Culture

An analysis of information from a large U.S. cancer database indicates that patients with liver cancer from rural regions and lower income households often have more advanced cancer at the time of diagnosis and face a higher risk of death compared with other patients. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS).

Screening for liver cancer is important for detecting tumors at an early stage, when treatment is most effective. To explore the impact of different factors on liver cancer stage at the time of diagnosis and on survival of patients with the disease, Robert J. Wong, MD, MS, of the Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine, and his colleagues analyzed the most recently updated Surveillance, Epidemiology and End Results (SEER) cancer database from the National Cancer Institute. This database includes information from 21 U.S. regions, representing approximately 35 percent of the U.S. population.

From 2004 to 2017, there were 83,237 adults with liver cancer, among which 49.1 percent had localized disease at the time of diagnosis and 14.4 percent had advanced disease that had spread.

The team found that compared with patients in large metro areas with a population of more than 1 million people, patients in more rural regions had 10 percent higher odds of having advanced liver cancer at the time of diagnosis and 5 percent higher odds of dying. Also, compared with patients with an annual household income of at least $70,000, patients with an annual household income below $40,000 had 15 percent higher odds of having advanced cancer at the time of diagnosis and 23 percent higher odds of dying.

"While our study could not specifically investigate the reasons for the worse liver cancer outcomes, we hypothesize that patients living in more rural regions and among lower income households likely experience healthcare disparities leading to sub-optimal access to high quality liver disease care, including timely receipt of liver cancer surveillance and access to liver disease specialists," said Dr. Wong. "Our study highlights the need to focus on understanding the drivers of poor liver cancer outcomes among underserved and vulnerable populations, including those in rural geographic regions or among low income households, so that targeted quality improvement interventions can more specifically address the needs of these populations. We also hope that our findings will raise greater awareness of challenges and limited resources that contribute to sub-optimal liver disease care experienced by patients from low-income and rural households."

October is Liver Cancer Awareness Month.

The Korea Institute of Civil Engineering and Building Technology (KICT) has announced the development of an effective structural strengthening method using a noncombustible carbon textile grid and cement mortar, which can double the load-bearing capacities of structurally deficient concrete structures and increase their usable lifespan by threefold.

More than 90% of infrastructures in South Korea, such as bridges and tunnels, as well as residential buildings were initially constructed out of concrete. For deteriorated or structurally deficient concrete structures in need of structural strengthening, carbon fiber sheets are typically applied to the surface of the concrete structure using organic adhesives. However, organic adhesives are susceptible to fire and cannot be applied to structures with wet surfaces. These carbon fiber sheets may detach and fall from the structure if they are exposed to moisture.

A research team in KICT, led by Dr. Hyeong-Yeol Kim, has developed an effective as well as efficient strengthening method for deteriorated concrete structures. With the developed method, thin precast textile reinforced mortar (TRM) panels, which are made of a carbon textile grid and a thin layer of cement mortar, are used. Furthermore, the TRM strengthening method can be applied in the form of cast-in-place construction. Employing KICT's method, 20 mm-thick TRM panels are attached to the surface of the existing structure, and then the space between the existing structure and the panels is filled with cement grout, with the cement grout serving as the adhesive.

Both the carbon textile and cement mortar are noncombustible materials that have a high resistance to fire, meaning that they can be effectively used to strengthen concrete buildings that may be exposed to fire hazards. The construction method can also be applied to wet surfaces as well as in the winter, and the panels do not fall off even in the event of water ingress. Additionally, unlike steel reinforcing bars, the carbon textile does not corrode, and thus it can be effectively used to strengthen highway facilities and parking buildings, where deicing agents are often used, as well as to strengthen offshore concrete structures that are exposed to a chloride-rich environment.

A failure test conducted in KICT indicates that the failure load of concrete structures strengthened with the TRC panel increased by at least 1.5 times compared to that of an unstrengthened structure. Furthermore, the chloride resistance of the TRM panel has been evaluated in order to assess its service life in a chloride-rich environment. The durability test and analysis of the TRM panel indicates that the lifespan of the panel is more than 100 years. This increase can be attributed to the cement mortar, developed by KICT, which contains 50% ground granulated blast furnace slag, an industrial byproduct generated at ironworks. The cement mortar, which has a higher fire resistance than conventional cement mortar, is also advantageous because its cost is half that of conventional mortar. In terms of economical efficiency, the newly developed method can reduce construction costs by about 40% compared to existing carbon sheet attachment methods.

