Culture

Sea urchins have gotten a bad rap on the Pacific coast. The spiky sea creatures can mow down entire swaths of kelp forest, leaving behind rocky urchin barrens. An article in the New York Times went so far as to call them "cockroaches of the ocean." But new research suggests that urchins play a more complex role in their ecosystems than previously believed.

A team led by Christie Yorke, a postdoctoral scholar at UC Santa Barbara's Marine Science Institute, studied how urchins might function to break up tough kelp into more manageable pieces that can feed other scavengers, also known as detritivores, living on the kelp forest floor. The paper, published in the Proceedings of the Royal Society B, is the first to look at sea urchins' role as shredders in the kelp forest ecosystem.

Urchins can have an outsized effect on kelp forests, especially when their predators aren't around to keep their population in check, Yorke explained. Overhunting of the sea otter, one of urchins' most significant predators, has allowed some urchin populations to clear cut vast tracts of kelp forest, drastically reducing the productivity and biodiversity of sites they've munched through. Some groups have even taken to indiscriminately smashing urchins to stem this scourge.

Nevertheless, urchins may be crucial to the health of the kelp forest ecosystem. Giant kelp is highly productive, growing up to 18 inches per day under ideal conditions. But a significant amount of this material gets transported away from the ecosystem, washing up on beaches, getting swept out to the open ocean or drifting into the deep sea. Kelp is also rather unpalatable compared to single-celled phytoplankton.

Despite its incredible growth rate and availability, giant kelp is not the first choice for many animals, as it is tough to digest.

Yorke and her colleagues were curious whether anything might be able to retain this food source within the kelp forest. "We know that kelp affects animals by providing habitat for fish and other species, but does it actually feed any of these animals?" said Bob Miller, a research biologist at the Marine Science Institute and one of the paper's coauthors.

Scientists have hypothesized that kelp sheds small particles that could be a food source. But the team's previous work found that kelp didn't appear to be nourishing the filter feeders in this way. The activity of sloppy sea urchins offered a promising alternative pathway for funneling nutrients from kelp to the ecosystem's detritivore.

Urchins as Marine Shredders

To test their hypothesis, Yorke set up several tanks with a number of detritivore from several species, along with some labeled kelp. Half of the tanks also got sea urchins.

To label the kelp, the team spiked it with rare forms of carbon and nitrogen by letting the algae photosynthesize in seawater enriched with these isotopes for three days, allowing them to trace the extent to which the tank residents ate the kelp. After 28 days, the researchers compared the isotope measurements for the specimens after the experiment to baselines they had established beforehand.

"We found that a whole host of detritivores can take advantage of kelp as long as urchins are there to process it for them, whereas otherwise they can't," said Miller. Indeed, only one species, a type of brittle star, ate a significant amount of kelp in the absence of sea urchins.

"Even then, the brittle stars used much more kelp when the urchins were present," added Yorke.

Urchins excel in their role of processing kelp for other detritivores. They are remarkably messy eaters, scattering all sorts of bits and pieces as they chow down on giant kelp. What's more, sea urchins digest remarkably little of what they actually eat. Meanwhile, their guts contain a rich assortment of microbes, some of which can pull nitrogen from the seawater itself, enriching the urchin's waste. Some studies have shown that urchin feces can be more nutritious than fresh algae, said Yorke.

"Essentially, they create a kelp smoothie for the reef," Miller said.

Yorke agreed and stated that "without the urchins there, it's possible that this kelp would just get washed out of the kelp forest by the current and be unavailable altogether."

A Broader Perspective

Extrapolating from small experiments in the lab to the processes out in the environment can be difficult, so the team used historical data collected by the Santa Barbara Coastal Long Term Ecological Research project (SBC LTER) to place their results in context. SBC is one of several long-term research sites throughout the country funded by the National Science foundation. It is one of two overseen by UC Santa Barbara.

The scientists looked at 11 years of relevant data, including the amount of kelp litter over time, as well as sea urchin abundance and biomass. Their analysis suggested that the amount of kelp that urchins shred and process could be a significant portion of the resources available to the creatures that live on the seafloor.

"A lot of times urchins are portrayed as grazers," said Yorke, "but that's actually an uncommon condition. Most of the time the urchins are just sedentary detritivores that wait for leaf litter from the kelp to fall and drift past them. They capture this detritus and consume it.

"Urchins switch from this sedentary behavior to active grazing if drift kelp becomes limited," she explained. This can happen for a number of reasons. If urchins become super-abundant there may not be enough drift kelp to sustain them. Alternatively, oceanographic conditions like El Niño can impact kelp productivity.

In this way, urchins are more like grasshoppers. Under normal conditions, grasshoppers are a healthy part of their ecosystem. But in certain circumstances, some species will swarm, becoming a plague of locusts.

"Urchins are generally cast as the villain in the kelp forest," said Miller, "but this study shows that they can play an important role as an intermediary in the food web."

"We should not go around and vilify or smash sea urchins before we understand their role in the ecosystem better," he added. "They're not necessarily always the bad guy they're made out to be."

Researchers at the University of Helsinki have discovered how regenerative capacity of intestinal epithelium declines when we age. Targeting of an enzyme that inhibits stem cell maintaining signaling rejuvenates the regenerative potential of an aged intestine. This finding may open ways to alleviate age-related gastrointestinal problems, reduce side-effects of cancer treatments, and reduce healthcare costs in the ageing society by promoting recovery.

"This study highlights the importance of cellular interactions. Alterations inside one cell resulted in secretion of an aging factor that can be targeted with drugs, providing multiple attractive points for interventions", says the principal investigator Pekka Katajisto, Associate Professor at the University of Helsinki and Karolinska Institutet.

