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  • Recent study unveils genetics behind human head shape.

    Recent study unveils genetics behind human head shape.

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    Newswise — Researchers at the University of Pittsburgh and KU Leuven have discovered a suite of genes that influence head shape in humans. These findings, published this week in Nature Communications, help explain the diversity of human head shapes and may also offer important clues about the genetic basis of conditions that affect the skull, such as craniosynostosis.

    By analyzing measurements of the cranial vault — the part of the skull that forms the rounded top of the head and protects the brain — the team identified 30 regions of the genome associated with different aspects of head shape, 29 of which have not been reported previously.

    “Anthropologists have speculated and debated the genetics of cranial vault shape since the early 20th century,” said co-senior author Seth Weinberg, Ph.D., professor of oral and craniofacial sciences in the Pitt School of Dental Medicine and co-director of the Center for Craniofacial and Dental Genetics. “We knew from certain rare human conditions and animal experiments that genes play an important role in vault size and shape, but very little was known about the genetic basis for typical features we see in the general population, such as what makes someone’s head long and narrow versus short and wide. This study reveals some of the key genes driving variation in this part of the human body.”

    According to the researchers, one application of better understanding the factors that drive natural variation in human head shape is informing paleoanthropology studies, potentially shedding light on the early development of modern humans.

    Weinberg and colleagues used magnetic resonance (MR) scans from more than 6,000 adolescents to extract 3D surfaces corresponding to the cranial vault. After dividing the 3D vault surfaces into incrementally smaller anatomical subparts and quantifying the shape of these subparts, they tested more than 10 million genetic variants for evidence of statistical association with measures of vault shape.

    “Previous genetic studies of the cranial vault involved a small number of relatively simple measures,” added Weinberg.  “While such measures are often easy to obtain, they may fail to capture features that are biologically relevant. Our analysis used an innovative approach capable of describing 3D vault shape in much more comprehensive and nuanced ways. This approach increased our ability to find genetic associations.”

    An important discovery was that many of the strong associations are near genes that play key roles in the early formation of the head and face and regulation of bone development. For example, variants in and near the gene RUNX2, a major player in coordinating development of the skull, were associated with multiple aspects of vault shape.

    While some genes, including RUNX2, had global effects involving the entire vault, others showed more localized effects that only impacted a specific portion of the vault, such as the central forehead.

    When the researchers compared the 30 genomic regions associated with head shape across participants with European, African and Indigenous American ancestry, they found that the majority of genetic associations were shared across these different ancestral groups.

    Although the study focused on healthy participants, the findings may reveal important clues about the biological basis of diseases involving the cranial vault, according to Weinberg.

    One of these conditions is craniosynostosis, which occurs when the bones of the skull fuse too early while the brain is still growing rapidly. Without neurosurgery, craniosynostosis can cause permanent disfigurement, brain damage, blindness and even death. The team showed that variants near three genes associated with vault shape, BMP2, BBS9 and ZIC2, were also associated with craniosynostosis, suggesting that these genes could play a role in the development of the disease.

    “This kind of study is possible due to the availability of publicly funded resources,” said Weinberg. “The original study that generated these MR scans is focused on understanding brain development and behavior. By creatively leveraging these resources, we have managed to advance discovery beyond that original scope.”

    Other authors on the study were Seppe Goovaerts, Hanne Hoskens, Ph.D., Meng Yuan, Dirk Vandermeulen, Ph.D., all of KU Leuven; Ryan J. Eller, Ph.D., Noah Herrick, Ph.D., and Susan Walsh, Ph.D., all of Indiana University–Purdue University Indianapolis; Anthony M. Musolf, Ph.D., and Cristina M. Justice, Ph.D., both of the National Human Genome Research Institute; Sahin Naqvi, Ph.D., and Joanna Wysocka, Ph.D., both of Stanford University; Myoung Keun Lee, Heather L. Szabo-Rogers, Ph.D., Mary L. Marazita, Ph.D., and John R. Shaffer, Ph.D., all of Pitt; Paul A. Romitti, Ph.D., of the University of Iowa; Simeon A. Boyadjiev, M.D., of the University of California, Davis; Mark D. Shriver, Ph.D., of Penn State University; and Peter Claes, Ph.D., of KU Leuven and Murdoch Children’s Research Institute.

    This research was supported by the National Institute of Dental and Craniofacial Research (R01DE027023, R01DE016886, R03DE031061 and X01HL14053) and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.

