bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferred Provider Organizations: Antitrust Aspects and Implications for the Hospital Industry
Authors: Batavia Andrew I.
Published: February 2021

The hospital industry is currently undergoing a substantial transformation as a result of changes in third party reimbursement mechanisms and a tendency toward a more competitive economic environment. Hospital administrators will have to demonstrate substantial flexibility in considering and implementing innovative institutional arrangements to ensure survival in this time of austerity. The Preferred Provider Organization (PPO) is a recent development in the health care industry involving the selective contracting for health care services. This Article examines the role of section 1 of the Sherman Antitrust Act in scrutinizing the PPO for anticompetitive effects, considering the divergent requisites for competition in the health care sector. The Article also proposes a modified Rule of Reason for application to the PPO and other innovative cost containment arrangements in the industry and considers the implications of such flexible application of conventional antitrust principles for the future of the hospital industry.
Private Credentialing of Health Care Personnel: A Pragmatic Response to Academic Theory
Authors: Rankin James W. , Hubbard Bruce A.
Published: February 2021

In a two-part article entitled “Private Credentialing of Health Care Personnel: An Antitrust Perspective,” Clark C. Havighurst and Nancy ‘M. P. King purport to set forth “a new and previously unexplored agenda for antitrust enforcement, one that the Authors believe will increase the quantity and quality of information available to consumers … .” Having concluded in Part One of the Article that antitrust courts and regulators should exercise only limited supervision over private credentialing in the health care field, in large part because of their “important procompetitive purpose of supplying useful information and advice to consumers,” the Authors reverse field and seek to use the antitrust laws to call into question the activities and structure of leading medical specialty boards, the Liasion Council on Medical Education, various accrediting, certifying and credentialing bodies in medicine and the allied health professions, and the Joint Commission on Accreditation of Hospitals (JCAH).
Nurses and Prescriptive Authority: A Legal and Economic Analysis
Authors: Hadley Elizabeth Harrison
Published: February 2021

This article identifies twenty-six jurisdictions where nurses have been granted legal authority to prescribe drugs. The jurisdictions are divided into two groups: those where nurses have authority to prescribe without the supervision of a physician and can therefore function as substitutes for physicians; and those where nurses may prescribe only in collaboration with a supervising physician, and are thereby limited to functioning in a complementary role.

The issue of prescriptive authority is discussed within the context of regulating the practice of nursing, and more generally, the health care professions. The article reviews the history of Nurse Practice Acts, focusing upon the Connecticut statute and the economic implications of this statutory approach. It is argued that the law should promote the use of nurses as substitutes for physicians whenever appropriate.

The article concludes with a two-part proposal for reform: an “authorized prescriber” statute requiring health care professionals desiring to prescribe drugs to pass an examination testing their knowledge of pharmacology and drug therapy; and the elimination of the “unauthorized practice” provisions of the statutes regulating all health care professions. The proposal promotes economic efficiency by eliminating artificial constraints on the substitutability of labor in the provision of health services.
Medical Privacy Issues in the Age of AIDS: Legislative Options
Authors: Edgar Harold , Sandomire Hazel
Published: February 2021

Promises of confidentiality of HIV-related medical records and protection from discrimination based on HIV seropositivity are two of the legislative inducements state governments have offered to encourage voluntary HIV testing. Yet neither can be granted without impact on others whose interests range from those of a lover to those of an insurer. Politics as well as practicalities prevent the absolute protection of records from unauthorized disclosure and of individuals from discrimination. This article details the already enacted statutory compromises that have been made to resolve the conflicts of these competing interests and closely examines the myriad fine decisions made in reaching those legislative decisions.
Medical Malpractice Arbitration Act: Michigan's Experience with Arbitration
Authors: Bedikian Mary
Published: February 2021

In the 1970's, Michigan and other states were confronted with a medical malpractice crisis of astronomical proportions. The escalating number of medical malpractice lawsuits and concomitant increase in malpractice premiums for health care providers fostered a divisive climate among doctors, lawyers and patients. In response to this crisis, the Michigan legislature enacted the Medical Malpractice Arbitration Act. The Act establishes a process whereby patients may agree to arbitrate any claims rather than pursue them through the courts.

Part II of this Article discusses the historical evolution of arbitration as a precursor to its establishment as a resolution modality for health care disputes. Part III describes the statutory framework of the Michigan Medical Malpractice Arbitration Act. Part IV discusses the contractual and constitutional challenges to the arbitration statute and their resolution in Morris v. Metriyakool.

