Culture

A new paper in The Journal of Urban Ecology, published by Oxford University Press, finds that rats can be baited to, or repelled from, locations using pheromones found in the scents of other rats.

Rats cost the world's economy more than $300 billion a year. In addition to causing fines and business closures, rats spread disease, start fires, and disable motor vehicles. In Manhattan alone, rodent activity has been found in 23% of all restaurants. Despite these impacts, little is known about the behavior of urban rats, whose behaviors differ from that of laboratory rats. This lack of information is due to several factors, including the difficulty of releasing pest animals back into cities after capturing and identifying them, the reluctance of property owners to provide access to researchers, and rat control programs.

Over a one year period, researchers trapped and implanted microchips in city rats in a waste recycling center in Brooklyn, New York. To overcome issues in using GPS to track movement in dense urban environments, they utilized radio-frequency identification sensors. Male and female scents were then placed on, or near, these sensors and replaced every two weeks. To determine whether risk impacted the findings, researchers positioned these devices in sheltered, safe areas that rats were familiar with and also in more risky, open environments where rats were vulnerable to predation.

Rats reacted differently to male and female scents. In general, when rats responded to sensors with male-scents, risk was unimportant. Rats briefly visited male scents equally in exposed and sheltered areas, and then stayed away. Female scents, however, were visited significantly more often than male scents (0.2 visits/day compared to 5.02 visits/day). This implies that attractants may be more useful near sheltered areas while deterrent scents may be more useful in exposed areas where animals are vulnerable to predators. These findings address a knowledge gap about rat-scent preference that could assist in urban wildlife management tools, such as the deployment of baits or immuno-contraceptives.

"Context is everything. If we can pinpoint the scents and contexts that are most useful, then we increase our chances of creating novel control tools, but further research is needed under a broad range of conditions"

The team at Fordham University, Columbia University and Arrow Exterminators Inc. has identified the primary reasons holding back scent-based control tools. They argue they need greater access to urban properties if they are to make scents useful in the war against rats.

Nothing in life is free. So how does Magnus Carlsen stay so superior at his chess game? How can Zlatan perform magic with an orange and Ada Hegerberg become the world's best footballer? How did Björk become such a creative and skilled musician? How did H. C. Andersen and Charles Darwin rise to the top in their respective fields?

"It seems that certain factors need to be present to become an expert within a given field," says Professor Hermundur Sigmundsson at NTNU's Department of Psychology.

These decisive factors are:

Focused training

Passion

Grit

Positive mindset

Mentors

The journal New Ideas in Psychology has just published an article that presents a theoretical model and a new scale that assesses passion in relation to a skill.

"A key concept in this context is to find an area that you're interested in. That's how we can light the spark," says Sigmundsson.

The commonly accepted refrain is that 10 000 hours of practice are necessary to become really good at something. Although the number of hours offers little more than a hint, there is no doubt that a lot of practice and focus are essential to get really good. In other words, you have to practice exactly what you want to excel in.

So who is inclined to devote this much time to an activity? What makes a person willing to put so much effort into being the best at bending free kicks like a banana, or giving that extra little push on the run up to the 50K race, or solving complicated equations or writing a novel?

"You need something more. You need a passion for what you're doing. You have to burn for it," says Sigmundsson.

But grit, the perseverance and motivation to keep at an activity over time, is also key.

"In addition, you need a positive mindset, an attitude of 'I can achieve this,'" Sigmundsson says.

And it's unlikely that you can manage the journey alone. You most likely need a mentor - someone who can show you the way and who supports you. This should be someone with the right knowledge base to stand by you for the long time required to become proficient.

Passion for an area or a topic or skill is thus a key factor in achieving one's goals.

"Passion sets the direction of your arrow, but grit determines the strength and size of the arrow," says Sigmundsson.

Men generally find the strongest connection between passion and grit. They spend a lot of energy on what they're passionate about. For women, the strongest connection seems to be between grit and a positive mindset.

The study included 126 participants and forms the basis for the article. This article is also linked to other articles and a book that has recently been written on the criteria for success. The research at NTNU on learning and skills development has been going on for almost 30 years.

Several researchers have been working on the Norwegian book Ekspertise. Utvikling av kunnskap og ferdigheter [Expertise. Development of knowledge and skills] during the past four to five years. In their research they studied what factors enabled selected individuals to excel in their fields. These characters include H. C. Andersen, Charles Darwin and Zlatan Ibrahimovic, among others.

In the book, Magnus Carlsen's father, Henrik Albert Carlsen, describes his son's path to becoming the world's best chess player. Vidar Halldorsson writes about the Icelanders and their success in sports such as handball.

Anders Ericsson writes about those prerequisite 10 000 hours of training and that experts are always "made, not born."

When immune cells detect harmful pathogens or cancer, they mobilise and coordinate a competent defence response. To do this effectively immune cells must communicate in a way that is tailored to the pathogenic insult. Consequently, the body's response to various health challenges depends on successful coordination among the cells of the immune system.

Key players of the immune system include helper T cells and antigen presenting cells, such as dendritic cells and the antibody-producing B cells. T cells communicate with antigen presenting cells through short-lived contacts called immune synapses. These contacts are highly specialised endowing cells with the appropriate platform for exchanging information in a timely and efficient manner. Key messages are dispatched across the immune synapse via nanometer size vesicles referred to as synaptic ectosomes.

Research led by Prof. Mike Dustin's group of the Kennedy Institute of Rheumatology at the University of Oxford has tracked the movement of ectosomes and unravelled their contents. As described in their research findings, published in eLIFE, the team developed a three dimensional synthetic cell and successfully intercepted and deciphered the messages contained in helper T cell derived ectosomes. Employing super resolution microscopy, called dSTORM, this work found that these T cell synaptic ectosomes have size scales of a millionth of a meter but despite their reduced size they can package enough information to orchestrate the response of dendritic cells. In addition, cell free ectosomes and their synthetically engineered versions result in dendritic cell maturation, an essential process for the establishment of adequate immune responses.

dSTORM experiments further highlighted how both antigen recognition and effector functions can coalesce in single ectosomes implying that help mediated by T cells is highly targeted. Finally, by employing mass spectrometry and CRISPR-Cas9 gene editing technology, the team further elucidated key molecular machinery, known as ESCRT proteins, responsible for the dispatch of ectosomes from helper T cells.