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  • Short-Term Use of Immunosuppressants Not Linked to Cancer Risk

    Short-Term Use of Immunosuppressants Not Linked to Cancer Risk

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    Newswise — Relatively short-term use of immunosuppressant medications to control an inflammatory disease was not associated with an increased risk of later developing cancer, according to new research led by scientists at the University of Pittsburgh and Mass Eye and Ear, a member of the Mass General Brigham health care system, and published today in the journal BMJ Oncology.

    The findings should provide reassurance to patients and clinicians who may hesitate to prescribe the medications because they are known to increase the risk of cancer in people who take them over many years or a lifetime to prevent dire consequences, such as organ rejection in transplant recipients.

    “When we got these results, I was reassured, and I hope patients will be, too,” said lead author Jeanine Buchanich, Ph.D., associate dean for research and associate professor of biostatistics at Pitt’s School of Public Health. “Immunosuppressants are widely used and transformative for care of patients with inflammatory diseases, but the potential concern that they carry a cancer risk has forced people to make difficult decisions without enough information. Alleviating that concern with use for inflammatory diseases will help people make the treatment decision that’s right for them.”

    The  new findings were from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort, which began two decades ago when principal investigator John Kempen, M.D., Ph.D., senior scientist and director of epidemiology for ophthalmology at Mass Eye and Ear and professor of ophthalmology at Harvard Medical School, approached Buchanich, who directs Pitt Public Health’s Center for Occupational Biostatistics and Epidemiology, to partner in evaluating cancer risk for people with non-infectious ocular inflammatory diseases taking immunosuppressants. These eye diseases are caused by immune dysfunction and do not themselves cause cancer but can be very serious, with blindness as a possible outcome.

    The diseases are commonly treated with immunosuppressive medications, which patients generally take for several months to several years.

    This new research adds evidence to the limited cancer risk associated with immunosuppressant treatments uncovered by the SITE study consortium. In a study published last month in Ophthalmology, the researchers found no increased risk in cancer-related and overall mortality in individuals taking commonly used immunosuppressants. The study included 15,938 SITE participants who were tracked for an average of 10 years.

    The BMJ Oncology study included 10,872 participants, ultimately encompassing 84% of the enrolled SITE participants who lived in one of the 12 states from which the research team obtained data linking participants to each state’s cancer registries. Though most states track cancer incidence, there is no centralized federal cancer registry, and different states require different permissions and use different interfaces to share data. For this reason, it is difficult to do large-scale epidemiological cancer studies in the U.S., making this study incorporating years of data from multiple states a rarity.

    The research team tracked each participant for an average of 10 years after they took immunosuppressant medications, or for a similar amount of time for those not taking immunosuppression, to see if they ever developed cancer. Four different categories of immunosuppressants – TNF-inhibitors, antimetabolites, alkylating agents and calcineurin inhibitors – were covered by the study, with some patients taking more than one type. Patients were on the medications for a median of one year.

    Across all four classes of immunosuppressant medications the scientists found no evidence of excess risk of cancer in patients who took them on a short-term basis, regardless of medication dose.

    While the study only looked at people with noninfectious eye diseases and the researchers caution that the results aren’t generalizable to everyone taking immunosuppressants, the results probably are generalizable to patients with inflammatory diseases, Kempen said.

    “The patients in our study actually tended to have a lower incidence of cancer than non-immunosuppressed patients, suggesting that an increased risk of overall cancer from commonly used immunosuppressants given for the short- to medium-term is very unlikely,” said Kempen. “This result is foundational for a large number of patients with inflammatory eye conditions and a broad range of patients with other inflammatory diseases.”

