bluuebunny/crossref_metadata_2025 huggingface dataset:
Biology and the Bill of Rights: Can Science Reframe the Constitution?
Authors: Jasanoff Sheila
Published: February 2021

The American public firmly believes both in the rule of law and in the progressive and beneficial effects of science. Public opinion polls show that legal and scientific institutions continue to command wide respect, even in a period of diminished trust. According to a recent survey conducted by the Office of Technology Assessment (OTA), the Supreme Court and the scientific community each received higher confidence ratings than political institutions, the media, education, and even organized religion. Yet the impacts of science and the law can at times be profoundly antithetical, for the former acts as a force for social transformation, while the latter seeks to maintain the stability and continuity of societal institutions and norms of conduct. Vannevar Bush's famous metaphor “the endless frontier“ captured the sense of limitless aspiration associated with science and technology through much of this century.
Medicare Reimbursement of Financial Transactions: Do Present Policies Promote Efficiency?
Authors: Morrison Kenneth P.
Published: February 2021

The Secretary of Health and Human Services denies Medicare reimbursement for certain indirect costs associated with health care delivery. This Note reviews arguments supporting and opposing reimbursement of costs that providers incur in three common financial transactions: the use of equity capital, acquisition of providers, and loan financing. The Note considers the Secretary’s regulations in light of the congressional mandate to encourage efficient delivery of health care and concludes that current reimbursement policy promotes inefficiency.
Biological Monitoring: The Employer's Dilemma
Authors: Miller Frances H.
Published: February 2021

The industrial workplace contains many potential health hazards that not only can cause great harm to workers, but also can destroy the employers’ economic stability. Often these hazards are documented and dealt with, but frequently they are unknown. When health-conscious employers monitor the physical well-being of their employees in an effort to avoid the terrible personal and economic costs these hazards can produce, they may be supplying their employees with the documentation necessary to recover financially for their industrial illnesses.

This Article analyzes this dilemma confronting employers. It describes the many factors employers must consider when deciding whether to institute a monitoring process that takes full advantage of technological developments in medical care. The Article suggests an approach employers may take until some of the disincentives surrounding the implementation of monitoring are removed.
The WHO European Program of Health Legislation and the Health for All Policy
Authors: Pinet Geneviève
Published: February 2021

The purpose of this paper is to provide a comprehensive review of the work of the World Health Organization (WHO), begun a decade ago in Europe, in the field of health legislation. This program is the result of the interaction between two important factors: the trends in national health policy and legislation at the country level, and the implementation of the Health for All policy, which has been collectively adopted by the European Member States in various WHO fora.

Health legislation has proved to be a valuable tool in supporting National Health Policies in European countries and a key element in international health activities. The paper will be presented in three main parts. The first examines the legislative implications of the Health for All policy and strategy. The second gives an overview of developments in health legislation in Europe, focusing on national achievements in three areas in which change is necessary to achieve Health for All: health care systems, the environment, and lifestyles. The third part gives an account of activities carried out by the Regional Office for Europe of WHO in the health legislation field, recalls the organization of the first WHO medium-term program in this field, and summarizes its four current subprograms on health policy, health situation, exchange of information, and training. The conclusion briefly outlines the prospects for further developments in Europe.
AIDS Prevention: Legislative Options
Authors: Clark Mary E.
Published: February 2021

This article reviews legislative options to prevent the transmission of HIV infection. It distinguishes between pre-exposure measures designed to prevent intitial exposure, and post-exposure measures aimed at preventing infected individuals from exposing others. Part I identifies education as the key component of a comprehensive prevention program, and reviews options for pre-exposure education programs designed to avoid or minimize exposure. Part II reviews post-exposure prevention measures, focusing on reporting and contact tracing provisions. Mandatory reporting by name of individuals testing HIV positive and mandatory contact tracing are opposed as counterproductive prevention measures; voluntary partner notification is supported. Part III examines various prevention efforts for settings where there may be either a real or perceived risk of transmission of HIV infection. Part IV sets out conclusions.
Surrogate Mothers: Whose Baby Is It?
Authors: Cohen Barbara
Published: February 2021

Advances in medical technology offer infertile couples who wish to raise children alternatives to adoption. The increasing number of surrogate mother contracts creates a myriad of legal issues surrounding the rights of the natural mother, the natural father and die child that is produced. In this Article, the Author discusses the legal issues and rights of the parties under the Constitution, the surrogate contract and family law principles. The Author proposes that courts should consider a surrogate contract as a revocable prebirdi agreement which allows the natural mother to keep the child if she chooses. In addition, die Audior advocates an interpretation of the statutes forbidding baby selling that would prohibit surrogate contracts in which the mother is paid a fee for the child.
Legal Recourse for the Cancer Patient-Returnee: The Rehabilitation Act of 1973
Authors: Sigel Carin J.
Published: February 2021

