Mixture toxicity, cumulative risk, and environmental justice in United States federal policy, 1980-2016 : Why, with much known, was little done?

Toxic chemicals - "toxicants" - have been studied and regulated as single entities, and, carcinogens aside, almost all toxicants, single or mixed and however altered, have been thought harmless in very low doses or very weak concentrations. Yet much work in recent decades has shown that toxicants can injure wildlife, laboratory animals, and humans following exposures previously expected to be harmless. Additional work has shown that toxicants can act not only individually and cumulatively but also collectively and even synergistically and that they affect disadvantaged communities inordinately - and therefore, as argued by reformers, unjustly. As late as December 2016, the last full month before the inauguration of a president promising to rescind major environmental regulations, the United States federal environmental-health establishment, as led by the Environmental Protection Agency (EPA), had not developed coherent strategies to mitigate such risks, to alert the public to their plausibility, or to advise leadership in government and industry about their implications. To understand why, we examined archival materials, reviewed online databases, read internal industry communications, and interviewed experts. We confirmed that external constraints, statutory and judicial, had been in place prior to EPA's earliest interest in mixture toxicity, but we found no overt effort, certainly no successful effort, to loosen those constraints. We also found internal constraints: concerns that fully committing to the study of complex mixtures involving numerous toxicants would lead to methodological drift within the toxicological community and that trying to act on insights from such study could lead only to regulatory futility. Interaction of these constraints, external and internal, shielded the EPA by circumscribing its responsibilities and by impeding movement toward paradigmatic adjustment, but it also perpetuated scientifically dubious policies, such as those limiting the evaluation of commercial chemical formulations, including pesticide formulations, to only those ingredients said by their manufacturers to be active. In this context, regulators' disregard of synergism contrasted irreconcilably with biocide manufacturers' understanding that synergism enhanced lethality and patentability. In the end, an effective national response to mixture toxicity, cumulative risk, and environmental injustice did not emerge. In parallel, though, the National Institute of Environmental Health Sciences, which was less constrained, pursued with scientific investigation what the EPA had not pursued with regulatory action.

Were our critics right about the Stasi?

BACKGROUND: Disinformation, now best known generically as "fake news," is an old and protean weapon. Prominent in the 1980s was AIDS disinformation, including the HIV-from-Fort-Detrick myth, for whose propagation some figures ultimately admitted blame while others shamelessly claimed credit. In 2013 we reported a comprehensive analysis of this myth, finding leading roles for the Soviet Union's state security service, the KGB, and for biologist and independent conspiracy theorist Jakob Segal but not for East Germany's state security service, the Stasi. We found Stasi involvement had been much less extensive and much less successful than two former Stasi officers had begun claiming following German reunification. In 2014 two historians crediting the two former Stasi officers coauthored a monograph challenging our analysis and portraying the Stasi as having directed Segal, or at least as having used him as a "conscious or unconscious multiplier," and as having successfully assisted a Soviet bloc AIDS-disinformation conspiracy that they soon inherited and thenceforth led. In 2017 a German appellate court found our 2013 analysis persuasive in a defamation suit brought by a filmmaker whose work the 2014 monograph had depicted as co-funded by the Stasi. Question and methods. Were our critics right about the Stasi? We asked and answered ten subsidiary questions bearing upon our critics' arguments, reassessing our own prior work and probing additional sources including archives of East Germany's Partei- und Staatsführung [party-and-state leadership] and the recollections of living witnesses. FINDINGS: Jakob Segal transformed and transmitted the myth without direction from the KGB or the Stasi or any element of East Germany's party-and-state leadership. The Stasi had trouble even tracking Segal's activities, which some officers feared would disadvantage East Germany scientifically, economically, and politically. Three officers in one Stasi section did show interest in myth propagation, but their efforts were late, limited, inept, and inconsequential. CONCLUSION: The HIV-from-Fort-Detrick myth, most effectively promoted by Jakob Segal acting independently of any state's security service, was not, contrary to claims, a Stasi success.

Solid-Cystic Hidradenoma: A Dorsal Foot Presentation.

Solid-cystic hidradenoma is a benign cutaneous tumor with eccrine sweat gland origins that is most commonly found in the head, neck, trunk, and upper extremity regions of patients in the middle to older age groups. These lesions are generally asymptomatic, slow-growing, solitary, and nonulcerative in presentation. Degenerative malignant transformation of this tumor is very rare. In this case report, the authors describe the marginal surgical excision and subsequent microscopic pathologic diagnosis of a moderate sized solid-cystic hidradenoma of the dorsolateral forefoot in a middle-aged male patient.

A sequence-based identification of the genes detected by probesets on the Affymetrix U133 plus 2.0 array.

One of the biggest problems facing microarray experiments is the difficulty of translating results into other microarray formats or comparing microarray results to other biochemical methods. We believe that this is largely the result of poor gene identification. We re-identified the probesets on the Affymetrix U133 plus 2.0 GeneChip array. This identification was based on the sequence of the probes and the sequence of the human genome. Using the BLAST program, we matched probes with documented and postulated human transcripts. This resulted in the redefinition of approximately 37% of the probes on the U133 plus 2.0 array. This updated identification specifically points out where the identification is complicated by cross-hybridization from splice variants or closely related genes. More than 5000 probesets detect multiple transcripts and therefore the exact protein affected cannot be readily concluded from the performance of one probeset alone. This makes naming difficult and impacts any downstream analysis such as associating gene ontologies, mapping affected pathways or simply validating expression changes. We have now automated the sequence-based identification and can more appropriately annotate any array where the sequence on each spot is known.