The newly developed strengthening method uses thin TRM panels that are very versatile and can be used as building facades, repair and strengthening materials, and in other applications. In the future, if the panels can be fabricated with thermal insulators, it is expected that they will replace building insulation materials that are susceptible to fires.

Dr. Kim said, "For easier production and shipping, the TRM panels are manufactured in a relatively small size of 1 m by 2 m and must be connected at the construction site. A method for effectively connecting the panels is currently being developed, and performance tests of the method will be conducted by the end of 2020."

A new drug designed to work on cancers with an altered BRAF gene has shown promise in an early patient trial presented at the 32nd EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics, which is taking place online.

The BRAF gene is involved in telling healthy cells when to grow and form new cells, but it is also known to go wrong, or mutate, in several types of cancer, including types of bowel, brain and skin cancer. A few BRAF inhibitor drugs have already proved effective in treating patients. However, these 'first generation' BRAF inhibitors do not work on all BRAF mutated cancers and in other cases cancers become resistant to the treatment.

The new drug, PLX8394, is a 'next generation' BRAF inhibitor, designed to avoid this resistance and work against cancers with a wider range of BRAF mutations.

Results of the phase I/II trial were presented to the Symposium by Dr Filip Janku, Associate Professor for Investigational Cancer Therapeutics (Phase I Clinical Trials Program) and Center Medical Director for Clinical and Translational Research Center at The University of Texas MD Anderson Cancer Center in Houston, Texas, USA.

In the trial so far, 75 patients have been treated with the next generation BRAF inhibitor PLX8394, taken twice a day by mouth, with or without another drug called cobicistat. Data on 45 of these patients with BRAF alterations, who received PLX8394 and cobicistat, were available for researchers to evaluate. These patients had advanced cancers and most had already received three different types of treatments before joining the trial.

The researchers reported that the addition of cobicistat resulted in doubling to tripling the level of PLX8394 in the blood.

Ten of the 45 patients (22%) had a partial response to the new drug, meaning their tumours shrank by at least 30%. This included three people with glioma (a type of brain tumour), two with ovarian cancer and others with bowel cancer, thyroid cancer or melanoma (a type of skin cancer). Ten of the 45 patients had remained on the treatment for at least two years when the data were analysed.

Serious side effects of the treatment experienced by some patients were high levels of a liver enzyme and bilirubin in the blood, indicating a risk of liver damage; these levels lowered when PLX-8394 was interrupted and the dose reduced. Some patients also experienced diarrhoea.

Dr Janku said: "Although we already have some BRAF inhibitor drugs, unfortunately they do not work for all patients with BRAF mutated cancers. In some cases, even when these drugs do work at first, cancers develop resistance. First generation BRAF inhibitors can also cause unpleasant skin lesions and skin cancers in some patients.

"The next generation BRAF inhibitor that we gave to patients in this trial was designed to avoid those problems. These results suggest that the combination of drugs we tested is relatively safe and may be effective for some patients."

Dr Janku and his colleagues continue to study the combination of PLX8394 and cobicistat for treating patients, particularly to discover the optimum dose of the drugs.

William R. Sellers, Professor of Medicine at the Dana-Farber Cancer Institute, Harvard Medical School, USA, is co-chair of the EORTC-NCI-AACR Symposium on behalf of the NCI and was not involved with the research. He commented: "Understanding which genes go wrong in cancer and how they are mutated is a crucial step towards finding treatments that are targeted to work effectively in individual patients. BRAF is a gene mutated in approximately half of melanoma patients as well as in smaller fractions of colorectal and lung cancer. It is, therefore, an important therapeutic target and, indeed, BRAF inhibitors have significant clinical benefit in such patients.

"This trial shows positive signs for using a next generation BRAF inhibitor to treat patients with a variety of different cancer types and we look forward to hearing further results from the next stage of this research."

Tokyo, Japan - Researchers from Tokyo Metropolitan University have discovered a new mechanism by which clumps of tau protein are created in the brain, killing brain cells and causing Alzheimer's disease. A specific mutation to an enzyme called MARK4 changed the properties of tau, usually an important part of the skeletal structure of cells, making it more likely to aggregate, and more insoluble. Getting to grips with mechanisms like this may lead to breakthrough treatments.

Alzheimer's disease is a life-changing, debilitating condition, affecting tens of millions of people worldwide. According to the World Health Organization, it is the most common cause of senile dementia, with numbers worldwide expected to double every 20 years if left unchecked.

Alzheimer's is said to be caused by the build-up of tangled clumps of a protein called "tau" in brain cells. These sticky aggregates cause neurons to die, leading to impairment in memory and motor functions. It is not yet clear how and why tau builds up in the brain cells of Alzheimer's patients. Understanding the cause and mechanism behind this unwanted clumping would open up the way to new treatments and ways to prevent the disease.