Recent advances in medical research have dramatically improved the survival rate for individuals with a history of cancer. Large numbers of these “cancer patient-returnees” encounter job discrimination since many employers believe that to hire or maintain them would pose substantial future business risks. This Note argues that cancer patientreturnees may seek relief under the Rehabilitation Act of 1973. The Note concludes that an employer's costs arising out of future risks are too insignificant to justify denial of job opportunities to cancer patientreturnees under the Act.
The Physician Self-Referral Dilemma: Enforcing Antitrust Law as a Solution
Authors: Mathews Julie E.
Published: February 2021

As health care reform pervades the United States, lawmakers have subjected physician self-referrals to heightened scrutiny. Recent evidence indicates that sending patients to facilities in which a physician has an ownership interest often causes overutilization, overpricing, and lower quality of care. This Note analyzes how physician self-referral arrangements can have negative effects on competition. To combat the adverse effects, the Note examines how enforcing antitrust laws can ameliorate the self-referral dilemma and aid in restoring competition to the health care market. This solution will maintain the doctor's right to invest while protecting the patient's vulnerability.
The Virtual Health Economy: Telemedicine and the Supply of Primary Care Physicians in Rural America
Authors: McCarthy Daniel
Published: February 2021

For years, people living in rural areas have struggled unsuccessfully to attract and retain primary care physicians to supply basic medical care to their residents. Rural areas continue to suffer from chronic shortages of physicians and mid-level practitioners, as well as high rates of hospital closures and increased levels of uninsurance and underinsurance, reducing both the physical and financial health of these communities. Physical and economic barriers unique to rural areas block the adequate delivery of health care and contribute to this shortage of health care personnel.

Although Congress has made some progress in identifying where health care shortages occur, it has not adequately identified the source of the shortages, and thus, it has not been able to find adequate solutions to rural health care ills. Past legislative action has involved identifying shortage areas and then providing financial incentives to attract physicians and increase the financial health of hospitals by subsidizing the difference between rural America's ability to pay and what physicians are willing to accept.
The Conversion Conundrum: The State and Federal Response to Hospitals’ Changes in Charitable Status
Authors: Singer Lawrence E.
Published: February 2021

The pressures encountered by hospitals in the current era of reimbursement declines and stiffened competition are well known. As the “ultimate” payors—primarily employers and government—aggressively continue to seek low cost care, the response of the hospital industry has been to move toward consolidation and efficiency-enhancing mechanisms.

Increasingly, nonprofit, tax-exempt hospitals have come to believe that they are at a significant disadvantage vis-á-vis their for-profit brethren in their ability to attract the capital needed to compete in the market. A growing trend among nonprofit hospitals, therefore, is to sell to or enter into a joint venture with a proprietary organization, or alternatively to convert to for-profit status. In 1995, fifty-eight nonprofit hospitals became for-profit; hospital conversions to for-profit status in 1996 are projected to outstrip the pace established the prior year.

The conversion trend has not gone unnoticed at the state level. Recently, several states have proposed or enacted laws regulating sales and conversions of nonprofit hospitals, and many more states are contemplating such legislation.
ERISA Preemption and Regulation of Managed Health Care: The Case for Managed Federalism
Authors: Farrell Margaret G.
Published: February 2021

The result ERISA compels us to reach means that the Corcorans [who lost their unborn child allegedly as a result of United Healthcare’s negligent determination that hospitalization was not medically necessary] have no remedy, state or federal, for what may have been a serious mistake. This is troubling....

In the words of its sponsor, Senator Jacob Javits, the Employee Retirement Income Security Act (ERISA) was enacted in 1974 “to maintain the voluntary growth of private [pension and employee benefit] plans while at the same time making needed structural reforms in such areas as vesting, funding, termination, etc. so as to safeguard workers against loss of their earned or anticipated benefits....” Ironically, one of ERISA’s provisions—its indeterminate provision for the preemption of state law—has probably created more uncertainty about the adequacy and security of health care benefits than any other piece of legislation. Neither ERISA nor any other federal statute comprehensively regulates the content of employer provided health care plans, including benefits provided through managed care organizations (MCOs).
Resource Allocation in the National Health Service
Authors: Newdick Christopher
Published: February 2021

In the United Kingdom, how does the National Health Service (NHS or the Service) respond to the pressures imposed on it by patients, doctors and the government? What techniques for distributing resources have been adopted for managing these pressures? Part I of this Article explains the administrative evolution of the NHS. Part II discusses the legal framework surrounding the allocation of resources throughout the different tiers of the NHS: (1) from the Secretary of State for Health to health authorities, (2) from health authorities to hospitals and general practitioners (GPs), and (3) from doctors to patients. Part III comments on the case for a standing committee to advise the government on matters of resource allocation within the NHS. It also considers the legal, political, and managerial contributions to the debate and, in particular, comments on the future of the traditional notion of clinical freedom.

