Culture

The team of researchers from the project "Flora iberica X(2)" have discovered two new native grass on the Iberian Peninsula and in Menorca, respectively. These two species, which are new to science, have been featured in the prestigious American review Systematic Botany. The article of the fruit of the collaboration between the Area of Botany and the University of Seville Herbarium, the Systematic and Evolution Unit for Vascular Plants at the Autonomous University of Barcelona, and researchers from other institutions in the Balearic Islands.

The new species belong to the genus Aira, delicate herbaceous plants, which enjoy their greatest diversity in the Mediterranean Region. One of them, Aira minoricensis is a native species of the siliceous sands of Menorca, where it was collected for the first time in 2014 by the botanist Pere Fraga, curator of the Marimutra Botanical Garden (Blanes) and great expert on the island's flora. The other new species is called Aira hercynica and is widely found in the area of the Iberia Peninsula which approximately coincides with the Iberian Massif (which is also called the Hesperic or Hercynian Massif) and the mountains that surround it. It is, therefore, a common species, which had previously been confused with other species. Its discovery is product of the experience in grass taxonomy of the University of Seville teacher, Carlos Romero Zarco, who, in 2016, identified for the first time the existence of two different species which had previously been considered just one.

The article, coordinated by the teacher Llorenç Sáez (Autonomous University of Barcelona), includes a detailed morphometric study, together with structural, ecological and distribution data, as well as the state of conservation of the population of the species (in accordance with the categories of the International Union for Conservation of Nature), which has shown the clear separation of these two species with regard to those already known in the Mediterranean Region.

"Currently, team continues working on this genus to try to clarify the relationship between these species by means of molecular markers", states the researcher Carlos Romero.

DURHAM, N.C. - A new study by researchers at Duke University and RTI International finds that reusing oilfield water that's been mixed with surface water to irrigate farms in the Cawelo Water District of California's Kern County does not pose major health risks, as some opponents of the practice have feared.

"We did not find any major water quality issues, nor metals and radioactivity accumulation in soil and crops, that might cause health concerns," said Avner Vengosh, professor of water quality and geochemistry at Duke's Nicholas School of the Environment, whose lab led the new study.

Faced with increasing droughts and water shortages, some farmers in the Cawelo district have used diluted oilfield produced water (OPW) for irrigation for their fields for more than 25 years, as permitted under California Water Board policy.

While the oilfield-mixed water contains slightly elevated levels of salts and boron relative to the local groundwater, those levels are still below the standards set by the state for safe drinking water and irrigation in the Cawelo district, Vengosh said.

Boron and salts from the OPW have however, accumulated over time in the irrigated soil. The district's farmers will need to plant boron-tolerant crops and keep mixing the OPW with fresh water to avoid boron toxicity and salinity buildup in their fields, and also to remain within state guidelines. "But all things considered, this is good news," Vengosh said.

The researchers published their peer-reviewed findings May 18 in the journal Science of the Total Environment.

The new study should help allay fears that contaminants in the Cawelo OPW, which is produced as a byproduct of oil and gas extraction at sites adjacent to many farm fields in the district, could impact water and soil quality, harm crop health or pose risks to human health, the researchers said.

"Those concerns assumed that the OPW generated by oil and gas wells in the Cawelo district contains similar mixtures of salts, metals and naturally occurring radioactivity as OPW generated in oil fields in other regions. But our study shows that's not the case," said Andrew Kondash, a research environmental scientist at RTI International, who led the study as part of his 2019 doctoral dissertation at Duke.

"The OPW produced in Kern County is much more diluted and low-saline than common OPW from other parts of the country, so it can be used for irrigation if it is mixed with surface water," Kondash said.

Determining whether it is safe to use OPW for irrigation in other locations would require a similar suite of water and soil testing, Kondash said. "You can't assume that the results in this study could be applied to OPW from other oilfields, where the salinity is typically much higher."

To conduct the new study, the researchers collected and analyzed soil samples, irrigation water samples, OPW samples and groundwater samples from sites across the Cawelo Water District from December 2017 to September 2018 and analyzed them for a wide range of contaminants including, salts, metals and radioactive elements.

The first COVID-19 vaccine to reach phase 1 clinical trial has been found to be safe, well-tolerated, and able to generate an immune response against SARS-CoV-2 in humans, according to new research published in The Lancet. The open-label trial in 108 healthy adults demonstrates promising results after 28 days--the final results will be evaluated in six months [1]. Further trials are needed to tell whether the immune response it elicits effectively protects against SARS-CoV-2 infection.

"These results represent an important milestone. The trial demonstrates that a single dose of the new adenovirus type 5 vectored COVID-19 (Ad5-nCoV) vaccine produces virus-specific antibodies and T cells in 14 days, making it a potential candidate for further investigation", says Professor Wei Chen from the Beijing Institute of Biotechnology in Beijing, China, who is responsible for the study. "However, these results should be interpreted cautiously. The challenges in the development of a COVD-19 vaccine are unprecedented, and the ability to trigger these immune responses does not necessarily indicate that the vaccine will protect humans from COVID-19. This result shows a promising vision for the development of COVID-19 vaccines, but we are still a long way from this vaccine being available to all." [2]

The creation of an effective vaccine is seen as the long-term solution to controlling the COVID-19 pandemic. Currently, there are more than 100 candidate COVID-19 vaccines in development worldwide.

The new Ad5 vectored COVID-19 vaccine evaluated in this trial is the first to be tested in humans. It uses a weakened common cold virus (adenovirus, which infects human cells readily but is incapable of causing disease) to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells. These cells then produce the spike protein, and travel to the lymph nodes where the immune system creates antibodies that will recognize that spike protein and fight off the coronavirus.

The trial assessed the safety and ability to generate an immune response of different dosages of the new Ad5-nCoV vaccine in 108 healthy adults between the ages of 18 and 60 years who did not have SARS-CoV-2 infection. Volunteers were enrolled from one site in Wuhan, China, and assigned to receive either a single intramuscular injection of the new Ad5 vaccine at a low dose (5 × 1010 viral particles/0·5ml, 36 adults), middle dose (1×1011 viral particles/1.0ml, 36 adults), or high dose (1.5 x 1011 viral particles/1.5ml, 36 adults).