Glomus Tumor of the Toe.

A glomus tumor is an uncommon, predominantly benign, neoplastic lesion that primarily involves a thermoregulatory microvascular apparatus, the glomus body. Although these lesions can occur anywhere in the body, the subungual tissue of the hand represents the most common presentation site. Glomus tumors are not often encountered in the foot. Symptoms traditionally include the classic triad of pain, pressure, and cold sensitivity. This case report describes a variant location for a glomus tumor in the subcuticular tissue adjacent to the medial middle phalanx of the second toe. The nonsubungual location for this presentation should prompt the inclusion of glomus tumor in a digital soft-tissue lesion differential diagnosis. The lesion was excised surgically and was subsequently diagnosed histopathologically as a glomus tumor.

Angioleiomyoma of the Lower Leg.

Angioleiomyomas are benign tumefactions that originate from smooth muscle in vascular structures and are difficult to definitively diagnose preoperatively. Although these lesions are rarely encountered in the foot, the lower extremity is the most common site of occurrence. An angioleiomyoma typically manifests as a small, painful, solitary, mobile lesion. This case report describes a lateral retromalleolar para-Achilles tendon insertional location for a moderately sized immobile solid tumefaction in the subcutaneous tissues. The lesion was nonpainful and progressively enlarged over 5 years. An excisional biopsy was performed, and the nodular lesion was subsequently diagnosed histopathologically as an angioleiomyoma. Owing to the ambiguous nature of the clinical findings, angioleiomyoma should be included in the differential diagnosis of lower-extremity soft-tissue manifestations.

Disinformation squared: Was the HIV-from-Fort-Detrick myth a Stasi Success? ­ CORRIGENDUM.

Doi: 10.2990/32_2_2 , published by Association for Politics and the Life Sciences at Texas Tech University and the University of Maryland School of Public Policy, October 2013.

Disinformation squared: was the HIV-from-Fort-Detrick myth a Stasi success?

BACKGROUND: When in May 1983 the acquired immunodeficiency syndrome (AIDS) was first securely attributed to a virus, eventually called the human immunodeficiency virus (HIV), many controversies arose. Among these was one centering on HIV's origin. A startling hypothesis, called here the "HIV-from-Fort-Detrick myth," asserted that HIV had been a product, accidental or intentional, of bioweaponry research. While its earliest identifiable contributors were in the West, this myth's most dynamic propagators were in the East. The Soviet security service, the KGB, took "active measures" to create and disseminate AIDS disinformation beginning no later than July 1983 and ending no earlier than October 1987. The East German security service, a complex bureaucracy popularly known as "the Stasi," was involved, too, but how early, how deeply, how uniformly, how ably, and how successfully has not been clear. Following German reunification, claims arose attributing to the Stasi the masterful execution of ingenious elements in a disinformation campaign they helped shape and soon came to dominate. We have tested these claims. QUESTION: Was the HIV-from-Fort-Detrick myth a Stasi success? METHODS: Primary sources were documents and photographs assembled by the Ministry of State Security (MfS) of the German Democratic Republic (GDR or East Germany), the Ministry of Interior of the People's Republic of Bulgaria, and the United States Department of State; the estate of myth principals Jakob and Lilli Segal; the "AIDS box" in the estate of East German literary figure Stefan Heym; participant-observer recollections, interviews, and correspondence; and expert interviews. We examined secondary sources in light of primary sources. FINDINGS: The HIV-from-Fort-Detrick myth had debuted in print in India in 1983 and had been described in publications worldwide prior to 1986, the earliest year for which we found any Stasi document mentioning the myth in any context. Many of the myth's exponents were seemingly independent conspiracy theorists. Its single most creative exponent was Jakob Segal, an idiosyncratic Soviet biologist long resident in, and long retired in, the GDR. Segal applied to the myth a thin but tenacious layer of plausibility. We could not exclude a direct KGB influence on him but found no evidence demonstrating it. The Stasi did not direct his efforts and had difficulty tracking his activities. The Stasi were prone to interpretive error and self-aggrandizement. They credited themselves with successes they did not achieve, and, in one instance, failed to appreciate that a major presumptive success had actually been a fiasco. Senior Stasi officers came to see the myth's propagation as an embarrassment threatening broader interests, especially the GDR's interest in being accepted as a scientifically sophisticated state. In 1986, 1988, and 1989, officers of HV A/X, the Stasi's disinformation and "active measures" department, discussed the myth in meetings with the Bulgarian secret service. In the last of these meetings, HV A/X officers tried to interest their Bulgarian counterparts in taking up, or taking over, the myth's propagation. Further efforts, if any, were obscured by collapse of the East German and Bulgarian governments. CONCLUSION: No, the HIV-from-Fort-Detrick myth was not a Stasi success. Impressions to the contrary can be attributed to reliance on presumptions, boasts, and inventions. Presumptions conceding to the Stasi an extraordinary operational efficiency and an irresistible competence - qualities we could not confirm in this case - made the boasts and inventions more convincing than their evidentiary basis, had it been known, would have allowed. The result was disinformation about disinformation, a product we call "disinformation squared."

The missing politics and unsettled science of the trend toward earlier puberty.

The age of puberty in many populations has declined steeply over recent centuries and may be declining still. Consequently, today's children tend to experience the hormonal stresses of rapid development at younger ages than did their ancestors, around whose later, if not more gradual, maturation traditional behavioral expectations formed. Little has been made of this "rush to puberty" outside the life sciences. This article reviews its historical documentation, scholarly appreciation, epidemiological correlations, putative physiological and environmental explanations, sociological implications, and largely latent politics.