As the law respecting arbitration becomes less vulnerable to judicial perforation, this Author suggests that other jurisdictions treat the Michigan Medical Arbitration Program as an archetype, susceptible to replication.
Employment Discrimination Implications of Genetic Screening in the Workplace under Title VII and the Rehabilitation Act
Authors: Canter Edith F.
Published: February 2021

The emergence of genetic screening techniques will permit employers to exclude hypersusceptible individuals from potentially hazardous workplace environments. The denial of employment opportunities to these individuals, however, may constitute discrimination. This Note analyzes genetic screening cases with respect to currently available remedies contained in Title VII of the Civil Rights Act of 1964 and the Rehabilitation Act of 1973. The Note concludes that Title VII claims may succeed but only in limited circumstances and that Rehabilitation Act claims will encounter numerous obstacles to relief. Additionally, the Note discusses some of the implications of the use of genetic screening in the workplace.
The Exclusion of Pregnant, Pregnable, and Once-Pregnable People (a.k.a. Women) from Biomedical Research
Authors: Merton Vanessa
Published: February 2021

The barriers to women's participation as subjects in biomedical research are currently being challenged as a matter of legislative policy, medicine, and law. This Article catalogs the ways in which women have been disadvantaged by their exclusion and recent developments to redress them, and goes on to dissect the underlying rationales for excluding women from clincial trials. The author reveals the ‘fundamental misconception’ behind exclusionary rationales, and argues that research sponsors in fact have more to fear in the way of potential liability from the exclusion of women, even pregnant women and women of child-bearing capacity, than from their inclusion. Finally, the Article suggests strategies for achieving reform of these exclusionary practices.
Regional Harmonization of Occupational Health Rules: The European Example
Authors: Raworth Philip
Published: February 2021

This study of the occupational health law of the European Union looks first at the jurisdiction of the Union and the history and scope of its legislation in this area.

The main body of the Article examines the level of protection that is afforded to the workforce under European Union law. The Article first considers the way in which assessment of risk is handled and then passes on to measures that are provided for both preventing and protecting against health risks. It notes the greater role given to protection. The Article also mentions the ancillary measures that are destined to make both prevention and protection effective. Finally, it looks at the Union's detailed provisions for worker involvement in occupational health matters and the more meager ones on employment rights and compensation.

The Article ends with a discussion of the problems faced by the Union in enforcing its rules and an assessment of the strengths and weaknesses of the European Union's occupational health law. It is suggested that, overall, it deserves a positive judgment.
Waived Consent for Emergency Research
Authors: Fost Norman
Published: February 2021

The voluntary consent of the human subject is absolutely essential.

Contrary to the first principle of the Nuremberg Code, the voluntary consent of the human subject is neither necessary nor sufficient for ethically and legally responsible research in the United States. That it is not sufficient has been well argued by Robert Burt and others. We would not say that the central problem of the Nazi experiments was their failure to obtain informed consent. Nor would the presentation of signed and witnessed consent forms change anyone's view on the moral justification for the experiments. For related reasons, institutional review boards (IRBs) sometimes reject or defer protocols for paternalistic or various other reasons, arguing that clinicians should not allow patients to consent to be subjects in a study.
Western Medicine Opens the Door to Alternative Medicine
Authors: Boozang Kathleen M.
Published: February 2021

Physicians have struggled to defeat alternative medicine, and to obtain a monopoly over the health care of their patients, since physicians began systematically organizing in the United States. They claim to oppose alternative medicine because it lacks efficacy, may waste precious health care dollars and may harm patients. Part II of this Article examines the ongoing debate about alternative medicine and the arguments that may wedge the door of Western medicine open to alternative treatment methods. Alternative medicine's successful entry into Western practice depends on convincing conventional medicine of the efficacy of alternative treatments, a task that remains largely undone. Part III explains why the debate about unproven alternative therapies differs from previous discussions about human research, and therefore merits independent consideration. Part IV argues that it is not ethically appropriate for physicians to offer or agree to provide alternative therapies whose efficacy remain unproven or are of dubious potential.
Marketing Health Care Products on the Internet: A Proposal for Updated Federal Regulations
Authors: Green Kristen
Published: February 2021

The Internet offers pharmaceutical companies and medical device manufacturers a dynamic new medium for promoting their products—a medium that might actually be better suited for health care product promotion than print or television. On the Internet's World Wide Web (Web) pages, drug and device makers can produce interactive marketing and advertising material that more easily complies with current Food and Drug Administration (FDA) and Federal Trade Commission (FTC) disclosure requirements. Navigation buttons and hypertext links can facilitate compliance with such information disclosure requirements by allowing drug and device makers to “hide” the brief summaries or labels until interested viewers “click” on them.

Despite the appropriateness of the medium, however, a Web search today will turn up less drug and medical device promotion than one might expect. In fact, the Web, which represented $7 billion in commerce in 1997 and is expected to account for $20 billion in 1998, is strangely quiet on this front.
Night Landings on an Aircraft Carrier: Hospital Mergers and Antitrust Law
Authors: Greaney Thomas L.
Published: February 2021

Justice Stewart’s 1966 dictum about the inevitability of government success in challenging mergers under Section 7 of the Clayton Act held true for another fifteen years or so. In the early 1980s, however, federal enforcement agencies, the Department of Justice (DOJ) and the Federal Trade Commission (FTC), began to find the federal courts less hospitable to antitrust merger cases as more sophisticated economic inquiries and changing proof burdens complicated the task of identifying anticompetitive mergers. Indeed, since the early 1980s, the government has lost more litigated merger cases than it has won and has come under criticism from some quarters for becoming gun shy and not adequately policing the wave of consolidations that have occurred over the past decade.

