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Science Times - Childhood death, Neanderthals, Breast Cancer, and Archival Tools
4 Germs Cause Most of Infants’ Severe Diarrhea
By DONALD G. McNEIL Jr., The New York Times, May 20, 2013
Just four germs are responsible for most of the severe and fatal diarrhea among the world’s infants, according to a large new study.
Diarrhea is a major killer of children, with an estimated 800,000 deaths each year; it has many causes, and doctors want to focus on the most common ones to bring death rates down.
The study, financed by the Bill and Melinda Gates Foundation and published by The Lancet, found that the most common causes were rotavirus; a protozoan called Cryptosporidium; and two bacteria, Shigella and a toxin-producing strain of E. coli. In some areas, other pathogens, including the bacteria that causes cholera, were also important.
The study followed more than 9,000 children with diarrhea seen at clinics in Bangladesh, Gambia, India, Kenya, Mali, Mozambique and Pakistan, and, for comparison, more than 13,000 children without the disease. The children with diarrhea were more likely to have stunted growth and eight times as likely to die during a two-month follow-up period.
Diarrhea seemed to be linked to chronic malnutrition, which causes gut inflammation that can make it harder to digest food.
The prominent role of Cryptosporidium came as a surprise to the authors; it had been best known as a killer of adults whose immune systems were suppressed by AIDS.
In an editorial accompanying the study, other experts said rotavirus vaccine could save many lives. The GAVI Alliance, which helps delivers vaccines to poor countries, recently included rotavirus in the vaccines it would buy at $2.50 per dose, and an Indian company said it would soon make a version that would cost $1. Zinc and oral rehydration packets continue to be important in treatment.
Similar large studies should be done to find the underlying causes of other common infections, the editorial said. An obvious candidate would be pneumonia, another major killer of infants that has many causes.
From Neanderthal Molar, Scientists Infer Early Weaning
By JOHN NOBLE WILFORD, The New York Times, May 22, 2013
Modern mothers love to debate how long to breast-feed, a topic that stirs both guilt and pride. Now — in a very preliminary finding — the Neanderthals are weighing in.
By looking at barium levels in the fossilized molar of a Neanderthal child, researchers concluded that the child had been breast-fed exclusively for the first seven months, followed by seven months of mother’s milk supplemented by other food. Then the barium pattern in the tooth enamel “returned to baseline prenatal levels, indicating an abrupt cessation of breast-feeding at 1.2 years of age,” the scientists reported on Wednesday in the journal Nature.
While that timetable conforms with the current recommendations of the American Academy of Pediatrics — which suggests that mothers exclusively breast-feed babies for 6 months and continue for 12 months if possible — it represents a much shorter span of breast-feeding than practiced by apes or a vast majority of modern humans. The average age of weaning in nonindustrial populations is about 2.5 years; in chimpanzees in the wild, it is about 5.3 years. Of course, living conditions were much different for our evolutionary cousins, the Neanderthals, extinct for the last 30,000 years.
The findings, which drew strong skepticism from some scientists, were meant to highlight a method of linking barium levels in teeth to dietary changes. In the Nature report, researchers from the United States and Australia described tests among human infants and captive macaques showing that traces of the element barium in tooth enamel appeared to accurately reflect transitions from mother’s milk through weaning. The barium levels rose during breast-feeding and fell off sharply on weaning.
The researchers then decided to apply the barium test to the fossilized molar of a Neanderthal child, collected in Belgium. The tooth’s fossilization, the researchers discovered, had not destroyed the barium biomarker, as had been feared.
This is the first documentation of diet transitions in a juvenile Neanderthal, the researchers said in interviews, suggesting that the barium technique may open the way to a more rigorous exploration of early-life dietary history of fossil hominins.
“Our studies on macaques and modern human children provide strong evidence that barium patterns in teeth do accurately reflect transitions from maternal milk to weaning,” said Manish Arora, a team member from the University of Sydney. He is also affiliated with the Icahn School of Medicine at Mount Sinai Hospital in New York City, and acted as the principal spokesman for the researchers.
But Michael Richards, a specialist in ancient teeth and bones at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, noted that the examination of trace elements, like barium, in archaeological samples went out of use in the 1970s and ‘80s, as scientists showed that bone and teeth incorporated elements from the soil they were buried in, not necessarily from a lifetime diet.
“Recently, perhaps as the generation that did this work retires,” Dr. Richards continued, a new generation has been “returning to these methods.” He said he was surprised that Nature published the report.
Other scientists who investigate Neanderthals and other extinct hominins were guarded in their assessment of the findings. They worried that the key element in the study was confined to only one fossil specimen.
Dr. Arora acknowledged that “it is, of course, not possible to generalize to all Neanderthals from a single sample, but our observation of the exclusive breast-feeding period” in one young Neanderthal “does extend existing concepts of Neanderthal behavior.”
Erik Trinkaus, a paleoanthropologist at Washington University in St. Louis, who is an authority on Neanderthals, said the onset of weaning in the test appeared to be too early. He also cautioned, “My impression is the physiology and chemistry of nursing is vastly more complicated, and the concentrations of barium are too low that it’s hard to get reliable data.”
Tanya Smith, an evolutionary biologist at Harvard and an author of the report, said in an e-mail that the team hoped “to examine additional fossils to determine at what age Neanderthals naturally weaned their infants.” In the report, the researchers conceded that the abrupt, possibly early weaning could not be readily explained.
“We are excited about this technique as we feel that it will allow us to look directly at weaning, an important aspect of life history, in expanded samples of Neanderthals and fossil Homo sapiens,” Dr. Smith said.