The age-induced reduction in tissue renewal makes dosing of many common drugs challenging. Targeting of inhibitor called Notum may provide a new way to increase the therapeutic window and to promote recovery in societies with the aging population. Researchers believe that in addition to direct targeting of Notum, lifestyle factors such as diet may also provide means to reduce Notum, and thus improve tissue renewal and repair.

Using organoid culture methods, researchers understood that poor function of tissue repairing stem cells in old intestine was due to aberrant signals from the neighboring cells, known as Paneth cells.

"Modern techniques allowed us to examine tissue maintenance at a single cell level, and revealed which cell types contribute to the decline in tissue function. We were surprised to find that even young stem cells lost their capacity to renew tissue when placed next to old neighbors", says the lead author, PhD candidate Nalle Pentinmikko from the University of Helsinki.

Normally intestinal epithelium is renewed by stem cells that rely on activity of Wnt-signaling pathway. Surrounding cells produce molecules that activate this pathway. The study shows that during ageing, Paneth cells begin to express a secreted Wnt-inhibitor called Notum. Notum enzymatically inactivates Wnt-ligands in the stem cell niche, decreasing regenerative potential of intestinal stem cells. However, pharmacologic inhibition of Notum rejuvenated stem cell activity and promoted the recovery of old animals after treatment with a commonly used chemotherapeutic drug with severe side-effects in the gut.

A study led by scientists of the Universitat Autònoma de Barcelona (UAB) and the National Centre for Genomic Analysis (CNAG-CRG) from the Centre for Genomic Regulation (CRG) reveals the three-dimensional genomic structure of male germ cells and how this structure determines their function.

The study, published in the journal Cell Reports, represents a significant advance in our understanding of how the dynamics of insulator proteins and transcriptional activity are coupled during the 3D genome re-organisation that takes place during the formation of male germ cells.

The code of life (genome) is not just a linear sequence of letters, but is also folded (compartmentalised) into a specifically tailored chromatin structure within the cell nuclei. This three-dimensional genomic structure is fundamental, given that it determines which genes "turn on" and which are "turned off" in each cell types.

A new study led by scientists from the UAB and the CNAG-CRG and published in Cell Reports reveals the three-dimensional genomic structure of male germ cells. The study, carried out on mice, shows that this structure is extremely dynamic during the formation of germ cells (gamete precursor cells). Moreover, the study revealed a fine-tuned balance between chromatin remodelling, architectural proteins such as cohesins and gene expression during this process.

All sexually reproducing organisms form haploid gametes (oocytes and sperm) - each cell type carrying only one copy of each chromosome - through two consecutive cell divisions preceded by one round of genome replication. This process is known as meiosis and implies that the genome must be packaged and unpackaged in a precise and highly regulated manner.

"Our work shows the dynamics of chromatin remodelling during the formation of male gametes, by comparing changes in chromatin folding and gene transcription at different moments throughout male meiosis", says coordinator of the study Aurora Ruiz-Herrera, researcher at the Department of Cell Biology, Physiology and Immunology of the Institute of Biotechnology and Biomedicine (IBB) at the UAB, where she leads the research group in Animal Genomics. "We have thus demonstrated the existence of different degrees of genome folding and how these different levels of genome organization are related to structural proteins such as cohesins and gene expression. The results will pave the way for new investigations into the molecular mechanisms regulating these changes."

"This study has been possible only thanks to the combination of complementary techniques in biology such as molecular genetics, microscope imaging and computer simulations. It truly is a multidisciplinary project", explains Marc A. Marti-Renom, ICREA researcher and head of the Structural Genomics Group at the CNAG-CRG and co-leader of the study.

The project represents a significant advance in the study of the mechanisms generating and regulating the 3D structure and function of the genome during the formation of gametes. Determining these mechanisms is fundamental, given that the deregulation of this process can lead to diseases such as infertility and chromosome alterations like trisomy 21.

According to scientists, the research also represents an example of the importance of synergy among specialists from different fields such as molecular and cell biology, genomics and bioinformatics in advancing in our knowledge of the regulation and structure of the genome. Participating in the study were seven research teams, including the UAB, the CNAG-CRG, the CSIC-University of Salamanca, the Sequentia Biotech and the University of New South Wales in Sydney.

Regions of the Universe containing very few or no galaxies - known as voids - can help measure cosmic expansion with much greater precision than before, according to new research.

The study looked at the shapes of voids found in data from the Sloan Digital Sky Survey (SDSS) collaboration. Voids come in a variety shapes, but because they have no preferred direction of alignment, a large enough sample of them can on average be used as "standard spheres" - objects which should appear perfectly symmetric in the absence of any distortions.

However, the observed shapes of these spheres are distorted by Doppler shifts in the redshifts of nearby galaxies caused by the local velocity field, and by the nature and amounts of dark matter and dark energy that make up 95% of the Universe. This distortion can be theoretically modelled, and the new work shows it can now be precisely measured.

The research was led by the University of Portsmouth, a world leader in cosmology, and is published this week in Physical Review D.

The new measurement of the distortion around voids used the Baryon Oscillation Spectroscopic Survey (BOSS) of galaxies from SDSS, that was designed to measure dark energy and the curvature of space.

For measuring a key aspect of the cosmic expansion, the new method greatly outperforms the standard baryon acoustic oscillation (BAO) technique that BOSS was designed for. The new results agree with the simplest model of a flat Universe with a cosmological constant dark energy, and tighten the constraints on alternative theories.

Lead author, Dr Seshadri Nadathur, research fellow at the University's Institute of Cosmology and Gravitation (ICG), said: "This measurement tremendously upgrades the previous best results from BOSS - the precision is equivalent to getting data from a hypothetical survey four times as large as BOSS, completely for free. It really helps pin down the properties of dark energy."

"These results also mean that the expected science results from facilities such as the European Space Agency's Euclid satellite mission and the Dark Energy Spectroscopic Instrument - in which the astronomy community have invested a lot of resources - can be even better than previously thought."