Section A describes the culture that developed within the NHS, Section B discusses the pressure for reform that developed during the 1980s, and Section C reviews the system of the “internal market” for health that was introduced in 1990.
Vicarious Liability: Relocating Responsibility For The Quality Of Medical Care
Authors: Havighurst Clark C.
Published: February 2021

Managed health care has recently generated a great deal of distrust, even anger, in the public mind. To be sure, much of this public reaction is based on anecdotal evidence and one-dimensional thinking. But many unbiased experts observing managed care today are themselves unhappy with the health care industry's performance. While these observers find little justification for the current political backlash against managed care, they are also disappointed that today's health plans have not made a more positive difference. Indeed, informed observers commonly regret that the new arrangements for the financing and delivery of care have done so little to get physicians to adopt truly efficient practices, achieving not only cost reductions but also substantial improvements in health status and patient outcomes— that is, in the quality of care. Although managed care has not demonstrably harmed the overall quality of health care in the United States, it has done little to improve it.
Broadcasting Clinical Guidelines on the Internet: Will Physicians Tune In?
Authors: Furrow Barry R.
Published: February 2021

Modern American medicine is far from ideal. Physicians practice by rules learned in medical school, rules often based on anecdotes or untested hypotheses. Medical opinion leaders shape practice by their own experience even though anecdotes are no substitute for clinical studies. Pressures to diagnose and treat come from pharmaceutical companies, equipment manufacturers, hospitals and managed care organizations (MCOs). The end result is often too much medicine or too little, but rarely the appropriate amount. Patients can end up suffering iatrogenic effects of infections picked up during hospital stays, complications from surgery or drug side effects or “cascade effects” that occur when several interventions fail in succession.
Alternative Medicine's Roadmap to Mainstream
Authors: Josefek Kristen J.
Published: February 2021

Alternative medicine has been rapidly expanding as consumers drive the demand for more cost-effective, accessible and individualized healthcare. A commonly cited survey in the New England Journal of Medicine (NEJM) found that more Americans were consulting alternative care providers than allopathic/conventional physicians. In 1998, David Eisenberg published a follow up to this landmark survey, showing a marked increase in both the use of alternative care and the number of individuals seeking such care. The study revealed that 42.1% of Americans consulted at least 1 of 16 alternative therapies during 1997, an increase from 33.8% in 1990. Total visits to alternative practitioners soared from 427 million in 1990 to 629 million in 1997. This explosion of alternative care in the United States has begun to force prominent medical schools across the country to offer courses in alternative medical techniques. Over seventy-five major medical schools have begun to teach courses in alternative modalities. Moreover, the alternative care industry has established several journals to cover its expanding field.
A Right to Personal Assistance Services: “Most Integrated Setting Appropriate” Requirements and the Independent Living Model of Long-term Care
Authors: Batavia Andrew I.
Published: February 2021

The United States is currently entering a period in which the demand for longterm care services is growing at a particularly rapid rate; it is projected that the inflation-adjusted expenditures for long-term care will double between 1993 and 2018. As the population continues to age and become more chronically ill and disabled, the need to expand our long-term care capacity, and the long-term care options available, has become self-evident. The question is how we can meet this need in a cost-effective manner that is satisfactory to the consumer of services.
Medical Records and Your Privacy: Developing Federal Legislation to Protect Patient Privacy Rights
Authors: Hussong Sharon J.
Published: February 2021

In 1997, Judi Selig, a secretary for a South Carolina machinery firm, probably did not anticipate her employer's extreme reaction to her medical history. When her employer discovered that Ms. Selig had been exposed to hepatitis several years before, it demanded that she undergo a blood test and sign a medical release form so that the doctors in the employer's health plan could access her records. When Ms. Selig consented to the test but refused to sign the release form, her employer punished her by suspending her for a week without pay. Ms. Selig quit the company mainly because it threatened her privacy.
Medicare Play-by-Play: A Review of Theodore Marmor's The Politics of Medicare
Authors: Thompson John Larkin
Published: February 2021

For at least seven decades the issue of financing health care has been debated in this country. While the intensity of the battle has varied greatly, the underlying drive for reform has been well identified and remarkably consistent. Theodore Marmor's The Politics of Medicare is an exceptional book which documents this period.

In its most general description the era has experienced persistent and growing support for financing reform that would have, at least, characteristics of universality, comprehensive coverage and delivery by a system capable of serving many diverse constituencies. Nothing in these attributes is novel, and each can be identified as present, to varying degrees, in health care financing systems operating throughout the industrial world. Broad goals always attract advocates of every stripe, but the scene changes rapidly when the process of definition commences. Even the most obvious component, universality, precipitates a conflict when the details of exactly who will be included in the covered population start to be hammered out. Endless examples of intense controversy exist over access to federal, state and local programs by the many different categories of individuals who live within this country.
The Genetic Revolution at Work: Legislative Efforts to Protect Employees
Authors: Roche Patricia A.
Published: February 2021

