Tag Archives: Brown University

Brown University study: Computer models provide new understanding of sickle cell disease

30 Jul

The National Heart, Lung and Blood Institute describes sickle cell disease:

The term sickle cell disease (SCD) describes a group of inherited red blood cell disorders. People with SCD have abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in their red blood cells.
Hemoglobin is a protein in red blood cells that carries oxygen throughout the body.
“Inherited” means that the disease is passed by genes from parents to their children. SCD is not contagious. A person cannot catch it, like a cold or infection, from someone else.
People who have SCD inherit two abnormal hemoglobin genes, one from each parent. In all forms of SCD, at least one of the two abnormal genes causes a person’s body to make hemoglobin S. When a person has two hemoglobin S genes, Hemoglobin SS, the disease is called sickle cell anemia. This is the most common and often most severe kind of SCD.
Hemoglobin SC disease and hemoglobin Sβ thalassemia (thal-uh-SEE-me-uh) are two other common forms of SCD…. https://www.nhlbi.nih.gov/health/health-topics/topics/sca/

The Centers for Disease Control and Prevention provide data about sickle cell disease:

In the United States
The exact number of people living with SCD in the U.S. is unknown. Working with partners, the CDC supports projects to learn about the number of people living with SCD to better understand how the disease impacts their health.
It is estimated that:
• SCD affects approximately 100,000 Americans.
• SCD occurs among about 1 out of every 365 Black or African-American births.
• SCD occurs among about 1 out of every 16,300 Hispanic-American births.
• About 1 in 13 Black or African-American babies is born with sickle cell trait (SCT).
Comprehensive Care
• People with SCD have less access to comprehensive team care than people with genetic disorders such as hemophilia and cystic fibrosis. [Read article]
Mortality
• Sickle cell-related death among Black or African-American children younger than 4 years of age fell by 42% from 1999 through 2002. This drop coincided with the introduction in 2000 of a vaccine that protects against invasive pneumococcal disease.
[Read summary]
• Relative to the rate for the period 1983 through 1986, the SCD mortality rate for the period 1999 through 2002 decreased by:
o 68% at age 0 through 3 years;
o 39% at age 4 through 9 years; and
o 24% at age 10 through 14 years.
[Read summary]
• Mortality Among Children with Sickle Cell Disease Identified by Newborn Screening During 1990-1994 — California, Illinois, and New York:
o Among the children with Hb SS disease, 1% died as a result of SCD-related causes during the first 3 years of life.
o In California and Illinois, by the end of 1995, the cumulative mortality rate was 1.5 per 100 Black or African-American children with SCD. The equivalent cumulative mortality rate for all Black or African-American infants born during this period in California and Illinois was 2.0 per 100 Black or African-American newborns.
[Read article]
Economic Costs
• During 2005, medical expenditures for children with SCD averaged $11,702 for children with Medicaid coverage and $14,772 for children with employer-sponsored insurance. About 40% of both groups had at least one hospital stay.
[Read summary]
• SCD is a major public health concern. From 1989 through 1993, an average of 75,000 hospitalizations due to SCD occurred in the United States, costing approximately $475 million.
[Read summary]
https://www.cdc.gov/ncbddd/sicklecell/data.html

See, American Society of Hematology http://www.hematology.org/Patients/Anemia/Sickle-Cell.aspx
Science Daily reported in Computer models provide new understanding of sickle cell disease:

Computer models developed by Brown University mathematicians show new details of what happens inside a red blood cell affected by sickle cell disease. The researchers said they hope their models, described in an article in the Biophysical Journal, will help in assessing drug strategies to combat the genetic blood disorder, which affects millions of people worldwide.
Sickle cell disease affects hemoglobin, molecules within red blood cells responsible for transporting oxygen. In normal red blood cells, hemoglobin is dispersed evenly throughout the cell. In sickle red blood cells, mutated hemoglobin can polymerize when deprived of oxygen, assembling themselves into long polymer fibers that push against the membranes of the cells, forcing them out of shape. The stiff, ill-shaped cells can become lodged in small capillaries throughout the body, leading to painful episodes known as sickle cell crisis….
The model uses detailed biomechanical data on how sickle hemoglobin molecules behave and bind with each other to simulate the assembly of a polymer fiber. Prior to this work, the problem had been that as the fiber grows, so does the amount of data the model must crunch. Modeling an entire polymer fiber at cellular scale using the details of each molecule was simply too computationally expensive….
The researchers’ solution was to apply what they call a mesoscopic adaptive resolution scheme or MARS. The MARS model calculates the detailed dynamics of each individual hemoglobin molecule only at the each end of polymer fibers, where new molecules are being recruited into the fiber. Once four layers of a fiber have been established, the model automatically dials back the resolution at which it represents that section. The model retains the important information about how the fiber behaves mechanically, but glosses over the fine details of each constituent molecule….
Using the new MARS simulations, the researchers were able to show how different configurations of growing polymer fibers are able to produce cells with different shapes. Though the disease gets its name because it causes many red blood cells take on a sickle-like shape, there are actually a variety of abnormal cell shapes present. This new modeling approach showed new details about how different fiber structures inside the cell produce different cell shapes….
There are only two drugs on the market that has been approved by the FDA for treating sickle cell, Karniadakis says. One of them, called hydroxyurea, is thought to work by boosting the amount of fetal hemoglobin — the kind of hemoglobin that babies are born with — in a patient’s blood. Fetal hemoglobin is resistant to polymerization and, when present in sufficient quantity, is thought to disrupt the polymerization of sickle cell hemoglobin.
Using these new models, Karniadakis and his colleagues can now run simulations that include fetal hemoglobin. Those simulations could help to confirm that fetal hemoglobin does indeed disrupt polymerization, as well as help to establish how much fetal hemoglobin is necessary. That could help in establishing better dosage guidelines or in developing new and more effective drugs, the researchers say. https://www.sciencedaily.com/releases/2017/07/170728153954.htm

Citation:

Computer models provide new understanding of sickle cell disease
Date: July 28, 2017
Source: Brown University
Summary:
Simulations developed by mathematicians provide new details of how sickle cell disease manifests inside red blood cells, which could help in developing new treatments.

Journal Reference:
1. Lu Lu, He Li, Xin Bian, Xuejin Li, George Em Karniadakis. Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions between Sickle Cell Fibers. Biophysical Journal, 2017; 113 (1): 48 DOI: 10.1016/j.bpj.2017.05.050

Here is the Brown press release:

Computer models provide new understanding of sickle cell disease
July 28, 2017 Media contact: Kevin Stacey 401-863-3766
Simulations developed by Brown University mathematicians provide new details of how sickle cell disease manifests inside red blood cells, which could help in developing new treatments.
PROVIDENCE, R.I. [Brown University] — Computer models developed by Brown University mathematicians show new details of what happens inside a red blood cell affected by sickle cell disease. The researchers said they hope their models, described in an article in the Biophysical Journal, will help in assessing drug strategies to combat the genetic blood disorder, which affects millions of people worldwide.
Sickle cell disease affects hemoglobin, molecules within red blood cells responsible for transporting oxygen. In normal red blood cells, hemoglobin is dispersed evenly throughout the cell. In sickle red blood cells, mutated hemoglobin can polymerize when deprived of oxygen, assembling themselves into long polymer fibers that push against the membranes of the cells, forcing them out of shape. The stiff, ill-shaped cells can become lodged in small capillaries throughout the body, leading to painful episodes known as sickle cell crisis.
“The goal of our work is to model both how these sickle hemoglobin fibers form as well as the mechanical properties of those fibers,” said Lu Lu, a Ph.D. student in Brown Division of Applied Mathematics and the study’s lead author. “There had been separate models for each of these things individually developed by us, but this brings those together into one comprehensive model.”
The model uses detailed biomechanical data on how sickle hemoglobin molecules behave and bind with each other to simulate the assembly of a polymer fiber. Prior to this work, the problem had been that as the fiber grows, so does the amount of data the model must crunch. Modeling an entire polymer fiber at cellular scale using the details of each molecule was simply too computationally expensive.
“Even the world’s fastest supercomputers wouldn’t be able to handle it,” said George Karniadakis, professor of applied math at Brown and the paper’s senior author. “There’s just too much happening and no way to capture it all computationally. That’s what we were able to overcome with this work.”
As the simulated fiber grows, the model dials back the resolution, representing established parts of the fiber with courser grain, which makes simulating the fibers computationally tractable.
The researchers’ solution was to apply what they call a mesoscopic adaptive resolution scheme or MARS. The MARS model calculates the detailed dynamics of each individual hemoglobin molecule only at the each end of polymer fibers, where new molecules are being recruited into the fiber. Once four layers of a fiber have been established, the model automatically dials back the resolution at which it represents that section. The model retains the important information about how the fiber behaves mechanically, but glosses over the fine details of each constituent molecule.
“By eliminating the fine details where we don’t need them, we develop a model that can simulate this whole process and its effects on a red blood cell,” Karniadakis said.
Using the new MARS simulations, the researchers were able to show how different configurations of growing polymer fibers are able to produce cells with different shapes. Though the disease gets its name because it causes many red blood cells take on a sickle-like shape, there are actually a variety of abnormal cell shapes present. This new modeling approach showed new details about how different fiber structures inside the cell produce different cell shapes.
“We are able to produce a polymerization profile for each of the cell types associated with the disease,” Karniadakis said. “Now the goal is to use these models to look for ways of preventing the disease onset.”
The researchers used their models to create “polymerization profiles” for different cell shapes associated with sickle cell disease. The model above shows a cell with multiple fibers forming.
There are only two drugs on the market that has been approved by the FDA for treating sickle cell, Karniadakis says. One of them, called hydroxyurea, is thought to work by boosting the amount of fetal hemoglobin — the kind of hemoglobin that babies are born with — in a patient’s blood. Fetal hemoglobin is resistant to polymerization and, when present in sufficient quantity, is thought to disrupt the polymerization of sickle cell hemoglobin.
Using these new models, Karniadakis and his colleagues can now run simulations that include fetal hemoglobin. Those simulations could help to confirm that fetal hemoglobin does indeed disrupt polymerization, as well as help to establish how much fetal hemoglobin is necessary. That could help in establishing better dosage guidelines or in developing new and more effective drugs, the researchers say.
“The models give us a way to do preliminary testing on new approaches to stopping this disease,” Karniadakis said. “Now that we can simulate the entire polymerization process, we think the models will be much more useful.”
Lu and Karniadakis’ co-authors on the paper were He Li, Xin Bian and Xuejin Li, all from Brown’s Division of Applied Mathematics. The work was supported by the National Institutes of Health (U01HL114476). Computer time and other resources were provided under grants from the Department of Energy (DE-AC02-06CH11357, DE-AC05-00OR22725).
Note to Editors:
Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews, and maintains an ISDN line for radio interviews. For more information, call (401) 863-2476.

The Brown study is a breakthrough because it may lead to advanced and individual specific treatment for sickle cell disease.

WebMD described current treatment for sickle cell disease:

Treatment involves getting routine tests to monitor health, managing pain events (crises), and treating related health problems as they arise.
Treatment for severe cases of sickle cell disease may include medicines. For more information, see Medications.
Treatment for children
When parents learn that their baby has sickle cell disease, it’s the beginning of a lifelong education process. Knowing as much as you can about the disease can help you control symptoms as they arise and know what to do in emergency situations. Treatment includes:
• Routine childhood immunizations. Immunizations in adulthood are important too.
• Daily antibiotics from 2 months to 5 years of age to prevent life-threatening infections. This practice stops at age 5 because older children don’t have as many severe infections.
• The medicine hydroxyurea.
• Multivitamin supplements with iron during infancy.
• Folic acid supplements daily.
• Protein supplements if there is a lag in weight gain.
Starting at age 2 years, your child should get screened every now and then with a transcranial ultrasound. This test measures blood flow in the arteries of the head and neck. If test results show a high chance for stroke, your child may get blood transfusions to lower the risk.3 http://www.webmd.com/a-to-z-guides/tc/sickle-cell-disease-treatment-overview#1