The researchers tested the volunteers' blood at regular intervals following vaccination to see whether the vaccine stimulated both arms of the immune system: the body's 'humoral response' (the part of the immune system that produces neutralising antibodies which can fight infection and could offer a level of immunity), and the body's cell-mediated arm (which depends on a group of T cells, rather than antibodies, to fight the virus). The ideal vaccine might generate both antibody and T cell responses to defend against SARS-CoV-2.

The vaccine candidate was well tolerated at all doses with no serious adverse events reported within 28 days of vaccination. Most adverse events were mild or moderate, with 83% (30/36) of those receiving low and middle doses of the vaccine and 75% (27/36) in the high dose group reporting at least one adverse reaction within 7 days of vaccination.

The most common adverse reactions were mild pain at the injection site reported in over half (54%, 58/108) of vaccine recipients, fever (46%, 50/108), fatigue (44%, 47/108), headache (39%, 42/108), and muscle pain (17%, 18/108). One participant given the higher dose vaccine reported severe fever along with severe symptoms of fatigue, shortness of breath, and muscle pain--however these adverse reactions persisted for less than 48 hours.

Within two weeks of vaccination, all dose levels of the vaccine triggered some level of immune response in the form of binding antibodies (that can bind to the coronavirus but do not necessarily attack it - low-dose group 16/36, 44%; medium dose 18/36, 50%; high dose 22/36, 61%), and some participants had detectable neutralising antibodies against SARS-CoV-2 (low-dose group 10/36, 28%; medium dose 11/36, 31%; high dose 15/36, 42%).

After 28 days, most participants had a four-fold increase in binding antibodies (35/36, 97% low-dose group; 34/36 (94%) middle-dose group, and 36/36, 100% in high-dose group), and half (18/36) of participants in the low- and middle-dose groups and three-quarters (27/36) of those in the high-dose group showed neutralising antibodies against SARS-CoV-2.

Importantly, the Ad5-nCoV vaccine also stimulated a rapid T cell response in the majority of volunteers, which was greater in those given the higher and middle doses of vaccine, with levels peaking at 14 days after vaccination (low-dose group (30/36; 83.3%), medium (35/36, 97.2%), and high-dose group (35/36, 97.2%) at 14 days).

Further analyses showed that 28 days after vaccination, the majority of recipients showed either a positive T cell response or had detectable neutralising antibodies against SARS-CoV-2 (low-dose group 28/36, 78%; medium-dose group 33/36, 92%; high-dose group 36/36, 100%).

However, the authors note that both the antibody and T-cell response could be reduced by high pre-existing immunity to adenovirus type 5 (the common cold virus vector/carrier)--in the study, 44%-56% of participants in the trial had high pre-existing immunity to adenovirus type 5, and had a less positive antibody and T-cell response to the vaccine.

"Our study found that pre-existing Ad5 immunity could slow down the rapid immune responses to SARS-CoV-2 and also lower the peaking level of the responses. Moreover, high pre-existing Ad5 immunity may also have a negative impact on the persistence of the vaccine-elicited immune responses", say Professor Feng-Cai Zhu from Jiangsu Provincial Center for Disease Control and Prevention in China who led the study.

The authors note that the main limitations of the trial are its small sample size, relatively short duration, and lack of randomised control group, which limits the ability to pick up rarer adverse reactions to the vaccine or provide robust evidence for its ability to generate an immune reaction. Further research will be needed before this trial vaccine becomes available to all.

A randomised, double-blinded, placebo-controlled phase 2 trial of the Ad5-nCoV vaccine has been initiated in Wuhan to determine whether the results can be replicated, and if there are any adverse events up to 6 months after vaccination, in 500 healthy adults--250 volunteers given a middle dose, 125 given a low dose, and 125 given a placebo as a control. For the first time, this will include participants over 60 years old, an important target population for the vaccine.

RETRACTION: "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis"

June 4, 2020

Today, three of the authors (Mandeep R. Mehra, MD, MSc, Frank Ruschitzka, MD, Amit N. Patel, MD) of the paper "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis" have retracted their study.

Please find their retraction below, followed by a statement from The Lancet.

The retraction is published here: https://www.thelancet.com/lancet/article/s0140673620313246

The Lancet Press Office
pressoffice@lancet.com

Retraction from the authors (published here: https://www.thelancet.com/lancet/article/s0140673620313246)

After publication of our Lancet Article [1], several concerns were raised with respect to the veracity of the data and analyses conducted by Surgisphere Corporation and its founder and our co-author, Sapan Desai, in our publication. We launched an independent third-party peer review of Surgisphere with the consent of Sapan Desai to evaluate the origination of the database elements, to confirm the completeness of the database, and to replicate the analyses presented in the paper.

Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements. As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process.

We always aspire to perform our research in accordance with the highest ethical and professional guidelines. We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologise to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.

Mandeep R Mehra, Frank Ruschitzka, Amit N Patel

[1] Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet 2020; published online May 22. https://doi.org/10.1016/S0140-6736(20)31180-6

Statement from The Lancet:

Today, three of the authors of the paper, "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis", have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they "can no longer vouch for the veracity of the primary data sources." The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics (COPE) and International Committee of Medical Journal Editors (ICMJE), institutional reviews of Surgisphere’s research collaborations are urgently needed.

The retraction notice is published today, June 4, 2020. The article will be updated to reflect this retraction shortly.

For COPE guidelines, please see: https://publicationethics.org/resources/guidelines-new/cooperation-between-research-institutions-and-journals-research-integrity

For ICMJE guidelines, please see: http://www.icmje.org/recommendations/browse/publishing-and-editorial-issues/scientific-misconduct-expressions-of-concern-and-retraction.html

A large observational study suggests that treatment with the antimalarial drug chloroquine or its analogue hydroxychloroquine (taken with or without the antibiotics azithromycin or clarithromycin) offers no benefit for patients with COVID-19. The study analysed data from nearly 15,000 patients with COVID-19 receiving a combination of any of the four drug regimens and 81,000 controls.

Treatment with these medications among patients with COVID-19, either alone or in combination with macrolide antibiotics, was linked to an increased risk of serious heart rhythm complications in these patients.

Researchers suggest these treatment regimens should not be used to treat COVID-19 outside of clinical trials until results from randomised clinical trials are available to confirm the safety and efficacy of these medications for COVID-19 patients.