A team led by Associate Professor Kanae Ando of Tokyo Metropolitan University has been exploring the role played by the MARK4 (Microtubule Affinity Regulating Kinase 4) enzyme in Alzheimer's disease. When everything is working normally, the tau protein is an important part of the structure of cells, or the cytoskeleton. To keep the arms of the cytoskeleton or microtubules constantly building and disassembling, MARK4 actually helps tau detach from the arms of this structure.

Problems start when a mutation occurs in the gene that provides the blueprint for making MARK4. Previous work had already associated this with an increased risk of Alzheimer's, but it was not known why this was the case. The team artificially introduced mutations into transgenic drosophila fruit flies that also produce human tau, and studied how the proteins changed in vivo. They discovered that this mutant form of MARK4 makes changes to the tau protein, creating a pathological form of tau. Not only did this "bad" tau have an excess of certain chemical groups that caused it to misfold, they found that it aggregated much more easily and were no longer soluble in detergents. This made it easier for tau to form the tangled clumps that causes neurons to degenerate.

MARK4 has also been found to cause a wide range of other diseases which involve the aggregation and buildup of other proteins. That's why the team's insights into tau protein buildup may lead to new treatments and preventative measures for an even wider variety of neurodegenerative conditions.

Oncotarget recently published “Evaluation of cellular alterations and inflammatory profile of mesothelial cells and/or neoplastic cells exposed to talc used for pleurodesis” which reported that in this study, PMC cultures, human lung and breast adenocarcinoma cells were divided in 5 groups: 100% PMC, 100% NC, 25% PMC 75% NC, 50% of each type and 75% PMC 25% NC. High IL-6, IL-1β and TNFRI levels were found in PMC and NC exposed to talc. In pure cultures TNFRI was higher in A549 followed by PMC and MCF7. LDH was higher in A549 than PMC. Apoptotic cells exposed to talc were higher in pure cultures of NC than in PMC. Mixed cultures of PMC and A549 showed lower levels of apoptosis in cultures with more NC.

Dr. Milena Marques Pagliarelli Acencio from the University of de São Paulo said, "Metastatic neoplasms are the most common type of pleural neoplastic disease and the principal primary sites are lung, breast, stomach and ovary."

The Oncotarget authors described that in an experimental model of pleurodesis acute inflammatory reaction to talc was observed with an increase in pleural fluid concentrations of IL-8, VEGF and TGF-β detected after intrapleural injection of talc and noted that the mesothelial cell layer was preserved.

Thus, mesothelial cells appear to participate in the response to talc and contribute to the acute inflammatory response.

Some authors discuss the importance of cell death caused mainly by apoptosis in mesothelial cells and/or neoplastic cells leading to the success or failure of pleurodesis, or even acting to decrease the tumor.

They explain that in preliminary experimental studies it has also been suggested that talc can induce apoptosis in tumor cells and inhibit angiogenesis, thus contributing to a better control of malignant pleural effusion.

The ultimate hypothesis of the Oncotarget study is to determine the role of mesothelial and/or neoplastic cells in the initiation and regulation of the acute inflammatory response following the instillation of talc in the pleural space, evaluating cellular aspects such as apoptosis and inflammatory mediators.

"The ultimate hypothesis of the Oncotarget study is to determine the role of mesothelial and/or neoplastic cells in the initiation and regulation of the acute inflammatory response."

The Acencio Research Team concluded in their Oncotarget Research Paper that these results permit them to infer that the normal mesothelium in contact with the talc particles is the main stimulus in the genesis of the inflammatory process.

From the mesothelial activation the production of molecular mediators occurs, and that probably contributes to the dynamics of the local inflammatory process and subsequent production of pleural fibrosis; these mechanisms are necessary to induce effective pleurodesis.

These data also allow them to observe that talc has an action in the neoplastic cells inducing higher rates of apoptosis than observed in normal mesothelial cells; this may even contribute in a modest way to tumoral decrease.

Also that different types of tumor cells may respond differently to exposure to talc.

Bone disease is becoming increasingly prevalence in modern society due to population aging among other factors, and the use of dental and orthopedic implants to treat bone disease has been on the rise. The history of implants can be traced back all the way to A.D. 1 when wrought iron dental implants were used in Ancient Rome. Despite the long history, however, there are still a number of issues associated with implant procedures such as a loose implant resulting from slow integration into the bone tissue or an inflammation necessitating a secondary surgical procedure.