In justifying the cost of the Human Genome Project, supporters predicted fantastic benefits would result from decoding the human genome: cures for fatal diseases, effective treatments for common illnesses burdening individuals and society and a greater understanding of ourselves as human beings. Fear that genetic information will be misused to harm individuals, however, casts a shadow over this glowing portrait of the future of genomic medicine. Over the last decade, these concerns have led approximately twenty-six states to enact genetic nondiscrimination laws. Although no similar law has been passed by Congress, many, including Francis Collins, Director of the National Center for Human Genome Research, have repeatedly endorsed proposed federal legislation aimed at prohibiting health insurers and employers from using predictive genetic information. The result has been growing bipartisan support for The Genetic Nondiscrimination in Health Insurance and Employment Act introduced in February of 2001 by Representative Louise Slaughter in the House and by Senators Kennedy and Daschle in the Senate.
The Class Action Suit As a Method of Patient Empowerment in the Managed Care Setting
Authors: Cerminara Kathy L.
Published: February 2021

The American health care system has undergone tremendous transformation over the past few decades. The fee-for-service (FFS) health care system in which physicians enjoyed a great deal of autonomy has become a managed care system in which cost and utilization considerations play a larger role in physician decision making. Although physicians and other health care professionals are still patient advocates, this role often results in a conflict between their own economic interests and their duties to their patients.

Rather than depending on self-sacrificing health care professionals to advocate for them, patients need to assert their own power in the managed care arena. One way to gain such power is to use the class action device in litigation aimed at improving medical care quality, cost and access. Class actions, in fact, are likely to proliferate as managed care organizations (MCOs) grow and affect more patients’ lives. There are well-recognized dangers to using the class action device, but if used properly, it could prove a valuable remedy for patients.
The Private Insurance Industry’s Tactics Against Suspected Homosexuals: Redlining Based on Occupation, Residence and Marital Status
Authors: Chi-Wen Li Katy
Published: February 2021

Society has long associated acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) with homosexual men. One reason for this association is the statistics that establish a close connection between the homosexual lifestyle and HIV infection and AIDS. While there are an abundance of statistics and widespread perceptions that indicate a strong correlation between AIDS and HIV and homosexual males, there are statistical justifications that oppose the assertion. According to projections, the majority of gay and bisexual men will not develop AIDS. Reports show that in many foreign countries, AIDS is largely a heterosexual phenomenon. In addition, the percentage of AIDS cases resulting from transmission through heterosexual contact is rising dramatically. Furthermore, groups such as racial minorities and intravenous drug users also constitute a large proportion of AIDS cases.

Statistics also demonstrate the high costs associated with treating AIDS patients and people infected with HIV. As the AIDS epidemic unfolded, the health insurance industry developed fears concerning the financial crisis that would result due to an increase in the number of AIDS cases and the emergence of expensive treatments.
Webster and Women's Equality
Authors: Johnsen Dawn , Wilder Marcy J.
Published: February 2021

The National Abortion Rights Action League (NARAL) and the Women's Legal Defense Fund (WLDF) co-authored an amicus curiae brief submitted to the United States Supreme Court in Webster v. Reproductive Health Services. The brief was authored on behalf of seventyseven organizations committed to women's equality. The brief argued that continued constitutional protection of a woman's fundamental right to choose abortion is guaranteed by the liberty-based right to privacy. Further, we argued that this right is essential to women's ability to achieve sexual equality. In order to participate in society as equals, women must be afforded the opportunity to make decisions concerning childbearing. Women's unique reproductive capabilities have long served as a principal justification for their unequal and disadvantageous treatment by the state. Restrictive abortion laws continue “our Nation['s] … long and unfortunate history of sex discrimination” by depriving women of the freedom to control the course of their lives.
Die Entwicklung und Anwendung konfliktspezifischer Geschichtenergänzungsaufgaben als Teil der OPD-Diagnostik im Kindesalter
Authors: König Franziska , Benecke Cord
Published: February 2021

Zusammenfassung. Die Studie verbindet die MacArthur Story Stem Battery (MSSB) mit der Operationalisierten Psychodynamischen Diagnostik im Kindes- und Jugendalter (OPD-KJ-2). Dargestellt wird die Entwicklung und Anwendung von konfliktspezifischen Geschichtenergänzungsaufgaben für eine systematische Einschätzung der Konflikt- und Strukturachse in der Altersgruppe 2 (6–12 Jahre). Für die Achsen Konflikt und Struktur wird die Interrater-Reliabilität bestimmt. Weiterhin werden explorativ Zusammenhänge zwischen der Konflikt- und Strukturachse und dem SDQ-Fragebogen (Strenghts and Difficulties Questionnaire) geprüft. Das vorgestellte Diagnostikverfahren ermöglicht eine reliable Einschätzung der Achsen Konflikt und Struktur. Zudem ergeben sich einige Zusammenhänge zwischen den Einschätzungen der OPD-KJ-2-Achsen und dem SDQ-Fragebogen.
Ionospheric Disturbances Over the Indian Sector During 8 September 2017 Geomagnetic Storm: Plasma Structuring and Propagation
Authors: Alfonsi L. , Cesaroni C. , Spogli L. , Regi M. , Paul A. , Ray S. , Lepidi S. , Di Mauro D. , Haralambous H. , Oikonomou C. , Shreedevi P. R. , Sinha A. K.
Published: February 2021