The timing of weaning can be critical in contemporary human societies. Completed too early, it can expose a child to more health problems; but shorter periods of breast-feeding lead to shorter intervals between births, which influences population growth. Human infants are often weaned earlier than close ape relatives, often by several years.
As for Neanderthals, lately, science has been getting up close and personal with them. When Neanderthals and modern humans first encountered each other in Eurasia, some paired off for a go at interspecies sex. How frequent these dalliances were, and over how long a time, is unknown. But the presence of at least 2.5 percent of Neanderthal DNA in most humans with European roots exposes the secret of viable interbreeding in the Stone Age caves.
In concluding their report, the researchers said the barium sampling would most likely be definitive in testing hypotheses about the consequences of later or earlier weaning on Neanderthals, compared with Homo sapiens. No one ventured speculation on any possible role maternal milk played in the downfall of Neanderthals after the arrival of modern humans in Europe.
No Easy Choices on Breast Reconstruction
By RONI CARYN RABIN, The New York Times, MAY 20, 2013
By almost any measure, Roseann Valletti’s reconstructive breast surgery was a success. Although it was a protracted process, involving some pain and a nightmarish nipple replacement, she is pleased with how she looks.
But she is uncomfortable. All the time. “It feels like I’m wrapped up in duct tape,” said Mrs. Valletti, 54, of the persistent tightness in her chest that many women describe after breast reconstruction.
“They look terrific, to the eye,” added Mrs. Valletti, a teacher who lives Valley Stream, N.Y., and who learned she had early-stage cancer in both breasts five years ago. “But it’s never going to feel like it’s not pulling or it’s not tight. It took me a while to accept that. This is the new normal.”
Last week the actress Angelina Jolie announced in The New York Times that she had had a double mastectomy in February after testing positive for a genetic mutation that put her at high risk for breast and ovarian cancer. She also had reconstructive surgery.
Her disclosure was lauded by some advocates as a bold move that will inspire women to be proactive, learn about their family histories and risks, and consider genetic testing.
At the same time, some breast surgeons are discomfited that some might infer from the article that reconstructive surgery is a quick and easy procedure, and worry that Ms. Jolie inadvertently may have understated the risks and potential complications.
For most patients, like Mrs. Valletti, breast reconstruction requires an extended series of operations and follow-up visits that can yield variable results. Some women experience so many complications that they just have the implants removed.
“We do not yet have the ability to wave a wand over you and take out breast tissue and put in an implant — we’re not at “Star Trek” medicine,” said Dr. Deanna J. Attai, a breast surgeon in Burbank, Calif., who is on the board of the American Society of Breast Surgeons.
Ms. Jolie said that she completed her reconstructive surgeries in nine weeks, but for many patients the process takes closer to nine months. “Three months is probably a little unusual,” said Dr. Gregory R. D. Evans, in Orange, Calif., president of the American Society of Plastic Surgeons. “I usually tell my patients it will take about a year.”
And it is major surgery. Even with the best plastic surgeon, breast reconstruction carries the risks of infection, bleeding, anesthesia complications, scarring and persistent pain in the back and shoulder. Implants can rupture or leak, and may need to be replaced. If tissue is transplanted to the breast from other parts of the body, there will be additional incisions that need to heal. If muscle is removed, long-term weakness may result.
A syndrome called upper quarter dysfunction — its symptoms include pain, restricted immobility and impaired sensation and strength — has been reported in over half of breast cancer survivors and may be more frequent in those who undergo breast reconstruction, according to a 2012 study in the journal Cancer.
“People have to understand it’s not a breeze,” said Geri Barish, president of 1 in 9: The Long Island Breast Cancer Action Coalition and a three-time survivor of breast cancer. “I don’t want people to think this is the cure-all, that this is it, hurry up, run out and get the test and have your ovaries and breasts removed.”
Types of Reconstruction
An array of new techniques, each with its own risks and potential benefits, makes for bewildering options for women. The first choice in breast reconstruction is whether to have implants or to make the new breast from muscle or fat and skin taken from elsewhere in the body, often from the abdomen — so-called autologous tissue transfer.
More plastic surgeons are familiar with implants, and the procedure is less expensive than tissue transfer. Of the 91,655 women who had reconstruction last year in the United States, a vast majority opted for implants, with 64,114 choosing silicone and 7,898 choosing saline, according to the American Society of Plastic Surgeons. Just over 19,000 women chose autologous tissue transfer.
Many surgeons believe silicone implants confer a more natural look than saline, despite a long-running controversy over their safety. The Food and Drug Administration allowed silicone implants back on the market in 2006, after studies showed they did not increase the risk of immune disease. A new type is filled with a thick gel that may pose less risk of leakage.
Whether they are silicone or saline, however, implants do not last a lifetime. As many as half need to be replaced or removed within 10 years, according to the American Cancer Society. The implants can rupture, cause infections and lead to pain. Scar tissue often forms around the implants, making the breast hardened or misshapen. Last year alone, there were 16,596 procedures done to remove breast implants.
Reconstruction may be started at the same time as the mastectomy, or later. Usually the first step is to place a so-called tissue expander under the chest muscle, which normally presses against the ribs. The surgeon injects saline into the balloonlike pouch at regular intervals several weeks apart to create space for the implant.
Eventually, the expander is removed and replaced with the implant. (Unlike breast tissue, which sits on top of the chest muscle, the implant is situated under the muscle, which holds it in place.) The process can take several months, longer if problems develop or the patient needs other treatment like radiation, which tends to damage the surrounding skin and make it less hospitable to an implant.
In autologous tissue transfers, muscle, skin or fat from another part of the patient’s body substitutes for an implant. Some surgeons believe this creates a more natural-feeling and natural-looking breast. There are several options.