To mitigate these issues, there has been an attempt to coat the implant material with "artificial bone" that has the same composition as the actual human bone. Conventional coating methods, however, require a synthesis process to manufacture the artificial bone material and a separate coating process, which takes a long time. Plus, the binding between the substrate and the artificial bone coating layer tends to be weak, resulting in damage or even drop-off, and strong coating methods that could be applied to actual patients in a clinical setting were rare.

Under these circumstances, Dr. Hojeong Jeon's research team at the Korea Institute of Science and Technology (KIST) Center for Biomaterials announced that they have developed a ceramic artificial bone coating with triple the adhesion strength compared to conventional coating materials.

The research team developed a technology to induce artificial bone coating, which had taken at least a day and required dozens of steps, in just one hour using a single process. By using the technique, there is no need to synthesize the raw material for artificial bone coating in a separate process, and it is possible to create the coating with a nanosecond laser without any expensive equipment or heat treatment process.

Not only that, it is possible to form a coating layer with a stronger binding power than the few artificial bone coating techniques applied clinically today. Also, in case of using this process, it results in robust coating not only on metal surfaces but even on the surfaces of polymer materials such as orthopedic plastic implants, which has not been possible with conventional processes.

In order to reduce the number of steps involved in the process as well as the duration and at the same time ensure robust coating, Dr. Jeon's team positioned the material to be coated in a solution containing calcium and phosphorous, the main components of the bone, and irradiated it with laser. The temperature was raised in a localized manner at the target site of the laser, causing a reaction involving the calcium and phosphorous to produce ceramic artificial bone (hydroxyapatite) and the formation of a coating layer.

Unlike the conventional coating methods, the synthesis of the artificial bone component is induced by laser and, at the same time, the surface of the substrate is heated above the melting point for the artificial bone material to get adsorbed on the melted surface and get hardened as is, which maximizes the binding strength.

Dr. Jeon said, "The hydroxyapatite coating method using nanosecond laser is a simple way to induce bioactivity in non-bio-active materials such as titanium and PEEK that are commonly used as biomaterials. I anticipate that it will become a game changer in that it will have wide applications to diverse medical devices where osseointegration is needed.

Highlights

In individuals with chronic kidney disease who received online peer mentoring, improved patient activation correlated with improvements in various aspects of quality of life.

Results from the study will be presented online during ASN Kidney Week 2020 Reimagined October 19-October 25.

Washington, DC (October 23, 2020) -- Researchers previously demonstrated that online peer mentoring for individuals with chronic kidney disease (CKD) improves patient activation--or patients' willingness and ability to take actions to manage their health and care--and quality of life (QOL). Now the investigators have looked at the correlation between QOL and patient activation among patients with CKD who participated in an online peer mentoring program, which provides guidance from others who live with CKD. The study that will be presented online during ASN Kidney Week 2020 Reimagined October 19-October 25.

The study randomized 155 patients with stage 4 or stage 5 CKD to online peer mentoring, face-to-face peer mentoring, or usual care. Among the online peer mentoring group, improvements in patient activation correlated with improvements in various aspects of QOL related to physical symptoms and burdens of kidney disease. There was no correlation between patient activation and mental aspects of QOL.

"Results from our study suggest that improved QOL in patients with CKD who received online peer mentoring may be a result of improved patient activation," said co-author Nasrollah Ghahramani, MD, MS (Pennsylvania State University).

Study: "The Correlation between Patient Activation and Quality of Life among Patients with Chronic Kidney Disease"

This research was funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (CDR-1310-07055). The statements presented are solely the responsibility of the authors and do not necessarily represent the views of PCORI or its Board of Governors or Methodology Committee.

ASN Kidney Week 2020 Reimagined, the largest nephrology meeting of its kind, will provide a forum for more than 13,000 professionals to discuss the latest findings in kidney health research and engage in educational sessions related to advances in the care of patients with kidney and related disorders. Kidney Week 2020 Reimagined will take place October 19-October 25.

Highlights

A new study indicates that Blacks and Hispanics have experienced higher rates of kidney failure compared with whites due to more rapid kidney function decline.

Results from the study will be presented online during ASN Kidney Week 2020 Reimagined October 19-October 25.

Washington, DC (October 23, 2020) -- A new study investigates the reasons behind higher incidences of kidney failure among US minorities. The findings will be presented online during ASN Kidney Week 2020 Reimagined October 19-October 25.

In the United States, Blacks and Hispanics have higher incidences of kidney failure than whites, but it's unclear if this is driven by inherently faster progression to kidney failure or by lower death rates prior to kidney failure (with more Blacks and Hispanics living longer to develop kidney failure).