The series of X and M class flares and associated coronal mass ejections that occurred on the first days of September 2017 induced significant perturbations on the low‐latitude ionospheric electrodynamics. On 8 September in the Indian sector, the storm caused a severe modification of the equatorial electrojet (EEJ) with a consequent variation of the ionospheric structuring and dynamics. In our analysis, we propose an original method to isolate and identify EEJ variations from geomagnetic data and we detect the presence of equatorial plasma bubbles (EPB) from L‐band total electron content (TEC) data in order to understand their movement. Our results provide evidence of independent EPBs appearance freshly generated and inherited from a migrating plasma structure. The EPB (or EPBs) occurring in the south of India is/are freshly generated just above the magnetic equator, and is/are likely triggered by the sudden increase of EEJ just before the local sunset, acting as a pre‐reversal enhancement. The EPB appearing in the North‐East Indian region is associated with a migrating structure, resulting in a northward movement with a velocity of about 650 m/s, possibly testifying the passage of a large‐scale traveling ionospheric disturbance. The occurrence of severe post‐sunset scintillations in the northeastern sector suggests a possible cascade process forming small‐scale irregularities from the migrating EPB.
Machine Learning Predicted Redox Conditions in the Glacial Aquifer System, Northern Continental United States
Authors: Erickson M. L. , Elliott S. M. , Brown C. J. , Stackelberg P. E. , Ransom K. M. , Reddy J. E.
Published: February 2021

Groundwater supplies 50% of drinking water worldwide and 30% in the United States. Geogenic and anthropogenic contaminants can, however, compromise water quality, thus limiting groundwater availability. Reduction/oxidation (redox) processes and redox conditions affect groundwater quality by influencing the mobility and transport of common geogenic and anthropogenic contaminants. In the glacial aquifer system, northern United States (GLAC, 1.87 million km2), groundwater with high arsenic or manganese concentration is associated with reducing conditions and high nitrate with oxidizing conditions. This study uses machine learning to identify the relative influence of drivers of redox conditions (e.g., residence time vs. reactivity) across the glacial landscape. We developed three‐dimensional boosted regression tree models to predict redox conditions using the likelihood of low dissolved oxygen or high iron as indicators of anoxic conditions. Results indicate that variation in redox condition is controlled primarily by residence time (e.g., groundwater age and relative depth) and to a lesser extent by geochemical reactivity (e.g., subsurface contact time, soil carbon). Older water and deeper wells, along with more water storage or slower water movement was associated with higher probability of anoxic conditions. Mapped model results illustrate regions where anoxic redox conditions may mobilize geogenic contaminants or oxic conditions may limit denitrification potential. Results may also provide simplified redox input for process or predictive models of, for example, arsenic, manganese, or nitrate. Machine learning modeling methods can lead to improved understanding of contaminant occurrence and what drives redox conditions, and the methods may be transferable to other settings.
The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer
Authors: Morgan Ethan L. , Patterson Molly R. , Barba-Moreno Diego , Scarth James A. , Wilson Adam , Macdonald Andrew
Published: February 2021

Protein ubiquitination is a critical regulator of cellular homeostasis. Aberrations in the addition or removal of ubiquitin can result in the development of cancer and key components of the ubiquitination machinery serve as oncogenes or tumour suppressors. An emerging target in the development of cancer therapeutics are the deubiquitinase (DUB) enzymes that remove ubiquitin from protein substrates. Whether this class of enzyme plays a role in cervical cancer has not been fully explored. By interrogating the cervical cancer data from the TCGA consortium, we noted that the DUB USP13 is amplified in ~15% of cervical cancer cases. We confirmed that USP13 expression was increased in cervical cancer cell lines, cytology samples from patients with cervical disease and in cervical cancer tissue. Depletion of USP13 inhibited cervical cancer cell proliferation. Mechanistically, USP13 bound to, deubiquitinated and stabilised Mcl-1, a pivotal member of the anti-apoptotic BCL-2 family. Furthermore, reduced Mcl-1 expression partially contributed to the observed proliferative defect in USP13 depleted cells. Importantly, the expression of USP13 and Mcl-1 proteins correlated in cervical cancer tissue. Finally, we demonstrated that depletion of USP13 expression or inhibition of USP13 enzymatic activity increased the sensitivity of cervical cancer cells to the BH3 mimetic inhibitor ABT-263. Together, our data demonstrates that USP13 is a potential oncogene in cervical cancer that functions to stabilise the pro-survival protein Mcl-1, offering a potential therapeutic target for these cancers.
A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma
Authors:   on behalf of the GWCA1208 study group, Twelves Chris , Sabel Michael , Checketts Daniel , Miller Sharon , Tayo Bola , Jove Maria , Brazil Lucy , Short Susan C.
Published: February 2021

Background

Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM.