The transverse rectus abdominis myocutaneous, or TRAM, flap procedure uses tissue and muscle from the lower abdomen to shape a breast mound. But the surgery weakens the abdominal area, and at Johns Hopkins Breast Center, the procedure has been abandoned because of the risk of hernias and abdominal bulges and limitations on lifting after surgery.
Instead, some surgeons now perform the deep inferior epigastric artery perforator, or DIEP, flap procedure, which uses only abdominal skin and tissue, not muscle, to create the breast. Both the TRAM and DIEP surgeries are lengthy procedures that can last 12 hours and can lead to a complication of necrosis, or tissue death, if there isn’t adequate blood supply, Dr. Attai said.
A third type of flap procedure relies on back muscle that is moved under the skin to the front of the chest, but this can weaken the back, shoulder or arm. In yet another procedure, the gluteal free flap, tissue and muscle from the buttocks are used to create a breast mound.
Simulating a Nipple
Reconstruction of the nipple has long been a challenge. Surgeons have used incision scar tissue or tissue taken from the groin or between the buttocks to craft nipples. Tattoos are also used to darken the areola, with 3-D tattoos that create the impression of a nipple.
With a nipple- and skin-sparing mastectomy, the surgeon removes all of the glandular breast tissue while preserving the skin, areola and nipple, much as one might scoop all the fleshy fruit out of an orange and leave the skin intact. This is the procedure Ms. Jolie had. Yet even when it is successful, the nipples usually lose sensation and are numb and cannot play the same role in sexual arousal as before surgery.
Residual breast cells may be left behind, and there is a concern that these may become cancerous. The American Society of Breast Surgeons has established a nipple-sparing mastectomy registry to track patient outcomes.
A potential complication of nipple-sparing surgery is necrosis of the nipple and areola. One recent study found that one-fourth of patients developed partial necrosis in the areola and nearby skin, and needed surgery to remove the dead tissue and to prevent infection.
The choices to be made in breast construction, or whether to have it at all, are highly individual.
“Some patients just don’t want more than one incision,” and want to avoid autologous tissue for that reason, Dr. Attai said. “Other patients want to avoid having a foreign body inside them” and therefore opt against implants.
Many women say plastic surgeons push them to choose larger implants. Some women worry that function can be sacrificed for form in the reconstruction process, leading to restricted mobility and pain that limits everyday tasks like driving and sitting at a computer, as well as more vigorous activities like biking or skiing. While women should know about the options, “all the options may not be good for you as an individual,” Dr. Attai said. It is wise to get several opinions, she added, because surgeons have their own preferred techniques and biases.
Bearing the Costs
Whatever procedure is chosen, infections are a common complication, requiring aggressive treatment with antibiotics and often surgery to remove implants. One 2012 study estimated infections occur in up to 35 percent of post-mastectomy reconstructive procedures.
Though rare, it is possible for cancer to occur or recur in a reconstructed breast, because some breast tissue remains. Recurrence happens in 1 percent to 5 percent of patients, according to Dr. Attai, as it does for women who have mastectomy without reconstruction. Recurring cancers can be somewhat easier to detect in breasts reconstructed with implants than with tissue transfer, she noted.
Though there has been concern that the nipple-sparing procedure might lead to more frequent recurrence of cancer, a recent review found that just 2.8 percent of patients experienced a recurrence over two years.
Cost is an important consideration. A federal law passed in 1998 required insurance plans and health maintenance organizations that pay for mastectomy to also cover the cost of reconstructive surgery. But the availability of plastic surgeons varies by region, and many do not accept insurance reimbursement.
Women may also face deductible payments as high as $10,000 with some plans, and those on Medicaid may face long waits because of a shortage of plastic surgeons who do breast reconstruction and accept this insurance.
While many women without cancer may now seek genetic testing for mutations in the BRCA 1 and BRCA 2 genes, they must meet certain criteria to be reimbursed by insurance, doctors say.
The criteria vary by insurer. United Health Care, for instance, covers testing if there is a known mutation in a family member or a first- or second-degree relative has developed breast or ovarian cancer. The test is expensive, about $3,000, and a negative test result for known genetic mutations does not necessarily mean a woman’s overall breast cancer risk is negligible, experts say.
“A lot of people with a strong family history of breast cancer discover they have no genetic mutation, at least not one we know about,” said Dr. Marisa Weiss, an oncologist and founder of Breastcancer.org. “While they may be relieved they don’t have BRCA 1 or 2, obviously something is going on if a family is significantly affected.”
Uncertain Results
The test results can be ambiguous, finding what is called a “variance of uncertain significance” or changes in the genetic code that are not well understood, said Dr. Susan M. Domchek, director of the Basser Research Center for BRCA at the University of Pennsylvania. Minority patients have a higher rate of such results, she said. The finding usually results in more frequent monitoring for cancer.
For all women, other options for reducing breast cancer risk include breast-feeding and avoiding both oral contraceptives and hormone therapy, Dr. Weiss said. Treatment with tamoxifen also appears to reduce the risk for BRCA mutation carriers.
None of these steps, however, will reduce the risk as significantly as prophylactic mastectomy and surgery to remove the ovaries, Dr. Weiss said.
Ms. Jolie has said indicated that she may undergo surgery to remove her ovaries. Ovarian cancer is so hard to detect that it often is found only at an advanced stage. But removal of the ovaries leads to immediate menopause and may adversely affect quality of life in drastic ways.
The multiplicity of treatment options and the persistent uncertainties about which is appropriate to an individual patient mean that decisions about preventive mastectomy have not grown easier, only harder. Many physicians are concerned that women, especially those traumatized by loss of a family member to cancer, may make hasty choices.
