Neural network based path collective variables for enhanced sampling of phase transformations

We propose a rigorous construction of a 1D path collective variable to sample structural phase transformations in condensed matter. The path collective variable is defined in a space spanned by global collective variables that serve as classifiers derived from local structural units. A reliable identification of local structural environments is achieved by employing a neural network based classification. The 1D path collective variable is subsequently used together with enhanced sampling techniques to explore the complex migration of a phase boundary during a solid-solid phase transformation in molybdenum

Where Is the There in Health Law - Can It Become a Coherent Field

Gerturde Stein complained of Oakland, There is no there there. Churchill complained of his pudding that it has no theme. And everybody complains of health law that it lacks an organizing principle. Health law scholars bemoan the pathologies of health law and its contradictory and competing paradigms\u27. which form a chaotic, dysfunctional patchwork. But it should not surprise us that any field which grows by accretion lacks a unifying idea or animating concern. And health law certainly grew by accretion. It began in the 1960s, when the Law-Medicine Center was established, concerned with medical proof in litigation, physicians\u27 malpractice, and public-health regulation. During the 1970s, bioethics was taken into the fold. And in the 1980s, economic and regulatory topics gained prominence in the field. Health law, then, is more the creature of history than of systematic and conceptual organization. It looks hardly more cohesive than a law of horses. As Judge Easterbrook once quipped about cyberlaw: Lots of cases deal with sales of horses; others deal with people kicked by horses; still more deal with the licensing and racing of horses, or with the care veterinarians give to horses, or with prizes at horse shows. Any effort to collect these strands into a course on \u27The Law of the Horse\u27 is doomed to be shallow and to miss unifying principles

When Patients Say No (To Save Money): an Essay on the Tectonics of Health Law.

The ultimate aim of health care public policy is good care at good prices. Managed care stalled at achieving this goal by trying to influence providers, so health policy has turned to the only market-based option left: treating patients like consumers. Health insurance and tax policy are now pressuring patients to spend their own money when they select health plans, providers, and treatments. Expecting patients to choose what they need at the price they want, consumerists believe that market competition will constrain costs while optimizing quality. This classic form of consumerism is today\u27s watchword. This Article evaluates this ideal type of consumerism and the regulatory mechanism of which it is essentially an example-legally mandated disclosure of information. We do so by assessing the crucial assumptions about human nature on which consumerism and mandated disclosure depend Consumerism operates in a variety of contexts in a variety of ways with a variety of aims. To assess so protean a thing, we ask what a patient\u27s life would really be like in a consumerist world. The literature abounds in suppositions about how medical consumers should behave. We look for empirical evidence about how real people actually buy health plans, choose providers, and select treatments. We conclude that consumerism, and thus mandated disclosure generally, are unlikely to accomplish the goals imagined for them. Consumerism\u27s prerequisites are too many and too demanding. First, consumers must have choices that include the coverage, care-takers, and care they want. Second, reliable information about those choices must be available. Third, information must be put before consumers, especially by doctors. Fourth, consumers must receive the information. Fifth, the information must be complete and comprehensible enough for consumers to use it. Sixth, consumers must understand what they are told. Seventh, consumers must be willing to analyze the information. Eighth, consumers must actually analyze the information and do so well enough to make good choices. Our review of the empirical evidence concludes that these prerequisites cannot be met reliably most of the time. At every stage people encounter daunting hurdles. Like so many other dreams of controlling costs and giving patients control, consumerism is doomed to disappoint. This does not mean that consumerist tools should never be used It means they should not be used unadvisedly or lightly, but discreetly, advisedly, soberly, and in the fear of error

Where is the There in Health Law? Can it Become a Coherent Field?