Hospital mergers, however, are a different story. Until two years ago, the government rode a streak of important victories in federal courts and FTC administrative proceedings, and had obtained consent decrees from scores of hospitals that had announced plans to merge.
Medicare's Future: Fact, Fiction and Folly
Authors: Marmor Theodore R. , McKissick Gary J.
Published: February 2021

Perhaps no single policy topic better illustrates the tensions within American politics at the beginning of a new millennium than does Medicare, the nation's thirty-five year commitment to ensuring senior citizens' financial protection against the costs of acute medical care. Our politics seems nearly overwhelmed by conflicting promises to balance the budget and pay down the national debt, enact tax cuts and protect broadly popular “entitlements.” Medicare, one of the largest of such entitlement programs, has become a lightning rod for conflicts over how to resolve these competing goals. As a result, the nation finds itself in the midst of a bewildering mix of crisis talk, fact throwing and ideological name calling, with all the confusion and distortion one would expect from such a mix.
Medically Futile Care: The Role of the Physician in Setting Limits
Authors: Veatch Robert M. , Spicer Carol Mason
Published: February 2021

In an effort to clarify the concept of “medically futile care,” two types offutilecare are identified: 1) care that produces no demonstrable effect; and 2) care that produces an effect that is believed by the speaker to be of no net benefit. It is the second type of futile care, when a patient or surrogate and the clinician disagree over the benefit that the patient will receive from an intervention, that is most interesting morally and that cannot properly be labelledmedicallyfutile. As such, decisions to limit access to care deemed futile should not rest with medical professionals. This Article argues for a limited duty of clinicians to provide life-prolonging and some other fundamental care that is equitably funded and desired by the patient while competent, even if the clinician believes that such interventions will produce no net benefit.
Denial of Health Care and Informed Consent in English and American Law
Authors: Miller Frances H.
Published: February 2021

Health care rationing has gained greater visibility in the United States and the United Kingdom, for quite different reasons. As patients in both countries become more aware that potentially beneficial medical services can be denied them on economic — as opposed to purely medical — grounds, they are beginning to seek help from the judiciary. This Article contends that as rationing becomes more explicit, the doctrine of informed consent will come under increased pressure. The Article suggests that courts and legislatures consider imposing a legal obligation on physicians to inform their patients when potentially effective treatment is to be withheld for economic or other non-clinical reasons.
Mothers and Children Last: The Oregon Medicaid Experiment
Authors: Rosenbaum Sara
Published: February 2021

“There is always a lofty goal in the research work of medicine but too often it has been the bodies of the poor on … whom the unholy testing is done.“

James Jones, Bad Blood: The Tuskeegee Syphilis Experiment

In 1989 and 1991, the Oregon legislature enacted a series of initiatives to extend health coverage to uninsured state residents. Among these initiatives is an act that seeks to extend a modified set of Medicaid benefits to state residents with family incomes below the federal poverty level. This act also reduces benefits the state is now required to provide to Medicaid-enrolled women of childbearing age and children. This Article explores the legal context in which the Oregon Medicaid experiment must be evaluated. It argues that by reducing the level of coverage to which tens of thousands of exceedingly poor, Medicaid-eligible women and children are entitled, the experiment falls outside the scope of valid research that the United States Department of Health and Human Services may either sanction or fund. The Article also discusses the implications of the Oregon experiment, if approved, for the future direction of the Medicaid program in particular, and for health care reform for the poor, generally.
System and Responsibility: Three Readings of the IOM Report on Medical Error
Authors: Latham Stephen R.
Published: February 2021

The most publicized finding of the Institute of Medicine (IOM) report is that between 44,000 and 98,000 patients die each year as a result of “adverse events” in medical care. The core concern of the report is to argue that a "systems" approach to medical practice holds out considerable promise for the elimination of the subset of those “adverse events” which are the result of medical error. The report outlines the “systems” approach and proposes various public policies which might encourage the adoption of that approach, enhance its effectiveness and protect it from potentially undermining legal assaults.
A Way Out of the Maze: Federal Agency Preemption of State Licensing and Regulation of Complementary and Alternative Medicine Practitioners
Authors: Van Hemel Peter J.
Published: February 2021

In recent years, complementary and alternative medicine (“CAM”) has grown in both popularity and economic import across all segments of society and is now an established presence in the lives of millions of Americans. It has generated its own field of adherents, practitioners, opponents, lobbyists and counter-lobbyists, case law, and regulations. On one side of the CAM equation stand the advocates of CAM: its practitioners and satisfied patients. On the other stand its detractors: its dissatisfied patients, groups within the established or mainstream medical community, and historically, the American Medical Association (“AMA”). In the aggregate, the two sides engage in large scale scientific and philosophical battles over how best to treat or address the health care needs of patients. On a smaller scale, individuals on each side are essentially lobbying to protect their professions and their jobs. The struggle between the two warring camps fills volumes of medical, legal and popular scholarship. However, it is not the point of this Note to address the validity of the debate between CAM and mainstream medicine.
DNA-Based Identity Testing and the Future of the Family: A Research Agenda
Authors: Anderlik Mary R. , Rothstein Mark A.
Published: February 2021