Chloroquine is an antimalarial drug and its analogue, hydroxychloroquine, is used to treat autoimmune diseases including lupus and arthritis. Both drugs have a good safety profile as treatments for those specific conditions, and the findings do not imply patients should stop taking these drugs if they are prescribed for approved conditions. They have also been shown to have antiviral effects in laboratory tests and are therefore of interest as potential treatments for COVID-19.

Prof Dr Mandeep R. Mehra, lead author of the study and Executive Director of the Brigham and Women's Hospital Center for Advanced Heart Disease in Boston, USA, said: "This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19. Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death. Randomised clinical trials are essential to confirm any harms or benefits associated with these agents. In the meantime, we suggest these drugs should not be used as treatments for COVID-19 outside of clinical trials." [1]

In the study, researchers analysed data from 96,032 patients hospitalised between 20 December 2019 and 14 April 2020 with laboratory confirmed SARS-CoV-2 infection from 671 hospitals. All of the patients included in the study had either been discharged or had died by 21 April 2020.

The team compared outcomes from patients treated with chloroquine alone (1,868), hydroxychloroquine alone (3,016), chloroquine in combination with a macrolide (3,783) or hydroxychloroquine with a macrolide (6,221). Patients from these four groups were compared with the remaining control group of 81,144 patients.

At the end of the study period, around one in 11 patients in the control group had died in hospital (9.3%, 7,530/81,144). All four of the treatments were associated with a higher risk of dying in hospital. Of those treated with chloroquine or hydroxychloroquine alone, around one in six patients had died (16.4%, 307/1,868 chloroquine and 18.0%, 543/3,016 hydroxychloroquine). When the drugs were used in combination with a macrolide, the death rate rose to more than one in five for chloroquine (22.2%, 839/3,783) and almost one in four for hydroxychloroquine (23.8%, 1,479/6,221).

Some of the difference in the rates of mortality is due to underlying differences between patients who received the treatments and those who didn't. After accounting for factors including age, race, body mass index and underlying health conditions including heart disease, lung disease and diabetes, the researchers found the drug regimens were associated with an increased risk of death.

They estimated that the excess risk attributable to the use of the drug regimen rather than other factors such as co-morbidities ranged from 34% to 45%. The authors explain that if the rate of mortality is 9.3% in the control group, after adjustment for the other clinical factors, the rate attributable to the use of the drug regimens would rise to 12.4-13.4% . However, the researchers caution that it is not possible to exclude the possibility that other, unmeasured factors were responsible for the apparent link between treatment with these drugs and the decrease in patient survival because such is the design of observational studies, and randomised trials are urgently needed.

The team also found that serious cardiac arrhythmias, which cause the lower chamber of the heart to beat rapidly and irregularly, were more common in the groups receiving either of the four treatment regimens.

The biggest increase was seen in the group treated with hydroxychloroquine in combination with a macrolide, where 8% of patients developed a heart arrhythmia (502/6,221) compared with 0.3% patients in the control group (226/81144). After accounting for demographic factors and pre-existing conditions, the team calculated that treatment with this combination of drugs is associated with a more than five-fold increase in risk of developing a serious heart arrhythmia while in hospital (as an example, an increase from 0.3% to 1.5% would be attributable to the drug regimen after adjustment for other clinical factors). Similarly, it is not possible to conclusively infer cause and effect between treatment with these medications and the onset of heart arrhythmias. Randomised clinical trials will be required before any conclusion can be reached regarding benefit of harm of these agents in COVID-19 patients.

Prof Dr. Frank Ruschitzka, Director of the Heart Center at University Hospital Zurich who also co-authored the study said: "Several countries have advocated use of chloroquine and hydroxychloroquine, either alone or in combination, as potential treatments for COVID-19. Justification for repurposing these medicines in this way is based on a small number of anecdotal experiences that suggest they may have beneficial effects for people infected with the SARS-CoV-2 virus. However, previous small-scale studies have failed to identify robust evidence of a benefit and larger, randomised controlled trials are not yet completed. However, we now know from our study that the chance that these medications improve outcomes in COVID-19 is quite low." [1]

Writing in a linked Comment article, Professor Christian Funck-Brentano, of the Sorbonne University in Paris, France (who was not involved in the study), said: "This well-conducted observational study adds to preliminary reports suggesting that chloroquine, hydroxychloroquine, alone or with azithromycin is not useful and may be harmful in hospitalized COVID-19 patients."

CHICAGO --- The placentas from 16 women who tested positive for COVID-19 while pregnant showed evidence of injury, according to pathological exams completed directly following birth, reports a new Northwestern Medicine study.

The type of injury seen in the placentas shows abnormal blood flow between the mothers and their babies in utero, pointing to a new complication of COVID-19. The findings, though early, could help inform how pregnant women should be clinically monitored during the pandemic.

The study was published today (May 22) in the journal American Journal of Clinical Pathology. It is the largest study to examine the health of placentas in women who tested positive for COVID-19.

"Most of these babies were delivered full-term after otherwise normal pregnancies, so you wouldn't expect to find anything wrong with the placentas, but this virus appears to be inducing some injury in the placenta," said senior author Dr. Jeffery Goldstein, assistant professor of pathology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine pathologist. "It doesn't appear to be inducing negative outcomes in live-born infants, based on our limited data, but it does validate the idea that women with COVID should be monitored more closely."

This increased monitoring might come in the form of non-stress tests, which examine how well the placenta is delivering oxygen, or growth ultrasounds, which measure if the baby is growing at a healthy rate, said co-author Dr. Emily Miller, assistant professor of obstetrics and gynecology at Feinberg and a Northwestern Medicine obstetrician.

"Not to paint a scary picture, but these findings worry me," Miller said. "I don't want to draw sweeping conclusions from a small study, but this preliminary glimpse into how COVID-19 might cause changes in the placenta carries some pretty significant implications for the health of a pregnancy. We must discuss whether we should change how we monitor pregnant women right now."

Previous research has found that children who were in utero during the 1918-19 flu pandemic, which is often compared to the current COVID-19 pandemic, have lifelong lower incomes and higher rates of cardiovascular disease. Flu doesn't cross the placenta, Goldstein said, so whatever is causing life-long problems in those people is most likely due to immune activity and injury to the placenta.