"This research revealed that the formation and composition of these ectosomes depends on direct molecular interactions at the immune synapse and has profound implications on understanding cell-to-cell communication" co-lead author of the study Dr. David Saliba said. Harnessing this new knowledge is important for the development of future therapies that can help shape the immune response to specific diseases.

The Penguin Genome Consortium sequences all living penguin species genomes to understand the evolution of life on the ice

Published today in the open-access journal GigaScience is an article that presents the first effort to capture the entirety of the genomic landscape of all living penguin species. The Penguin Genome Consortium --bringing together researchers from China, Denmark, New Zealand, Australia, Argentina, South Africa, the UK, the US, France and Germany-- has produced 19 high-coverage penguin genome sequences that, together with two previously published genomes, encompass all surviving penguin species. This extensive study provides an unparalleled amount of information that covers an entire biological order, which will promote research in a wide variety of areas from evolution to the impact of human activities and environmental changes.

Penguins are a diverse order of species that span the Southern hemisphere, ranging from the Galápagos Islands on the equator, to the oceanic temperate forests of New Zealand, to the rocky coastlines of the sub-Antarctic islands, finally reaching the sea-ice around Antarctica. This iconic bird group have transitioned from flying seabirds to powerful, flightless marine divers. With their specialized skin and feathers and an enhanced thermoregulation system they are able to inhabit environments from the extreme cold Antarctic sea ice to the tropical Galápagos Islands.

These birds also serve as the figurative "canary in a coal mine"; warning of environmental and climate change. Many penguin populations have experienced rapid declines in recent decades, some having extreme population drops, such as the crash of the King penguin population, which has declined by 88% in just 3 decades. And more penguin species are predicted to decline in the near future. The dwindling populations have been linked to climate warming, environmental degradation, exploitation of the marine environment, fisheries bycatch, pollution, and the introduction of exotic predators. Penguins have thus become the focus of many ecosystem monitoring studies. Having high-quality genomes sequences of all extant penguin species serves as an outstanding new resource for understanding the specific reasons for species population loss.

Author Theresa Cole from the University of Otago in New Zealand says of this work: "The population history of different penguin species can be seen in their genome. We will provide new insights into the population history of all penguins over dramatic climate events, to predict population trends under future climate change scenarios. This research will help us understand how future climate change may affect other species, to help us develop conservation strategies."

As with the work done on Darwin's finches, studying the radiation of the 20 penguin species provides similar enlightening case study for researching unique penguin morphological and physiological adaptations. The consortium are also sequencing the genomes of recently extinct penguin taxa, as well as undertaking population genomic studies using multiple genomes per species.

Senior author Guojie Zhang from the University of Copenhagen, BGI, and Kunming Institute of Zoology says of this: "The penguin ancestor experienced rapid radiation leading to the current approximate 20 extant species, accompanied by many ancient lineages that are now extinct. The radiation of penguin thus provides an excellent example for the study of speciation."

There were logistical challenges to get hold of high-quality specimens for all of these species as many come from some of the most inhospitable and far-flung corners of the globe. However, an additional challenge was cultural rather than technical. The process by which this consortium handled these sensitive issues serves as a model for building trust and collaboration with cultures that have equally important links to other native species.

Co-author Bruce McKinlay from the New Zealand Department of Conservation highlights this, saying: "Genome research in New Zealand is currently moving into novel cultural contexts, especially for penguins, which are Taonga or treasured possessions in Māori culture. As such, our consortium have undertaken rigorous indigenous consultation to sequence the genomes from six New Zealand Taonga species. We believe these genomes will be important for a cultural context."

The goal of the first stage of the Penguin Genome Consortium project was purely to sequence high-quality genomes, but initial validation studies have demonstrated these genomes are already producing valuable insight into evolutionary history of the penguin tree of life and the evolutionary patterns of their adaptation to Antarctica. For example, an initial phylogenetic tree presented in this study demonstrates that penguins have adapted to Antarctica on multiple occasions.

This and further comparative and evolutionary genomic analyses are currently being carried out, and the penguin genome consortium welcomes new members interested in joining the open consortium and contributing to this work. While this work is still underway early access to the 19 penguin genomes data has been provided, while the researchers ask groups intending to use this data for similar cross-species comparisons to follow the long running Fort Lauderdale and Toronto rules.

Professional drivers, manufacturing workers and cleaners have a threefold increased risk of type 2 diabetes (T2D) compared with university teachers and physiotherapists, according to a new study presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) and published in Diabetologia (the journal of EASD).

The differences are apparently linked, say the authors, to the prevalence of lifestyle risk factors. If workplace interventions could reduce weight and increase physical activity among employees in these occupations, major health gains may be made.

While previous studies have shown that diabetes risk increases with lower socioeconomic status, little research exists on occupation and risk of T2D. This study -- by Dr Sofia Carlsson, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues -- considered possible associations between risk of T2D and the 30 most common occupations.

The Swedish Total Population Register was used to identify all Swedish citizens born between 1937 and 1979. Of these, a total of 4,550,892 persons were gainfully employed, between 2001 and 2013; this constituted the study population. Information on occupation and education was obtained from LISA - the Longitudinal Integrated Database for Health Insurance and Labour Market Studies - with employment categorised using the Swedish Standard Classification of Occupations. To be categorised into a specific occupation, a person had to have that occupation for 2 consecutive years.

Follow up, for incidence of diabetes at age 35 or over, was from 2006 until 31st December 2015, using the National Patient and Prescribed Drug Registers. During the follow up period, 201,717 new cases were identified. Prevalent cases (total number at a set point) were identified using the same registers; in 2013 these were numbered at 150,131. Historical information on height, weight, fitness and smoking was obtained from the Military Conscription and Medical Birth Registers, to produce BMI calculations for men conscripted at age 18 (57% of the female study population) and women at first trimester (mean age 29, 50% of the male study population).