Methods

Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored.

Results

The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK.

Conclusions

With personalised dosing, nabiximols had acceptable safety and tolerability with no drug–drug interaction identified. The observed survival differences support further exploration in an adequately powered randomised controlled trial.

Clinical trial registration

ClinicalTrials.gov: Part 1– NCT01812603; Part 2– NCT01812616.
OutFin, a multi-device and multi-modal dataset for outdoor localization based on the fingerprinting approach
Authors: Alhomayani Fahad , Mahoor Mohammad H.
Published: February 2021

In recent years, fingerprint-based positioning has gained researchers’ attention since it is a promising alternative to the Global Navigation Satellite System and cellular network-based localization in urban areas. Despite this, the lack of publicly available datasets that researchers can use to develop, evaluate, and compare fingerprint-based positioning solutions constitutes a high entry barrier for studies. As an effort to overcome this barrier and foster new research efforts, this paper presents OutFin, a novel dataset of outdoor location fingerprints that were collected using two different smartphones. OutFin is comprised of diverse data types such as WiFi, Bluetooth, and cellular signal strengths, in addition to measurements from various sensors including the magnetometer, accelerometer, gyroscope, barometer, and ambient light sensor. The collection area spanned four dispersed sites with a total of 122 reference points. Each site is different in terms of its visibility to the Global Navigation Satellite System and reference points’ number, arrangement, and spacing. Before OutFin was made available to the public, several experiments were conducted to validate its technical quality.
Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model
Authors: Dirk Brennan S. , Weir Genevieve , Quinton Tara , Hrytsenko Olga , Stanford Marianne M.
Published: February 2021

DPX is a novel delivery platform that generates targeted CD8 + T cells and drives antigen-specific cytotoxic T cells into tumours. Cancer cells upregulate phosphatidylserine (PS) on the cell surface as a mechanism to induce an immunosuppressive microenvironment. Development of anti-PS targeting antibodies have highlighted the ability of a PS-blockade to enhance tumour control by T cells by releasing immunosuppression. Here, C57BL/6 mice were implanted with HPV16 E7 target-expressing C3 tumours and subjected to low dose intermittent cyclophosphamide (CPA) in combination with DPX-R9F treatment targeting an E7 antigen with and without anti-PS and/or anti-PD-1 targeting antibodies. Immune responses were assessed via IFN-γ ELISPOT assay and the tumour microenvironment was further analyzed using RT-qPCR. We show that the combination of DPX-R9F and PS-targeting antibodies with and without anti-PD-1 demonstrated increased efficacy compared to untreated controls. All treatments containing DPX-R9F led to T cell activation as assessed by IFN-γ ELISPOT. Furthermore, DPX-R9F/anti-PS treatment significantly elevated cytotoxic T cells, macrophages and dendritic cells based on RT-qPCR analysis. Overall, our data indicates that anti-tumour responses are driven through a variety of immune cells within this model and highlights the need to investigate combination therapies which increase tumour immune infiltration, such as anti-phosphotidylserine.
Analyzing the impact of 900 MHz EMF short-term exposure to the expression of 667 miRNAs in human peripheral blood cells
Authors: Lamkowski Andreas , Kreitlow Matthias , Radunz Jörg , Willenbockel Martin , Stiemer Marcus , Fichte Lars Ole , Rädel Carl Friedrich , Majewski Matthäus , Ostheim Patrick , Port Matthias , Abend Michael
Published: February 2021

More than ever before, people around the world are frequently exposed to different sections of the electromagnetic spectrum, mainly emitted from wireless modern communication technologies. Especially, the level of knowledge on non-thermal biological EMF effects remains controversial. New technologies allow for a more detailed detection of non-coding RNAs which affect the post-transcriptional control. Such method shall be applied in this work to investigate the response of human blood cells to electromagnetic irradiation. In this ex vivo in vitro study, we exposed peripheral blood cells from 5 male donors to a continuous wave of 900 MHz EMF for 0, 30, 60 and 90 min. Significant micro RNA (miRNA) expression changes (p ≤ 0.05) above or below the SHAM exposed samples were evaluated using a quantitative real time PCR platform for simultaneous detection of 667 miRNAs called low density array. Only significant miRNA expression changes which were detectable in at least 60% of the samples per exposure group were analyzed. The results were compared with data from room temperature + 2 °C (RT + 2 °C) samples (here referred to as hyperthermia) to exclude miRNA expression altered by hyperthermia. The validation study by using the same donors and study design was performed after an interval of 2 years. When analyzing a total of 667 miRNAs during the screening study, 2 promising candidate miRNAs were identified, which were down regulated almost twice and showed a complete separation from the unexposed control group (miR-194 at 30 min and miR-939 at 60 min). The p-values even survived the Bonferroni correction for multiple comparisons (p = 0.0007 and p = 0.004, respectively). None of these miRNAs were expressed at a second time point after EMF exposure. Following an alternative analysis approach, we examined for miRNAs revealing an expected significant association of differential miRNA expression with the dose-time EMF exposure product, separately for each donor. Donors 2 and 3 revealed 11 and 10 miRNA species being significantly associated with EMF exposure which differed significantly from the other donors showing a minor number of differentially expressed miRNAs and could identify donors 2 and 3 as particularly EMF-responsive. The measurements were repeated after 2 years. The number of expressed/non-expressed miRNAs was almost similar (97.4%), but neither the number nor the previously differentially expressed miRNAs could be reproduced. Our data neither support evidence of early changes at miRNA expression level in human whole blood cells after 900 MHz EMF exposure nor the identification of EMF-responsive individuals.
Observation of direction instability in a fiber ring laser
Authors: Arshad Muhammad Assad , Hartung Alexander , Pratiwi Arni Candra , Jäger Matthias
Published: February 2021

