Endocranial volumes and human evolution.

Enlarging brains have been held up as the classic (if not the only) example of a consistent long-term trend in human evolution.  And hominin endocranial volumes certainly expanded four-fold over the subfamily's seven-million-year history, while on a very coarse scale later hominids showed a strong tendency to have larger brains than earlier ones.  However, closer scrutiny of this apparent trend reveals that it was extremely episodic and irregular, a fact that argues against the notion that it was driven by social interactions internal to the hominin clade.  In addition, an overall tendency to brain volume increase was expressed independently and concurrently within at least three separate lineages of the genus Homo - suggesting that, whatever the exact influences were that promoted this global trend, they need to be sought among stimuli that acted comprehensively over the entire vast range of periods, geographies and environments that members of our subfamily occupied.  Significantly, though, the dramatic recent shrinkage of the brain within the species Homo sapiens implies that the emergence of modern human cognition (via the adoption of the symbolic information processing mode, likely driven by the spontaneous invention of language in an exaptively enabled brain) was not the culmination of the overall hominin trend towards brain enlargement, but rather a departure from it.

Risk of Radiation Dermatitis in Patients With Skin of Color Who Undergo Radiation to the Breast or Chest Wall With and Without Regional Nodal Irradiation.

PURPOSE: Acute radiation dermatitis (ARD) is common after radiation therapy for breast cancer, with data indicating that ARD may disproportionately affect Black or African American (AA) patients. We evaluated the effect of skin of color (SOC) on physician-reported ARD in patients treated with radiation therapy. METHODS AND MATERIALS: We identified patients treated with whole breast or chest wall ± regional nodal irradiation or high tangents using 50 Gy in 25 fractions from 2015 to 2018. Baseline skin pigmentation was assessed using the Fitzpatrick scale (I = light/pale white to VI = black/very dark brown) with SOC defined as Fitzpatrick scale IV to VI. We evaluated associations among SOC, physician-reported ARD, late hyperpigmentation, and use of oral and topical treatments for RD using multivariable models. RESULTS: A total of 325 patients met eligibility, of which 40% had SOC (n = 129). On multivariable analysis, Black/AA race and chest wall irradiation had a lower odds of physician-reported grade 2 or 3 ARD (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.030-0.397; P = .001; OR, 0.377; 95% CI, 0.161-0.883; P = .025), whereas skin bolus (OR, 8.029; 95% CI, 3.655-17.635; P = 0) and planning target volume D0.03cc (OR, 1.001; 95% CI, 1.000-1.001; P = .028) were associated with increased odds. On multivariable analysis, SOC (OR, 3.658; 95% CI, 1.236-10.830; P = .019) and skin bolus (OR, 26.786; 95% CI, 4.235-169.432; P = 0) were associated with increased odds of physician-reported late grade 2 or 3 hyperpigmentation. There was less frequent use of topical steroids to treat ARD and more frequent use of oral analgesics in SOC versus non-SOC patients (43% vs 63%, P < .001; 50% vs 38%, P = .05, respectively). CONCLUSIONS: Black/AA patients exhibited lower odds of physician-reported ARD. However, we found higher odds of late hyperpigmentation in SOC patients, independent of self-reported race. These findings suggest that ARD may be underdiagnosed in SOC when using the physician-rated scale despite this late evidence of radiation-induced skin toxicity.

Radiation-induced skin changes after breast or chest wall irradiation in patients with breast cancer and skin of color: a systematic review.

INTRODUCTION: The purpose of this study is to systematically review data pertaining to breast cancer and radiation-induced skin reactions in patients with skin of color (SOC), as well as data pertaining to objective measurements of skin pigmentation in the assessment of radiation dermatitis (RD). METHODS AND MATERIALS: We conducted a systematic review utilizing MEDLINE electronic databases to identify published studies until August 2022. Key inclusion criteria included studies that described RD in breast cancer with data pertaining to skin of color and/or characterization of pigmentation changes after radiation. RESULTS: We identified 17 prospective cohort studies, 7 cross-sectional studies, 5 retrospective studies and 4 randomized controlled trials. Prospective cohort and retrospective series demonstrate worse RD in African American (AA) patients using subjective physician-graded scales. There is more limited data in patients representing other non-White racial subgroups with SOC. 2 studies utilize patient reported outcomes and 15 studies utilize objective methods to characterize pigmentation change after radiation. There are no prospective and randomized studies that objectively describe pigmentation changes with radiotherapy in SOC. CONCLUSIONS: AA patients appear to have worse RD outcomes, though this is not uniformly observed across all studies. There are no studies that describe objective measures of RD and include baseline skin pigmentation as a variable, limiting the ability to draw uniform conclusions on the rate and impact of RD in SOC. We highlight the importance of objectively characterizing SOC and pigmentation changes before, during and after radiotherapy to understand the incidence and severity of RD in SOC.

Evolutionary theory, systematics, and the study of human origins.