A questionnaire-based management algorithm for major depressive disorder in primary care is feasible to implement, though attrition from treatment is high. Among 25,000 patients in primary care clinics in a large metropolitan area, 4,325 (17%) screened positive for depression with 2,426 having a clinician-diagnosed depressive disorder. Of the 2,160 patients who had 18 weeks of follow-up care, 65% were treated with medication. Remission, defined as a PHQ-9 score of less than five, was more common in patients who experienced three or more follow-up visits. Of those who returned for three or more visits, 41.7% achieved remission. However, more than one-half of those diagnosed did not return for any follow-up care. The findings of this study suggest that patients suffering from depression can be successfully treated using measurement-based care within the primary care setting, and stronger emphasis on patient education and other approaches to reduce attrition may be needed for patients who fail to return for follow-up care.

The advent of the Affordable Care Act has led to millions of new patients seeking primary care. Because the number of primary care physicians has remained stable, access to care has been a concern. This "secret shopper" study performed between 2012 and 2016 showed that the proportion of primary care appointments scheduled for Medicaid patients with nonphysician advanced practitioners, like nurse practitioners and physician assistants, increased from 7.7% to 12.9% across a sample of 3,742 randomly selected primary care practices in 10 states. This roughly corresponds with the decrease in the rate of uninsured Americans and with the increase in Medicaid recipients since the Affordable Care Act began. The number of appointments scheduled with nonphysician advanced practitioners was higher at federally qualified health centers than other non-FQHC clinics. The findings suggest that practices may be relying on nonphysician health professionals to accommodate new Medicaid beneficiaries.

Astronomers have spotted a distant pair of titanic black holes headed for a collision.

Each black hole's mass is more than 800 million times that of our sun. As the two gradually draw closer together in a death spiral, they will begin sending gravitational waves rippling through space-time. Those cosmic ripples will join the as-yet-undetected background noise of gravitational waves from other supermassive black holes.

Even before the destined collision, the gravitational waves emanating from the supermassive black hole pair will dwarf those previously detected from the mergers of much smaller black holes and neutron stars.

"Supermassive black hole binaries produce the loudest gravitational waves in the universe," says co-discoverer Chiara Mingarelli, an associate research scientist at the Flatiron Institute's Center for Computational Astrophysics in New York City. Gravitational waves from supermassive black hole pairs "are a million times louder than those detected by LIGO."

The study was led by Andy Goulding, an associate research scholar at Princeton University. Goulding, Mingarelli and collaborators from Princeton and the U.S. Naval Research Laboratory in Washington, D.C., report the discovery July 10 in The Astrophysical Journal Letters.

The two supermassive black holes are especially interesting because they are around 2.5 billion light-years away from Earth. Since looking at distant objects in astronomy is like looking back in time, the pair belong to a universe 2.5 billion years younger than our own. Coincidentally, that's roughly the same amount of time the astronomers estimate the black holes will take to begin producing powerful gravitational waves.

In the present-day universe, the black holes are already emitting these gravitational waves, but even at light speed the waves won't reach us for billions of years. The duo is still useful, though. Their discovery can help scientists estimate how many nearby supermassive black holes are emitting gravitational waves that we could detect right now.

Detecting the gravitational wave background will help resolve some of the biggest unknowns in astronomy, such as how often galaxies merge and whether supermassive black hole pairs merge at all or become stuck in a near-endless waltz around each other.

"It's a major embarrassment for astronomy that we don't know if supermassive black holes merge," says study co-author Jenny Greene, a professor of astrophysical sciences at Princeton. "For everyone in black hole physics, observationally this is a long-standing puzzle that we need to solve."

Supermassive black holes contain millions or even billions of suns' worth of mass. Nearly all galaxies, including the Milky Way, contain at least one of the behemoths at their core. When galaxies merge, their supermassive black holes meet up and begin orbiting one another. Over time, this orbit tightens as gas and stars pass between the black holes and steal energy.

Once the supermassive black holes get close enough, though, this energy theft all but stops. Some theoretical studies suggest that black holes then stall at around 1 parsec (roughly 3.2 light-years) apart. This slowdown lasts nearly indefinitely and is known as the final parsec problem. In this scenario, only very rare groups of three or more supermassive black holes result in mergers.

Astronomers can't just look for stalled pairs because long before the black holes are 1 parsec apart, they're too close to distinguish as two separate objects. Moreover, they don't produce strong gravitational waves until they overcome the final-parsec hurdle and get closer together. (Observed as they were 2.5 billion years ago, the newfound supermassive black holes appear about 430 parsecs apart.)

If the final parsec problem doesn't exist, then astronomers expect that the universe is filled with the clamor of gravitational waves from supermassive black hole pairs. "This noise is called the gravitational wave background, and it's a bit like a chaotic chorus of crickets chirping in the night," says Goulding. "You can't discern one cricket from another, but the volume of the noise helps you estimate how many crickets are out there." (When two supermassive black holes finally collide and combine, they send out a thundering chirp that dwarfs all others. Such an event is brief and extraordinarily rare, though, so scientists don't expect to detect one any time soon.)

The gravitational waves generated by supermassive black hole pairs are outside the frequencies currently observable by experiments such as LIGO and Virgo. Instead, gravitational wave hunters rely on arrays of special stars called pulsars that act like metronomes. The rapidly spinning stars send out radio waves in a steady rhythm. If a passing gravitational wave stretches or compresses the space between Earth and the pulsar, the rhythm is slightly thrown off.

Detecting the gravitational wave background using one of these pulsar timing arrays takes patience and plenty of monitored stars. A single pulsar's rhythm might be disrupted by only a few hundred nanoseconds over a decade. The louder the background noise, the bigger the timing disruption and the sooner the first detection will be made.