Many of the societal challenges associated with the genetic revolution rest on predictions about the effects of the future development and diffusion of technologies for manipulating the human genome. Identity testing is different. Relatively sophisticated techniques for identity testing using DNA currently exist, and these techniques are already creating conflicts and challenges for families and policymakers. More precisely, scientific advances and social trends are raising difficult questions about the source and nature of parental obligation, the steps required to protect the privacy of individuals when suspicion begins to corrode family relationships and the role of attorneys and other professionals in these volatile situations.
Regulation of Managed Care Incentive Payments to Physicians
Authors: Latham Stephen R.
Published: February 2021

A large and growing number of physicians in today’s managed care market are paid for their services according to incentive schemes that offer financial rewards for the provision of less, and less expensive, medical care. Such schemes typically reward physicians for reducing their own costs of care and reward primary care physicians for reducing the number and cost of referrals for inpatient and specialty care. Consumers, fearful that such schemes will prompt physicians to deny them medically necessary care, have protested the implementation of such incentive plans. Various states are considering bills to ban or to limit physician incentive payments.

Federal policy with regard to incentive schemes has been confused and contradictory. On one hand, regulators concerned with controlling health care costs and limiting the provision of unnecessary care have encouraged such financial incentives. For example, federal Stark regulations, which ban referrals tied to physician compensation, include explicit exceptions for incentive schemes.
Webster, Vagueness and the First Amendment
Authors: Bopp James , Coleson Richard E.
Published: February 2021

The State of Missouri forbids the expenditure of public funds “for the purpose of encouraging or counseling a woman to have an abortion not necessary to save her life.” This provision is part of a comprehensive scheme adopted by Missouri to advance its legitimate state interest in preferring childbirth over abortion by ensuring that state funds, facilities and personnel are not used to promote abortion.

This provision was invalidated by the United States Court of Appeals for the Eighth Circuit on the grounds that the language “encourage or counsel” was “void for vagueness and violative of the right to privacy.” The district court had found that in addition to these two grounds, the provision violated the first amendment.
Dynamics and risk of transmission of bovine tuberculosis in the emerging dairy regions of Ethiopia
Authors: Mekonnen G. A. , Conlan A. J. K. , Berg S. , Ayele B. T. , Mihret A. , Olani A. , Asgedom H. ,   The ETHICOBOTS consortium, Wood J. L. N. , Ameni G.
Published: February 2021

The Ethiopian government has several initiatives to expand and intensify the dairy industry; however, the risk of bovine tuberculosis (bTB) spread is a challenge. To assess the rate of expansion and risk factors for transmission of bTB within-herds, we carried out a repeated cross-sectional survey at two time points, 2016/17 and 2018, in three regional cities, namely, Gondar, Hawassa and Mekelle, representing the emerging dairy belts of Ethiopia. The total number of herds involved was 128, comprising an average of 2303 cattle in each round. The Single Intradermal Comparative Cervical Tuberculin (SICCT) test was used to identify reactor status and data on herd-level risk factors were collected using a structured questionnaire. In the first survey, the apparent prevalence of bTB, as measured by the SICCT test, was 4.5% (95% CI 3.7–5.4%) at the individual animal-level and 24% (95% CI 17.5–32%) at the herd-level. There was no statistically significant change in the overall apparent prevalence or regional distribution at the second survey, consistent with the infection being endemic. The incidence rate was estimated at 3.6 (95% CI 2.8–4.5) and 6.6 (95% CI 3.0–12.6) cases/100 cattle (or herd)-years at the animal- and herd-levels, respectively. Risk factors significantly associated with the within-herd transmission of bTB were age group and within-herd apparent prevalence at the start of the observation period. We noted that farmers voluntarily took steps to remove reactor cattle from their herds as a consequence of the information shared after the first survey. Removal of reactors between surveys was associated with a reduced risk of transmission within these herds. However, with no regulatory barriers to the sale of reactor animals, such actions could potentially lead to further spread between herds. We therefore advocate the importance of setting up regulations and then establishing a systematic bTB surveillance programme to monitor the impact prior to implementing any control measures in Ethiopia.
Mechanism of the adverse effect of hyaluronidase used for oocyte denudation on early development of bovine embryos
Authors: Ashibe Shiori , Irisawa Kanade , Yokawa Ken , Nagao Yoshikazu
Published: February 2021