As with any chronic disease, early diagnosis and treatment by qualified medical personnel is essential. See, Children’s Hospital Directory https://www.childrenshospitals.org/Directories/Hospital-Directory

Resources:

Sickle cell anemia patient ‘cured’ by gene therapy, doctors say
http://www.cnn.com/2017/03/03/health/sickle-cell-anemia/index.html

What Is Sickle Cell Disease?
https://www.nhlbi.nih.gov/health/health-topics/topics/sca/

Sickle Cell Anemia
http://www.nytimes.com/health/guides/disease/sickle-cell-anemia/overview.html

Sickle Cell Anemia Treatment & Management
http://emedicine.medscape.com/article/205926-treatment

Where information leads to Hope. © Dr. Wilda.com

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Brown University study: Sexually active girls more likely to be bullied

28 Sep

Moi wrote in Sexualization of girls: A generation looking much too old for their maturity level:
Just ride the bus, go to the mall or just walk down a city street and one will encounter young girls who look like they are ten going on thirty. What’s going on with that? Moi wrote about the sexualization of girls in Study: Girls as young as six think of themselves as sex objects:
In Children too sexy for their years, moi said:
Maybe, because some parents may not know what is age appropriate for their attire, they haven’t got a clue about what is appropriate for children. There is nothing sadder than a 40 something, 50 something trying to look like they are twenty. What wasn’t sagging when you are 20, is more than likely than not, sagging now.

Kristen Russell Dobson, the managing editor of Parent Map, has a great article in Parent Map. In Are Girls Acting Sexing Too Young?
http://www.parentmap.com/article/are-girls-acting-sexy-too-young
The culture seems to be sexualizing children at an ever younger age and it becomes more difficult for parents and guardians to allow children to just remain, well children, for a bit longer. Still, parents and guardians must do their part to make sure children are in safe and secure environments. A pole dancing fourth grader is simply unacceptable.

Moi loves fashion and adores seeing adult looks on adults. Many 20 and 30 somethings prefer what I would charitably call the “slut chic” look. This look is questionable fashion taste, in my opinion, but at least the look involves questionable taste on the part of adults as to how they present themselves to the public. https://drwilda.wordpress.com/2011/11/11/children-too-sexy-for-their-years/ https://drwilda.com/tag/study-girls-as-young-as-6-are-thinking-of-selves-as-sex-objects/

Alexandra Svokos reported in the Huffington Post article, Sexually Active Teen Girls More Likely To Be Bullied Than Similar Boys, Study Finds:

Using data from a 2011 national survey of over 13,000 high school students, Brown researchers found that sexually active high school girls report being bullied 2.27 times more often than their male counterparts.
In addition, both girls and boys were more likely to report bullying if they also reported being sexually active without using condoms or other contraceptives. (Overall, 64 percent of sexually active students said they used a condom during their last engagement in intercourse.) The report suggested that while “engaging in sexual behaviors may be associated with greater levels of popularity” in some cases, that doesn’t happen when their peers think the teens behave sexually in ways that are “risky or dangerous to one’s health….” http://www.huffingtonpost.com/2014/09/26/sexual-activity-bullying-study_n_5877168.html?utm_hp_ref=education&ir=Education

Here is a portion of Kate Talerico’s Brown Daily Herald article, Sex, bullying linked in girls, study suggests:

The sexual double standard — the concept that women are more highly criticized for sexual activity than men are — may play a role in bullying victimization among high school girls, according to a new study led by a team of University researchers.
“Sexually active girls have 2.27 times the odds of being bullied compared to boys who are also sexually active,” said Hailee Dunn, the former manager of the Center for Evidence-Based Medicine and lead author of the study. The study was co-authored by three other Brown researchers and was released in this month’s issue of the journal Women’s Health Issues.
Girls who have engaged in sexual intercourse are almost twice as likely to be bullied, Dunn said. “If you look at boys, it’s not as significant.”
Girls who became sexually active at younger ages were found to be more prone to bullying than those who were not sexually active until they were older.
This same correlation does not exist with boys, “so that may be indicative of some sort of sexual double standard,” Dunn said.
In regard to use of condoms and other forms of contraception, there are no significant gender differences, according to the study.
From this finding, the researchers “interpreted that maybe our health education programs are working,” Dunn said. “There is this sort of stigma if you’re not using a form of protection that applies to both boys and girls.” Both boys and girls who had not used condoms reported higher rates of bullying than those who had.
The study analyzed the results of 13,065 high school boys and girls who took the Youth Risk Behavior Survey in 2011, Dunn said….http://www.browndailyherald.com/2014/09/22/sex-bullying-linked-girls-study-suggests/