Gerturde Stein complained of Oakland, There is no there there. Churchill complained of his pudding that it has no theme. And everybody complains of health law that it lacks an organizing principle. Health law scholars bemoan the pathologies of health law and its contradictory and competing paradigms\u27. which form a chaotic, dysfunctional patchwork. But it should not surprise us that any field which grows by accretion lacks a unifying idea or animating concern. And health law certainly grew by accretion. It began in the 1960s, when the Law-Medicine Center was established, concerned with medical proof in litigation, physicians\u27 malpractice, and public-health regulation. During the 1970s, bioethics was taken into the fold. And in the 1980s, economic and regulatory topics gained prominence in the field. Health law, then, is more the creature of history than of systematic and conceptual organization. It looks hardly more cohesive than a law of horses. As Judge Easterbrook once quipped about cyberlaw: Lots of cases deal with sales of horses; others deal with people kicked by horses; still more deal with the licensing and racing of horses, or with the care veterinarians give to horses, or with prizes at horse shows. Any effort to collect these strands into a course on \u27The Law of the Horse\u27 is doomed to be shallow and to miss unifying principles

Patients as Consumers: Courts, Cotnracts, and the New Medical Marketplace

The persistent riddle of health-care policy is how to control the costs while improving the quality of care. The riddle\u27s oncepromising answer-managed care-has been politically ravaged, and consumerist solutions are now winning favor This Article examines the legal condition of the patient-as-consumer in today\u27s health-care market. It finds that insurers bargain with some success for rates for the people they insure. The uninsured, however, must contract to pay whatever a provider charges and then are regularly charged prices that are several times insurers\u27pricesa nd providers\u27 actual costs. Perhaps because they do not understand the healthcare market, courts generally enforce these contracts. This Article proposes legal solutions to the plight of the patient-as-consumer and asks what that plight tells us about market solutions to the health-care quandary

Can Consumers Control Health-Care Costs?

The ultimate aim of health care policy is good care at good prices. Managed care failed to achieve this goal through influencing providers, so health policy has turned to the only market-based option left: treating patients like consumers. Health insurance and tax policy now pressure patients to spend their own money when they select health plans, providers, and treatments. Expecting patients to choose what they need at the price they want, consumerists believe that market competition will constrain costs while optimizing quality. This classic form of consumerism is today’s health policy watchword. This article evaluates consumerism and the regulatory mechanism of which it is essentially an example – legally mandated disclosure of information. We do so by assessing the crucial assumptions about human nature on which consumerism and mandated disclosure depend. Consumerism operates in a variety of contexts in a variety of ways with a variety of aims. To assess so protean a thing, we ask what a patient’s life would really be like in a consumerist world. The literature abounds in theories about how medical consumers should behave. We look for empirical evidence about how real people actually buy health plans, choose providers, and select treatments. We conclude that consumerism is unlikely to accomplish its goals. Consumerism’s prerequisites are too many and too demanding. First, consumers must have choices that include the coverage, care-takers, and care they want. Second, reliable information about those choices must be available. Third, information must be put before consumers in helpful ways, especially by doctors. Fourth, the information must be complete and comprehensible enough for consumers to use it. Fifth, consumers must understand what they are told. Sixth, consumers must actually analyze the information and do so well enough to make good choices. Our review of the empirical evidence concludes that these prerequisites cannot be met reliably most of the time. At every stage people encounter daunting hurdles. Like so many other dreams of controlling costs and giving patients control, consumerism is doomed to disappoint. This does not mean that consumerist tools should never be used. If all that consumerism accomplished is to raise general cost-consciousness among patients, still, it could make a substantial contribution to the larger cost-control efforts by insurers and the government. Once patients bear responsibility for much dayto-day spending on their health needs, they should be increasingly sensitized to the difficult trade-offs that abound in medical care and might even begin to understand that public and private health insurers have a legitimate interest in controlling medical spending

Use of Stand-Biased Desks to Reduce Sedentary Time in High School Students: A Pilot Study

Background: The purpose of this pilot study was to identify differences between sitting and standing time in high school students’ pre and post stand-biased desk intervention. Methods: ActivPal3™ activity monitors were affixed to 25 Bryan Collegiate High School students’ to monitor their standing time and activity levels. Data were collected at the beginning of the school year (fall) in traditional seated desks and in the spring in stand-biased desks. After attrition, 18 of the original 25 students were included in the final analysis. The physical activity data (steps) as well as standing and sitting time data provided by the monitors was used for within subject intervention analyses. Results: Descriptive statistics and a two-sided t-test were used to analyse differences between pre and post intervention sitting and standing times. Analysis indicated a significant reduction of sitting time post stand-biased desk intervention (p<0.0001) and a significant increase in standing time, post stand-biased desk intervention (p<0.0001). Analysis also revealed a non-statistically significant (p < 0.0619) average increase of 2,286 steps per school day when comparing mean steps pre-intervention (6,612) and post-intervention (8,898). Conclusions: Standing desks have the potential to reduce sedentary behavior and increase light to moderate physical activity for high school students during the school day

TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death

Abstract Sigma-2 receptors have been implicated in both tumor proliferation and neurodegenerative diseases. Recently the sigma-2 receptor was identified as transmembrane protein 97 (TMEM97). Progesterone receptor membrane component 1 (PGRMC1) was also recently reported to form a complex with TMEM97 and the low density lipoprotein (LDL) receptor, and this trimeric complex is responsible for the rapid internalization of LDL. Sigma-2 receptor ligands with various structures have been shown to induce cell death in cancer cells. In the current study, we examined the role of TMEM97 and PGRMC1 in mediating sigma-2 ligand-induced cell death. Cell viability and caspase-3 assays were performed in control, TMEM97 knockout (KO), PGRMC1 KO, and TMEM97/PGRMC1 double KO cell lines treated with several sigma-2 ligands. The data showed that knockout of TMEM97, PGRMC1, or both did not affect the concentrations of sigma-2 ligands that induced 50% of cell death (EC50), suggesting that cytotoxic effects of these compounds are not mediated by TMEM97 or PGRMC1. Sigma-1 receptor ligands, (+)-pentazocine and NE-100, did not block sigma-2 ligand cytotoxicity, suggesting that sigma-1 receptor was not responsible for sigma-2 ligand cytotoxicity. We also examined whether the alternative, residual binding site (RBS) of 1,3-Di-o-tolylguanidine (DTG) could be responsible for sigma-2 ligand cytotoxicity. Our data showed that the binding affinities (K i) of sigma-2 ligands on the DTG RBS did not correlate with the cytotoxicity potency (EC50) of these ligands, suggesting that the DTG RBS was not fully responsible for sigma-2 ligand cytotoxicity. In addition, we showed that knocking out TMEM97, PGRMC1, or both reduced the initial internalization rate of a sigma-2 fluorescent ligand, SW120. However, concentrations of internalized SW120 became identical later in the control and knockout cells. These data suggest that the initial internalization process of sigma-2 ligands does not appear to mediate the cell-killing effect of sigma-2 ligands. In summary, we have provided evidence that sigma-2 receptor/TMEM97 and PGRMC1 do not mediate sigma-2 ligand cytotoxicity. Our work will facilitate elucidating mechanisms of sigma-2 ligand cytotoxicity

Neuroanatomy of the Subadult and Fetal Brain of the Atlantic White-Sided Dolphin (Lagenorhynchus acutus) from In Situ Magnetic Resonance Images

This article provides the first anatomically labeled, magnetic resonance imaging (MRI) -based atlas of the subadult and fetal Atlantic white-sided dolphin (Lagenorhynchus acutus) brain. It differs from previous MRI-based atlases of cetaceans in that it was created from images of fresh, postmortem brains in situ rather than extracted, formalin-fixed brains. The in situ images displayed the classic hallmarks of odontocete brains: fore-shortened orbital lobes and pronounced temporal width. Olfactory structures were absent and auditory regions (e.g., temporal lobes and inferior colliculi) were enlarged. In the subadult and fetal postmortem MRI scans, the hippocampus was identifiable, despite the relatively small size of this structure in cetaceans. The white matter tracts of the fetal hindbrain and cerebellum were pronounced, but in the telencephalon, the white matter tracts were much less distinct, consistent with less myelin. The white matter tracts of the auditory pathways in the fetal brains were myelinated, as shown by the T2 hypointensity signals for the inferior colliculus, cochlear nuclei, and trapezoid bodies. This finding is consistent with hearing and auditory processing regions maturing in utero in L. acutus, as has been observed for most mammals. In situ MRI scanning of fresh, postmortem specimens can be used not only to study the evolution and developmental patterns of cetacean brains but also to investigate the impacts of natural toxins (such as domoic acid), anthropogenic chemicals (such as polychlorinated biphenyls, polybrominated diphenyl ethers, and their hydroxylated metabolites), biological agents (parasites), and noise on the central nervous system of marine mammal species