"Our study, and other studies like it, are trying to get on the ground floor for this exposure so we can think about what research questions we should be asking in these kids and what can or should we do now to mitigate these same types of outcomes," Goldstein said.

Fifteen patients delivered live infants in the third trimester, however one patient had a miscarriage in the second trimester. "That patient was asymptomatic, so we don't know whether the virus caused the miscarriage or it was unrelated," Goldstein said, "We are aware of four other cases of miscarriage with COVID. The other reported patients had symptoms and three of four had severe inflammation in the placenta. I'd like to see more before drawing any conclusions."

The placenta is the first organ to form in fetal development. It acts as the fetus' lungs, gut, kidneys and liver, taking oxygen and nutrients from the mother's blood stream and exchanging waste. The placenta also is responsible for many of the hormonal changes within the mother's body. Examining a woman's placenta allows a pathologist to follow a retroactive roadmap of a woman's pregnancy to learn what happened to the baby in utero or what could happen to both the mother and the infant after birth.

"The placenta acts like a ventilator for the fetus, and if it gets damaged, there can be dire outcomes," Miller said. "In this very limited study, these findings provide some signs that the ventilator might not work as well for as long as we'd like it to if the mother tests positive for SARS-CoV2."

The placentas in these patients had two common abnormalities: insufficient blood flow from the mother to the fetus with abnormal blood vessels called maternal vascular malperfusion (MVM) and blood clots in the placenta, called intervillous thrombi.

In normal cases of MVM, the mother's blood pressure is higher than normal. This condition is typically seen in women with preeclampsia or hypertension. Interestingly, only one of the 15 patients in this study had preeclampsia or hypertension.

"There is an emerging consensus that there are problems with coagulation and blood vessel injury in COVID-19 patients," Goldstein said. "Our finding support that there might be something clot-forming about coronavirus, and it's happening in the placenta."

The 16 women in the study delivered their babies at Northwestern Medicine Prentice Women's Hospital. All tested positive for COVID-19. Four patients came in with flu-like symptoms three to five weeks before delivery and tested positive for the virus. The remaining patients all tested positive when they came in to deliver. Five patients never developed symptoms, others were symptomatic at delivery.

Between 30 and 40 patients deliver at Prentice daily. The team began testing placentas of COVID-19-positive mothers in early April. Fourteen of the live-born infants in the study were born full term and with normal weights and Apgar scores. One live-born infant was premature.

"They were healthy, full-term, beautifully normal babies, but our findings indicate a lot of the blood flow was blocked off and many of the placentas were smaller than they should have been," Miller said. "Placentas get built with an enormous amount of redundancy. Even with only half of it working, babies are often completely fine. Still, while most babies will be fine, there's a risk that some pregnancies could be compromised."

In February, before the pandemic was known to have reached Chicago, Goldstein assembled his research team.

"If you get the flu and you're pregnant, we know nothing about what that looks like in your placenta, so I began thinking how we'd study this flu-like epidemic if it came through Chicago," Goldstein said. "We started setting things up and then lo and behold, the epidemic came here, so we were ready."

Pinnacle Point, a series of archaeological sites that overlook a now submerged section of South Africa's coastline and one of the world's most important localities for the study of modern human origins, was as much of an Eden for animals as it was for early humans. Jamie Hodgkins, PhD, assistant professor of anthropology at University of Colorado Denver, and her team drilled ancient herbivore teeth to find that many local animals stayed put in the ecologically rich ecosystem, which may explain why humans flourished there, too.

Their study was published in a Quaternary Science Reviews special issue: The Palaeo-Agulhas Plain: a lost world and extinct ecosystem this month.

Home to the Earliest Modern Humans

Home to some of the richest evidence for the behavior and culture of the earliest clearly modern humans, the submerged shelf called the Palaeo-Agulhas Plain (PAP) once formed its own ecosystem. Co-author Curtis Marean, PhD, Arizona State University, has worked with teams of scientists for decades to reconstruct the locale back into the Pleistocene, the time period that spanned from 2.6 million to 11,700 years ago.

In this study, the researchers looked specifically at antelope migratory patterns at Pinnacle Point. This series of cave sites that sit on the modern South African coast offers archaeological materials from humans who were living and hunting there back to 170,000 years ago.

"During glacial cycles, the coastal shelf was exposed," said Hodgkins. "There would have been a huge amount of land in front of the cave sites. We thought it was likely that humans and carnivores were hunting animals as they migrated east and west over the exposed shelve."

A Lack of Migratory Pattern

Hodgkins and her team wanted to understand those migratory patterns. They studied the carbon and oxygen isotopes within the tooth enamel of many large herbivores, including Redunca, or reedbuck, a nonmigratory antelope. Tooth enamel can reveal a pattern of migration by tracking changing levels of carbon from the plants an animal eats as its teeth grow.

In general, wetter, cooler environments are home to C3 plants; hotter, drier environments are home to C4 plants. Animals like lush vegetation, which means they tend to follow the rain patterns: in this case east for summer rain (C4 grasses), and west for winter rain (C3 grasses). If animals were migrating between summer and winter rainfall zones, their tooth enamel would register that annual C3 and C4 plant rotation as a sinusoidal curve as their teeth grew.

A) Map of South Africa (SA) showing the distribution of C4 grasses associated with the percentage of summer rain from east to west along the coast, and with the winter rainfall zone in the west (modified from Vogel, 1978); B) A map of SA showing the area of the Greater Cape Floristic Region with the expanded PAP and hypothesized animals migration (i.e. It is hypothesized that animals would have been undertaking long-distance migrations between the east coast in summer rainfall zone and west coast in the winter rainfall zone)

But when Hodgkins and her team used the nonmigratory reedbuck as their control animal, they found that the enamel from its typically migratory pals--like the wildebeest, hartebeest, and springbok--showed no discernible migratory pattern. Most animals seemed happy right where they were.

"They weren't struggling at Pinnacle Point," says Hodgkins. "We now know that powerful river systems supplied the expanded coast, thus animals didn't have to be migratory. It was a great location, resource-wise. During interglacials when the coast moved closer to the caves humans had shellfish and other marine resources, and when the coast expanded in glacial times hunters had access to a rich, terrestrial environment. Hunters wouldn't need to be as mobile with all of these herbivores wandering around."