    Additional researchers on this study are Craig Newcomb, M.S., Nirali Bhatt, M.D., Tonetta Fitzgerald, Ebenezer Daniel, Ph.D., and Naira Khachatryan, M.D., Dr.P.H., all of the University of Pennsylvania (Penn); Terri Washington, of Pitt; C. Stephen Foster, M.D., of the Massachusetts Eye Research and Surgery Institution (MERSI) and Harvard Medical School; Lucia Sobrin, M.D., of Mass Eye and Ear and Harvard Medical School; Jennifer Thorne, M.D., Ph.D., Douglas Jabs, M.D., M.B.A., Kurt Dreger, Hosne Begum and Kathy Helzlsouer, M.D., all of Johns Hopkins University; Eric Suhler, M.D., M.P.H., James Rosenbaum, M.D., and Teresa Liesegang, all of the Oregon Health & Science University; H. Nida Sen, M.D., of George Washington University; Grace Levy-Clarke, M.D., of West Virginia University; the late Robert Nussenblatt, M.D., of the National Eye Institute; Careen Lowder, M.D., Ph.D., of the Cleveland Clinic; Debra Goldstein, M.D., of Northwestern University; Yannek Leiderman, M.D., Ph.D., of the University of Illinois, Chicago; Nisha Acharya, M.D., of the University of California San Francisco; Gary Holland, M.D., of the University of California Los Angeles; Russel Read, M.D., Ph.D., of the University of Alabama at Birmingham; James Dunn, M.D., of the Wills Eye Hospital; Pichaporn Artornsombudh, M.D., of Somdech Phra Pinkloa Hospital, Thailand; Srishti Kothari, of Penn and MERSI; Abhishek Payal, M.D., of Mahatme EyeBank Eye Hospital, India; Sapna Gangaputra, M.D., of Vanderbilt University Medical Center; R. Oktay Kacmaz, M.D., of Santen Pharmaceutical Co Ltd; Siddharth Pujari, M.D., of Siddharth Netralaya Superspecialty Eye Hospital, India; Armin Maghsoudlou, M.D., of Northwell Health; Hilkiah Suga, M.D., Myungsung Christian Medical Center (MCM), Ethiopia; and Clara Pak, of MCM and University of Rochester.

    This research was supported by National Institutes of Health (NIH) grants R01 EY14943 and R21 EY02617, NIH University of Pennsylvania Core Grant for Vision Research 2P30EYEY001583, the Massachusetts Eye and Ear Global Surgery Program, Sight for Souls and Research to Prevent Blindness.

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    About the University of Pittsburgh School of Public Health

    Founded in 1948, the University of Pittsburgh School of Public Health is a top-ranked institution of seven academic departments partnering with stakeholders locally and globally to create, implement and disseminate innovative public health research and practice. With hands-on and high-tech instruction, Pitt Public Health trains a diverse community of students to become public health leaders who counter persistent population health problems and inequities. 

    About Mass Eye and Ear

    Massachusetts Eye and Ear, founded in 1824, is an international center for treatment and research and a teaching hospital of Harvard Medical School. A member of Mass General Brigham, Mass Eye and Ear specializes in ophthalmology (eye care) and otolaryngology–head and neck surgery (ear, nose and throat care). Mass Eye and Ear clinicians provide care ranging from the routine to the very complex. Also home to the world’s largest community of hearing and vision researchers, Mass Eye and Ear scientists are driven by a mission to discover the basic biology underlying conditions affecting the eyes, ears, nose, throat, head and neck and to develop new treatments and cures. In the 2022–2023 “Best Hospitals Survey,” U.S. News & World Report ranked Mass Eye and Ear #4 in the nation for eye care and #4 for ear, nose and throat care. For more information about life-changing care and research at Mass Eye and Ear, visit our blog, Focus, and follow us on Instagram, Twitter and Facebook.

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  • 800,000 tons of drilling, fracking waste unnaccounted for in NY, PA, Ohio

    800,000 tons of drilling, fracking waste unnaccounted for in NY, PA, Ohio

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    Newswise — Sanitary landfills in Pennsylvania can accept the liquid waste byproducts of drilling and fracking for oil and gas as long as it is “immobilized,” mixed with wood chips or sawdust, for example.

    This waste can contain high levels of heavy metals, like arsenic; salts such as chloride and bromide; and naturally occurring radioactive materials.

    Sanitary landfills are those designed to let waste decompose; they are not necessarily designed to manage radioactive waste.

    A collaborative research study led by Daniel Bain, University of Pittsburgh associate professor of geology and environmental science, analyzed records as well as soil samples to better understand the effects of disposing of this waste in facilities that were not built to contain radioactive waste. The team, in an article written in Ecological Indicators by Lauren Badertscher, then a masters student at Duquesne University and now with the EPA, found that poor records and a lack of monitoring are a barrier to fully understanding the impact of this method of immobilized oil and gas waste disposal.

    Sediment samples taken upstream and downstream from 17 facilities that treat water from landfills in New York, Ohio and Pennsylvania — all states that accepted such waste in 2019, when the samples were taken — often showed elevated levels of radium, implicating the wastewater as a its source. 

    Discharge permits for these landfills do not commonly require monitoring of materials found in oil and gas waste.

    The research team sought out reports to the Pennsylvania Department of Environmental Protection Oil and Gas Division from oil and gas wells, indicating that they shipped wastewater to sanitary landfills in New York, Ohio and Pennsylvania.