Goulding, Greene and the other observational astronomers on the team detected the two titans with the Hubble Space Telescope. Although supermassive black holes aren't directly visible through an optical telescope, they are surrounded by bright clumps of luminous stars and warm gas drawn in by the powerful gravitational tug. For its time in history, the galaxy harboring the newfound supermassive black hole pair "is basically the most luminous galaxy in the universe," Goulding says. What's more, the galaxy's core is shooting out two unusually colossal plumes of gas. After the researchers pointed the Hubble Space Telescope at the galaxy to uncover the origins of its spectacular gas clouds, they discovered that the system contained not one but two massive black holes.

The observationalists then teamed up with gravitational wave physicists Mingarelli and Princeton graduate student Kris Pardo to interpret the finding in the context of the gravitational wave background. The discovery provides an anchor point for estimating how many supermassive black hole pairs are within detection distance of Earth. Previous estimates relied on computer models of how often galaxies merge, rather than actual observations of supermassive black hole pairs.

Based on the findings, Pardo and Mingarelli predict that in an optimistic scenario there are about 112 nearby supermassive black holes emitting gravitational waves. The first detection of the gravitational wave background from supermassive black holes should therefore come within the next five years or so. If such a detection isn't made, that would be evidence that the final parsec problem may be insurmountable. The team is currently looking at other galaxies similar to the one harboring the newfound supermassive black hole pair. Finding additional pairs will help them further hone their predictions.

A wild group of endangered Barbary macaques have been observed, for the first time, "consoling" and adopting an injured juvenile from a neighbouring group. The observations by a scientist from Oxford University and the International Fund for Animal Welfare (ifaw) are published today in the journal Primates.

'Pipo', a nearly three-year-old juvenile, was seriously injured and became separated from his group following a road traffic accident.

He was found distressed and alone two days later by a neighbouring Barbary macaque group. Although these monkeys had no social relationship with Pipo, they approached, groomed and affiliated with him, and accepted him into their group. Pipo made a full recovery and stayed with them for four months until returning to his own group.

The observation in Ifrane National Park in the Middle Atlas Mountains of Morocco - one of the Barbary macaque's last remaining areas of habitation - provides valuable information and offers hope to researchers and local communities who are trying to safeguard and boost the endangered species, which is under threat following habitat loss and poaching.

The cute-looking baby monkeys are illegally taken from the wild when very young to be used as pets or street entertainment, but are often abandoned within a few years once their cute currency has diminished.

Returning macaques rescued from illegal trade to the wild through rehabilitation and release programmes has multiple benefits of freeing space in sanctuaries to allow continued confiscations from illegal trade, improving individual welfare, minimising captive care costs, and reinforcing wild populations.

The scientist, Liz Campbell, from the Wildlife Conservation Research Unit (WildCRU) in Oxford University's Department of Zoology, said: 'We thought fostering may only be an option for very young monkeys, but Pipo's case shows even older juveniles can be accepted by wild foster groups. This observation provides valuable information for rehabilitation and release strategies, which will help improve welfare of rescued macaques, strengthen wild populations, and free space in sanctuaries to allow continued confiscations to fight illegal trade.'

Barbary macaques are known for their willingness to provide care to non-direct descendants (known as allo-parental care). As such, in addition to group releases, release into wild foster groups could be a promising strategy for supporting this threatened species. The observed spontaneous fostering of Pipo at nearly three years old offers hope that even older confiscated juveniles could be candidates for fostering, if they meet critical requirements of suitability.

The response by the neighbouring group to approach and groom the injured and distressed juvenile is unusual, since wild Barbary macaques are not usually friendly towards monkeys from other groups. There is growing evidence from several species of empathy-like behaviours, such as "consolation" (providing friendly or comforting behaviour to alleviate another's distress), but this case is unusual by being directed towards an unknown individual. This suggests wild monkeys can exhibit what may be basic forms of empathy towards even unfamiliar individuals, providing a rare example of potential consolation of an unknown individual, and attesting to the social character of this species.

Barbary macaques are unusual among primates in that the males of the species adore babies, regardless of them being theirs or not. They will often form baby "sandwiches" with other males, which helps them bond with the babies and with other males. Barbary macaques form huddle groups with monkeys they are socially bonded with to protect against the sometimes harsh environments in the snowy Atlas Mountains.

Liz Campbell, from Oxford University's Department of Zoology, said: 'Barbary macaques are very social, so to return them to the wild they must be with a group, not as lone individuals. The conventional method for returning primates to the wild is rehabilitation and release of groups formed in captivity, but because of the attention and care that Barbary macaques, especially males, give to young, there is the possibility not only to release rehabilitated groups but also to release individual young into foster groups in the wild.'

There are currently no drugs that stop or inhibit Alzheimer's disease. Despite drug trials showing plaque reduction in the brain, the patients' cognitive function did not improve. Would the results be different if it were possible to design studies that intervene much earlier on in the disease, before cognition is affected? This is what an international study, led by Lund University in Sweden, has attempted to facilitate. The findings have now been published in Neurology.

While several expensive drug trials for Alzheimer's disease in recent years have had negative outcomes, early diagnosis of the disease has improved. Research is underway to develop simpler and less costly methods, such as those involving biomarkers, to detect the disease at an early stage before the patient shows any symptoms.

"One problem is that most drug trials are designed to evaluate the effect of anti-amyloid treatments on patients in the dementia stage of the disease. At that stage, the patient already has serious memory impairment, with beta-amyloid having accumulated in the brain for many years.

Understanding the connection between amyloid pathology and cognition is important to evaluate cognitive decline in people who do not yet show cognitive impairment", says Philip Insel, doctoral student at the unit for clinical memory research at Lund University and first author of the article.

"Because the disease starts long before an individual shows any symptoms, it is important to observe the process at a preclinical stage of the disease. We must also observe larger cohorts of people to get a reliable and reproducible result", he continues.

