Nuclear quantum effects in liquid water from path-integral simulations using an ab initio force matching approach

We have applied path integral simulations, in combination with new ab initio based water potentials, to investigate nuclear quantum effects in liquid water. Because direct ab initio path integral simulations are computationally expensive, a flexible water model is parameterized by force-matching to density functional theory-based molecular dynamics simulations. The resulting effective potentials provide an inexpensive replacement for direct ab inito molecular dynamics simulations and allow efficient simulation of nuclear quantum effects. Static and dynamic properties of liquid water at ambient conditions are presented and the role of nuclear quantum effects, exchange-correlation functionals and dispersion corrections are discussed in regards to reproducing the experimental properties of liquid water.Comment: 15 pages, 11 figures, 2 table

Ventricular Tachycardia in the Absence of Structural Heart Disease

In up to 10% of patients who present with ventricular tachycardia (VT), obvious structural heart disease is not identified. In such patients, causes of ventricular arrhythmia include right ventricular outflow tract (RVOT) VT, extrasystoles, idiopathic left ventricular tachycardia (ILVT), idiopathic propranolol-sensitive VT (IPVT), catecholaminergic polymorphic VT (CPVT), Brugada syndrome, and long QT syndrome (LQTS). RVOT VT, ILVT, and IPVT are referred to as idiopathic VT and generally do not have a familial basis. RVOT VT and ILVT are monomorphic, whereas IPVT may be monomorphic or polymorphic. The idiopathic VTs are classified by the ventricle of origin, the response to pharmacologic agents, catecholamine dependence, and the specific morphologic features of the arrhythmia. CPVT, Brugada syndrome, and LQTS are inherited ion channelopathies. CPVT may present as bidirectional VT, polymorphic VT, or catecholaminergic ventricular fibrillation. Syncope and sudden death in Brugada syndrome are usually due to polymorphic VT. The characteristic arrhythmia of LQTS is torsades de pointes. Overall, patients with idiopathic VT have a better prognosis than do patients with ventricular arrhythmias and structural heart disease. Initial treatment approach is pharmacologic and radiofrequency ablation is curative in most patients. However, radiofrequency ablation is not useful in the management of inherited ion channelopathies. Prognosis for patients with VT secondary to ion channelopathies is variable. High-risk patients (recurrent syncope and sudden cardiac death survivors) with inherited ion channelopathies benefit from implantable cardioverter-defibrillator placement. This paper reviews the mechanism, clinical presentation, and management of VT in the absence of structural heart disease

Prescribing unproven cancer drugs: Physician perspectives on expanded access and right to try

BACKGROUND: For gravely ill patients who have no treatment options and who are ineligible for clinical trials, the US Food and Drug Administration (FDA) established the Expanded Access Program (EAP). Motivated by efforts to weaken FDA regulation and sold as providing greater access to experimental drugs, the federal Right to Try Act (RTT) was passed in 2017. It reduces FDA oversight by not requiring physicians to report safety data and foregoes approval of protocols by local institutional review boards. METHODS: This study explored the views of 17 neuro-oncologists from 15 different academic medical centers with varying experience with EAP and RTT using convenience sampling. We conducted semi-structured interviews and qualitative analysis to identify emerging themes. RESULTS: Most oncologists were confused between the two pathways, had little familiarity with RTT, and had little knowledge about experimental medicine available through either pathway. Oncologists reported a preference of enrolling patients in clinical trials over off-trial preapproval pathways with scant data. As a result, oncologists revealed concerns over properly evaluating risks for their patients. CONCLUSION: Our findings suggest that neuro-oncologists need better resources and clearer mechanisms at their institutions to help navigate EAP and RTT in order to counsel patients interested in experimental medicine

DNA Fingerprinting of Mycobacterium tuberculosis: Lessons Learned and Implications for the Future

DNA fingerprinting of Mycobacterium tuberculosis—a relatively new laboratory technique—offers promise as a powerful aid in the prevention and control of tuberculosis (TB). Established in 1996 by the Centers for Disease Control and Prevention (CDC), the National Tuberculosis Genotyping Surveillance Network was a 5-year prospective, population-based study of DNA fingerprinting conducted from 1996 to 2000. The data from this study suggest multiple molecular epidemiologic and program management uses for DNA fingerprinting in TB public health practice. From these data, we also gain a clearer understanding of the overall diversity of M. tuberculosis strains as well as the presence of endemic strains in the United States. We summarize the key findings and the impact that DNA fingerprinting may have on future approaches to TB control. Although challenges and limitations to the use of DNA fingerprinting exist, the widespread implementation of the technique into routine TB prevention and control practices appears scientifically justified

1970 Problems in Legal Education

Five problems in legal education, much discussed recently, were posed by the Editors of this Review to a number of administrative figures in the law school world. These questions were and are frankly difficult and controversial, but their answers are important to our system of legal education and to our society. Capsule answers given by these concerned legal education administrators are believed to be interesting and significant. Each is a personal rather than a representative opinion. Brief answers such as these, of course, are not expected to be, nor do they pretend to be, complete or profound. Their purpose is to indicate succinctly the approach of some law school administrative opinion makers to difficult policy problems of legal education

1970 Problems in Legal Education

Five problems in legal education, much discussed recently, were posed by the Editors of this Review to a number of administrative figures in the law school world. These questions were and are frankly difficult and controversial, but their answers are important to our system of legal education and to our society. Capsule answers given by these concerned legal education administrators are believed to be interesting and significant. Each is a personal rather than a representative opinion. Brief answers such as these, of course, are not expected to be, nor do they pretend to be, complete or profound. Their purpose is to indicate succinctly the approach of some law school administrative opinion makers to difficult policy problems of legal education

Democracy Derived? New Trajectories in Pluripotent Stem Cell Research

How has the development of human induced pluripotent stem cells (hiPSCs) modified the trajectory of stem cell research? Here, coauthorship networks of stem cell research articles and analysis of cell lines used in stem cell research indicate that hiPSCs are not replacing human embryonic stem cells, but instead, the two cell types are complementary, interdependent research tools. Thus, we conclude that a ban on funding for embryonic stem cell research could have unexpected negative ramifications on the nascent field of hiPSCs