    They also analyzed records from the environmental agencies of New York, Ohio and Pennsylvania documenting the acceptance of oil and gas wastewater.

    When the researchers compared the two, they found that, at the very best, there was still a 30% discrepancy between records of what was sent and what was received.

    Almost half of the landfills examined had either a record of shipment or a record of receipt, but no associated record on the other end in 2019

    ​​When totaled, these gaps in record keeping leave over 800,000 tons of oil and gas waste unaccounted for.

    Researchers concluded that insufficient regulatory recordkeeping and a lack of mandatory monitoring and testing are a barrier to fully understanding the impact on local water systems of sanitary landfills accepting wastewater resulting from drilling and fracking for oil and gas.

    “The mismatch in regulatory records creates the potential for contamination,” Bain said. “And while we don’t have the data to unambiguously tie increases in stream sediment radium to disposal of these wastes in landfills, the observations clearly indicated we should really start scrutinizing, and probably rethink, the disposal of oil and gas waste in landfills.”

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  • What Does It Take to Be a ‘Minority-Serving Institution’?

    What Does It Take to Be a ‘Minority-Serving Institution’?

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    A group of researchers has recommended a new classification system for minority-serving institutions that they hope will ultimately direct more money to colleges that are serving minority students well, and not just enrolling them in large numbers.

    The MSI Data Project, the researchers said in a news release Sunday, is a response to “inaccurate and inconsistent data used to identify minority-serving institutions (MSIs) for funding and analysis.”

    “Our hope is … for MSI leaders, advocates, and policymakers to use this body of research, as well as our data dashboards, to make better informed decisions that promote equitable educational outcomes for students,” said Mike Hoa Nguyen, the principal investigator and an assistant professor of education at New York University.

    The data project, launched this month, examines 11 categories of minority-serving institutions. It includes dashboards that detail individual campuses’ eligibility for federal funds, institutional characteristics, enrollment, and graduation metrics over a five-year period, from 2017 to 2021.

    For instance, the dashboard shows, 219 Hispanic-serving institutions received funding from the U.S. Department of Education in 2021, but 462 were eligible for such money. Colleges still have to apply for competitive grants from a limited pool of money. Some applied and were denied, while other colleges may not have even known they were eligible.

    The researchers hope their recommendations will spur changes in how colleges are designated as MSIs and clear up confusion about who should be able to claim that status, and the federal money that can come with it.

    In an accompanying article in Educational Researcher, titled “What Counts as a Minority-Serving Institution?” Nguyen and two of the project’s co-creators raise the concern that federal money isn’t necessarily going to the most deserving institutions.

    “For example, perhaps an institution, not identified as an MSI under the federal statute, is found to serve students of color much better than those that are identified. Such findings could offer important suggestions for policy changes. Additionally, if institutions are receiving federal MSI funds but are not serving students of color well, this would be an important consideration to amend practices and policies so that federal funding is used in the manner in which it was intended.”

    “The MSI landscape is so unbelievably complex, in the way all 11 designations were created over a long period of time, using a patchwork legislative process,” Nguyen said in an interview. By getting everyone “speaking the same language” in how they examine minority-serving institutions, “our hope is that we can find out how well those students are being served” by the federal money set aside and where equity gaps exist.

    Nguyen’s fellow authors were Joseph J. Ramirez, an institutional research and assessment associate at the California Institute of Technology, and Sophia Laderman, an associate vice president at the State Higher Education Executive Officers Association (SHEEO).

    About one in five postsecondary institutions are eligible for federal money as MSIs, but more than half of all undergraduate students of color attend these colleges, the authors wrote. President Biden has pledged significant increases in the amount of money directed toward minority-serving institutions.

    Researchers, including Gina Ann Garcia, an associate professor of educational foundations, organizations, and policy at the University of Pittsburgh, have pointed out that the nation’s demographic changes have resulted in hundreds of campuses being designated as Hispanic serving based on numbers alone. The data-project researchers acknowledge that some colleges engage in “the strategic manipulation of enrollment trends in order to meet eligibility requirements.”

    Hispanic-serving institutions, which were first designated by the federal government in 1994, are among the minority-serving institutions that get that designation based on share of enrollment. For HSIs, the threshold is 25 percent of the undergraduate population.

    By contrast, Historically Black and Tribal-Serving colleges achieve that designation based on their histories and missions. Colleges that weren’t designated in those categories can’t join their ranks, regardless of their own changing demographics. That has caused longstanding tensions between Historically Black and predominantly Black institutions over who should have access to the federal money set aside for minority-serving institutions.