To investigate, Guofen Yan, PhD (University of Virginia) and her colleagues examined information on 834,270 individuals who were diagnosed with chronic kidney disease (CKD) in the US Veterans Health Administration between 2002 and 2015 and were followed through 2016.

Ten years after CKD onset, the cumulative incidence of developing kidney failure were 1.3-2.5 times greater for Blacks and Hispanics compared with whites across 6 age groups. The kidney failure risk was 2.1-2.9 times greater for Blacks and 1.2-2.7 times greater for Hispanics vs. whites. Risk of death before kidney failure was similar for Blacks and only modestly lower for Hispanics vs. whites across ages.

"Following CKD onset, Blacks and Hispanics were 2 times more likely than whites to develop kidney failure, and this was truly driven by a greater risk of kidney failure due to faster decline in kidney function after CKD onset, rather than because of lower risks of death prior to kidney failure," said Dr. Yan. "Delineation and elimination of the causes of faster kidney function declines in Blacks and Hispanics are therefore the appropriate strategies to improve clinical outcomes in Blacks and Hispanics with CKD. Slowing the faster progression in Blacks and Hispanics with CKD should be a major focus in research, practice, and healthcare policy to achieve the goal of reducing the disparities in CKD."

Study: "Mechanism of Higher Incidence of End-Stage Kidney Disease (ESKD) among Blacks and Hispanics versus Whites in the U.S."

ASN Kidney Week 2020 Reimagined, the largest nephrology meeting of its kind, will provide a forum for more than 13,000 professionals to discuss the latest findings in kidney health research and engage in educational sessions related to advances in the care of patients with kidney and related disorders. Kidney Week 2020 Reimagined will take place October 19-October 25.

WHAT:

The plant compound apigenin improved the cognitive and memory deficits usually seen in a mouse model of Down syndrome, according to a study by researchers at the National Institutes of Health and other institutions. Apigenin is found in chamomile flowers, parsley, celery, peppermint and citrus fruits. The researchers fed the compound to pregnant mice carrying fetuses with Down syndrome characteristics and then to the animals after they were born and as they matured. The findings raise the possibility that a treatment to lessen the cognitive deficits seen in Down syndrome could one day be offered to pregnant women whose fetuses have been diagnosed with Down syndrome through prenatal testing. The study appears in the American Journal of Human Genetics.

Down syndrome is a set of symptoms resulting from an extra copy or piece of chromosome 21. The intellectual and developmental disabilities accompanying the condition are believed to result from decreased brain growth caused by increased inflammation in the fetal brain. Apigenin is not known to have any toxic effects, and previous studies have indicated that it is an antioxidant that reduces inflammation. Unlike many compounds, it is absorbed through the placenta and the blood brain barrier, the cellular layer that prevents potentially harmful substances from entering the brain. Compared to mice with Down symptoms whose mothers were not fed apigenin, those exposed to the compound showed improvements in tests of developmental milestones and had improvements in spatial and olfactory memory. Tests of gene activity and protein levels showed the apigenin-treated mice had less inflammation and increased blood vessel and nervous system growth.

The NIH portion of the study was conducted at the National Human Genome Research Institute (NHGRI). Additional funding was provided by the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

WHO:

Diana W. Bianchi, M.D., NICHD Director and senior investigator of the NHGRI Medical Genetics Branch, is available for comment.

ARTICLE:

Guedj, F. et al. Apigenin as a candidate prenatal treatment for Trisomy 21: effects in human amniocytes and the Ts1Cje mouse model. American Journal of Human Genetics. 2020.

ASPB is pleased to announce the publication of noteworthy research investigating water-saving alternatives for photosynthesis in temperate environments, which are likely to become hotter and drier in the future.

Drought causes major crop losses in many regions of the world, and climate change threatens to exacerbate the occurrence of drought in temperate as well as arid regions. In new work published in The Plant Cell, Dr. Nadine Töpfer from the Leibniz Institute of Plant Genetics and Crop Plant Research, along with colleagues from the University of Oxford in the U.K., analyzed the potential for engineering drought-resistant plants via introduction of Crassulacean acid metabolism (CAM). They used a sophisticated mathematical modelling approach to study the effects of introducing CAM photosynthesis, which is used by plants that are able to thrive in arid conditions, into C3 plants, which tend to thrive only in areas where sunlight intensity and temperatures are moderate and water is plentiful.

