals may be less likely to go out, particularly to settings where listening can be difficult (e.g., restaurants), and even if they do go out, they may feel isolated from the conversation and not able to engage with others.

MedicalResearch.com: What should readers take away from your report?

Response: Readers should understand that we’re increasingly understanding that hearing loss can detrimentally impact our thinking and memory abilities, risk of dementia, and our ability to remain engaged with others. Ongoing research is now studying to what extent our current hearing loss therapies can reduce and mitigate these risks and promote healthy aging.

MedicalResearch.com: Is there anything else you would like to add?

Response: Readers should know that hearing loss is a growing public health issue. It has been estimated that by 2050 1.2 billion people will suffer from hearing loss, underscoring the need for us to address it and recognize the burden of hearing loss on wider health. To learn more visit,www.linresearch.org and www.nas.edu/hearing

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Cochlear’s Global Research Symposium October 2016

Disclosure:  Symposium supported by Cochlear Limited (ASX: COH), together with Macquarie University and the Australian Hearing Hub

www.cochlear.com

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Do People Wearing Activity Trackers Really Exercise More?

MedicalResearch.com Interview with:
Aarti Sahasranaman, PhD
Duke-NUS Gradaute Medical School
Singapore

MedicalResearch.com: What is the background for this study?

Response: More than half of adults in developed countries do not achieve recommended levels of physical activity. Despite the popularity of activity trackers as a tool for motivating and monitoring activity levels, little research exists on whether they can help people lead healthier lives, or if financial incentives could encourage people to wear them for longer and achieve higher fitness levels. One in ten US adults owns an activity tracker but research suggests that about a third of people abandon them within 6 months of purchase.

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Brain Scans Can Predict Specific Spontaneous Emotions

MedicalResearch.com Interview with:

Kevin S. LaBar, Ph.D. Professor and Head, Cognition & Cognitive Neuroscience Program Co-Director of Undergraduate Studies in Neuroscience Center for Cognitive Neuroscience Duke University Durham, NC

Dr. Kevin LaBar

Kevin S. LaBar, Ph.D.
Professor and Head, Cognition & Cognitive Neuroscience Program
Co-Director of Undergraduate Studies in Neuroscience
Center for Cognitive Neuroscience
Duke University
Durham, NC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Emotion research is limited by a lack of objective markers of emotional states. Most human research relies on self-report, but individuals may not have good insight into their own emotions. We have developed a new way to identify emotional states using brain imaging and machine learning tools. First, we induced emotional states using film and music clips while individuals were in an MRI scanner. We trained a computer algorithm to identify the brain areas that distinguished 7 emotions from each other (fear, anger, surprise, sadness, amusement, contentment, and a neutral state). This procedure created a brain map for each of the 7 emotions. Then, a new group of participants self-reported their emotional state every 30 seconds in an MRI scanner while no stimuli were presented. We could predict which emotion was spontaneously reported by the subjects by comparing their brain scans to each of the 7 emotion maps. Finally, in a large group of 499 subjects, we found that the presence of the fear map during rest predicted state and trait anxiety while the presence of the sadness map predicted state and trait depression.

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Most Gastric Bypass Patients Keep Weight Off After Surgery

MedicalResearch.com Interview with:

Matthew Leonard Maciejewski, PhD Professor in the Division of General Internal Medicine Department of Medicine Duke University School of Medicine Research Career Scientist and Director of the Health Economics and Policy Unit in the Center for Health Services Research in Primary Care Durham VA Medical Center

Dr. Matt Maciejewski

Matthew Leonard Maciejewski, PhD
Professor in the Division of General Internal Medicine
Department of Medicine
Duke University School of Medicine
Research Career Scientist and Director of the Health Economics and Policy Unit in the Center for Health Services Research in Primary Care
Durham VA Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: No study based on a US cohort undergoing current procedures has examined weight change comparing surgical patients and nonsurgical patients for as long as we have. This is the first study to report 10-year outcomes on gastric bypass patients and compare them to matched patients who did not get surgery. At 1 year, gastric bypass patients lost 31% of their baseline weight compared controls who only lost 1.1% of their baseline weight. At 10 years, gastric bypass had lost 28% of their baseline weight.

We also compared weight loss at 4 years for Veterans who received the 3 most common procedures (gastric bypass, sleeve gastrectomy, and adjustable gastric banding). At 4 years, patients undergoing gastric bypass lost more weight than patients undergoing sleeve gastrectomy or gastric banding. Given that few high quality studies have examined sleeve gastrectomy to 4 years, the 4-year sleeve outcomes contribute to filling this important evidence gap as the sleeve gastrectomy is now the most commonly performed bariatric procedure worldwide.

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Persistent Postpartum Pain Linked To Higher Risk of Depression

MedicalResearch.com Interview with:
MS WEI DU, First author
Third Year Medical Student
DUKE-NUS Medical School and
DR BAN LEONG SNG, Senior Author
Senior Consultant Department of Women’s Anesthesia KK
Women’s and Children’s Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

MS WEI DU: We performed a cohort study involving 200 healthy women who received epidural pain relief during the deliveries of their firstborns to investigate the relationship between persistent childbirth pain, psychological and pain vulnerability with postnatal depression. Postnatal depression was evaluated using the Edinburgh Postnatal Depression Score (EPDS).

Patients with persistent pain (>4 weeks postpartum) had significantly higher EPDS scores as compared to patients whose pain resolved by 4 weeks by a difference of 2.44 mean score, and compared to patients who never had pain postpartum by a difference of 4.07 mean score. Other significant factors that were associated with higher EDPS score included higher levels of stress, greater pain vulnerability during the intrapartum period and higher anxiety level at 6 to 8 weeks postpartum.