Striking differences were found between the occupational groups. The overall prevalence of diabetes in the Swedish working population in 2013 was 4.2% (5.2% in men; 3.2% in women) However prevalence ranged from 7.8% in male manufacturing labourers and 8.8 % in motor vehicle drivers, to only 2.5% in male computer scientists. In women, diabetes prevalence was highest in manufacturing workers (6.4%), kitchen assistants (5.5%) and cleaners (5.1%) and lowest amongst specialist managers (1.2%). Separate analysis of the over 55s revealed that, in men, diabetes prevalence was 14.9% in manufacturing workers, 14.2% in motor vehicle drivers and 13.1% in office clerks. In women over 55 years, the highest prevalence was seen in manufacturing workers (10.7%), kitchen assistants (8.7%) and cleaners (8.3%). (see link to online appendix for detailed information on diabetes rates, and also figures 1-3 of paper).

Age standardised incidence of diabetes (number of new cases per 1000 people per year) was 5.19 overall (6.36 in men; 4.03 in women); but again considerable occupational differences were noted. Amongst men, incidence was highest amongst manufacturing workers (9.41), motor vehicle drivers (9.32), mobile plant operators including agricultural (8.31), personal carers (8.17), and stores and transport clerks (7.87) - and lowest amongst university teachers (3.44), architects and civil engineers (3.83). For women, the incidence was highest amongst manufacturing labourers (7.2), cleaners (6.18), kitchen assistants (5.65), cooks, waitresses and housekeepers (5.01) and personal carers (5.00) - and lowest amongst physiotherapists and dental hygienists (2.20), writers and creative or performing artists (2.27).

Further analysis revealed that manufacturing, male workers were at a 49% higher risk of developing diabetes, and female workers at an 80% higher risk, when compared with the total Swedish working population. In contrast, a 46% reduced incidence was seen in male college and university teachers, and a 45% reduced incidence was found in female physiotherapists and dental hygienists. The authors estimate that almost half (45-46%) of cases of T2D would be eliminated if the total working population had the same incidence as college / university teachers, physiotherapists and dental hygienists.

For people recorded as having no occupation in the study period, for example, people on disability pension or unemployed (12.1% of individuals born 1937-1979), incidence of T2D was also high; 8.29 new cases per 1000 people per year overall, and higher in men (8.89) than in women (7.72). In 2013, prevalence in this group was 8.9% in total (9.7% in men and 8.2% in women).

There was a strong, positive association found between incidence of T2D and mean BMI in both men and women. The prevalence of being overweight at conscription age 18 was found to be high in men who subsequently went on to work as mobile plant operators (including agricultural, crane and lifting-truck operators) (16.8%) motor vehicle drivers (16.3%), and manufacturing workers (14.1%); whereas in future college and university teachers, only 6.5% were overweight at conscription age; with similar inverse patterns for physical fitness. In women, 29-30% of cleaners, manufacturing workers and kitchen assistants were overweight during the first pregnancy (mean age 29 years), and 24-30% were smokers. In writers, creative/ performing artists, physiotherapists and dental hygienists the corresponding estimates were 18% for being overweight and 6% for smoking.

The authors say: "The association between occupation and T2DM coincided with vast differences in prevalence of lifestyle factors - individuals in high risk occupations were more likely to be overweight, smoke and have lower physical fitness than those in low risk occupations, and this most likely contributes to a high prevalence and incidence of type 2 diabetes".

These differences were seen at young ages (conscription and first pregnancy), adding to the findings of previous studies that metabolic differences can be seen in diabetic individuals up to 25 years prior to diagnosis. However the authors note that differences in lifestyle factors might be even higher at older ages and that, on top of lifestyle selection into different occupations, it is possible that "working life adds more risk factors in the form of long sitting times, irregular working hours and stress." They recommend the role of working conditions in the development of T2DM as a subject for future investigation.

As in previous research, an association between low socioeconomic status and T2DM was noted - however this comprehensive, nationwide study has shown that job title is a much more specific indicator of diabetes risk - with above 7% (men and women combined) of employees diagnosed with the condition in occupations such as manufacturing work and 8.5% in motor vehicle driving (also men and women combined). Prevalence in these occupations was even higher in the over 55s. This is potential issue, the authors note, when most countries are looking to increase retirement age, as diabetes may potentially hinder prolonged working life.

The authors say: "To reduce the future diabetes burden it is crucial to curb the inflow of new patients. Intervention studies have consistently shown it is possible to reduce diabetes incidence in high-risk groups by lifestyle modification. If job title can be used as a risk indicator of T2DM, it can be used to identify groups for targeted interventions, and hopefully inspire employers to implement diabetes prevention programmes tailored to their workforces".

New research presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 Sept) shows that where you live has an impact on how likely you are to die for patients with type 2 diabetes (T2D), and how likely you are to be readmitted to hospital for patients with type 1 diabetes (T1D) following hospital discharge. The study is by Dr Tim Robbins, Institute of Digital Healthcare, WMG, University of Warwick, Coventry, UK, and colleagues from both the University of Warwick and University Hospitals Coventry & Warwickshire NHS Trust, UK.

Patients with diabetes face an increased risk of negative outcomes following hospital discharge, regardless of their reason for admission. In addition, socioeconomic factors are known to drive poor health outcomes in people with diabetes generally. Despite this, there has been little research done to assess the impact of socioeconomic factors on health outcomes when patients with diabetes are discharged from hospital. This has mainly been due to the difficulty of linking the various datasets required to get a complete picture of the health outcomes and socioeconomic statuses of these patients.

This new study was based on a retrospective evaluation of data from the electronic health records (EHR) of a large UK specialist referral centre (University Hospitals Coventry & Warwickshire NHS Trust, Coventry, UK) and included all adult patients discharged with a diabetes diagnosis over a 3-year period. These comprised 46,357 distinct discharges and were matched at a patient level with postcode sector socioeconomic data extracted from the Office of National Statistics Census and Population Density datasets.

Information on 19 socioeconomic variables was available including index of multiple deprivation, employment status, ethnicity, activity levels, unpaid care provision, and density of population and housing, which could then be used to determine the socioeconomic status of each patient. The clinical outcome measures chosen were readmission within 28 days, and incidence of mortality within 180 days (approximately six months) of discharge from hospital.