Most plants, including some major crops such as rice, wheat, oats, and barley, use C3 carbon fixation, in which CO2 taken up during the day through stomatal pores in the leaf is used immediately in light-driven photosynthesis reactions. Unfortunately, this leads to significant water loss through these pores in hot, dry conditions. CAM is an alternative carbon fixation pathway that temporally separates CO2 uptake from carbon fixation, allowing the plant to open stomata for CO2 uptake in the cool of the night and store the carbon internally. The CAM plant then closes its stomata during the heat of the day to minimize water loss, and releases the stored CO2 inside the leaf cells to be used for light-driven photosynthesis during the day.

Using simulations across a range of temperature and relative humidity conditions, the authors asked: Would full CAM or alternative water-saving methods be more productive in settings where C3 crops typically are grown? They found both that vacuolar storage capacity in a leaf is a major factor that limits water-use efficiency during CAM and that the environmental conditions shapes the occurrence of different phases of the CAM cycle. Mathematical modeling also identified an alternative CAM cycle that involves mitochondrial isocitrate dehydrogenase as a potential contributor to initial carbon fixation at night.

Lead author Nadine Töpfer, who did the work during the tenure of a Marie-Curie Postdoctoral Fellowship in Professor Lee Sweetlove's group in Oxford, said: "Modelling is a powerful tool for exploring complex systems and it provides insights that can guide lab and field-based work. I believe that our results will provide encouragement and ideas for the researchers who aim to transfer the water-conserving trait of CAM plants into other species."

Their results revealed not only that the water-saving potential of CAM photosynthesis strongly depends on the environment, with the daytime environment more important than that at night, but also that alternative metabolic modes, distinct from those of the naturally occurring CAM cycle, may be beneficial under certain conditions such as during shorter days with less extreme temperatures. This timely work provides valuable insights that will help us prepare for the challenges of growing food crops in increasingly hot and dry temperate environments.

What The Study Did: This study examined the seropositive prevalence of antibodies against SARS-CoV-2 in Wuhan, China, by sex and age group.

Authors: Yongman Lv, M.D., of the Huazhong University of Science and Technology in Wuhan, China, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.25717)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

HANOVER, N.H. - October 23, 2020 - A phenomenon of quantum mechanics known as superposition can impact timekeeping in high-precision clocks, according to a theoretical study from Dartmouth College, Saint Anselm College and Santa Clara University.

Research describing the effect shows that superposition--the ability of an atom to exist in more than one state at the same time--leads to a correction in atomic clocks known as "quantum time dilation."

The research, published in the journal Nature Communications, takes into account quantum effects beyond Albert Einstein's theory of relativity to make a new prediction about the nature of time.

"Whenever we have developed better clocks, we've learned something new about the world," said Alexander Smith, an assistant professor of physics at Saint Anselm College and adjunct assistant professor at Dartmouth College, who led the research as a junior fellow in Dartmouth's Society of Fellows. "Quantum time dilation is a consequence of both quantum mechanics and Einstein's relativity, and thus offers a new possibility to test fundamental physics at their intersection."

In the early 1900s, Albert Einstein presented a revolutionary picture of space and time by showing that the time experienced by a clock depends on how fast it is moving -- as the speed of a clock increases, the rate at which it ticks decreases. This was a radical departure from Sir Isaac Newton's absolute notion of time.

Quantum mechanics, the theory of motion governing the atomic realm, allows for a clock to move as if it were simultaneously traveling at two different speeds: a quantum "superposition" of speeds. The research paper takes this possibility into account and provides a probabilistic theory of timekeeping, which led to the prediction of quantum time dilation.

To develop the new theory, the team combined modern techniques from quantum information science with a theory developed in the 1980s that explains how time might emerge out of a quantum theory of gravity.

"Physicists have sought to accommodate the dynamical nature of time in quantum theory for decades," said Mehdi Ahmadi, a lecturer at Santa Clara University who co-authored the study. "In our work, we predict corrections to relativistic time dilation which stem from the fact that the clocks used to measure this effect are quantum mechanical in nature."

In the same way that carbon dating relies on decaying atoms to determine the age of organic objects, the lifetime of an excited atom acts as a clock. If such an atom moves in a superposition of different speeds, then its lifetime will either increase or decrease depending on the nature of the superposition relative to an atom moving at a definite speed.

The correction to the atom's lifetime is so small that it would be impossible to measure in terms that make sense at the human scale. But the ability to account for this effect could enable a test of quantum time dilation using the most advanced atomic clocks.

Just as the utility of quantum mechanics for medical imaging, computing, and microscopy, might have been difficult to predict when that theory was being developed in the early 1900s, it is too early to imagine the full practical implications of quantum time dilation.