Hyaluronidase is widely used in animal and human assisted reproductive technologies (ARTs) to remove cumulus cells around oocytes. However, adverse effects of hyaluronidase treatment, such as increased rates of degeneration and parthenogenesis, have been found after treatment of human and mouse oocytes. Currently, the mechanism(s) of the detrimental effects are unclear. The present study was initiated to identify the mechanism of adverse responses to hyaluronidase treatment in bovine oocytes and early embryos. Cumulus cells were removed from cumulus–oocyte complexes (COCs) with or without hyaluronidase and the oocytes were subjected to intracytoplasmic sperm injection (ICSI) orin vitrofertilization (IVF). Significantly lower rates of blastocyst formation were obtained in the hyaluronidase treatment group after ICSI (22.4%) and IVF (21.2%) compared with the non-hyaluronidase control groups: 36.1% after ICSI and 30.4% after IVF. Next, we examined the effect of hyaluronidase on parthenogenetic development rates and on the cytoplasmic levels of free calcium ions (Ca2+), reactive oxygen species (ROS) and reduced glutathione (GSH). No differences in parthenogenesis rates were found between treated and untreated groups. Ca2+levels in oocytes from the hyaluronidase treatment group indicated using mean fluorescence intensity were significantly higher (68.8 ± 5.3) compared with in the control group (45.0 ± 2.5). No differences were found in the levels of ROS or GSH between the treated and untreated groups. We conclude that hyaluronidase might trigger an increase in Ca2+levels in oocytes, resulting in a decreased potential for normal embryonic development.
Outcomes of adults with repaired tetralogy of Fallot from the national Scottish Cohort
Authors: Dobson Richard J. , Ramparsad Nitish , Walker Niki L. , McConnachie Alex , Danton Mark H. D.
Published: February 2021

Background:

The adult population of repaired tetralogy of Fallot is increasing and at risk of pre-mature death and arrhythmia. This study evaluates risk factors for adverse outcome and the effect of pulmonary valve replacement within a national cohort.

Methods:

A retrospective cohort study of 341 adult repaired tetralogy of Fallot (16–72 years) managed through a single national service was undertaken incorporating over 1200 patient-years of follow-up. Demographics, cardiopulmonary exercise testing, cardiac magnetic resonance, reintervention (including pulmonary valve replacement), and clinical events were analysed. The influence of these parameters on a primary outcome (death or arrhythmia) was evaluated.

Results:

Compared with an age-/gender-matched population, patients experienced a reduced survival, particularly males over 55 years (standardised mortality ratio : 6.12, 95% CI: 1.64–15.66, p = 0.004). Cox proportional hazards modelling identified increased indexed right ventricle (RV) end-diastolic volume (hazard ratio (HR): 2.86, 95% CI: 1.4–5.85, p = 0.004) and female gender (HR (male): 0.37, 95% CI: 0.14–0.98, p = 0.045) to be predictors significantly associated with the primary outcome. Pulmonary valve replacement undertaken at indexed RV end-diastolic volume = 145 ml/m2 reduced RV volumes and QRS duration but did not improve cardiopulmonary exercise testing nor NYHA class. Pulmonary valve replacement during cohort period was associated with increased risk of primary outcome (HR: 2.82, 95% CI: 1.36–5.86, p = 0.005).

Conclusions:

Although the majority of adult tetralogy of Fallot were asymptomatic in NYHA 1, cardiopulmonary exercise testing revealed important deficits. Tetralogy of Fallot survival was reduced compared to the general population. Female gender and increasing RV end-diastolic volume predicted adverse events. Pulmonary valve replacement reduced RV volumes and QRS duration but did not improve primary outcome.
Factors associated with a lower chance of having gaps in care in adult congenital heart disease
Authors: Ko Jong Mi , Yanek Lisa R. , Cedars Ari M.
Published: February 2021

Background:

To promote good health in patients with congenital heart disease (CHD), prevention of gaps in care is essential, as adverse prognosis is associated with care gaps. A well-organised, formal transition programme may help prevent loss to follow up after leaving paediatric care. To inform the development of a transition programme, we investigated factors associated with care gaps in adults with CHD.

Methods:

Between 15 October 2018 and 15 November 2019 data on patient characteristics and patient experiences with transition-related education, difficulties, and gaps in care were collected and assessed in 87 adults with CHD. Two groups (with gaps in care versus without gaps) were compared to identify informative differences using chi-squared, Fisher’s exact tests, or Wilcoxon rank-sum tests. To assess the relationship between care gaps and identified variables, factors with significant difference (p < 0.05) in bivariate analyses were employed as covariates in multivariable logistic regression analysis.

Results:

About half of the study cohort reported having gaps in care. In a multivariate model, patients having thorough discussion about the importance of receiving adult care in paediatric care were 70% less likely to experience gaps (odds ratio 0.303, 95% CI 0.14, 0.66). Forty-seven percent of patient-perceived barriers to transitioning originated from negative feelings associated with transfer.