For over six years, researchers in an international study studied cognition in preclinical Alzheimer's disease in a total of 1 120 people with no cognitive difficulties. In this group, 350 showed signs of Alzheimer's disease.

The participants in the study were recruited on three continents in three comparatively heterogeneous cohorts in Sweden (Lund/Malmö), North America (ADNI) and Australia (AIBL). Despite differences between the individuals in the groups, the researchers observed the same pattern of cognitive development in those who had beta-amyloid in the brain.

The researchers carefully analysed how various cognitive tests changed over time in pre-clinical Alzheimer's disease, and compared this with results in those with no sign of amyloid pathology in the brain.

"If we can find out when in the course of the disease a person's cognition will start being affected by Alzheimer's, it would be possible to design more efficient drug trials at a much earlier stage, long before dementia emerges, when we believe treatment will be the most effective.

One possible explanation for the failure of previous drug trials could be that the disease has progressed too far and the patients at this later stage of the disease are treated with a candidate drug targeting a protein that has already been present in the brain for many, many years", says Philip Insel.

"Our results show that drugs should be tested on patients early on, at a preclinical stage of Alzheimer's disease, at least six years before symptoms appear. Future drug trial designers must prepare to conduct larger and longer tests than previously", says Niklas Mattsson, research team leader at Lund University.

"If we can find ways to slow down the development of Alzheimer's disease, it would bring great benefits to patients, their loved ones and healthcare providers. Eventually, it could also bring down the significant costs to society incurred in public healthcare for dementia patients", he concludes.

Diabetes Patients Experiencing Empathy From Primary Care Practitioners Have Lower Risk of Mortality

A United Kingdom study designed to examine the association between primary care practitioner empathy and incidence of cardiovascular disease and all-cause mortality among type 2 diabetes patients found that those patients experiencing greater empathy in the year following their diagnosis saw beneficial long-term clinical outcomes. Using the consultation and relational empathy (CARE) questionnaire, which measures patients' experience of care with a focus on empathy, a numerical score for 628 participants from 49 general practices in East Anglia, UK, was computed 12 months after diagnosis. Those patients reporting better experiences of empathy had a lower risk (40-50%) of all-cause mortality over the subsequent 10 years compared with those reporting low practitioner empathy. While medicine moves increasingly towards precision, target-driven health care and technology-based assessment models, these findings suggest that interpersonal, empathic care may be an important determinant in the risk of mortality.

Association Between Primary Care Practitioner Empathy and Risk of Cardiovascular Events and All-Cause Mortality Among Patients With Type 2 Diabetes: A Population-Based Prospective Cohort Study
Hajira Dambha-Miller, MRCGP, PhD et al
University of Cambridge, United Kingdom
http://www.annfammed.org/content/17/4/311

Metformin Could Lower Risk of Dementia in African Americans With Type 2 Diabetes

A large observational cohort study examining male veterans aged over 50 years with type 2 diabetes found that metformin use was associated with a significantly lower risk of dementia in African American patients. The study included data from 73,500 patients who received care through the Veteran's Health Administration from 2000-2015 and were diabetes- and dementia-free at baseline and who subsequently developed type 2 diabetes and began treatment with either metformin or sulfonylurea. Cox proportional hazards models, using propensity scores and inverse probability treatment to balance confounding factors, were computed to measure the association of both drugs and incident dementia across race and age groups. For African American patients aged 50-64 years, the hazard ratio for developing dementia was 0.60 (CI, 0.45-0.81), and for African American patients aged 65-74 years, the hazard ratio was 0.71 (CI, 0.53-0.94). The study showed modest to no association between metformin and lower risk for dementia in white patients 65-74 and no association in other age groups. The present results may point to a novel approach for reducing dementia risk in African Americans with type 2 diabetes mellitus.

Association Between Metformin Initiation and Incident Dementia Among African American and White Veterans Health Administration Patients
Jeffrey F. Scherrer, PhD, et al
Saint Louis University, St. Louis, Missouri
http://www.annfammed.org/content/17/4/352

Redesign of Opioid Medication Management Shows Impact in Rural Clinics

In rural practice, a system redesign resulted in declines in the proportion of patients on high dose opioids and the number of patients receiving opioids. The "Six Building Blocks," a team-based redesign of opioid medication management within smaller practice settings addressing policy changes, patient agreements, patient tracking, in-clinic support, and success metrics, was implemented in 20 clinic locations across eastern Washington and central Idaho. Among patients aged 21 years and over, there was a 2.2% decline in patients receiving high dose opioids over a period of 15 months, compared to a 1.3% decline in the control group. Similarly, a 14% decline was observed in the total number of patients receiving opioids in the intervention clinics compared to a 4.8% control group decline. The results indicate that efforts to redesign care by primary care teams, guided by the Six Building Blocks framework, can improve opioid prescribing practices and possibly reduce dependency.

Team-Based Clinic Redesign of Opioid Medication Management in Primary Care: Effect on Opioid Prescribing
Michael L. Parchman, MD, MPH, et al
Kaiser Permanente Washington Health Research Institute, Seattle
http://www.annfammed.org/content/17/4/319

Many Still Uninsured After Affordable Care Act Implementation

In community health centers in Medicaid expansion states, among established patients who were uninsured prior to the Affordable Care Act, many remained uninsured after implementation of the Obama-era law. Using electronic health record data across 11 Medicaid expansion states, an Oregon Health & Science University study tracking uninsured patients before and after the implementation of the ACA found that 21% of those patients remained continuously uninsured, 15% gained Medicaid, 12% gained other insurance, and 51% did not visit their Community Health Center post ACA implementation. The 21% who remained uninsured were largely Hispanic and spoke Spanish as their primary language, indicating both a language and potential legal barrier to enrollment in the ACA. These uninsured patients continued to have frequent healthcare visits and the majority had at least one health condition that would require continuous care. The results of this study point to a need for additional funding to support the needs of Community Health Centers serving the uninsured.