Thriving in an Ecogeological Haven

Hodgkins' team's findings of this prehistoric Eden echoed another recent discovery. Seventy-four-thousand years ago, one of Earth's largest known eruptions at Mount Toba in Sumatra, Indonesia, created a global winter, causing population crashes. In 2018, researchers from Marean's group found that humans at Pinnacle Point not only survived, but thrived in the haven.

Hodgkins says this is just a first attempt at using isotopic data to test the hypothesis of east and west migration patterns at these sites and further research will be done.

"It is quite possible that animal migration patterns changed as the coastline moved in and out during glacial and interglacial cycles," said Hodgkins.

The paper "Hydroxychloroquine or Chloroquine with or without a Macrolide and Outcome in COVID-19: A Multinational Registry Analysis" referenced in this release has been retracted by The Lancet. Please see the retaction letter below.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31324-6/fulltext

"After publication of our Lancet Article,1 several concerns were raised with respect to the veracity of the data and analyses conducted by Surgisphere Corporation and its founder and our co-author, Sapan Desai, in our publication. We launched an independent third-party peer review of Surgisphere with the consent of Sapan Desai to evaluate the origination of the database elements, to confirm the completeness of the database, and to replicate the analyses presented in the paper.

Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements. As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process.

We always aspire to perform our research in accordance with the highest ethical and professional guidelines. We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologise to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused."

Boston, MA -- A research team led by investigators from Brigham and Women's Hospital has evaluated real-world evidence related to outcomes for COVID-19 patients who were treated with hydroxychloroquine or chloroquine analogues (with or without a macrolide). Investigators found no evidence that either drug regimen reduced the death rate among patients. Patients treated with hydroxychloroquine or chloroquine regimens were far more likely to experience abnormal, rapid heart rhythms (known as ventricular arrhythmias) than their counterparts who had not received the drugs. The team's findings are published in The Lancet.

"No matter which way you examine the data, use of these drug regimens did not help," said corresponding author Mandeep R. Mehra, MD, executive director of the Brigham's Center for Advanced Heart Disease. "If anything, patients had a higher likelihood of death. We also saw a quadrupling in the rate of significant ventricular arrhythmias in patients with COVID-19 who had been treated with hydroxychloroquine or chloroquine regimens."

Mehra and colleagues conducted their study using the Surgical Outcomes Collaborative database, an international registry comprised of de-identified data from 671 hospitals across six continents. The analysis included data on more than 96,000 patients hospitalized with COVID-19. This included almost 15,000 patients who had received the anti-malarial drug chloroquine or its analog hydroxyquinone with or without an antibiotic (macrolides such as azithromycin and clarithromycin) early after COVID-19 diagnosis. The study's primary endpoint was death or discharge from the hospital.

Mehra and colleagues found that 10,698 patients died in the hospital (11.1 percent) and 85,334 survived to discharge. The team compared death rates for those taking one of the drug regimens to that of a control group, after accounting for confounding variables, such as age, sex and underlying risk factors. The death rate among the control group was 9.3 percent. Each of the drug regimens of chloroquine or hydroxychloroquine alone, or in combination with a macrolide, was associated with an increased risk of in-hospital death with COVID-19.

In addition, each of the drug regimens was associated with an increase in the risk of ventricular arrhythmia. Among the treatment groups, between 4 and 8 percent of patients experienced a new ventricular arrhythmia, compared to 0.3 percent of patients in the control group.

Chloroquine and hydroxychloroquine have been known to cause cardiovascular toxicity and previous studies have shown that macrolides can increase the risk of sudden cardiac death. A preliminary analysis of patients in Brazil treated with chloroquine and an antibiotic has suggested a high dose of chloroquine may be a safety hazard. Results from randomized, controlled clinical trials are not expected until the summer.

The authors caution that the current study is observational in nature -- this means that it cannot absolutely answer the question of whether the drug regimens were solely responsible for the changes in survival. Randomized clinical trials will be required before any conclusion can be reached regarding harm.

"These findings suggest that these drug regimens should not be used outside of the realm of clinical trials and urgent confirmation from randomized clinical trials is needed," the authors conclude.

The development and maintenance of the Surgical Outcomes Collaborative database was funded by the Surgisphere Corporation. The present analysis was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital, Boston. Mehra reports no direct conflicts pertinent to the development of this paper. Other general conflicts include consulting relationships with Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, NupulseCV, FineHeart, Leviticus, Roivant and Triple Gene. Dr. Desai is the founder of Surgisphere Corporation, Chicago. The other authors have no pertinent conflicts to report.

Scientists have found that adding cognitive behavioural therapy (CBT) to standardised medical care gives patients with dissociative seizures longer periods of seizure freedom, less bothersome seizures and a greater quality of life, in a study published in Lancet Psychiatry today and by the Cognitive behavioural therapy for adults with dissociative seizures (CODES) study group funded by National Institute for Health Research (NIHR).

Dissociative seizures, also called functional and non-epileptic seizures, look similar in appearance to epileptic seizures or fainting but are related to a different type of involuntary blackout that is typically distressing and disabling for patients and their carers. Up to 1 in 5 adults presenting in epilepsy clinics have this hidden condition which is one of several types of Functional Neurological Disorder (FND). Historically patients with dissociative seizures have often been ignored or disbelieved by doctors and research on treatment is limited. They are more likely to be found in women and usually have a poor outcome with a worse quality of life than people with epilepsy alone. People with dissociative seizures have a marked increase in health service use.

In the largest treatment trial to date for dissociative seizures, 368 patients from centres across England, Scotland, and Wales were followed up 6 months and 12 months after treatment courses began. Researchers found patients treated with dissociative seizure specific CBT alongside standardised medical care reported the highest number of consecutive dissociative seizure-free days in the previous 6 months, along with greater functional status, self-rated and doctor-rated change in global impression scores, and satisfaction with treatment when compared with standardised medical care alone.

Lead author Laura Goldstein, Professor of Clinical Neuropsychology at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London said, "We have delivered the first large-scale multi-centre and multi-professional trial investigating treatments for adults with dissociative seizures. This is especially important as the availability of treatment for people with this disorder has been so variable in the UK and elsewhere.