Conclusion:

Gaps in care are highly prevalent in adults with CHD. For a transition programme to be most effective, curriculum development may need to consider the differential impact of various factors and target areas to mitigate the psychological stress associated with transfer.
The application of the principle of distinction in the cyber context: A Chinese perspective
Authors: Huang Zhixiong , Ying Yaohui
Published: February 2021

Up to now, the Chinese government has only made very general comments on the application of international humanitarian law to cyberspace. There are indeed Chinese academic papers concerning this issue, but the discussion of the principle of distinction is limited both in length and in academic depth. Compared with the West, research by Chinese scholars on this topic is still in a relatively preliminary stage. At present, there is no specific deconstruction or clarification of the application of the principle of distinction in cyberspace in Chinese academia. As the first paper written by Chinese scholars specifically devoted to this question, this piece provides a different perspective by injecting the positions of Chinese officials and the views of Chinese scholars. The authors aim to clarify whether the existing rules are still completely applicable in the cyber context, and if needed, to find out what kind of improvements and clarifications can be made. Weighing in on these debates, we argue that despite the potential technical challenges and uncertainties, the principle of distinction should be applied to cyberspace. It should also be carefully re-examined and clarified from the standpoint of preventing over-militarization and maximizing the protection of the interests of civilians. For human targets, the elements of combatant status identified in customary international law and relevant treaties are not well suited to the digital battlefield. Nevertheless, cyber combatants are still obligated to distinguish themselves from civilians. In applying the principle of distinction, we argue that it makes more sense to focus on substantive elements over formal elements such as carrying arms openly or having a fixed distinctive sign recognizable at a distance. In interpreting “direct participation in hostilities”, the threshold of harm requires an objective likelihood instead of mere subjective intention; the belligerent nexus should be confirmed, and the causal link should be proximate. Applying the “cyber kill chain” model by analogy helps us to grasp the whole process of direct participation in hostilities during cyber warfare. For non-human targets, all military objectives must cumulatively fulfil both the “effective contribution” and “definite military advantage” criteria, which are equally indispensable. The same requirements apply to dual-use objects. Furthermore, certain data should fall within the ambit of civilian objects.
Constraining 20th‐Century Sea‐Level Rise in the South Atlantic Ocean
Authors: Frederikse Thomas , Adhikari Surendra , Daley Tim J. , Dangendorf Sönke , Gehrels Roland , Landerer Felix , Marcos Marta , Newton Thomas L. , Rush Graham , Slangen Aimée B. A. , Wöppelmann Guy
Published: February 2021

Sea level in the South Atlantic Ocean has only been measured at a small number of tide‐gauge locations, which causes considerable uncertainty in 20th‐century sea‐level trend estimates in this basin. To obtain a better‐constrained sea‐level trend in the South Atlantic Ocean, this study aims to answer two questions. The first question is: can we combine new observations, vertical land motion estimates, and information on spatial sampling biases to obtain a likely range of 20th‐century sea‐level rise in the South Atlantic? We combine existing observations with recovered observations from Dakar and a high‐resolution sea‐level reconstruction based on salt‐marsh sediments from the Falkland Islands and find that the rate of sea‐level rise in the South Atlantic has likely been between 1.1 and 2.2 mm year−1 (5%–95% confidence intervals), with a central estimate of 1.6 mm year−1. This rate is on the high side, but not statistically different compared to global‐mean trends from recent reconstructions. The second question is: are there any physical processes that could explain a large deviation from the global‐mean sea‐level trend in the South Atlantic? Sterodynamic (changes in ocean dynamics and steric effects) and gravitation, rotation, and deformation effects related to ice mass loss and land water storage have probably led to a 20th‐century sea‐level trend in the South Atlantic above the global mean. Both observations and physical processes thus suggest that 20th‐century sea‐level rise in the South Atlantic has been about 0.3 mm year−1 above the rate of global‐mean sea‐level rise, although even with the additional observations, the uncertainties are still too large to distinguish a statistically significant difference.
Evaluating the Relationship Between Meander‐Bend Curvature, Sediment Supply, and Migration Rates
Authors: Donovan Mitchell , Belmont Patrick , Sylvester Zoltán
Published: February 2021

River meander migration plays a key role in the unsteady “conveyor belt” of sediment redistribution from source to sink areas. The ubiquity of river meandering is evident from remotely sensed imagery, which has allowed for long‐term, high‐resolution studies of river channel change and form‐process relationships. Empirical, experimental, and theoretical research approaches have described two distinct relationships between channel curvature and river channel migration rates. In this study, we employ a novel application of time‐series algorithms to calculate migration rates and channel curvature at sub‐meander bend length scales using 6 decades of aerial imagery spanning 205 km of the Minnesota River and Root River, Minnesota, USA. Results from the Minnesota River provide the first empirical evidence demonstrating how migration‐curvature relations break down for rivers with low sediment supply, which is supported by the Root River data set. This not only highlights the importance of sediment supply as a driver of river migration, but also supports a simple means to detect river reaches lacking sediment supply. Furthermore, results from both rivers demonstrate that sub‐meander bend measurement scales are most appropriate for studying channel migration rates and further indicate that a quasi‐linear relationship—rather than the more commonly inferred peaked relationship—exists between channel curvature and migration rates. The highest migration rates are associated with the highest measured channel curvatures in our data set, after accounting for a spatial lag of channel widths. These findings are consistent with flume experiments and empirical data across diverse geologic and climatic environments.
Tectonic Controls on Surface Erosion Rates in the Longmen Shan, Eastern Tibet
Authors: Wang Wei , Godard Vincent , Liu‐Zeng Jing , Zhang Jinyu , Li Zhigang , Xu Sheng , Yao Wenqian , Yuan Zhaode , Aumaître Georges , Bourlès Didier L. , Keddadouche Karim
Published: February 2021