“We have had a rush of phone calls coming in with this idea, ‘Should I be getting my mastectomy?’ ” Dr. Domchek said. “But every surgical procedure comes with potential complications, and we need to attempt to balance the risk and benefit.”
This post has been revised to reflect the following correction:
Correction: May 22, 2013
A capsule summary on Tuesday for an article about options in breast reconstruction surgery left the incorrect impression that the complex and often painful procedures described in the article referred to mastectomy. As the article explained, it is the elective reconstruction of the breast or breasts that is often a protracted process involving the risk of complications and variable results.
New Research Tools Kick Up Dust in Archives
By JOHN MARKOFF, The New York Times, May 20, 2013
Seated recently in the special collections room at the Massachusetts Institute of Technology library, Anders Fernstedt raced through an imposing set of yellowing articles and correspondence.
Several years ago Mr. Fernstedt, an independent Swedish scholar who is studying the work of the 20th-century philosopher Karl Popper and several of his colleagues, would have scratched out notes and set aside documents for photocopying.
Now, however, his tool of choice is the high-resolution camera on his iPhone. When he found a document of interest, he quickly snapped a photo and instantly shared his discovery with a colleague working hundreds of miles away. Indeed, Mr. Fernstedt, who conducts his research on several continents, now packs his own substantial digital Popper library on the disk of his MacBook Air laptop computer — more than 50,000 PDF files that he can browse through in a flash.
In just a few years, advances in technology have transformed the methods of historians and other archival researchers. Productivity has improved dramatically, costs have dropped and a world distinguished by solo practitioners has become collaborative. In response, developers are producing an array of computerized methods of analysis, creating a new quantitative science.
However, the transformation has also disrupted many of the world’s historical archives, long known as sleepy places distinguished by vast and often musty collections of documents that only rarely saw the light of day. It has also created new challenges for protecting intellectual property and threatened revenue streams from document copying, creating financial challenges for some institutions.
“It gives me a bit of a chill,” said Henry Lowood, curator for History of Science and Technology Collections and Film and Media Collections in the Stanford University Libraries. “It’s not so much that we try to control things, it’s that we have agreements with people who give us their papers, and in order for us to monitor those agreements we need to monitor things at some level.”
The shift in archival research was documented in a report in December, “Supporting the Changing Research Practices of Historians,” financed by the National Endowment for the Humanities.
“Increasingly powerful search and other discovery tools have really transformed academia in the past decade,” said Roger C. Schonfeld, a program director at Ithaka S+R, an educational research and consulting group, and an author of the report.
The report notes that the widespread use of digital cameras and other scanning gear “is perhaps the single most significant shift in research practices among historians,” and that the change has a range of implications for the field.
In one case described in the report, a professor at a university in the United States was able to direct a graduate student working in archives in Europe. At the end of each day the student would upload the photographs he had collected, allowing the professor to focus his tasks for the following day.
Researchers say these new efficiencies have transformed their practices.
“I’ve used digital camera strategies for reducing the length of archival trips,” Shane Landrum, a graduate student in history at Brandeis University, wrote on his Web site. “Instead of building a giant research budget to support months on end in a particular faraway collection, I’ve put together short travel grants, and I’ve been able to collect research materials that wouldn’t otherwise have been easy to amass.”
The report also pointed out that there are benefits to the archival institution — and to future researchers. In one case, a researcher scanned documents in a local archive that had never been scanned before, then contributed his scanned work to the archives, in the hope that it would make the work more accessible to others in the future.
But for all its academic potential and efficiency benefits, some see the opening of the world’s archives as a mixed blessing. Archivists who are in charge of caring for documents that have in the past been looked at rarely, and by a relative handful of historians, worry about damage to bindings from careless researchers who flatten books to obtain better images. They also worry about the loss of control, which in some cases can lead to violations of agreements that the archives have with donors of historical materials.
Libraries have also had to adapt their policies to the new copying technology, something with which they are just now coming to terms, said Dr. Lowood. For example, initially Stanford’s archives charged people when they used their own equipment to copy material, but a year ago the practice was halted. That has eliminated a source of revenue, and prompted new guidelines: Now researchers are permitted to bring their own gear to copy documents. They are, however, required to show that they can use the equipment correctly.
And Stanford may be ahead of the curve, said Robert G. Trujillo, head of special collections at the library. He said many collections still charge researchers, even if only a flat fee, for the privilege of making their own digital copies.
Beyond the intellectual property issue, the new technology has created a surfeit of material for researchers, and that in turn has spawned a new challenges — principally, how to manage the wealth of material that is now accessible.
“The rapidity with which the technology allows you to copy has really challenged people on what to do with all of this material, how to contextualize it,” said Francis Blouin, a historian who is director of the Bentley Historical Library at the University of Michigan.
But that development, too, has had mixed consequences: The rapid rise of “digital humanities” has also prompted innovation, and now new data mining tools specifically designed for the mass of unstructured textual documents are becoming available to historians — and in turn transforming the possibilities for analysis.
“This opens up whole new categories of research,” said Joanna Guldi, a historian of Britain and an assistant professor at Brown University.
For example, she was able to use textual analysis tools and data from Google Books to determine changes in how strangers interacted on the streets in England before the 20th century.
She is one of the designers of a text analysis tool called Paper Machines that makes it possible for historians to visually examine large digital libraries to look for changes in language and other clues about social, political and economic behavior.
For some researchers, however, it has become a brave new world of specialized technologies and methods.
“I was trained in the methods of get myself to an archive and request the boxes, and pull out the documents and review the documents and request my copies and bring my copies home,” said Leslie Berlin, project historian for the Silicon Valley Archives at Stanford University. Now she often begins with electronic records. “Now my methodology has changed for the better in terms of efficiency. What’s lost in the change is the serendipity of what else might be in this box of materials, if I had gone there.”