The authors found that socioeconomic status measured by 14 of the 19 variables was significantly associated with 180-day mortality in the T2D patient cohort, while in the T1D cohort they found no statistically significant association between mortality and socioeconomic variables. Among T2D patients, the strongest links with mortality were found to be language (non-English), ethnicity (ethnic minorities), and index of multiple deprivation.

For hospital readmissions, only 1 of the 19 variables showed a significant association in T2DM patients, compared to 9 statistically significant variables in the T1DM group, with the strongest being deprivation indices and health-related activity impairment.

The authors say: "There is a strong association between geographic socioeconomic status and readmission to hospital in patients with type 1 diabetes, but no clear link with mortality. In contrast in patients with type 2 diabetes, mortality is strongly associated with socioeconomic status whilst readmission to hospital is not. In summary, where you live has an impact on how likely you are to be readmitted to hospital for patients with type 1 diabetes, and how likely you are to die for patients with type 2 diabetes following hospital discharge."

They add: "Use of geographic postcode sector data can be readily incorporated into electronic healthcare systems and future risk models to enable personalised data-driven care, for example more intensive, or different models, or more intensive follow up for those from areas of known deprivation."

Dr Tim Robbins is following up on this research through a prestigious European Foundation for the Study of Diabetes (EFSD) Albert Renold Travel Fellowship, looking at digital approaches to diabetes integrated care, in the Basque County, Spain. EFSD has been created by EASD to stimulate diabetes research in Europe.

Early signs of adulthood type 2 diabetes can be seen in children as young as 8 years old, decades before it is likely to be diagnosed, according to a new genetic study being presented at this year's European Association for the Study of Diabetes (EASD) Annual Meeting in Barcelona, Spain (16-20 September).

Analysing genetic information known to increase the chances of type 2 diabetes (T2D)in adulthood together with measures of metabolism across early life, researchers found that being more susceptible to adult diabetes affected a child's levels of high-density lipoprotein (HDL) (good) cholesterol, essential amino acids, and a chronic inflammatory trait measured in the blood. Certain types of HDL lipids were among the earliest features of susceptibility to T2D.

These metabolic features could be targeted to prevent young people from going on to develop T2D in the future, researchers say.

"It's remarkable that we can see signs of adult diabetes in the blood from such a young age--this is about 50 years before it's commonly diagnosed", says Dr Joshua Bell from the MRC Integrative Epidemiology Unit at the University of Bristol, UK who co-led the research. "This is not a clinical study; nearly all participants were free of diabetes and most will not go on to develop it. This is about liability to disease and how genetics can tell us something about how the disease develops."

The study tracked over 4,000 participants of the Children of the 90s study-a birth cohort established in Bristol, UK in the early 1990s. Researchers combined genetics with an approach called 'metabolomics', which involves measuring many small molecules in a blood sample to try and identify patterns that are unique to type 2 diabetes.

The effects of a genetic risk score (including 162 genetic elements) for adult type 2 diabetes were examined on over 200 metabolic traits measured 4 times on the same participants--once in childhood (when aged 8 years), twice in adolescence (when aged 16 years and 18 years), and once in young adulthood (when aged 25 years).

The study was conducted among young healthy people who were generally free of type 2 diabetes and other chronic diseases to see how early in life the effects of diabetes susceptibility become visible. In particular, HDL cholesterol was reduced at age 8 before other types of cholesterol including LDL (bad cholesterol) were raised, and inflammatory glycoprotein acetyls and amino acids were elevated by 16 and 18 years old. These differences widened over time.

"If we want to prevent diabetes, we need to know how it starts. Genetics can help with that, but our aim here is to learn how diabetes develops, not to predict who will and will not develop it. Other methods may help with prediction but won't necessarily tell us where to intervene", says Dr Bell. "Knowing what early features of type 2 diabetes look like could help us to intervene much earlier to halt progression to full blown diabetes and its complications."

The ancestor of some of the largest flying birds ever has been found in Waipara, North Canterbury.

Bony-toothed birds (Pelagornithids), an ancient family of huge seafaring birds, were thought to have evolved in the Northern Hemisphere - but that theory has been upended by the discovery of the family's oldest, but smallest member in New Zealand.

At 62 million-years-old, the newly-discovered 'Protodontopteryx ruthae', is one of the oldest named bird species in the world. It lived in New Zealand soon after the dinosaurs died out.

While its descendants were some of the biggest flying birds ever, with wingspans of more than 5 metres, 'Protodontopteryx' was only the size of an average gull. Like other members of its family, the seabird had bony, tooth-like projections on the edge of its beak.

The seabird fossil was identified by the same team that recently announced the discovery of a 1.6 metre-high giant penguin from the same site.

Amateur palaeontologist Leigh Love found the partial 'Protodontopteryx' skeleton last year at the Waipara Greensand fossil site. The bird was named 'Protodontopteryx ruthae' after Love's wife Ruth. Love wanted to thank her for tolerating his decades-long passion for palaeontology.

Fellow amateur Alan Mannering prepared the bones, and a team comprising Love, Mannering, Canterbury Museum Curators Dr Paul Scofield and Dr Vanesa De Pietri and Dr Gerald Mayr of Senckenberg Research Institute and Natural History Museum in Frankfurt, Germany, described 'Protodontopteryx'.

Dr Scofield says the age of the fossilised bones suggests pelagornithids evolved in the Southern Hemisphere. "While this bird was relatively small, the impact of its discovery is hugely significant in our understanding of this family. Until we found this skeleton, all the really old pelagornithids had been found in the Northern Hemisphere, so everyone thought they'd evolved up there."

"New Zealand was a very different place when 'Protodontoperyx' were in the skies. It had a tropical climate - the sea temperature was about 25 degrees so we had corals and giant turtles," he adds.

Dr Mayr says the discovery of 'Protodontopteryx' was "truly amazing and unexpected. Not only is the fossil one of the most complete specimens of a pseudotoothed bird, but it also shows a number of unexpected skeletal features that contribute to a better understanding of the evolution of these enigmatic birds."