DR BAN LEONG SNG: Patients with persistent pain (>4 weeks postpartum) had significantly higher EPDS scores as compared to patients whose pain resolved by 4 weeks by a difference of 2.44 mean score, and compared to patients who never had pain postpartum by a difference of 4.07 mean score. Other significant factors that were associated with higher EDPS score included higher levels of stress, greater pain vulnerability during the intrapartum period and higher anxiety level at 6 to 8 weeks postpartum.

MedicalResearch.com: What should readers take away from your report?

MS WEI DU: We concluded that greater pain vulnerability and stress during intrapartum period, and presence of persistent pain or higher anxiety during postpartum period are positively associated with higher scores on postnatal depression tests.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

DR BAN LEONG SNG: The research findings support the need to address pain comprehensively to lessen the risk of developing postnatal depression. We are currently conducting a larger study to evaluate the impact of pain and postnatal depression in pregnant women.

MedicalResearch.com: Is there anything else you would like to add?

DR BAN LEONG SNG: Postnatal evaluation and management of childbirth pain and postnatal depression is important in our care of mothers and their newborns.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

World Congress of Anaesthesiologists abstract discussing:

Persistent childbirth pain increases risk of postnatal depression

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Same Genes Predict Educational Attainment and Socioeconomic Success

MedicalResearch.com Interview with:

Daniel Belsky, PhD Assistant Professor of Medicine Duke University School of Medicine Durham, NC 27708

Dr. Daniel Belsky

Daniel Belsky, PhD
Assistant Professor of Medicine
Duke University School of Medicine
Durham, NC 27708

MedicalResearch.com: What is the background for this study?

Dr. Belsky: The genome-wide association study
(GWAS) of educational attainment by the Social Science Genetic Association Consortium was the first large-scale genetic investigation of a human social/behavioral trait. Follow-up studies, including studies some of us were involved in, established that the genetic signature uncovered by this GWAS was highly reproducible; people who carried more education-associated alleles completed more schooling—and this was true even when studies compared siblings in the same family. Because getting a good education requires many of the same skills and abilities needed to get ahead in life more generally, we hypothesized that the same genetics that predicted success in schooling would predict success in life.

To ask this question, we designed a study to do three things.
• First, we wanted to test if the genetics of success in schooling would predict social and economic success through midlife (better jobs, salaries, and credit scores, fewer financial problems, etc.).
• Second, if the genetics of educational success did predict broader economic outcomes, we wanted to test how this came about:
o When and how did differences develop between children whose genomes predicted more educational success and children whose genomes predicted less success?
o The goal of this analysis was to try and learn something about pathways to success – pathways that any child could take advantage of, regardless of their genetics.
• Third, we wanted to know what kinds of psychological characteristics linked genetics with behavior. The goal of this analysis was to begin building a bridge between statistical models of the genome and the biological mechanisms that connect DNA sequence with behavior.

MedicalResearch.com: What are the main findings?

Dr. Belsky: There are four major take home points:
(1) Genetic discoveries for educational attainment are not discoveries for education only. The same genetics predict socioeconomic success well beyond the completion of schooling.
(2) Genetic discoveries were associated with social mobility — children with higher polygenic scores tended to achieve more socioeconomic success even if they were born poor.
(3) The psychological characteristics that mediated genetic associations with life outcomes included intelligence, but also self-control and interpersonal skills, for example being friendly.
(4) The pattern of characteristics and behaviors that connects DNA sequence with life outcomes begins early in life and extends through adulthood. Kids with higher polygenic scores started talking and reading earlier, and they had higher IQ scores, more self-control, and were more skilled interpersonally. As they grew into adolescence and adulthood, they were more ambitious, more willing to move away from home in search of opportunity, more successful in attracting better educated and higher earning spouses, and better at managing their money.

MedicalResearch.com: What should readers take away from your report?

Dr. Belsky: Our research speaks to three audiences. To scientists — behavioral/social and genetic — our results highlight the need for interdisciplinary collaborations to untangle genetic influences on human outcomes. We found that children’s genes shaped the environments they grew up in, suggesting that social and behavioral scientists may need to pay more attention to genetics. We also found that genes influenced life outcomes through patterns of behavior that are also affected by environmental circumstances, suggesting that geneticists may need to pay more attention to the social and behavioral sciences.
To policy makers, our research highlights the importance of developing regulations for the use of genetic information. “Precision education” or other tailoring of environments to children’s genomes is not possible with the data we have in hand today. But our findings suggest that such data may someday become available. It is vital to have the conversation about what that might mean and how we will deal with it BEFORE it happens.
Finally, to the general public, our research emphasizes the small effects of known-genetics on important human outcomes. Our findings provide a provocative window into how our genes may shape our lives. But we can make only very weak predictions about how far a child can go in life based on their genes.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Belsky: Two big questions are “How do children’s environments affect the relationship between their genomes and their outcomes as adults?” and “How may genetics linked to educational success affect adult health and aging?”

MedicalResearch.com: Is there anything else you would like to add?

Dr. Belsky: I was most surprised to find the very same genetics that predicted better cognitive and social functioning in children were unrelated to their physical health. When we tested if the polygenic score predicted children’s physical health – measured from repeated clinical exams across childhood – we found no association whatsoever.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

D. W. Belsky, T. E. Moffitt, D. L. Corcoran, B. Domingue, H. Harrington, S. Hogan, R. Houts, S. Ramrakha, K. Sugden, B. S. Williams, R. Poulton, A. Caspi. The Genetics of Success: How Single-Nucleotide Polymorphisms Associated With Educational Attainment Relate to Life-Course Development. Psychological Science, 2016; DOI:10.1177/0956797616643070

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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