Citation:

Association between Sexual Behaviors, Bullying Victimization and Suicidal Ideation in a National Sample of High School Students: Implications of a Sexual Double Standard
Hailee K. Dunn, MPH
,
Annie Gjelsvik, PhD
,
Deborah N. Pearlman, PhD
,
Melissa A. Clark, PhD
Received: November 5, 2013; Received in revised form: April 24, 2014; Accepted: June 19, 2014;
DOI: http://dx.doi.org/10.1016/j.whi.2014.06.008
Abstract
Purpose
The sexual double standard is the notion that women are more harshly judged for their sexual behaviors than men. The purpose of this study was to investigate if the sexual double standard could explain gender differences in bullying victimization among adolescents and the extent to which that relationship correlated with depression and suicidal ideation.
Methods
Analyses were conducted using a sample of high school students (n = 13,065) from the 2011 Youth Risk Behavior Survey, a cross-sectional and national school-based survey conducted by the Centers for Disease Control and Prevention. Data were assessed using multiple logistic regression, gender-stratified analyses, and interaction terms.
Findings
Students who engaged in sexual intercourse (sexually active) had higher odds of being bullied. When this association was stratified by gender, odds of being bullying increased for girls (odds ratio [OR], 1.83; 95% CI, 1.58–2.13) and decreased for boys (OR, 0.94; 95% CI, 0.77–1.16). Sexually active students who were bullied also displayed more than five times (OR, 5.65; 95% CI, 4.71–6.78) the adjusted odds of depression and three times (adjusted OR, 3.38; 95% CI, 2.65–4.32) the adjusted odds of suicidal ideation compared with students who reported neither of those behavioral characteristics. When stratified by gender, girls had slightly higher odds of depression and suicidal ideation but overall, the odds remained strong for both genders.
Conclusions
Results provide some evidence that a sexual double standard exists and may play a prominent role in bullying victimization among girls. Therefore, addressing the sexual double may be important to consider when tailoring school bullying intervention programs.

Moi supposes there are a group of parents who don’t want conflict and give in because “everyone else is doing it.” Remember the everyone else is often the lowest common denominator. Some parents feel they must be their child’s BFF. Wrong. You are supposed to be the parent. Some one has to be in charge. Russell provide some excellent resources for managing the media. Find resources for managing media https://www.parentmap.com/article/resources-for-managing-kids-media

Dr. Wilda has been just saying for quite a while.

Resources

Popwatch’s Miley Cyrus Pole Dance Video http://popwatch.ew.com/2009/08/10/miley-cyrus-pole-dancing-at-the-teen-choice-awards-rather-unfortunate-yes/

Baby Center Blog Comments About Miley Cyrus Pole Dance http://blogs.babycenter.com/celebrities/billy-ray-cyrus-defends-mileys-artistic-pole-dancing/

The Sexualization of Children http://www.tellinitlikeitis.net/2009/03/the-sexualization-of-children-and-adolescents-epidemic.html

Related:

Let’s speak the truth: Values and character training are needed in schools http://drwildaoldfart.wordpress.com/2013/03/02/lets-speak-the-truth-values-and-character-training-are-needed-in-schools/

Do ‘grown-ups’ have to be reminded to keep their clothes on in public? Apparently so http://drwildaoldfart.wordpress.com/2013/02/09/do-grown-ups-have-to-be-reminded-to-keep-their-clothes-on-in-public-apparently-so/

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Dr. Wilda says this about that ©

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http://drwildareviews.wordpress.com/

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