Boston, Mass. - The COVID-19 pandemic has fundamentally disrupted U.S. healthcare organizations. Hospitals have faced drug and device shortages and created new ICUs overnight. Care plans have evolved out of necessity, and hospitals' carefully constructed patient flow systems were up-ended.

In an article published today in NEJM Catalyst Innovations in Care Delivery, leaders and clinician researchers from Beth Israel Lahey Health (BILH) propose using complexity science -- a field concerned with understanding dynamic, unpredictable systems, such as the human brain, economies or climates -- to identify strategies that healthcare organizations can use to respond better to the ongoing pandemic and to anticipate future challenges to healthcare delivery.

"COVID-19 has been a painful reminder that healthcare -- both as an industry and as a series of complex organizations -- has evolved slowly over time, as have the metrics and models we use to assess quality, safety and accommodate future needs," said lead author Jennifer Stevens, MD, MS, Director of the Center for Healthcare Delivery Science at Beth Israel Deaconess Medical Center (BIDMC), part of Beth Israel Lahey Health. "The principles of complexity science offer three strategies healthcare leaders can employ to manage operations during the COVID-19 pandemic: engaging diverse perspectives in leadership teams, staying open to new metrics, and creating forecasting tools that reflect complex healthcare systems."

Engage diverse thinkers in a dashboard design

Noting that individuals are often unable to see the "big picture" from within a complex system like healthcare, Stevens and colleagues recommend bringing additional, perhaps unexpected voices to leadership teams. For example, while epidemiologists naturally guided healthcare leadership teams in the context of COVID-19, Stevens and colleagues suggest including patient and/or community representatives, physicians from disciplines that may be more tangentially related to the current crisis, or clinical and operations staff from the communities disproportionately affected by the pandemic to crisis response teams. "Voices from these various perspectives can expand the vantage point, allowing healthcare leaders see more of the complex system and implement strategies that anticipate future needs," said Stevens.

Identify metrics that triangulate different sides of a complex healthcare system

Identifying a broader range of relevant metrics can also expand leaderships' view of the complex system. For example, patient demographics were a largely unreported variable early on the in pandemic -- before physicians had a clear picture of how tightly race, ethnicity and other socioeconomic factors were linked to the risk of contracting and dying of COVID-19.

"Having a better understanding about the disparate impact of COVID-19 on communities of color could have helped healthcare leaders better anticipate the flow of patients coming into clinics, well as the implications for clinical staff, and personal protective equipment needs," said Stevens. "Healthcare leaders must be open to new metrics and watchful for undervalued variables, or we may find ourselves so focused on one set of metrics that we miss the significance of more meaningful data."

As an example of a metric with shifting value, Stevens and colleagues described how the significance of the number of patients with COVID-19 in BIDMC's ICU changed as spring turned into summer in 2020. In the spring, patients with COVID-19 presented to the hospital with severe respiratory symptoms and required immediate critical care services. The rising number of patients admitted with COVID-19 meant the hospital would need additional ICU beds and ventilators, personal protective equipment and other healthcare resources.

However, once the state of Massachusetts and the hospital deemed it safe to reinstate urgent and elective procedures as summer began, all patients were tested for COVID-19 upon admission. The universal testing yielded infected but asymptomatic patients who had come to the hospital for reasons unrelated to COVID-19.

"Suddenly, we were admitting asymptomatic patients with COVID-19 who wouldn't require the same resources and care as the patients critically ill with the novel coronavirus," said Stevens. "So the meaning behind the number of COVID-19 patients at BIDMC really shifted over the early months of the pandemic."

Create forecasting tools that reflect healthcare's complex systems

The team also suggests that forecasting tools must truly reflect the complex realties of the COVID-19 pandemic. To build a model that does that, the team used machine learning to pull relevant data from each of the 13 hospitals and three business units that make up the Beth Israel Lahey Health system, rather than depending on published reports from China or Italy. Next, they added publicly available local cellphone data to the model, revealing how much people were moving around and interacting with other people. Taken together, these data sources -- reflecting both shifting local public health policies as well as the shifting new social norms of behavior as the pandemic wore on -- contributed to a model capable of providing timely and locally relevant predictions.

"Our model leverages the principles of complexity to guide hospital leadership, providing weekly updates to a group of healthcare leaders about how and when a new surge of infections may arrive," Stevens said. "Models need to reflect the shifting health and policy landscape - to allow for the complexity of the pandemic itself - for any healthcare organization to meaningful make use of them.