Following Uninsured Patients Through Medicaid Expansion: Ambulatory Care Use and Diagnosed Conditions
Nathalie Huguet, PhD, et al
Oregon Health & Science University, Portland
http://www.annfammed.org/content/17/4/336

"Flash Mob" Study Puts Clinical Decision Rules for ACS to the Test

A novel "flash mob" study finds that, in emergency care, acute coronary syndrome cannot be safely ruled out using the Marburg Heart Score or the family physicians' clinical assessment. In a period of only two weeks, researchers at Maastricht University collected data on 258 ACS-suspected patients by mobilizing one in five family physicians throughout the Netherlands to participate in the study. This mobilization was done by enlisting ambassadors among the FP community in the Netherlands who then spread the word through traditional professional and social networks. The study found that among 243 patients receiving a final diagnosis, 45 (18.5%) were diagnosed with acute coronary syndrome. Sensitivity for the FP rating was 86.7% and sensitivity for the MHS was 94.4%. While large, prospective studies can be time consuming and costly, this innovative "flash mob" method of research, named after the large-scale public collaborations/gatherings driven by social media, allowed for the fast investigation of one simple question on a large scale in a short timeframe.

A Nationwide Flash-Mob Study for Suspected Acute Coronary Syndrome
Jochen W.L. Cals, MD, PhD, et al
Maastricht University, The Netherlands
http://www.annfammed.org/content/17/4/296

The Next Generation of Connectivity in Family Medicine Research

In an accompanying editorial, Mohammed (Ahmed) Rashid, MD, MPH, and Larry A. Green, MD, point out that in a more connected world, the innovative flash mob method "prompts consideration of a potentially important benefit of conducting clinical research in a connected world: time." The potential for cost savings and benefits for clinicians and patients alike are great, but more research needs to be done to establish best practices for such things as spreading awareness on social media and whether to introduce on a large institutional scale or smaller word-of mouth scale. Rashid and Green also voice concern over whether this approach is sustainable and viable across the field of family medicine, writing, "It will be important to consider how networks can be maintained and energized in the longer term, including how the process and bureaucracy can be best simplified, and whether or not there will be any kind of incentives for physicians or health care organizations to take part." Likening the innovativeness of this approach to practice-based research networks, they note that the Cals paper expands on innovative approaches to studying problems in a primary care setting.

The Next Generation of Connectivity in Family Medicine Research
Mohammed A. Rashid, MD, MPH
University College, London, United Kingdom
Larry A. Green, MD
University of Colorado Denver, Aurora
http://www.annfammed.org/content/17/4/291

Caught in the Middle: Family Physicians Discuss Their Role in the Opioid Crisis

Family physicians prescribe the greatest volume of opioids (22.9%) and number of prescriptions (31.2%) to individuals with chronic noncancer pain, making them targets for quality improvements in safer prescribing practices. Interviews with 22 family physicians in Ontario, Canada, from June to July 2017, identified key themes driving the over prescription of opioids in managing chronic pain: the contrast between doctors' training and current expectations; navigating patient and system expectations; and the duration and quality of therapeutic relationships. Physicians with five or fewer years' professional experience emphasized the need to create trusting relationships with their patients as well as the difficulties arising in conversations about chronic pain, including surveillance and urine screening. Physicians with longstanding, stable practices of around 15 years or more, described stronger, more trusting therapeutic relationships that lessened the need for strict enforcement measures. Both groups complained of a lack of resources to support effective pain management. A combination of outside pressures and system expectations around the issue of opioid prescriptions places family physicians at the center of an emotionally-charged debate, and at a heightened risk of burnout.

Family Physician Perceptions of Their Role in Managing the Opioid Crisis
Laura Desveaux, PT, PhD, et al
Women's College Hospital / University of Toronto, Canada
http://www.annfammed.org/content/17/4/345

A Structured Approach to Detecting and Treating Depression in Primary Care

A questionnaire-based management algorithm for major depressive disorder in primary care is feasible to implement, though attrition from treatment is high. Among 25,000 patients in primary care clinics in a large metropolitan area, 4,325 (17%) screened positive for depression with 2,426 having a clinician-diagnosed depressive disorder. Of the 2,160 patients who had 18 weeks of follow-up care, 65% were treated with medication. Remission, defined as a PHQ-9 score of less than five, was more common in patients who experienced three or more follow-up visits. Of those who returned for three or more visits, 41.7% achieved remission. However, more than one-half of those diagnosed did not return for any follow-up care. The findings of this study suggest that patients suffering from depression can be successfully treated using measurement-based care within the primary care setting, and stronger emphasis on patient education and other approaches to reduce attrition may be needed for patients who fail to return for follow-up care.

A Structured Approach to Detecting and Treating Depression in Primary Care
Madhukar Trivedi, MD, et al
University of Texas Southwestern Medical Center, Dallas
http://www.annfammed.org/content/17/4/326

Are Physical Examinations Really Necessary?

As technology has gained ground in medicine and critics have called into question the diagnostic accuracy of physical examinations, what place does the practice of the physical exam have in today's clinic? In depth, qualitative interviews with 16 family physicians in Canada revealed a common view that physical examinations help promote a healthy patient-physician relationship and constitute an integral part of being a good doctor. Guided by principles of phenomenology, which considers how human beings experience a certain phenomenon--in this case, the physical examination itself--the research found that in addition to diagnostic information gained in physical examinations, the empathic benefits of "laying on hands" served as an important reminder of the physician's role as healer. At a time when contemporary clinical practice is grappling with the influx of emerging diagnostic technology, the physical exam is seen by many doctors as a grounding and centering element of the time-honored art of family medicine.