We report on the observation of a new phenomenon occurring in a fiber ring laser. This phenomenon is about the transition from an initially bidirectional emission of a reciprocal fiber ring laser to a unidirectional emission at a certain pump power threshold. In addition, the final direction is not predefined but appears to be randomly chosen every time the threshold is exceeded. Therefore, we term this new phenomenon direction instability. Furthermore, we provide a first discussion of how the instability threshold is influenced by the length and the loss of the cavity. We show that the threshold follows a power times length scaling, indicating a nonlinear origin.
Natural depolymerization of waste poly(ethylene terephthalate) by neutral hydrolysis in marine water
Authors: Stanica-Ezeanu Dorin , Matei Danuta
Published: February 2021

Polyethylene terephthalate (PET) is one of the most widely used materials for food packaging and fishing nets. After use it become waste and, due to poor collection, most will be found floating in marine waters. This paper presents the results of a study of PET depolymerization by hydrolysis. We observed that marine water is a perfect reactant because it contains a multitude of metal ions that act as catalysts. A first-order kinetic model was developed and experimental data fitted to it. An activation energy of 73.5 kJ/mole and a pre-exponential factor of 5.33 × 107 h–1 were obtained. Considering that the global ocean is a huge batch reactor operating under isothermal conditions, the solution of the mathematical model shows that in tropical regions only 72 years is needed for total and only 4.5 years for 50% PET conversion.
Pseudohomogeneous metallic catalyst based on tungstate-decorated amphiphilic carbon quantum dots for selective oxidative scission of alkenes to aldehyde
Authors: Rezaei Aram , Hadian-Dehkordi Leila , Samadian Hadi , Jaymand Mehdi , Targhan Homa , Ramazani Ali , Adibi Hadi , Deng Xiaolei , Zheng Lingxia , Zheng Huajun
Published: February 2021

Herein, we present an interesting role of tungstate-decorated amphiphilic carbon quantum dots (A-CQDs/W) in the selective oxidative cleavage of alkenes to aldehydes. In this work, for the first time, we disclose an unprecedented tungstate-based oxidative system incorporating A-CQDs as a bridge to the homogeneous catalyst for selective and efficient cleavage of a wide substrate scope of alkenes into aldehydes. The A-CQDs/W were synthesized via a one-step hydrothermal synthesis approach using 1-aminopropyl-3-methyl-imidazolium chloride and stearic acid for the surface modification, following by anion-exchange to immobilize WO4–2 to A-CQDs. The A-CQDs/W act as a pseudohomogeneous metallic catalyst (PMC) for selective oxidative scission of alkenes under phase transfer catalysts (PTC) free condition without over oxidation to acids, using water and H2O2 as a green oxidant. Thanks to the sub-nanometric size and novel engineered chemical structure, this PMC and reactants are in the same phase, besides they can be easily isolated from each other by extraction processes. The synthesized PMC exhibited excellent solubility and stability in various solvents. Interestingly, the system’s high conversion efficiency was preserved even after eight catalytic cycles indicating the recyclability of the synthesized PMC. We believe that this study provides a significant and conceptually novel advance in oxidative cleavage chemistry.
Stress hormone-mediated antipredator morphology improves escape performance in amphibian tadpoles
Authors: Fraker Michael E. , Ludsin Stuart A. , Luttbeg Barney , Denver Robert J.
Published: February 2021