The Longmen Shan range, located on the eastern margin of the Tibetan Plateau, is characterized by steep topography and a shortening rate of <3 mm/yr. This peculiar configuration is a source of controversy and questions about the topographic evolution and dynamics of this orogenic plateau margin. Investigating the variations in surface denudation over different spatial and temporal scales is important for a better understanding of topographic evolution, but there is still a lack of erosion‐rate data averaged over millennial timescales along the frontal range of the Longmen Shan, especially in its southern part. We present 25 new catchment‐wide denudation rates derived from 10Be concentrations in river sediments across the southern Longmen Shan. Our results show that average denudation rates increase from <0.15 mm/yr near Ya'an, located in the Sichuan Basin, northwestward to >0.50 mm/yr inside the southern Longmen Shan. The denudation rates correlate with slope gradient, relief, channel steepness, and specific stream power but exhibit a fair degree of scattering at high values. In combination with previous 10Be and low‐temperature thermochronology analyses, we found the denudation rates over kyr‐ to Myr‐timescales to be roughly consistent across the southern Longmen Shan, suggesting this part of the range is close to an exhumational steady state. In terms of spatial distribution, high rates of exhumation and denudation are localized in the hanging walls of major thrust faults, highlighting the role of tectonic structures in regulating the pattern of denudation and topography across the Longmen Shan. Our results favor the “brittle crustal shortening” model in which rock uplift pattern across the Longmen Shan is largely controlled by upper crustal shortening. Along‐strike variations in the distribution of denudation rates and topography can probably be attributed to segmentation of subsurface fault structures.
Effect of prenatal lifestyle intervention on maternal postpartum weight retention and child body mass index z-score at 36 months
Authors: Phelan Suzanne , Hart Chantelle N. , Jelalian Elissa , Muñoz-Christian Karen , Alarcon Noemi , McHugh Angelica , Ventura Alison K. , Wing Rena R.
Published: February 2021

Background/Objectives

We previously reported results from a randomized trial showing that a behavioral intervention during pregnancy reduced excess gestational weight gain but did not impact maternal weight at 12 months. We now examine the longer-term effects of this prenatal intervention on maternal postpartum weight retention and toddler body-mass-index z scores (BMIz) over 36 months.

Subjects/Methods

Pregnant women (N = 264; 13.7 weeks’ gestation; 41.6% Hispanic) with overweight or obesity were randomized into usual care or prenatal intervention. Anthropometric assessments in mothers and toddlers occurred at baseline, 35 weeks’ gestation and after delivery at 6, 12, 18, 24, and 36 months.

Results

At 36 months, prenatal intervention vs. usual care had no significant effect on the proportion of participants who returned to their early pregnancy weight or below (33.3% vs. 39.5%;p = 0.12) and had no effect on the magnitude of weight retained (2.8 [0.8, 4.8] vs 3.0 kg [1.0, 4.9], respectively; mean difference = 0.14 [−3.0, 2.7]). There was also no statistically significant intervention vs. usual care effect on infant BMIz or skinfold changes over time; toddler BMIz increased by 1.4 [−1.7, 1.0] units in the intervention group and 1.6 [−1.2, 1.8] units in the usual care group from delivery to 36 months (difference = 0.16 [−0.32. 0.63]). The proportion of toddlers at risk for obesity at 36 months was similar in intervention and usual care groups (28/77 [36.4%] vs 30/80 [37.5%];p = 0.77).

Conclusions

Compared with usual care, lifestyle intervention during pregnancy resulted in similar maternal and toddler anthropometric outcomes at 36-months postpartum in a diverse US sample of women with overweight and obesity. To sustain improved maternal weight management initiated during pregnancy, continued intervention during the postpartum years may be needed.
Metabolites and diabetes remission after weight loss
Authors: Kwee Lydia Coulter , Ilkayeva Olga , Muehlbauer Michael J. , Bihlmeyer Nathan , Wolfe Bruce , Purnell Jonathan Q. , Xavier Pi-Sunyer F. , Chen Haiying , Bahnson Judy , Newgard Christopher B. , Shah Svati H. , Laferrère Blandine
Published: February 2021