Family Physicians' Experiences of Physical Examination
Martina Kelly, MA, MBBCh, FRCGP, CCFP, et al
University of Calgary, Alberta, Canada
http://www.annfammed.org/content/17/4/304

Nonphysician Advanced Practitioners Absorbing More New Patient Requests Post Affordable Care Act

The advent of the Affordable Care Act has led to millions of new patients seeking primary care. Because the number of primary care physicians has remained stable, access to care has been a concern. This "secret shopper" study performed between 2012 and 2016 showed that the proportion of primary care appointments scheduled for Medicaid patients with nonphysician advanced practitioners, like nurse practitioners and physician assistants, increased from 7.7% to 12.9% across a sample of 3,742 randomly selected primary care practices in 10 states. This roughly corresponds with the decrease in the rate of uninsured Americans and with the increase in Medicaid recipients since the Affordable Care Act began. The number of appointments scheduled with nonphysician advanced practitioners was higher at federally qualified health centers than other non-FQHC clinics. The findings suggest that practices may be relying on nonphysician health professionals to accommodate new Medicaid beneficiaries.

Primary Care Appointments for Medicaid Beneficiaries With Advanced Practitioners
Molly Candon, PhD, et al
University of Pennsylvania, Philadelphia
http://www.annfammed.org/content/17/4/363

A New Approach to Primary Care: Advanced Team Care With In-Room Support

In this special report, the authors argue that the current primary care team paradigm is underpowered, in that most of the administrative responsibility still falls mainly on the physician. Jobs not requiring a medical education, such as entering data into electronic health records, should not be handled by physicians and advanced practitioners. The authors propose a model where a physician with two or three highly trained "care team coordinators" share patient responsibilities, with the CTCs organizing the visit, completing documentation, and coordinating follow-up care, and the physician handling components of the visit that require more complex decision making. There is evidence that this model improves patient care, reduces physician burnout, and is financially sustainable. The authors identify a number of themes, or mindsets, such as the idea that technology can replace people, that are barriers to implementation of these models in family medicine.

Powering-Up Primary Care Teams: Advanced Team Care With In-Room Support
Thomas Bodenheimer, MD, MPH
University of California, San Francisco
Christine A. Sinsky, MD
American Medical Association, Chicago
http://www.annfammed.org/content/17/4/367

How Primary Care Physicians Can Make Astana Work

The Astana Declaration, adopted by the World Health Organization in October 2018, acknowledges the importance of primary health care to achieve better health outcomes globally. But how, the authors ask, can physicians make this declaration work? Family physicians, the authors argue, can serve an important role in improving primary health care if they are better integrated "horizontally," translating their localized knowledge of health trends to wider populations and communities. Conversely, data on wider populations needs to be better translated to specific communities to "help primary health care address social determinants of health as part of individual care." Besides ongoing advocacy for comprehensive primary care, and strengthening of professionalism through teaching and practice development, the Astana declaration should be amended to include: "engagement with policy makers and public health to detail the professional contribution of primary care in the broader context of primary health care to secure person centered, population oriented integrated care."

The essential role of Primary care professionals in achieving Health for all - how to make "Astana" work.
Prof. Chris van Weel
Prof. Maria van den Muijsenbergh
Radboud University Medical Center, Nijmegen, Netherlands
http://www.annfammed.org/content/17/4/293

Innovations in Primary Care

Innovations in Primary Care are brief 1-page articles that describe novel innovations from health care's front lines. In this issue:

Utilizing PHATE: A Population Health-Mapping Tool to Identify Areas of Food Insecurity - An easy-to-use population health tool enables clinicians to better identify geographic regions with high concentrations of patients who screen positive for food insecurity.
http://www.annfammed.org/content/17/4/372.full

EMR Happy Hour: New Approach to Electronic Medical Record Continuous Learning - Monthly online meetings between clinical faculty and other EMR users encourages sharing challenges and proposing solutions while improving provider self-efficacy, a tool in reducing burnout.
http://www.annfammed.org/content/17/4/373.full

Family physicians prescribe the greatest volume of opioids (22.9%) and number of prescriptions (31.2%) to individuals with chronic noncancer pain, making them targets for quality improvements in safer prescribing practices. Interviews with 22 family physicians in Ontario, Canada, from June to July 2017, identified key themes driving the over prescription of opioids in managing chronic pain: the contrast between doctors' training and current expectations; navigating patient and system expectations; and the duration and quality of therapeutic relationships. Physicians with five or fewer years' professional experience emphasized the need to create trusting relationships with their patients as well as the difficulties arising in conversations about chronic pain, including surveillance and urine screening. Physicians with longstanding, stable practices of around 15 years or more, described stronger, more trusting therapeutic relationships that lessened the need for strict enforcement measures. Both groups complained of a lack of resources to support effective pain management. A combination of outside pressures and system expectations around the issue of opioid prescriptions places family physicians at the center of an emotionally-charged debate, and at a heightened risk of burnout.

CHAMPAIGN, Ill. -- A new paper co-written by a University of Illinois expert who studies labor economics says the minimum wage is an effective tool to increase the incomes of older workers who are at or near retirement and - contrary to the notion that higher minimum wages force earlier retirements - has no discernible "disemployment" effects.

In an era of rising inequality and aging populations, the effect of the minimum wage on the labor market for older workers is increasingly important, said Mark Borgschulte, a professor of economics at Illinois.

"From a public policy perspective, lawmakers are really interested in incentivizing people to work longer - it's the uniform prescription across the political spectrum for how we can tackle aging-related budget issues," Borgschulte said. "For programs like Social Security, getting people to work longer is very helpful."

Borgschulte and co-author Heepyung Cho, a graduate student at Illinois, studied the effect of the minimum wage on the employment outcomes and Social Security claiming of older U.S. workers from 1983-2016. According to the paper, the probability of work at or near the minimum wage increases substantially near retirement, and previous research suggests that older workers may be particularly vulnerable to any disemployment effects of the minimum wage.