By DONALD G. McNEIL Jr., The New York Times, May 20, 2013
Just four germs are responsible for most of the severe and fatal diarrhea among the world’s infants, according to a large new study.
Diarrhea is a major killer of children, with an estimated 800,000 deaths each year; it has many causes, and doctors want to focus on the most common ones to bring death rates down.
The study, financed by the Bill and Melinda Gates Foundation and published by The Lancet, found that the most common causes were rotavirus; a protozoan called Cryptosporidium; and two bacteria, Shigella and a toxin-producing strain of E. coli. In some areas, other pathogens, including the bacteria that causes cholera, were also important.
The study followed more than 9,000 children with diarrhea seen at clinics in Bangladesh, Gambia, India, Kenya, Mali, Mozambique and Pakistan, and, for comparison, more than 13,000 children without the disease. The children with diarrhea were more likely to have stunted growth and eight times as likely to die during a two-month follow-up period.
Diarrhea seemed to be linked to chronic malnutrition, which causes gut inflammation that can make it harder to digest food.
The prominent role of Cryptosporidium came as a surprise to the authors; it had been best known as a killer of adults whose immune systems were suppressed by AIDS.
In an editorial accompanying the study, other experts said rotavirus vaccine could save many lives. The GAVI Alliance, which helps delivers vaccines to poor countries, recently included rotavirus in the vaccines it would buy at $2.50 per dose, and an Indian company said it would soon make a version that would cost $1. Zinc and oral rehydration packets continue to be important in treatment.
Similar large studies should be done to find the underlying causes of other common infections, the editorial said. An obvious candidate would be pneumonia, another major killer of infants that has many causes.
From Neanderthal Molar, Scientists Infer Early Weaning
By JOHN NOBLE WILFORD, The New York Times, May 22, 2013
Modern mothers love to debate how long to breast-feed, a topic that stirs both guilt and pride. Now — in a very preliminary finding — the Neanderthals are weighing in.
By looking at barium levels in the fossilized molar of a Neanderthal child, researchers concluded that the child had been breast-fed exclusively for the first seven months, followed by seven months of mother’s milk supplemented by other food. Then the barium pattern in the tooth enamel “returned to baseline prenatal levels, indicating an abrupt cessation of breast-feeding at 1.2 years of age,” the scientists reported on Wednesday in the journal Nature.
While that timetable conforms with the current recommendations of the American Academy of Pediatrics — which suggests that mothers exclusively breast-feed babies for 6 months and continue for 12 months if possible — it represents a much shorter span of breast-feeding than practiced by apes or a vast majority of modern humans. The average age of weaning in nonindustrial populations is about 2.5 years; in chimpanzees in the wild, it is about 5.3 years. Of course, living conditions were much different for our evolutionary cousins, the Neanderthals, extinct for the last 30,000 years.
The findings, which drew strong skepticism from some scientists, were meant to highlight a method of linking barium levels in teeth to dietary changes. In the Nature report, researchers from the United States and Australia described tests among human infants and captive macaques showing that traces of the element barium in tooth enamel appeared to accurately reflect transitions from mother’s milk through weaning. The barium levels rose during breast-feeding and fell off sharply on weaning.
The researchers then decided to apply the barium test to the fossilized molar of a Neanderthal child, collected in Belgium. The tooth’s fossilization, the researchers discovered, had not destroyed the barium biomarker, as had been feared.
This is the first documentation of diet transitions in a juvenile Neanderthal, the researchers said in interviews, suggesting that the barium technique may open the way to a more rigorous exploration of early-life dietary history of fossil hominins.
“Our studies on macaques and modern human children provide strong evidence that barium patterns in teeth do accurately reflect transitions from maternal milk to weaning,” said Manish Arora, a team member from the University of Sydney. He is also affiliated with the Icahn School of Medicine at Mount Sinai Hospital in New York City, and acted as the principal spokesman for the researchers.
But Michael Richards, a specialist in ancient teeth and bones at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, noted that the examination of trace elements, like barium, in archaeological samples went out of use in the 1970s and ‘80s, as scientists showed that bone and teeth incorporated elements from the soil they were buried in, not necessarily from a lifetime diet.
“Recently, perhaps as the generation that did this work retires,” Dr. Richards continued, a new generation has been “returning to these methods.” He said he was surprised that Nature published the report.
Other scientists who investigate Neanderthals and other extinct hominins were guarded in their assessment of the findings. They worried that the key element in the study was confined to only one fossil specimen.
Dr. Arora acknowledged that “it is, of course, not possible to generalize to all Neanderthals from a single sample, but our observation of the exclusive breast-feeding period” in one young Neanderthal “does extend existing concepts of Neanderthal behavior.”
Erik Trinkaus, a paleoanthropologist at Washington University in St. Louis, who is an authority on Neanderthals, said the onset of weaning in the test appeared to be too early. He also cautioned, “My impression is the physiology and chemistry of nursing is vastly more complicated, and the concentrations of barium are too low that it’s hard to get reliable data.”
Tanya Smith, an evolutionary biologist at Harvard and an author of the report, said in an e-mail that the team hoped “to examine additional fossils to determine at what age Neanderthals naturally weaned their infants.” In the report, the researchers conceded that the abrupt, possibly early weaning could not be readily explained.
“We are excited about this technique as we feel that it will allow us to look directly at weaning, an important aspect of life history, in expanded samples of Neanderthals and fossil Homo sapiens,” Dr. Smith said.
The timing of weaning can be critical in contemporary human societies. Completed too early, it can expose a child to more health problems; but shorter periods of breast-feeding lead to shorter intervals between births, which influences population growth. Human infants are often weaned earlier than close ape relatives, often by several years.