There is marked heterogeneity in the response to weight loss interventions with regards to weight loss amount and metabolic improvement. We sought to identify biomarkers predictive of type 2 diabetes remission and amount of weight loss in individuals with severe obesity enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples using a nested design for diabetes remission over five years (n = 93 LABS,n = 80 Look AHEAD;n = 87 remitters), and for extremes of weight loss at five years (n = 151 LABS;n = 75 with high weight loss). Principal components analysis (PCA) was used for dimensionality reduction, with PCA-derived metabolite factors tested for association with both diabetes remission and weight loss. Metabolic markers were tested for incremental improvement to clinical models, including the DiaRem score. Two metabolite factors were associated with diabetes remission: one primarily composed of branched chain amino acids (BCAA) and tyrosine (odds ratio (95% confidence interval) [OR (95% CI)] = 1.4 [1.0–1.9],p = 0.045), and one with betaine and choline (OR [95% CI] = 0.7 [0.5–0.9],p = 0.02).These results were not significant after adjustment for multiple tests. Inclusion of these two factors in clinical models yielded modest improvements in model fit and performance: in a constructed clinical model, the C-statistic improved from 0.87 to 0.90 (p = 0.02), while the net reclassification index showed improvement in prediction compared to the DiaRem score (NRI = 0.26,p = 0.0013). No metabolite factors associated with weight loss at five years. Baseline levels of metabolites in the BCAA and trimethylamine-N-oxide (TMAO)-microbiome-related pathways are independently and incrementally associated with sustained diabetes remission after weight loss interventions in individuals with severe obesity. These metabolites could serve as clinically useful biomarkers to identify individuals who will benefit the most from weight loss interventions.
E3 ligase-inactivation rewires CBL interactome to elicit oncogenesis by hijacking RTK–CBL–CIN85 axis
Authors: Ahmed Syed Feroj , Buetow Lori , Gabrielsen Mads , Lilla Sergio , Sibbet Gary J. , Sumpton David , Zanivan Sara , Hedley Ann , Clark William , Huang Danny T.
Published: February 2021

Casitas B-lineage lymphoma (CBL) is a ubiquitin ligase (E3) that becomes activated upon Tyr371-phosphorylation and targets receptor protein tyrosine kinases for ubiquitin-mediated degradation. Deregulation of CBL and its E3 activity is observed in myeloproliferative neoplasms and other cancers, including breast, colon, and prostate cancer. Here, we explore the oncogenic mechanism of E3-inactive CBL mutants identified in myeloproliferative neoplasms. We show that these mutants bind strongly to CIN85 under normal growth conditions and alter the CBL interactome. Lack of E3 activity deregulates CIN85 endosomal trafficking, leading to an altered transcriptome that amplifies signaling events to promote oncogenesis. Disruption of CBL mutant interactions with EGFR or CIN85 reduces oncogenic transformation. Given the importance of the CBL–CIN85 interaction in breast cancers, we examined the expression levels of CIN85, CBL, and the status of Tyr371-phosphorylated CBL (pCBL) in human breast cancer tissue microarrays. Interestingly, pCBL shows an inverse correlation with both CIN85 and CBL, suggesting that high expression of inactivated CBL could coordinate with CIN85 for breast cancer progression. Inhibition of the CBL–CIN85 interaction with a proline-rich peptide of CBL that binds CIN85 reduced the proliferation of MDA-MB-231 cells. Together, these results provide a rationale for exploring the potential of targeting the EGFR–CBL–CIN85 axis in CBL-inactivated mutant cancers.
CRL4ADTL degrades DNA-PKcs to modulate NHEJ repair and induce genomic instability and subsequent malignant transformation
Authors: Feng Maoxiao , Wang Yunshan , Bi Lei , Zhang Pengju , Wang Huaizhi , Zhao Zhongxi , Mao Jian-Hua , Wei Guangwei
Published: February 2021

Genomic instability induced by DNA damage and improper DNA damage repair is one of the main causes of malignant transformation and tumorigenesis. DNA double strand breaks (DSBs) are the most detrimental form of DNA damage, and nonhomologous end-joining (NHEJ) mechanisms play dominant and priority roles in initiating DSB repair. A well-studied oncogene, the ubiquitin ligase Cullin 4A (CUL4A), is reported to be recruited to DSB sites in genomic DNA, but whether it regulates NHEJ mechanisms of DSB repair is unclear. Here, we discovered that the CUL4A-DTL ligase complex targeted the DNA-PKcs protein in the NHEJ repair pathway for nuclear degradation. Overexpression of either CUL4A or DTL reduced NHEJ repair efficiency and subsequently increased the accumulation of DSBs. Moreover, we demonstrated that overexpression of either CUL4A or DTL in normal cells led to genomic instability and malignant proliferation. Consistent with the in vitro findings, in human precancerous lesions, CUL4A expression gradually increased with increasing malignant tendency and was negatively correlated with DNA-PKcs and positively correlated with γ-H2AX expression. Collectively, this study provided strong evidence that the CUL4A-DTL axis increases genomic instability and enhances the subsequent malignant transformation of normal cells by inhibiting NHEJ repair. These results also suggested that CUL4A may be a prognostic marker of precancerous lesions and a potential therapeutic target in cancer.