Later pelagornithid species evolved to soar over oceans with some species measuring up to 6.4 metres across the wings. 'Protodontopteryx's' skeleton suggests it was less suited for long-distance soaring than later pelagornithids and probably covered much shorter ranges. Its short, broad pseudoteeth were likely designed for catching fish. Later species had needle-like pseudoteeth which were likely used to catch soft-bodied prey like squid.

Dr De Pietri says "because 'Protodontopteryx' was less adapted to sustained soaring than other known pelagornithids, we can now say that pseudoteeth evolved before these birds became highly specialised gliders."

The last pelagornithid species died out around 2.5 million years ago, just before modern humans evolved.

The Waipara Greensand site where the 'Protodontopteryx' skeleton was found has yielded several important scientific discoveries in recent years, including ancient penguins and the world's oldest tropicbird fossil.

Some of these discoveries, including the 'Protodontopteryx' fossil, will be displayed in an exhibition about ancient New Zealand at the Museum later this year.

This research was funded by the Royal Society of New Zealand's Marsden Fund and is published today in the journal 'Papers in Palaeontology'.

Severe bacterial infections are a leading cause of death globally. Delays in effective treatment can increase the chance that a patient dies but treating a patient before blood cultures are drawn may make it impossible to identify the bacteria causing the infection and make it challenging to identify the best choice of treatment. Current clinical guidelines recommend that blood cultures be drawn before treatment begins, but no previous studies have definitively compared drawing a blood culture shortly after a patient begins antimicrobial treatment with drawing blood cultures prior to treatment. In a new study led by investigators from Brigham and Women's Hospital, a team performed a prospective study in seven centers across North America and found that blood cultures drawn after antimicrobial administration resulted in a loss of almost 50 percent of available clinical information. The team reports these findings, which provide a basis for clinical guidelines for the care of patients with sepsis, in Annals of Internal Medicine.

"These findings are important in considering the optimal balance between prompt antimicrobial administration and the need for accurate microbiological data in the care of patients with sepsis," said corresponding author Matthew Cheng, MD, a clinical instructor in the Brigham's Division of Infectious Diseases. "Given the global burden of sepsis, deepening our understanding of how best to treat this condition is critically important."

Cheng and colleagues conducted a study known as FABLED (eFfect of Antimicrobial administration on BLood culture positivity in patients with severe manifestations of sepsis in the Emergency Department), a patient-level, single-group, diagnostic study. Between November 2013 and September 2018, the team enrolled adult patients who presented to the emergency department with severe manifestations of sepsis. Each patient had two blood cultures drawn before treatment initiation and repeat blood cultures drawn within two hours after starting treatment.

Pre-treatment blood cultures were positive for one or more microbial pathogens in 102-of-325 (31.4 percent) patients. After-treatment blood cultures were positive for one or more microbial pathogens in 63-of-325 (19.4 percent) patients. The sensitivity of post-treatment cultures, or percentage of samples accurately identified as having the same pathogens pre-treatment, was 52.9 percent.

Patients with sepsis are generally treated initially with a broad-spectrum antibiotic, but Cheng and colleagues note the importance of identifying the right narrow-spectrum antibiotic based on a patient's blood culture. Without an accurate picture of the microbial landscape prior to initiating treatment, it may be extremely challenging for physicians to select the right antibiotic.

"When it comes to treating sepsis safely and effectively, microbiological diagnosis is key," said Cheng. "Despite the importance of starting treatment early for sepsis patients, our results support the Surviving Sepsis Campaign guidelines and suggest that blood cultures should not be routinely deferred."

The expression "you are what you eat" has taken on new meaning. In an experiment in fruit flies, or Drosophila melanogaster, researchers at the University of Pennsylvania have found that adding different species of microbes to the flies' food caused populations to diverge genetically, racking up significant genomic changes in just five generations.

"Our work is very suggestive that microbial community composition drives, at least in part, how the organisms in which they live are evolving," says Paul Schmidt, a biologist at Penn and senior author on the work, which appears in the journal PNAS. "The fact that we can see this effect in experiments done over such a short time scale suggests that the magnitude of the fitness effects the microbes have is incredible."

Unlike a laboratory experiment, where every possible aspect of the environment is controlled, from the genetics of the flies themselves to the temperature and diet, in order to magnify differences between treatments this set of experiments took place outdoors, at Pennovation Works on Penn's campus. The setting more closely mirrors nature, subject to weather, seasonal changes, even the odd spider or fleck of dirt intruding in the enclosures.

The fact that, despite the potential influences of these outside factors, the researchers still found the microbiome shifts to have a significant effect on the genomes of fly populations, makes the finding even more compelling, Schmidt says.

"I think it's fair to say we preserved as much ecological realism as we could at the expense of detecting large effects," he says. "We just shifted the relative abundance of these microbes in the flies' diet, and that was enough to see an effect."

Schmidt and postdoctoral fellow Seth Rudman, the lead author on the paper, took advantage of the fact that flies have relatively simple microbiome communities compared to other organisms, such as humans.

"If you do a survey of a mammalian microbiome, many of the bacteria you find in the gut are unknown," says Rudman. "But that's not the case with flies. It just happens that Drosophila have only about 100 species in their microbiome community."

Other benefits of fruit flies for this type of study include their short generation time--one can study several generations in a matter of months--and the fact that they can be reared to extremely high population sizes. In this case, that meant hundreds of thousands of flies in each experiment.

From earlier work, scientists had an inkling that the microbiome was linked to changes in the fitness of the fly. Flies from more northern latitudes tend to have more Lactobacillus bacteria as part of their microbiome, and also live longer, have fewer eggs and are more tolerant to stress. More southerly populations, on the other hand, which tend to have more of the bacteria Acetobacter, had shorter lifespans, more eggs, and were less stress-tolerant. Work in the lab showed that exposing flies to these two types of bacteria elicited these same traits.

But could the microbes drive the evolution of whole populations of flies? To test that, Schmidt, Rudman, and colleagues designed an experimental setup to manipulate the flies' microbiomes. They introduced a thousand flies into each of several outdoor mesh enclosures, 2 cubic meters in size and adorned with groundcover and a peach tree. They varied the food in some of the enclosures, supplementing it with either Acetobacter or Lactobacillus.