"Healthcare is facing one of its greatest challenges, in part because our comfortably familiar metrics and dashboards, which were designed to handle the problems of a complex system, couldn't see the 'big one' coming," said Kevin Tabb, MD, president and CEO of Beth Israel Lahey Health. "Adapting to new realities that COVID-19 brought to the fore requires that healthcare leaders build new models that reflect the true complexity we are facing, engage new voices, and remain flexible and curious about our metrics. We are still squarely in the middle of this earthquake, and we have many aftershocks ahead."

Women living in poorer households of Dhaka, Bangladesh are unwilling to give birth at maternal healthcare facilities.

A new study, published in PLOS ONE, found that the women living in Dhaka slums were reluctant to use institutionalised maternal health care for fear of having to make undocumented payments, unfamiliar institutional processes, lack of social and family support, matters of honour and shame, a culture of silence and inadequate spousal communication on health issues.

Based on her PhD study undertaken at Flinders University, Associate Professor Sanzida Akhter of Dhaka University and her Flinders University supervisors, Associate Professors Gouranga Dasvarma and Udoy Saikia highlighted the reasons behind these women's reluctance to give birth in hospitals, despite government efforts to expand services across the country.

The authors of the paper say that their research highlights the importance of providing pregnant women with information to help them break free of fears about hospital childbirth, the hidden costs of healthcare and bridging cultural relations with providers.

"Even though low-cost health care facilities may be within their reach in terms of physical distance and affordable, these women and their families are unwilling to deliver their babies at such health facilities," say the authors.

"The financial, physical and social limitations of the women and those of their family members prevent them from seeking maternal health care at health facilities. They do not make any effort to overcome these barriers because they appear to be content with their age-old perception of pregnancy and childbirth as part of nature and not a special event worth giving any special attention to."

The contrast in the practice of maternal healthcare and childbirth between lower and upper socio-economic status women was also identified, with an example where 61% of the richer women opt for Caesarean Section deliveries compared to only 13% of the poorer women.

"This difference in maternal health care services and childbirth practised by the Bangladesh women clearly indicates that childbirth is influenced by a woman's socio-economic status and her cultural perception of childbirth."

The study also found poor behaviour by doctors and a lack of interpersonal communication with healthcare providers added to the pregnant women's reluctance to rely on traditional medical options.

"The women rightly expect to be treated respectfully and get information explained to them clearly but when their expectations aren't fulfilled, they rejected the thought of going there again. This is a situation, where 'interpersonal relations' go beyond simply only providing accurate information."

BUFFALO, N.Y. - The prescription of potentially inappropriate medications to older adults is linked to increased hospitalizations, and it costs patients, on average, more than $450 per year, according to a new University at Buffalo study.

The research, which sought to determine the impact of potentially inappropriate medications on health care utilization and costs in the United States, also found that more than 34% of adults age 65 and older were prescribed these problematic drugs.

"Although efforts to de-prescribe have increased significantly over the last decade, potentially inappropriate medications continue to be prescribed at a high rate among older adults in the United States," says David Jacobs, PharmD, PhD, lead investigator and assistant professor of pharmacy practice in the UB School of Pharmacy and Pharmaceutical Sciences.

Collin Clark, PharmD, first author on the paper and clinical assistant professor in the School of Pharmacy and Pharmaceutical Sciences, adds, "The average age of the U.S. population is rising, and older adults account for a disproportionate amount of prescription medications. Harm to older adults caused by potentially inappropriate medications is a major public health challenge."

As the human body ages, the risk of experiencing harmful side effects from medications increases. Potentially inappropriate medications are drugs that should be avoided by older adults due to these risks outweighing the benefits of the medication, or when effective but lower risk alternative treatments are available.

The study, which was published in August in the Journal of the American Geriatrics Society, used the 2011-2015 Medical Expenditure Panel Survey - conducted annually by the U.S. Public Health Service and the Centers for Disease Control and Prevention (CDC) - to examine the prescription of 33 potentially inappropriate medications or classes of medications to adults 65 and older.

Among the potentially inappropriate medications examined were antidepressants, barbiturates, androgens, estrogens, nonsteroidal anti-inflammatory drugs, first-generation antihistamines, and antipsychotics.

Among the 218 million-plus older adults surveyed, more than 34% were prescribed at least one potentially inappropriate medication. Those patients were, on average, prescribed twice as many drugs, were nearly twice as likely to be hospitalized or visit the emergency department, and were more likely to visit a primary care physician compared to older adults who were not prescribed potentially inappropriate medication.

Patients who received these medications also spent an additional $458 on health care, including an extra $128 on prescription drugs.

"De-prescribing is currently at an early stage in the United States. Further work is needed to implement interventions that target unnecessary and inappropriate medications in older adults," says Jacobs.