While overall there appeared to be a reduction in how often people in both groups of the study were having dissociative seizures at the end of the trial, with no clear difference between the groups, the group who had received our package of dissociative seizure-specific CBT were reporting better functioning across a range of everyday situations. They described their dissociative seizures as less bothersome, they were less distressed, reported better health and fewer symptoms, and were more satisfied with their treatment. It is important to consider providing dissociative seizure-specific CBT in addition to specialist care from neurologists and psychiatrists to treat people with dissociative seizures."

In the UK, there is currently no standardised care pathway for people with dissociative seizures. The researchers recommend the incorporation of seizure-specific CBT within specialist care from neurologists and psychiatrists. Furthermore, as participants received treatment in varied medical settings, this study suggests that the CBT combination intervention does not have to be limited to highly specialised centres and can be delivered by a range of clinical psychologists or cognitive behavioural psychotherapists. Researchers suggest future work is needed to identify which patients would benefit most from a dissociative seizure-specific CBT approach.

Neurologist, Professor Jon Stone, who was a co-investigator in the study said, "The CODES Trial is a landmark study for a condition which has, for too long, been ignored by health services. The trial has encouraged participating neurologists, psychiatrists and psychotherapists across the UK to raise their standard of care for these patients. The trial has set a new bar for evidence in this area, making it clear that there are thousands of new patients with this condition in the UK every year who we need to keep doing better for in terms of treatment and research in the future."

Babies with Hirschsprung's disease are born with an incomplete or absent gut nervous system. Children's Hospital Los Angeles investigator Tracy Grikscheit, MD, runs a laboratory that investigates the therapeutic potential of tissue engineering - the induced growth of healthy tissue using stem cells. In a new study, Dr. Grikscheit successfully grew a fully functional gut nervous system - or ENS - in a pre-clinical model. While not yet available clinically, the finding brings surgeons like Dr. Grikscheit one step closer to helping babies in need.

Dr. Grikscheit, Chief of Pediatric Surgery at CHLA, published her findings this week in the Journal of Tissue Engineering. The growth of new, fully-functional nervous system tissue is an important milestone for research into a condition called Hirschsprung's disease. "The ENS forms when cells migrate down a major nerve throughout the digestive tract," explains Dr. Grikscheit. "In Hirschsprung's disease, the nerves don't make it all the way down the intestines." In the worst cases, she says, kids have no gut nervous system at all. This leaves intestinal tissue that cannot function. "When a baby has this disease, the situation is dire," she says. "And current medical therapies are not adequate." But the complex technique developed by Dr. Grikscheit could change this.

After years of searching for a model of Hirschsprung's disease, Dr. Grickscheit was unsatisfied with what was available to researchers. "The models weren't reliable," she explains, saying they didn't address growing the ENS from scratch. So, she made the model herself.

Growing a fully functional ENS is no simple feat. "The enteric nervous system is called the second brain because it is so beautifully diverse," says Dr. Grikscheit. The ENS coordinates intestinal muscle movement, hormone release and maintenance of stem cells, which are needed to maintain the intestinal lining.

"These cells are incredibly multi-faceted," she says. "The fact that we can implant them and they grow into this complex nervous system is a big step towards offering hope for these babies."

Bypassing clinical trials for a potential SARS-CoV-2 vaccine would be "catastrophic," says Science Advances deputy editor Douglas Green in this Editorial. Instead, it's vital to take time to ensure any vaccine candidate's safety and investigate potential adverse effects, he says. A vaccine able to trigger strong neutralizing antibody responses in clinical tests will still not be ready for widespread implementation without comprehensive safety tests. For example, vaccines must be examined for causing an effect known as antibody-dependent enhancement (ADE), whereby vaccine-induced antibodies that bind to the virus also attach to the body's cells, facilitating infection of these cells - a concerning phenomenon that has been observed in vaccines against dengue, Ebola, HIV, and feline coronavirus. Ethical accelerated testing on humans should not be ruled out completely, but extreme risks must be weighed against potential benefits, Green says. There are currently 95 vaccines in development against SARS-CoV-2, with most expected to clear Phase I and two experimental vaccines already moving into Phase II trials.

Given the present-day rate of global sea-level rise, remaining marshes in the Mississippi Delta are likely to drown, according to a new Tulane University study.

A key finding of the study, published in Science Advances, is that coastal marshes experience tipping points, where a small increase in the rate of sea-level rise leads to widespread submergence.

The loss of 2,000 square miles (5,000 km2) of wetlands in coastal Louisiana over the past century is well documented, but it has been more challenging to predict the fate of the remaining 6,000 square miles (15,000 km2) of marshland.

The study used hundreds of sediment cores collected since the early 1990s to examine how marshes responded to a range of rates of sea-level rise during the past 8,500 years.

"Previous investigations have suggested that marshes can keep up with rates of sea-level rise as high as half an inch per year (10 mm/yr), but those studies were based on observations over very short time windows, typically a few decades or less," said Torbjörn Törnqvist, lead author and Vokes Geology Professor in the Tulane Department of Earth and Environmental Sciences.

"We have taken a much longer view by examining marsh response more than 7,000 years ago, when global rates of sea-level rise were very rapid but within the range of what is expected later this century."

The researchers found that in the Mississippi Delta most marshes drown in a few centuries once the rate of sea-level rise exceeds about one-tenth of an inch per year (3 mm/yr). When the rate exceeds a quarter of an inch per year (7.5 mm/yr), drowning occurs in about half a century.

"The scary thing is that the present-day rate of global sea-level rise, due to climate change, has already exceeded the initial tipping point for marsh drowning," Törnqvist said. "And as things stand right now, the rate of sea-level rise will continue to accelerate and put us on track for marshes to disappear even faster in the future."

While these findings indicate that the loss of remaining marshes in coastal Louisiana is probably inevitable, there are still meaningful actions that can be taken to prevent the worst possible outcomes. The most important one, Törnqvist said, is to drastically curb greenhouse gas emissions to prevent sea-level rise from ramping up to rates where marshes will drown within a matter of decades.

The other one is to implement major river diversions as quickly as possible, so at least small portions of the Mississippi Delta can survive for a longer time. However, the window of opportunity for these actions to be effective is rapidly closing, he said.

EVANSTON, Ill. --- Winter may be behind us, but do you remember the challenge of waking up on those cold, dark days? Temperature affects the behavior of nearly all living creatures, but there is still much to learn about the link between sensory neurons and neurons controlling the sleep-wake cycle.