The researchers confirmed that the feeding altered the microbiomes of the flies, though just slightly. That was enough, however, to affect their genes. Comparing the genomes of the flies at the start of the study to the conclusion, after five generations, the team could pick out distinct changes in the frequency of certain alleles--one variant of a gene--that were consistent with what has been seen in natural populations of flies.

"We found that the allele that was more common in the Lactobacillus solution cages was also the allele that's more common in the north, where Lactobacillus itself is more common," says Rudman. "And the allele that was more common in the Acetobacter cages was also the allele that is more common in the south, where Acetobacter is more common."

To the researchers, that finding hammered home the significance of the microbes' influence.

"The bottom line is, microbes drive rapid adaptation," Schmidt says.

Whether that effect translates to humans and other animals is a matter for further study, the authors say, but numerous studies have underscored the potent effect of the microbiome.

In future work, the researchers will be flipping the script, testing to see whether changes in the flies' genetic profiles influence which microbes can gain a foothold in their microbiomes. And they'll also probe more deeply into determining precisely how the changing microbiome affects its host.

ATLANTA--Creating mutations in a key Ebola virus protein that helps the deadly virus escape from the body's defenses can make the virus unable to produce sickness and activate protective immunity in the infected host, according to a study by the Institute for Biomedical Sciences at Georgia State University.

The mutated virus even works as a vaccine to protect animals from infection with the virulent Ebola virus, researchers said.

The study suggests that VP35, a protein that enables Ebola virus to block early immune responses to infection, is critical for virulence and is a potential drug target. The findings are published in the journal Cell Reports.

Zaire ebolavirus, a member of the filovirus family, is a dangerous pathogen that causes outbreaks of severe, often lethal, disease in humans. A 2013-16 epidemic affected more than 28,000 people and resulted in more than 11,000 deaths, with cases spreading from West Africa to Europe and the United States. Outbreaks in the Democratic Republic of the Congo from 2018 to the present have resulted in nearly 1,800 deaths and emphasize the importance of understanding the factors that contribute to the virulence of the virus.

The researchers have been studying VP35 for a while, and in previous work they discovered the protein is fundamental in blocking innate immune responses to Ebola virus infections.

In this study, the research team wanted to determine how VP35 affects Ebola virus disease and host immune responses in animals that most closely resemble human disease. They built mutations into VP35 to create a mutant Ebola virus that was viable and could grow in cell culture. While most current vaccine candidates express a single Ebola virus protein, this mutant virus expresses all of the Ebola virus genes and has the structure of an actual Ebola virus particle.

This mutant virus poses a decreased risk for scientists and shows mutant viruses could be useful for safely studying many Ebola virus functions.

The researchers found that Ebola virus with a mutated VP35 induces immune responses that are strong enough to protect non-human primates from infection with wildtype Ebola virus. VP35 mutant viruses have been studied in other animals, such as mice and guinea pigs, but these animals aren't the best model for Ebola virus disease. The animal studies were performed at the University of Texas Medical Branch.

Administering 1,000 infectious units of wildtype Ebola virus would result in 100 percent mortality. Because the researchers expected the mutant virus to be less able to cause disease, they gave non-human primates 20,000 infectious units of the mutant virus and the animals didn't become ill.

"We think that VP35 is affecting immune responses overall, so after giving this virus that doesn't cause disease, we thought maybe it will protect animals if you challenge them with the wildtype Ebola virus," said Dr. Christopher Basler, senior author of the study, director of the Center for Microbial Pathogenesis, a professor in the Institute for Biomedical Sciences at Georgia State and a Georgia Research Alliance Eminent Scholar in Microbial Pathogenesis.

The researchers challenged non-human primates who had previously received the mutant virus with 1,000 infectious units of wildtype Ebola virus. Two of the animals showed no signs of disease. They administered 300,000 infectious units of the mutant virus and challenged the non-human primates with wildtype Ebola virus. The animals developed a robust immune response to the mutant virus and didn't exhibit the inflammation and mortality found in normal Ebola virus infections.

"They were completely protected. None of them showed any sign of disease to the parental virus," Basler said. "The big take home message is that we can make an Ebola virus that grows, but if we disable this function, we can now make a virus that is very highly attenuated in the animals. I think that says that the VP35 protein really does manipulate the immune system to allow the virus to grow to cause disease. This function of VP35 would be a good target for therapies if we find a drug that would disable that function."

In the future, the researchers would like to show that this approach could be used to weaken other members of the filovirus family, such as Marburg virus.

Inoculation with an Ebola virus that has mutations in a protein called VP35 does not cause disease and elicits protection in monkeys, researchers show September 17 in the journal Cell Reports. The findings suggest that the immune-evasion function of VP35 is a potential drug target, and it may be possible to develop a live attenuated Ebola virus vaccine in the future if precautions are taken to prevent reversion to virulence.

"This is not the next Ebola virus vaccine, but the study does show that it is possible to generate Ebola viruses that can grow in cell culture and induce strong immune responses but pose a decreased risk for scientists," says co-senior study author Christopher Basler of Georgia State University. "Such mutant viruses may be useful to safely study many Ebola virus functions."

Ebola virus disease is a rare but severe--often fatal--illness in humans. Until late in 2013, Ebola virus caused sporadic and isolated outbreaks mostly in Central Africa. But the 2013-2016 epidemic that affected more than 28,000 individuals resulted in more than 11,000 deaths and the spread of cases from West Africa to Europe and the United States. Subsequent outbreaks in the Democratic Republic of the Congo further highlight the importance of understanding factors that contribute to Ebola virus virulence.

Currently, there is no licensed treatment proven to neutralize the virus, but a range of therapies are under development. Vaccines to protect against Ebola are also under development and have been used to help control the spread of outbreaks in Guinea and in the Democratic Republic of the Congo. "Most current Ebola vaccine candidates express only a single viral protein, the glycoprotein, but patients who survive infection develop robust T cell responses to other viral proteins," Basler says. "This suggests that a vaccine candidate expressing all viral proteins may elicit a broader, potentially more effective immune response."

In the new study, Basler teamed up with Thomas Geisbert of the University of Texas Medical Branch, Ilhem Messaoudi of the University of California, Irvine, and Hideki Ebihara of the Mayo Clinic in Rochester, Minnesota, to develop a mutant virus that expresses all of the Ebola virus genes and has the structure of an actual Ebola virus particle. They generated a virus with three mutations in the VP35 protein, which plays an important role in evading host immune responses.