As for Neanderthals, lately, science has been getting up close and personal with them. When Neanderthals and modern humans first encountered each other in Eurasia, some paired off for a go at interspecies sex. How frequent these dalliances were, and over how long a time, is unknown. But the presence of at least 2.5 percent of Neanderthal DNA in most humans with European roots exposes the secret of viable interbreeding in the Stone Age caves.
In concluding their report, the researchers said the barium sampling would most likely be definitive in testing hypotheses about the consequences of later or earlier weaning on Neanderthals, compared with Homo sapiens. No one ventured speculation on any possible role maternal milk played in the downfall of Neanderthals after the arrival of modern humans in Europe.
No Easy Choices on Breast Reconstruction
By RONI CARYN RABIN, The New York Times, MAY 20, 2013
By almost any measure, Roseann Valletti’s reconstructive breast surgery was a success. Although it was a protracted process, involving some pain and a nightmarish nipple replacement, she is pleased with how she looks.
But she is uncomfortable. All the time. “It feels like I’m wrapped up in duct tape,” said Mrs. Valletti, 54, of the persistent tightness in her chest that many women describe after breast reconstruction.
“They look terrific, to the eye,” added Mrs. Valletti, a teacher who lives Valley Stream, N.Y., and who learned she had early-stage cancer in both breasts five years ago. “But it’s never going to feel like it’s not pulling or it’s not tight. It took me a while to accept that. This is the new normal.”
Last week the actress Angelina Jolie announced in The New York Times that she had had a double mastectomy in February after testing positive for a genetic mutation that put her at high risk for breast and ovarian cancer. She also had reconstructive surgery.
Her disclosure was lauded by some advocates as a bold move that will inspire women to be proactive, learn about their family histories and risks, and consider genetic testing.
At the same time, some breast surgeons are discomfited that some might infer from the article that reconstructive surgery is a quick and easy procedure, and worry that Ms. Jolie inadvertently may have understated the risks and potential complications.
For most patients, like Mrs. Valletti, breast reconstruction requires an extended series of operations and follow-up visits that can yield variable results. Some women experience so many complications that they just have the implants removed.
“We do not yet have the ability to wave a wand over you and take out breast tissue and put in an implant — we’re not at “Star Trek” medicine,” said Dr. Deanna J. Attai, a breast surgeon in Burbank, Calif., who is on the board of the American Society of Breast Surgeons.
Ms. Jolie said that she completed her reconstructive surgeries in nine weeks, but for many patients the process takes closer to nine months. “Three months is probably a little unusual,” said Dr. Gregory R. D. Evans, in Orange, Calif., president of the American Society of Plastic Surgeons. “I usually tell my patients it will take about a year.”
And it is major surgery. Even with the best plastic surgeon, breast reconstruction carries the risks of infection, bleeding, anesthesia complications, scarring and persistent pain in the back and shoulder. Implants can rupture or leak, and may need to be replaced. If tissue is transplanted to the breast from other parts of the body, there will be additional incisions that need to heal. If muscle is removed, long-term weakness may result.
A syndrome called upper quarter dysfunction — its symptoms include pain, restricted immobility and impaired sensation and strength — has been reported in over half of breast cancer survivors and may be more frequent in those who undergo breast reconstruction, according to a 2012 study in the journal Cancer.
“People have to understand it’s not a breeze,” said Geri Barish, president of 1 in 9: The Long Island Breast Cancer Action Coalition and a three-time survivor of breast cancer. “I don’t want people to think this is the cure-all, that this is it, hurry up, run out and get the test and have your ovaries and breasts removed.”
Types of Reconstruction
An array of new techniques, each with its own risks and potential benefits, makes for bewildering options for women. The first choice in breast reconstruction is whether to have implants or to make the new breast from muscle or fat and skin taken from elsewhere in the body, often from the abdomen — so-called autologous tissue transfer.
More plastic surgeons are familiar with implants, and the procedure is less expensive than tissue transfer. Of the 91,655 women who had reconstruction last year in the United States, a vast majority opted for implants, with 64,114 choosing silicone and 7,898 choosing saline, according to the American Society of Plastic Surgeons. Just over 19,000 women chose autologous tissue transfer.
Many surgeons believe silicone implants confer a more natural look than saline, despite a long-running controversy over their safety. The Food and Drug Administration allowed silicone implants back on the market in 2006, after studies showed they did not increase the risk of immune disease. A new type is filled with a thick gel that may pose less risk of leakage.
Whether they are silicone or saline, however, implants do not last a lifetime. As many as half need to be replaced or removed within 10 years, according to the American Cancer Society. The implants can rupture, cause infections and lead to pain. Scar tissue often forms around the implants, making the breast hardened or misshapen. Last year alone, there were 16,596 procedures done to remove breast implants.
Reconstruction may be started at the same time as the mastectomy, or later. Usually the first step is to place a so-called tissue expander under the chest muscle, which normally presses against the ribs. The surgeon injects saline into the balloonlike pouch at regular intervals several weeks apart to create space for the implant.
Eventually, the expander is removed and replaced with the implant. (Unlike breast tissue, which sits on top of the chest muscle, the implant is situated under the muscle, which holds it in place.) The process can take several months, longer if problems develop or the patient needs other treatment like radiation, which tends to damage the surrounding skin and make it less hospitable to an implant.
In autologous tissue transfers, muscle, skin or fat from another part of the patient’s body substitutes for an implant. Some surgeons believe this creates a more natural-feeling and natural-looking breast. There are several options.