Complete functional descriptions of the induction sequences of phenotypically plastic traits (perception to physiological regulation to response to outcome) should help us to clarify how plastic responses develop and operate. Ranid tadpoles express several plastic antipredator traits mediated by the stress hormone corticosterone, but how they influence outcomes remains uncertain. We investigated how predator-induced changes in the tail morphology of wood frog (Rana sylvatica) tadpoles influenced their escape performance over a sequence of time points when attacked by larval dragonflies (Anax junius). Tadpoles were raised with no predator exposure, chemical cues of dragonflies added once per day, or constant exposure to caged dragonflies crossed with no exogenous hormone added (vehicle control only), exogenous corticosterone, or metyrapone (a corticosteroid synthesis inhibitor). During predation trials, we detected no differences after four days, but after eight days, tadpoles exposed to larval dragonflies and exogenous corticosterone had developed deeper tail muscles and exhibited improved escape performance compared to controls. Treatment with metyrapone blocked the development of a deeper tail muscle and resulted in no difference in escape success. Our findings further link the predator-induced physiological stress response of ranid tadpoles to the development of an antipredator tail morphology that confers performance benefits.
Smartphone-based symbol-digit modalities test reliably captures brain damage in multiple sclerosis
Authors: Pham Linh , Harris Thomas , Varosanec Mihael , Morgan Vanessa , Kosa Peter , Bielekova Bibiana
Published: February 2021

As the burden of neurodegenerative diseases increases, time-limited clinic encounters do not allow quantification of complex neurological functions. Patient-collected digital biomarkers may remedy this, if they provide reliable information. However, psychometric properties of digital tools remain largely un-assessed. We developed a smartphone adaptation of the cognitive test, the Symbol-Digit Modalities Test (SDMT) by randomizing the test’s symbol-number codes and testing sequences. The smartphone SDMT showed comparable psychometric properties in 154 multiple sclerosis (MS) patients and 39 healthy volunteers (HV). E.g., smartphone SDMT achieved slightly higher correlations with cognitive subscores of neurological examinations and with brain injury measured by MRI (R2 = 0.75, Rho = 0.83, p < 0.0001) than traditional SDMT. Mathematical adjustment for motoric disability of the dominant hand, measured by another smartphone test, compensates for the disadvantage of touch-based test. Averaging granular home measurements of the digital biomarker also increases accuracy of identifying true neurological decline.
Real-time clinician text feeds from electronic health records
Authors: Teo James T. H. , Dinu Vlad , Bernal William , Davidson Phil , Oliynyk Vitaliy , Breen Cormac , Barker Richard D. , Dobson Richard J. B.
Published: February 2021

Analyses of search engine and social media feeds have been attempted for infectious disease outbreaks, but have been found to be susceptible to artefactual distortions from health scares or keyword spamming in social media or the public internet. We describe an approach using real-time aggregation of keywords and phrases of freetext from real-time clinician-generated documentation in electronic health records to produce a customisable real-time viral pneumonia signal providing up to 4 days warning for secondary care capacity planning. This low-cost approach is open-source, is locally customisable, is not dependent on any specific electronic health record system and can provide an ensemble of signals if deployed at multiple organisational scales.
Fluid separation and network deformation in wetting of soft and swollen surfaces
Authors: Cai Zhuoyun , Skabeev Artem , Morozova Svetlana , Pham Jonathan T.
Published: February 2021

When a water drop is placed onto a soft polymer network, a wetting ridge develops at the drop periphery. The height of this wetting ridge is typically governed by the drop surface tension balanced by elastic restoring forces of the polymer network. However, the situation is more complex when the network is swollen with fluid, because the fluid may separate from the network at the contact line. Here we study the fluid separation and network deformation at the contact line of a soft polydimethylsiloxane (PDMS) network, swollen with silicone oil. By controlling both the degrees of crosslinking and swelling, we find that more fluid separates from the network with increasing swelling. Above a certain swelling, network deformation decreases while fluid separation increases, demonstrating synergy between network deformation and fluid separation. When the PDMS network is swollen with a fluid having a negative spreading parameter, such as hexadecane, no fluid separation is observed. A simple balance of interfacial, elastic, and mixing energies can describe this fluid separation behavior. Our results reveal that a swelling fluid, commonly found in soft networks, plays a critical role in a wetting ridge.
Density matrix and purity evolution in dissipative two-level systems: II. Relaxation
Authors: Chatterjee Sambarta , Makri Nancy
Published: February 2021

We investigate the time evolution of the reduced density matrix (RDM) and its purity in the dynamics of a two-level system coupled to a dissipative harmonic bath, when the system is initially placed in one of its eigenstates.
Deep reinforcement learning of transition states
Authors: Zhang Jun , Lei Yao-Kun , Zhang Zhen , Han Xu , Li Maodong , Yang Lijiang , Yang Yi Isaac , Gao Yi Qin
Published: February 2021

RL‡can automatically locate the transition states of chemical reactions through deep reinforcement learning of feedback from molecular simulations.
Unravelling the dissolution mechanism of polyphosphate glasses by 31P NMR spectroscopy: ligand competition and reactivity of intermediate complexes
Authors: Avila Salazar Dahiana A. , Bellstedt Peter , Miura Atsuhiro , Oi Yuki , Kasuga Toshihiro , Brauer Delia S.
Published: February 2021

Metal ion complexes influence hydrolysis during phosphate glass dissolution.