Specifically, VP35 is known to suppress the production of immune system proteins called type I interferons and inhibit the maturation of dendritic cells, which present antigens to T cells and serve as messengers between the innate and adaptive immune systems. "We wanted to determine how these functions of VP35 impacted Ebola virus disease and host immune responses in the animal model that most closely reflects human disease," Basler says.

A previous study showed that infection with a VP35-mutant Ebola virus protects guinea pigs against subsequent challenge with a guinea-pig-adapted Ebola virus. But in general, rodent models are more readily protected from challenge by antiviral or vaccine approaches than non-human primate models, which are susceptible to the same Ebola virus strains that cause disease in humans. "The prior studies also have not carefully assessed immune responses to the VP35-mutant Ebola virus, as we have done in our study," Basler says.

To test whether their mutant virus would protect non-human primates against Ebola infection, the researchers used it to inoculate three cynomolgus macaques--the animal model that serves as the gold standard for evaluating Ebola virus virulence. Infection with the mutant virus activated antigen presentation and innate immunity pathways and elicited increased frequencies of proliferating memory T cells and B cells and the production of antibodies.

After 28 days, the researchers challenged the monkeys with a lethal dose of unmodified Ebola virus. Two monkeys survived with no indications of illness, but one died nine days later. To induce a more protective response, the researchers inoculated five macaques with a higher dose of the mutant virus. Vaccination caused mild illness in three of the monkeys. This time, all of the animals survived with no detectable clinical signs after being challenged with a 300-fold higher dose than the standard 100 percent lethal challenge dose of unmodified Ebola virus. But most monkeys showed temporary hematological changes such as low platelet count or low numbers of white blood cells.

"These data demonstrate that VP35 is a critical Ebola virus immune-evasion factor and provide insights into immune mechanisms of Ebola virus control," Basler says. "We show that VP35 suppression of interferon responses is a key requirement for Ebola virus to cause disease, and VP35 function impacts not only innate antiviral defenses but also adaptive immune responses. Because it is critical for virulence, the interferon-suppressing function of VP35 is a potential drug target."

Even though the mutant Ebola virus is highly attenuated and can immunize non-human primates, it exhibits surprisingly robust replication in cell culture. "This combination of features makes the mutant Ebola virus potentially suitable for research without the challenging constraints imposed by biosafety level 4 containment, which is used for the most dangerous microbes," Basler says.

The authors say that the mutant virus is not yet suitable as a vaccine because it would first be necessary to overcome regulatory hurdles and make sure that multiple different attenuating mutations would prevent the virus from reverting and becoming virulent. In future studies, the researchers plan to investigate whether a similar approach could be used to attenuate related viruses. They are also interested in identifying additional mutations that that would still allow the virus to replicate while preventing it from causing disease.

Virtual reality is becoming increasingly present in our everyday lives, from online tours of homes for sale to high-tech headsets that immerse gamers in hyper-realistic digital worlds. While its entertainment value is well-established, virtual reality also has vast potential for practical uses that are just beginning to be explored.

Arne Ekstrom, director of the Human Spatial Cognition Lab in the University of Arizona Department of Psychology, uses virtual reality to study spatial navigation and memory. Among the lab's interests are the technology's potential for socially beneficial uses, such as training first responders, medical professionals and those who must navigate hazardous environments. For those types of applications to be most effective, though, we need to better understand how people learn in virtual environments.

In a new study published in the journal Neuron, Ekstrom and co-author Derek Huffman, a post-doctoral researcher in the Center for Neuroscience at the University of California, Davis, advance that understanding by looking at whether or not being able to physically move through virtual spaces improves how we learn them.

"One of the big concerns or drawbacks with virtual reality is that it fails to capture the experience that we actually have when we navigate in the real world," said Ekstrom, an associate professor of psychology and the study's senior author. "That's what we were trying to address in this study: What information is sufficient for forming spatial representations that are useful in actually knowing where things are?"

The researchers had study participants explore three virtual cities while wearing virtual reality headsets. The participants navigated each city in one of three ways:

Participants wore the headset while walking on an omnidirectional, or 360-degree, treadmill, which allows users to walk freely in any direction. In this condition, the participants could navigate through the virtual environment by walking and turning their heads.

Participants navigated through the virtual environments using only a handheld joystick; they were not able to navigate by moving their heads or walking.

Participants navigated by moving their bodies side to side and moving a joystick back and forth; they were not able to walk around.

Participants spent two to three hours, on average, exploring the virtual cities and locating certain shops they were instructed to find. Once they'd had an opportunity to learn the environments well, they were asked a series of questions to test their spatial memory. For example, they might be asked to imagine they were standing at the coffee shop, facing the bookstore. They would then be asked to point in the direction of the grocery store.

The accuracy of participants' responses did not vary based on which condition they were in.

Participants then underwent an MRI scan while answering a similar set of questions. This allowed the researchers to see what was happening in the brain as participants retrieved spatial memories.

The researchers found that the same areas of the brain were activated for participants in all three situations. In addition, the patterns of interaction between different regions of the brain were similar among the three conditions.

"What we found was that the neural codes were identical between the different conditions," Ekstrom said. "This suggests - as far as the brain is concerned and what we were also able to measure with behavior - that there is sufficient information with just seeing things in a virtual environment. The information you get from moving your body, once you know the environment well enough, doesn't really add that much."

The findings address a long-standing scientific debate around whether or not body movements aid in learning physical spaces.

"There's been this idea that how you learn might make a huge difference, and that if you don't have body-based cues, then you're lacking a big part of what might be important for forming memories of space," said Huffman, the study's first author. "Our research would suggest that once you have a well-formed memory of an environment, it doesn't matter as much how you learned it."

"We would say you don't need body immersion, and you don't need body cues to form complex spatial representations," Ekstom added. "That can happen with sufficient exposure in simple virtual reality applications."

From a practical standpoint, the research suggests that even basic virtual reality systems may be useful in instructional applications.