The transverse rectus abdominis myocutaneous, or TRAM, flap procedure uses tissue and muscle from the lower abdomen to shape a breast mound. But the surgery weakens the abdominal area, and at Johns Hopkins Breast Center, the procedure has been abandoned because of the risk of hernias and abdominal bulges and limitations on lifting after surgery.
Instead, some surgeons now perform the deep inferior epigastric artery perforator, or DIEP, flap procedure, which uses only abdominal skin and tissue, not muscle, to create the breast. Both the TRAM and DIEP surgeries are lengthy procedures that can last 12 hours and can lead to a complication of necrosis, or tissue death, if there isn’t adequate blood supply, Dr. Attai said.
A third type of flap procedure relies on back muscle that is moved under the skin to the front of the chest, but this can weaken the back, shoulder or arm. In yet another procedure, the gluteal free flap, tissue and muscle from the buttocks are used to create a breast mound.
Simulating a Nipple
Reconstruction of the nipple has long been a challenge. Surgeons have used incision scar tissue or tissue taken from the groin or between the buttocks to craft nipples. Tattoos are also used to darken the areola, with 3-D tattoos that create the impression of a nipple.
With a nipple- and skin-sparing mastectomy, the surgeon removes all of the glandular breast tissue while preserving the skin, areola and nipple, much as one might scoop all the fleshy fruit out of an orange and leave the skin intact. This is the procedure Ms. Jolie had. Yet even when it is successful, the nipples usually lose sensation and are numb and cannot play the same role in sexual arousal as before surgery.
Residual breast cells may be left behind, and there is a concern that these may become cancerous. The American Society of Breast Surgeons has established a nipple-sparing mastectomy registry to track patient outcomes.
A potential complication of nipple-sparing surgery is necrosis of the nipple and areola. One recent study found that one-fourth of patients developed partial necrosis in the areola and nearby skin, and needed surgery to remove the dead tissue and to prevent infection.
The choices to be made in breast construction, or whether to have it at all, are highly individual.
“Some patients just don’t want more than one incision,” and want to avoid autologous tissue for that reason, Dr. Attai said. “Other patients want to avoid having a foreign body inside them” and therefore opt against implants.
Many women say plastic surgeons push them to choose larger implants. Some women worry that function can be sacrificed for form in the reconstruction process, leading to restricted mobility and pain that limits everyday tasks like driving and sitting at a computer, as well as more vigorous activities like biking or skiing. While women should know about the options, “all the options may not be good for you as an individual,” Dr. Attai said. It is wise to get several opinions, she added, because surgeons have their own preferred techniques and biases.
Bearing the Costs
Whatever procedure is chosen, infections are a common complication, requiring aggressive treatment with antibiotics and often surgery to remove implants. One 2012 study estimated infections occur in up to 35 percent of post-mastectomy reconstructive procedures.
Though rare, it is possible for cancer to occur or recur in a reconstructed breast, because some breast tissue remains. Recurrence happens in 1 percent to 5 percent of patients, according to Dr. Attai, as it does for women who have mastectomy without reconstruction. Recurring cancers can be somewhat easier to detect in breasts reconstructed with implants than with tissue transfer, she noted.
Though there has been concern that the nipple-sparing procedure might lead to more frequent recurrence of cancer, a recent review found that just 2.8 percent of patients experienced a recurrence over two years.
Cost is an important consideration. A federal law passed in 1998 required insurance plans and health maintenance organizations that pay for mastectomy to also cover the cost of reconstructive surgery. But the availability of plastic surgeons varies by region, and many do not accept insurance reimbursement.
Women may also face deductible payments as high as $10,000 with some plans, and those on Medicaid may face long waits because of a shortage of plastic surgeons who do breast reconstruction and accept this insurance.
While many women without cancer may now seek genetic testing for mutations in the BRCA 1 and BRCA 2 genes, they must meet certain criteria to be reimbursed by insurance, doctors say.
The criteria vary by insurer. United Health Care, for instance, covers testing if there is a known mutation in a family member or a first- or second-degree relative has developed breast or ovarian cancer. The test is expensive, about $3,000, and a negative test result for known genetic mutations does not necessarily mean a woman’s overall breast cancer risk is negligible, experts say.
“A lot of people with a strong family history of breast cancer discover they have no genetic mutation, at least not one we know about,” said Dr. Marisa Weiss, an oncologist and founder of Breastcancer.org. “While they may be relieved they don’t have BRCA 1 or 2, obviously something is going on if a family is significantly affected.”
Uncertain Results
The test results can be ambiguous, finding what is called a “variance of uncertain significance” or changes in the genetic code that are not well understood, said Dr. Susan M. Domchek, director of the Basser Research Center for BRCA at the University of Pennsylvania. Minority patients have a higher rate of such results, she said. The finding usually results in more frequent monitoring for cancer.
For all women, other options for reducing breast cancer risk include breast-feeding and avoiding both oral contraceptives and hormone therapy, Dr. Weiss said. Treatment with tamoxifen also appears to reduce the risk for BRCA mutation carriers.
None of these steps, however, will reduce the risk as significantly as prophylactic mastectomy and surgery to remove the ovaries, Dr. Weiss said.
Ms. Jolie has said indicated that she may undergo surgery to remove her ovaries. Ovarian cancer is so hard to detect that it often is found only at an advanced stage. But removal of the ovaries leads to immediate menopause and may adversely affect quality of life in drastic ways.
The multiplicity of treatment options and the persistent uncertainties about which is appropriate to an individual patient mean that decisions about preventive mastectomy have not grown easier, only harder. Many physicians are concerned that women, especially those traumatized by loss of a family member to cancer, may make hasty choices.
“We have had a rush of phone calls coming in with this idea, ‘Should I be getting my mastectomy?’ ” Dr. Domchek said. “But every surgical procedure comes with potential complications, and we need to attempt to balance the risk and benefit.”