    Among the minority-serving institutions the database tracks are those representing Hispanic students, Asian American and Pacific Islanders, both tribal and non-tribally-controlled Native American colleges, and colleges that are either Historically Black or predominantly Black.

    Many colleges are designated in more than one category, but they may only be able to receive funding under one. Designating their multiple identities is important, the authors write, because it “recognizes the diversity and complexity of the institution, and does not render invisible the students of color who attend that institution.”

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  • What does Polly say? Community science data reveal species differences in vocal learning by parrots

    What does Polly say? Community science data reveal species differences in vocal learning by parrots

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    Newswise — While most animals don’t learn their vocalizations, everyone knows that parrots do – they are excellent mimics of human speech. But how large is the vocabulary of different parrot species? Do males “talk” more than females? Does a parrot’s vocabulary expand with age? A new study publishing Dec. 5 in the Nature journal Scientific Reports, titled “A survey of vocal mimicry in companion parrots,” adds to what we know about animal vocal learning by providing the largestcomparative analysis to date of parrot vocal repertoires.

    The paper documents species differences in vocal mimicry, shows that many parrots use words in appropriate contexts, and highlights the value of crowd-sourced data.

    Data were collected as part of a community science project entitled “What does Polly Say?” Humans who live with companion parrots reported on the number of human “words” and “phrases” used by their parrots, as well as human-associated sounds (such as whistling a tune) and contextual use of sounds. This approach allowed researchers to collect standardized data on vocal learning by nearly 900 parrots from 73 species, a sample that would have been impossible to gather on wild parrots.

    What researchers from the University of Northern Colorado (UNC) and the University of Pittsburgh at Johnstown (UPJ) found:

    Species matters — “As it turns out, Polly’s species might have a strong impact on what she says” said co-author Lauryn Benedict, professor and associate director of UNC’s School of Biological Sciences. Some species are much better mimics than others. African grey parrots, long understood to be the best at learning human sounds, were found to have the largest repertoires, averaging about 60 human words. Cockatoos, Amazons, and Macaws also were excellent mimics, with average repertoires of 20-30 words.Most species learned more phrases than sounds, but a few, including Cockatiels and Fischer’s Lovebirds,learned more human sounds than phrases.

    Learning over time — The study concludes that age and sex are weak predictors of vocal mimicry. Age-based analyses showed that juveniles expanded their repertoires until they reached maturity, but after that repertoire sizes reached a plateau. Fifty-year–old birds did not have larger repertoires than 5–year–old birds.

    Males versus females — Sex-based analyses showed that males and females of most species were equally good mimics. There are, however, some exceptions, including Budgerigars, in which males had larger vocal repertoires, Pacific Parrotlets, among which only males were reported to “talk,” and Yellow-headed Amazons, among which females learned more sounds.

    Although most males and females were equally good human mimics, the researchers documented a reporting bias whereby birds of uncertain sex were more often marked as male (74%). They conclude that humans who live with parrots of uncertain sex overwhelmingly, and often mistakenly, assume those birdsare male.

    Parrots have timing — Human survey-takers reported that a very high proportion of companion parrots (89 %) spontaneously used human mimicry in appropriate contexts, with most birds doing so frequently. The researchers conclude that parrots learn both what to say, and also when to say it.

    “This research highlights just how much parrots still have to teach us,” said co-author Christine Dahlin, associate professor of Biology from UPJ. “Approximately 30% of parrot species in the wild are declining to the point of being threatened, endangered or critically endangered, primarily from poaching and habitat loss. Without conservation of remaining populations, we risk losing the opportunity to understand the evolution of complex communication in these amazing animals.”

    As vocal learners, parrots are important research subjects for understanding the physiological, neurobiological, and evolutionary underpinnings of acoustic communication in nature. It is clear that both companion and wild parrots use vocal mimicry to navigate their complex social and cognitive worlds. The species and sex specific differences documented by this research can spur new avenues of research andlead to increased appreciation for parrots.


    Anyone who lives with a parrot is invited to join the community science team and contribute to this ongoing research by filling out the survey at this link: https://bit.ly/2S7nx3K.

    For reference, here are public links highlighting parrots known for their large repertoires: Alex, a Grey Parrot: https://alexfoundation.org/; and Sparkie Williams, a Budgerigar: https://blogs.bl.uk/sound-and-vision/2017/02/recording-of-the-week-sparkie-williams-the-talking-budgerigar.html

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