Northwestern University neurobiologists have uncovered a clue to what's behind this behavior. In a study of the fruit fly, the researchers have identified a "thermometer" circuit that relays information about external cold temperature from the fly antenna to the higher brain. They show how, through this circuit, seasonally cold and dark conditions can inhibit neurons within the fly brain that promote activity and wakefulness, particularly in the morning.

"This helps explains why -- for both flies and humans -- it is so hard to wake up in the morning in winter," said Marco Gallio, associate professor of neurobiology in the Weinberg College of Arts and Sciences. "By studying behaviors in a fruit fly, we can better understand how and why temperature is so critical to regulating sleep."

The study, led by Gallio and conducted in Drosophila melanogaster, was published today (May 21) in the journal Current Biology.

The paper describes for the first time "absolute cold" receptors residing in the fly antenna, which respond to temperature only below the fly's "comfort zone" of approximately 77 degrees Fahrenheit. Having identified those neurons, the researchers followed them all the way to their targets within the brain. They found the main recipients of this information are a small group of brain neurons that are part of a larger network that controls rhythms of activity and sleep. When the cold circuit they discovered is active, the target cells, which normally are activated by morning light, are shut down.

Drosophila is a classic model system for circadian biology, the area in which researchers study the mechanisms controlling our 24-hour cycle of rest and activity. The focus of much current work is on how changes in external cues such as light and temperature impact rhythms of activity and sleep and how the cues reach the specific brain circuits that control these responses.

While detection of environmental temperature is critical for small "cold-blooded" fruit flies, humans are still creatures of comfort and are continually seeking ideal temperatures. Part of the reason humans seek optimal temperatures is that core and brain temperatures are intimately tied to the induction and maintenance of sleep. Seasonal changes in daylight and temperature are also tied to changes in sleep.

"Temperature sensing is one of the most fundamental sensory modalities," said Gallio, whose group is one of only a few in the world that is systematically studying temperature sensing in fruit flies. "The principles we are finding in the fly brain -- the logic and organization -- may be the same all the way to humans. Whether fly or human, the sensory systems have to solve the same problems, so they often do it in the same ways."

Gallio is the corresponding author of the paper. Michael H. Alpert, a postdoctoral fellow in Gallio's lab, and Dominic D. Frank, a former Ph.D. student in Gallio's lab, are the paper's co-first authors.

"The ramifications of impaired sleep are numerous -- fatigue, reduced concentration, poor learning and alteration of a myriad of health parameters -- yet we still do not fully understand how sleep is produced and regulated within the brain and how changes in external conditions may impact sleep drive and quality," Alpert said.

The study, a collaborative effort many years in the making, was performed in the Gallio lab by a range of scientists at different stages of their careers, ranging from undergraduate students to the principal investigator.

"It is crucial to study the brain in action," Frank said. "Our findings demonstrate the importance of functional studies for understanding how the brain governs behavior."

Overall, the study heavily relied on the ability to study both the activity of neurons and the role of these neurons on behavior. To do this, the researchers developed new tools and used a combination of functional and anatomical studies, neurogenetic and behavioral monitoring approaches to conduct these experiments in both wild type and transgenic flies.

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach

As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors from McMaster University and St. Joseph's hospital suggest that there is convincing evidence to support this recommendation. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-2567.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Catherine M. Clase, MB BChir, MSc can be reached through Veronica McGuire at vmcguir@mcmaster.ca.

2. Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence

Researchers from McMaster University reviewed evidence about the benefits and harms of alternative noninvasive and invasive ventilation strategies in acute hypoxic respiratory failure in patients infected with COVID-19. Indirect evidence related to other coronaviruses and evidence related to virus transmission to health care workers was also examined. Based on the evidence, they conclude that use of noninvasive ventilation, similar to invasive mechanical ventilation, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-2306.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Holger J. Schünemann, MD, PhD, MSc, can be reached at schuneh@mcmaster.ca or through Veronica McGuire at vmcguir@mcmaster.ca.

Aside from Indira Gandhi, Margaret Thatcher, and more recently Angela Merkel and Jacinda Ardern, women continue to be scarce in the halls of power.

To rectify this inequality, a majority of countries (or at least one political party in most) have imposed female electoral quota systems, or rules designed to increase the representation of women. The catch? Boosting gender may well curtail representation in other respects.

An unintended consequence of such quotas is the reduction of other underrepresented minorities, finds a recent University of Rochester study in the American Journal of Political Science.

The Rochester study looked at India's caste system and female representation in local government, where female-reserved seats have been enshrined in the 73rd and 74th Amendments of the Indian Constitution since the early 1990s.

"The effect of electoral quotas for women in India was to reduce the representation of lower caste groups," says lead author Alexander Lee, an associate professor in the Department of Political Science at the University of Rochester, who looked specifically at what happened in Delhi in local elections once gender quotas were introduced.

"In many poorer or developing countries electoral quotas can reduce the representation of marginalized groups."

For their study, Lee and his coauthor, Varun Karekurve-Ramachandra, a PhD graduate student in the same department, examined the consequences of women quotas on the electoral representation of caste groups in local government bodies in Delhi. They found that constituencies reserved for women were less likely--compared to unreserved constituencies--to elect members of groups where the status of women was low.

In practice, this meant that those reserved constituencies were less likely to elect members of several traditionally underprivileged groups--especially of the so called "Other Backward Class" or OBC castes--a collective term used by the Indian Government to classify castes, which are educationally or socially disadvantaged. Instead, the scientists discovered, voters in women-reserved constituencies tended to elect candidates from the Hindu upper castes.

"In India if you have a policy that lets you choose only women, a disproportionate number of these women will be upper caste," says Lee.

The author of From Hierarchy to Ethnicity: The Politics of Caste in Twentieth-Century India (Cambridge University Press, 2020), Lee is interested in the factors governing the success or failure of political institutions in South Asia and other areas of the developing world. In particular, his work focuses on the historical evolution of state capacity, the causes and consequences of identity politics, and bureaucratic politics.

Key findings

In countries where women have a higher social standing among elite groups, women quotas and/or rules to improve female representation will lead to increases in the representation of the elite and simultaneously lead to a reduction in the representation of people from historically marginalized groups.