This post has been revised to reflect the following correction:
Correction: May 22, 2013
A capsule summary on Tuesday for an article about options in breast reconstruction surgery left the incorrect impression that the complex and often painful procedures described in the article referred to mastectomy. As the article explained, it is the elective reconstruction of the breast or breasts that is often a protracted process involving the risk of complications and variable results.
New Research Tools Kick Up Dust in Archives
By JOHN MARKOFF, The New York Times, May 20, 2013
Seated recently in the special collections room at the Massachusetts Institute of Technology library, Anders Fernstedt raced through an imposing set of yellowing articles and correspondence.
Several years ago Mr. Fernstedt, an independent Swedish scholar who is studying the work of the 20th-century philosopher Karl Popper and several of his colleagues, would have scratched out notes and set aside documents for photocopying.
Now, however, his tool of choice is the high-resolution camera on his iPhone. When he found a document of interest, he quickly snapped a photo and instantly shared his discovery with a colleague working hundreds of miles away. Indeed, Mr. Fernstedt, who conducts his research on several continents, now packs his own substantial digital Popper library on the disk of his MacBook Air laptop computer — more than 50,000 PDF files that he can browse through in a flash.
In just a few years, advances in technology have transformed the methods of historians and other archival researchers. Productivity has improved dramatically, costs have dropped and a world distinguished by solo practitioners has become collaborative. In response, developers are producing an array of computerized methods of analysis, creating a new quantitative science.
However, the transformation has also disrupted many of the world’s historical archives, long known as sleepy places distinguished by vast and often musty collections of documents that only rarely saw the light of day. It has also created new challenges for protecting intellectual property and threatened revenue streams from document copying, creating financial challenges for some institutions.
“It gives me a bit of a chill,” said Henry Lowood, curator for History of Science and Technology Collections and Film and Media Collections in the Stanford University Libraries. “It’s not so much that we try to control things, it’s that we have agreements with people who give us their papers, and in order for us to monitor those agreements we need to monitor things at some level.”
The shift in archival research was documented in a report in December, “Supporting the Changing Research Practices of Historians,” financed by the National Endowment for the Humanities.
“Increasingly powerful search and other discovery tools have really transformed academia in the past decade,” said Roger C. Schonfeld, a program director at Ithaka S+R, an educational research and consulting group, and an author of the report.
The report notes that the widespread use of digital cameras and other scanning gear “is perhaps the single most significant shift in research practices among historians,” and that the change has a range of implications for the field.
In one case described in the report, a professor at a university in the United States was able to direct a graduate student working in archives in Europe. At the end of each day the student would upload the photographs he had collected, allowing the professor to focus his tasks for the following day.
Researchers say these new efficiencies have transformed their practices.
“I’ve used digital camera strategies for reducing the length of archival trips,” Shane Landrum, a graduate student in history at Brandeis University, wrote on his Web site. “Instead of building a giant research budget to support months on end in a particular faraway collection, I’ve put together short travel grants, and I’ve been able to collect research materials that wouldn’t otherwise have been easy to amass.”
The report also pointed out that there are benefits to the archival institution — and to future researchers. In one case, a researcher scanned documents in a local archive that had never been scanned before, then contributed his scanned work to the archives, in the hope that it would make the work more accessible to others in the future.
But for all its academic potential and efficiency benefits, some see the opening of the world’s archives as a mixed blessing. Archivists who are in charge of caring for documents that have in the past been looked at rarely, and by a relative handful of historians, worry about damage to bindings from careless researchers who flatten books to obtain better images. They also worry about the loss of control, which in some cases can lead to violations of agreements that the archives have with donors of historical materials.
Libraries have also had to adapt their policies to the new copying technology, something with which they are just now coming to terms, said Dr. Lowood. For example, initially Stanford’s archives charged people when they used their own equipment to copy material, but a year ago the practice was halted. That has eliminated a source of revenue, and prompted new guidelines: Now researchers are permitted to bring their own gear to copy documents. They are, however, required to show that they can use the equipment correctly.
And Stanford may be ahead of the curve, said Robert G. Trujillo, head of special collections at the library. He said many collections still charge researchers, even if only a flat fee, for the privilege of making their own digital copies.
Beyond the intellectual property issue, the new technology has created a surfeit of material for researchers, and that in turn has spawned a new challenges — principally, how to manage the wealth of material that is now accessible.
“The rapidity with which the technology allows you to copy has really challenged people on what to do with all of this material, how to contextualize it,” said Francis Blouin, a historian who is director of the Bentley Historical Library at the University of Michigan.
But that development, too, has had mixed consequences: The rapid rise of “digital humanities” has also prompted innovation, and now new data mining tools specifically designed for the mass of unstructured textual documents are becoming available to historians — and in turn transforming the possibilities for analysis.
“This opens up whole new categories of research,” said Joanna Guldi, a historian of Britain and an assistant professor at Brown University.
For example, she was able to use textual analysis tools and data from Google Books to determine changes in how strangers interacted on the streets in England before the 20th century.
She is one of the designers of a text analysis tool called Paper Machines that makes it possible for historians to visually examine large digital libraries to look for changes in language and other clues about social, political and economic behavior.
For some researchers, however, it has become a brave new world of specialized technologies and methods.
“I was trained in the methods of get myself to an archive and request the boxes, and pull out the documents and review the documents and request my copies and bring my copies home,” said Leslie Berlin, project historian for the Silicon Valley Archives at Stanford University. Now she often begins with electronic records. “Now my methodology has changed for the better in terms of efficiency. What’s lost in the change is the serendipity of what else might be in this box of materials, if I had gone there.”