"Virtual reality has the potential to allow us to understand situations that we might not otherwise be able to directly experience," Ekstrom said. "For example, what if we could train first responders to be able to find people after an attack on a building, without them actually ever having been to that building?

"Our findings suggest there's promise for using virtual reality - even simple applications where you're just moving a joystick - to teach people fairly complex knowledge about spatial environments."

DALLAS - Sept. 17, 2019 - Exercising several times a week may delay brain deterioration in people at high risk for Alzheimer's disease, according to a study that scientists say merits further research to establish whether fitness can affect the progression of dementia.

Research from UT Southwestern found that people who had accumulation of amyloid beta in the brain - a hallmark of Alzheimer's disease - experienced slower degeneration in a region of the brain crucial for memory if they exercised regularly for one year.

Although exercise did not prevent the eventual spread of toxic amyloid plaques blamed for killing neurons in the brains of dementia patients, the findings suggest an intriguing possibility that aerobic workouts can at least slow down the effects of the disease if intervention occurs in the early stages.

"What are you supposed to do if you have amyloid clumping together in the brain? Right now doctors can't prescribe anything," said Dr. Rong Zhang, who led the clinical trial that included 70 participants ages 55 and older. "If these findings can be replicated in a larger trial, then maybe one day doctors will be telling high-risk patients to start an exercise plan. In fact, there's no harm in doing so now."

Reduced brain atrophy

The study published in the Journal of Alzheimer's Disease compared cognitive function and brain volume between two groups of sedentary older adults with memory issues: One group did aerobic exercise (at least a half-hour workout four to five times weekly), and another group did only flexibility training.

Both groups maintained similar cognitive abilities during the trial in areas such as memory and problem solving. But brain imaging showed that people from the exercise group who had amyloid buildup experienced slightly less volume reduction in their hippocampus - a memory-related brain region that progressively deteriorates as dementia takes hold.

"It's interesting that the brains of participants with amyloid responded more to the aerobic exercise than the others," said Dr. Zhang, who conducted the trial at the Institute for Exercise and Environmental Medicine. "Although the interventions didn't stop the hippocampus from getting smaller, even slowing down the rate of atrophy through exercise could be an exciting revelation."

However, Dr. Zhang notes that more research is needed to determine how or if the reduced atrophy rate benefits cognition.

Elusive answers

The search for dementia therapies is becoming increasingly pressing: More than 5 million Americans have Alzheimer's disease, and the number is expected to triple by 2050.

Recent research has helped scientists gain a greater understanding of the molecular genesis of the disease, including a UT Southwestern discovery published last year that is guiding efforts to detect the condition before symptoms arise. Yet the billions of dollars spent on trying to prevent or slow dementia have yielded no proven treatments that would make an early diagnosis actionable for patients.

Fitness and brain health

Dr. Zhang is among a group of scientists across the world trying to determine if exercise may be the first such therapy.

His latest research builds upon numerous studies suggesting links between fitness and brain health. For example, a 2018 study showed that people with lower fitness levels experienced faster deterioration of vital nerve fibers in the brain called white matter. Research in mice has similarly shown exercise correlated with slower deterioration of the hippocampus - findings that prompted Dr. Zhang to investigate whether the same effects could be found in people.

"I'm excited about the results, but only to a certain degree," Dr. Zhang said. "This is a proof-of-concept study, and we can't yet draw definitive conclusions."

Expanded research

Dr. Zhang is leading a five-year national clinical trial that aims to dig deeper into potential correlations between exercise and dementia.

The trial, which includes six medical centers across the country, involves more than 600 older adults (ages 60-85) at high risk of developing Alzheimer's disease. The study will measure whether aerobic exercise and taking specific medications to reduce high blood pressure and cholesterol can help preserve brain volume and cognitive abilities.

"Understanding the molecular basis for Alzheimer's disease is important," Dr. Zhang said. "But the burning question in my field is, 'Can we translate our growing knowledge of molecular biology into an effective treatment?' We need to keep looking for answers."

WASHINGTON, D.C., September 17, 2019 -- Despite advances in medical imaging, the mechanisms leading to the irregular contractions of the heart during heart rhythm disorders remain poorly understood.

Research from the University of Göttingen in Germany suggests existing data from ultrasound imaging can be used to work backwards to reconstruct the underlying electrical causes of arrhythmias. The scientists describe the work in Chaos, from AIP Publishing.

"The heart wall is pretty thick, and current imaging can't see through it," said author Jan Christoph, a biomedical physicist at the University Medical Center Göttingen. "Cardiologists can only map the surface of the heart by inserting catheters into a patient's heart, and it's currently impossible to measure the electric activity deep within and throughout the heart muscle all at once."

However, to better locate possible origins of heart rhythm disorders, cardiologists need to be able to look deeper into the tissue. To help overcome this obstacle, Christoph and his colleagues tested a computational approach to see if it would be possible to extract information about the electrical activity within the heart without directly observing it but inferring it from the heart's mechanical deformations. They believe the approach could be combined with ultrasound or MRI imaging.

The researchers made computer models of two systems interacting with each other - one representing a piece of a heart wall with a rhythm disorder and the other representing a virtual heart. In the virtual heart, the electrical activity is carefully adjusted so it starts to deform in the same way as the arrhythmic heart. Similar approaches have been used in computer weather predictions, in which measurement data from weather stations is assimilated by computer models.

By studying the mechanical characteristics of the two heart models, the researchers found they were able to reconstruct the initial electrical wave patterns almost exactly in the arrhythmic heart.

Applied to a heart, this means studying mechanical cardiac behavior -- such as the contractions and deformations that characterize arrhythmias -- may reveal information about the electrical activity within the heart previously out of reach. "That would give you the hidden electric excitation," said Christoph.

Though the work has only been tested in computer simulations so far, the researchers anticipate the reconstruction approach can soon be applied when imaging patients. The group will be conducting a preliminary study on the feasibility of the method on patients who suffer from heart rhythm disorders, such as ventricular tachycardia, with medical colleagues in Göttingen and Hamburg.

"We want to image patients as they undergo ablation procedures using 3D ultrasound imaging," Christoph said. "We then hope we can apply the reconstruction technique to estimate the abnormal electrical patterns throughout the heart."