When trying to increase the representation of one identity (such as female) through quotas--the representation of the second identity (such as social class, race, or religion) depends on the number of potential candidates who possess both traits.

If the number of candidates with both traits is disproportionately low, quotas will reduce the representation of the second identity even further.

A society's attitudes toward gender are important when it comes to candidate pools: female candidates are less common among groups, societies, and in countries where the social involvement of women outside the home is discouraged.

So-called "proxy candidates" are especially common among marginalized (here lower caste groups) groups--women who are running for office in name only and are really stand-ins for their husbands.

When women quotas were introduced in India the proportion of proxy candidates (identifiable because they don't give an occupation and have never paid income taxes in their lives, which means they have never worked outside their homes) increased.

In women-reserved constituencies in India the number of candidates decreased and fewer people ran for public office.

Among the small number of women in India who run for office a disproportionately large number come from the upper castes.

While the gender quotas imposed for local government elections in Delhi specifically achieved their narrow aim of upping the representation of women to just above 50 percent, the change had clear implications for caste groups. The proportion of winning candidates from castes with traditional gender norms (i.e., lower caste groups) decreased by 7.7 percentage points for a seat reserved for women. The team notes that the number may still understate the effect for active female politicians, because it counts also so-called proxy candidates. "Without the ability to run proxies, the effects would probably be larger," says Lee.

In practice, this meant that the representation of members of the OBC category declined, while the numbers for members of the Hindu upper castes increased, in particular among the Brahmins and Banias.

"Gender quotas tend to politically strengthen groups at the top of traditional caste hierarchies and favor empowered groups over disempowered ones," says Karekurve-Ramachandra. "These unintended consequences are plausible because we think that women from marginalized groups--at the intersection of two disadvantaged identities--tend be especially disadvantaged."

The results highlight the difficulties of balancing descriptive representation on multiple, crosscutting dimensions, and the possible unintended consequences of the type of single-dimension quotas currently proposed for inclusion in the Indian constitution.

Do the findings from India translate to other parts of the world, to the US?

Not directly, say the researchers. In many rich countries the opposite actually holds true. For starters, the United States does not have legislative gender quotas, although the Democratic Party added language to its charter in 2018 that the party's National Committee, the Executive Committee, and other similar bodies "shall be as equally divided as practicable according to gender" in an attempt to address the prevailing gender gap.

The Rochester team theorizes that the effects of women quotas depend on the relative social standing of women in the pool of political candidates for the underrepresented group. In a situation with many qualified female candidates, Lee says, the quotas will raise the proportion of minorities in politics. However, if there are disproportionately low numbers of qualified female candidates in the minority pool, it'll result in fewer minority politicians.

In the United States, for instance, the proportion of women among African American members the US House of Representatives is higher than the proportion of women among white House members. Also, the proportion of Muslim women in legislative bodies in many European countries is higher than that of Muslim men.

"Why this happens is debated a lot," says Lee, who ascribes part of the effect to stereotyping. "If you have a minority that is seen by some as potentially threatening, women of that minority may be perceived as less threatening by members of the majority group and are therefore more likely to be elected."

The relative status of women within minority groups may also play a central role when it comes to being perceived as a qualified candidate. Generally, the level of educational attainment among African American women is higher than among African American men for a variety of reasons, Lee notes.

The team believes that their findings in India can be generalized to a broad set of countries where the status of women is lower within underprivileged groups, including many developing nations. The exact effects, the researchers caution, depend on the exact natures of the imposed quotas, the role of partisanship, and social attitudes.

One thing, however, is clear: quotas for women can have consequences that go well beyond gender. And that effect, they caution, should be carefully considered in the design of any gender and ethnic electoral quota system.

Genetic adaptations of early Italian ancestors to environmental changes, such as those that occurred soon after the Last Glacial Maximum, may explain some of the genetic differences between northern and southern Italian populations today, according to a study published in BMC Biology. The research suggests that northern and southern Italian populations may have begun to diverge genetically as early as 19,000-12,000 years ago and constitutes the earliest known evidence of genetic divergence in Italy so far.

A team of researchers at the University of Bologna sequenced the genomes of 38 unrelated participants from different regions in Italy, each the third generation of their family native to each region. The genomes were selected as representative of known genetic differences across the Italian population and over 17 million distinct genetic variants were found between individuals. The authors compared these variations with existing genetic data from 35 populations across Europe and the Mediterranean and with variants previously observed in 559 ancient human remains, dating from the Upper Palaeolithic (approx. 40,000 years ago) to the Bronze Age (approx. 4,000 years ago).

Prof. Marco Sazzini, lead author of the study said: "When comparing sequences between modern and ancient genome samples, we found early genetic divergence between the ancestors of northern and southern Italian groups dating back to the Late Glacial, around 19,000-12,000 years ago. Migrations during the Neolithic and Bronze Age periods, thousands of years later, then further differentiated their gene pools. Divergence between these ancestral populations may have occurred as a result of temperature rises and subsequent shrinking of glaciers across Northern Italy during this time, allowing ancestors who survived the glaciation period to move north, separating from groups who remained in the south."

Further analyses also revealed signatures ascribable to specific biological adaptations in northern and southern Italian genomes suggestive of habitation in differing climates. The genetic history of northern Italians showed changes in the genes responsible for regulating insulin, body-heat production and fat metabolism, whilst southern Italians showed adaptations in genes regulating the production of melanin and responses to pathogens.

Prof. Sazzini said: "Our findings suggest that the ancestors of northern Italians adapted to lower environmental temperatures and the related high-calorie diets by optimising their energy metabolism. This adaptation may play a role in the lower prevalence of Type 2 Diabetes recorded in Northern Italy today. Conversely, southern Italian ancestors adapted to a warmer climate with higher UV levels by increasing melanin production, which may explain the lower incidence rates of skin cancers recorded across Southern regions. The genomes of southern Italians also showed changes in the genes encoding mucins, which play a role in protection against pathogens, and genetic variants linked to a longer lifespan. Further research in this area may help us understand how the observed genetic differences can impact population health or predisposition to a number of diseases."

The authors caution that although correlations may be drawn between evolutionary adaptations and current disease prevalence among populations, they are unable to prove causation, or rule out the possibility that more recent gene flow from populations exposed to diverse environmental conditions outside of Italy may have also contributed to the different genetic signatures seen between northern and southern Italians today.