But results show no evidence that the minimum wage causes earlier retirements, Borgschulte said.

"If we think the minimum wage has harmful effects on employment - which is a controversial position in economics, but one that a lot of economists subscribe to - then it's going to potentially undermine our public policy goals of trying to get people to work longer," he said. "We find that the minimum wage not only increases the financial resources of these older households, it also more than offsets whatever small, negative unemployment effects may exist, which are statistically indistinguishable from zero."

Instead, the researchers found that higher minimum wages increase earnings and may have small positive effects on the labor supply of workers in the key age 62-70 demographic.

"Higher minimum wages result in increased earnings and delayed retirement in that cohort, which translates into a decrease in the number of Social Security beneficiaries as well as the amount of benefits disbursed," Borgschulte said. "The way the Social Security systems works in the U.S. should not disincentivize work, but for whatever reason, many retirees perceive Social Security claiming as indicative of an exit from the labor force. And so we were able to show that there is no harmful effect of the minimum wage on older workers' employment - and, in fact, it seems to delay Social Security claiming, which would be consistent with increased financial resources for older households."

If anything, employment goes up for workers who are at retirement age, which suggests that minimum wage jobs keeps people in the labor force a little bit longer, Borgschulte said.

"Public policymakers have not spent as much time as they should thinking about how we should keep people in the labor force," he said. "So in that way, having a minimum wage is an effective policy for keeping people in the labor force for longer. And economists haven't spent enough time studying why people retire. So this paper is a small step in that direction. The reality is that many older workers are working for low wages, so the minimum wage is particularly relevant for this part of the labor market."

The federal minimum wage is $7.25 per hour, and the minimum wage at the state level can go as high as $11.50 per hour. If it were to be increased to $15 per hour, then you might see some disemployment effects, Borgschulte said.

"An absolutely essential caveat to any minimum wage paper is that we're only able to study - empirically, at least - the range of minimum wages observed in the data," he said. "And the theories about how the labor market works suggests that small changes in the minimum wage likely will have small changes in employment. Firms have some wage-setting power, and if they make changes at the margins, a higher minimum wage will likely only have a marginal effect or no change at all."

Raising the minimum wage to $15 per hour would potentially run into a disincentive to hiring more workers, "particularly if we're going from $8-$10 per hour to $15," Borgschulte said.

"There's room to raise the minimum wage without expecting negative consequences for older workers' employment status, but it's not clear what happens when it goes up to $15 per hour," he said. "It's harder for economists to predict when you make large changes because you're moving out of the range of what the previous data can tell you, and so you need something to extrapolate out of your sample."

In this special report, the authors argue that the current primary care team paradigm is underpowered, in that most of the administrative responsibility still falls mainly on the physician. Jobs not requiring a medical education, such as entering data into electronic health records, should not be handled by physicians and advanced practitioners. The authors propose a model where a physician with two or three highly trained "care team coordinators" share patient responsibilities, with the CTCs organizing the visit, completing documentation, and coordinating follow-up care, and the physician handling components of the visit that require more complex decision making. There is evidence that this model improves patient care, reduces physician burnout, and is financially sustainable. The authors identify a number of themes, or mindsets, such as the idea that technology can replace people, that are barriers to implementation of these models in family medicine.

The Astana Declaration, adopted by the World Health Organization in October 2018, acknowledges the importance of primary health care to achieve better health outcomes globally. But how, the authors ask, can physicians make this declaration work? Family physicians, the authors argue, can serve an important role in improving primary health care if they are better integrated "horizontally," translating their localized knowledge of health trends to wider populations and communities. Conversely, data on wider populations needs to be better translated to specific communities to "help primary health care address social determinants of health as part of individual care." Besides ongoing advocacy for comprehensive primary care, and strengthening of professionalism through teaching and practice development, the Astana declaration should be amended to include: "engagement with policy makers and public health to detail the professional contribution of primary care in the broader context of primary health care to secure person centered, population oriented integrated care."

DURHAM, N.C. - A newer form of shingles vaccine reduced outbreaks of the painful rash among patients who were transplanted with their own stem cells, according to a study led by a Duke Health researcher and published today in JAMA.

The vaccine appears to offer protection from one of the most common and painful side effects of cell therapy and shows promise for patients with immune-compromising conditions.

Using a non-live form of the herpes zoster virus that causes shingles, the researchers tested vaccination among people whose immune systems are wiped out during hematopoietic stem cell transplantation (HSCT). HSCT patients are especially prone to bouts of shingles, which is caused by reactivation of the latent varicella-zoster virus that also causes chicken pox.

The outbreak results in red, painful, burning blisters and rash, typically on one side of the body and often occurs in older adults or people with weakened immune systems. In some cases, shingles causes excruciating and long-lasting neurologic pain.

"This trial is important because it demonstrates that the vaccine works in severely immunosuppressed patients," said oncologist Keith Sullivan, M.D., the James B. Wyngaarden Professor of Medicine at Duke. "That suggests it could also work with others whose immune systems are not normal -- including patients with HIV, breast cancer and auto-immune conditions."

Sullivan and colleagues at 167 centers in 28 countries enrolled more than 1,800 transplant recipients. Half were randomly assigned to received two vaccine doses shortly after transplant and half received placebo.

At a median follow-up of 21 months, the vaccine group had 30 cases of shingles per 1,000 person-years compared to 94 cases per 1,000 person-years among patients receiving placebo injections.

The vaccine also apparently reduced the incidence of painful post-therapeutic neuralgia, shingles-related hospitalizations and complications and duration of pain.

"Among HSCT patients, a shingles outbreak is often more feared than the transplant itself, and I've had patients tell me they'd undergo two transplants before facing another episode of shingles," Sullivan said. "It's hugely gratifying, and a welcome surprise, to see such a strong immune response among this study population."