Paleoanthropology's relationship with evolutionary theory has not been entirely happy. The anatomists who dominated paleoanthropology for its first century had little interest in biological diversity and its causes, or in hominins' place in that diversity, or in the rules and principles of zoological nomenclature - which they basically ignored entirely. When, as the twentieth century passed its midpoint, Ernst Mayr introduced theory to paleoanthropology in the form of the gradualist Modern Evolutionary Synthesis (in its most hardened form), he shocked students of human evolution not only into a strictly linear evolutionary mindset, but into a taxonomic minimalism that would for years obscure the signal of phylogenetic diversity and vigorous evolutionary experimentation among hominins that was starting to emerge from a rapidly enlarging hominin fossil record. Subsequently, the notion of episodic as opposed to gradualist evolution re-established phylogenies as typically branching, and species as bounded entities with births, histories, and deaths; but the implications of this revised perspective were widely neglected by paleoanthropologists, who continued to reflexively cram diverse new morphologies into existing taxonomic pigeonholes. For Pleistocene hominins, the effective systematic algorithm became, "if it isn't Australopithecus, it must be Homo" (or vice versa), thereby turning both taxa into wastebaskets. The recent development of the "Extended Evolutionary Synthesis" has only exacerbated the resulting caricature of phylogenetic structure within Homininae, by offering developmental/phenotypic plasticity as an excuse for associating wildly differing morphologies within the same taxon. Homo erectus has been a favorite victim of this foible. Biological species are indeed morphologically variable. But they are only variable within limits; and until we stop brushing diverse morphologies under the rug of developmental plasticity, paleoanthropology will remain at a major impasse.

What kind of hominin first left Africa?

Recent discoveries of stone tools from Jordan (2.5 Ma) and China (2.1 Ma) document hominin presence in Asia at the beginning of the Pleistocene, well before the conventional Dmanisi datum at 1.8 Ma. Although no fossil hominins documenting this earliest Out of Africa phase have been found, on chronological grounds a pre-Homo erectus hominin must be considered the most likely maker of those artifacts. If so, this sheds new light on at least two disputed subjects in paleoanthropology, namely the remarkable variation among the five Dmanisi skulls, and the ancestry of Homo floresiensis.

Cutaneous immune-related adverse events to checkpoint inhibitors.

The development of immunotherapy has led to a paradigm shift in the treatment of both solid and hematologic malignancies. As immunomodulatory therapies are employed with increasing frequency, a greater number of immune-related adverse reactions are being reported, and the majority of these involve the skin. As a result, dermatologists are increasingly becoming involved in the management of these cutaneous adverse reactions-often providing critical recommendations regarding ongoing cancer treatment. Cutaneous immune-related adverse reactions can vary significantly from patient to patient, making early recognition and timely intervention imperative to mitigate associated morbidity and potential treatment interruption. Although there is considerable overlap in the cutaneous adverse events caused by these immune checkpoint inhibitors, specific eruptions are characteristically associated with particular checkpoint inhibitors. In addition, a patient's comorbidities or immune status can play a significant role in the presentation and management of such adverse reactions. This review characterizes and provides management guidelines for the various cutaneous toxicities associated with checkpoint inhibitor therapy, including CTLA-4 inhibitors, PD-1 inhibitors, and PD-L1 inhibitors. © 2020 Elsevier Inc. All rights reserved.

Cutaneous Toxicities of Immune Checkpoint Inhibitors: The Role of the Dermatologist.

The advent of immune checkpoint inhibition represents a paradigm shift in the treatment of an increasing number of cancers. However, the incredible therapeutic promise of immunotherapy brings with it the need to understand and manage its diverse array of potential adverse events. The skin is the most common site of immune-related adverse vents (irAEs), which can present with a wide variety of disparate morphologies and severities. These toxicities can endanger patient health and the ability to continue on therapy. This review summarizes our current understanding of the presentation and management of the most common and clinically significant cutaneous irAEs associated with immune checkpoint inhibitor (ICI) therapy. Effective management of these cutaneous irAEs requires an understanding of their morphology, their appropriate clinical characterization, and their potential prognostic significance. Their treatment is additionally complicated by the desire to minimize compromise of the patient's anti-neoplastic regimen and emphasizes the use of non-immunosuppressive interventions whenever possible. However, though cutaneous irAEs represent a challenge to both oncologist and dermatologist alike, they offer a unique glimpse into the mechanisms that underlie not only carcinogenesis, but many primary dermatoses, and may provide clues to the treatment of disease even beyond cancer.

How assumptions shape the paleosciences.

Science is a very special form of storytelling, one in which the stories told have to be testable against empirical observation. But the world is a complicated place; and, to provide a coherent account of it, scientists often find themselves obliged to join up their observable dots using untestable or as-yet-untested lines. This is a necessary part of constructing many valuable and predictive scientific scenarios; and it is perfectly good procedure as long as the assumptions involved are fully compatible with what is known and testable. But it also means that, in formulating their ideas about how the world works (or worked), scientists must remain keenly aware not only of what is and is not assumption in those complex ideas, but of how untested elements may color their beliefs. The contributions to this volume cover many interesting examples of how assumptions have affected ideas in diverse areas of the paleosciences, both practical and theoretical, and they serve together as a salutary reminder that vigilance and a willingness to rethink are always in order.

The Minimalist Program and the Origin of Language: A View From Paleoanthropology.

In arguing that articulate language is underpinned by an algorithmically simple neural operation, the Minimalist Program (MP) retrodicts that language emerged in a short-term event. Because spoken language leaves no physical traces, its ancient use must be inferred from archeological proxies. These strongly suggest that modern symbolic human behavior patterns - and, by extension, cognition - emerged both abruptly and late in time (subsequent to the appearance of Homo sapiens as an anatomical entity some 200 thousand years kyr ago). Because the evidence is compelling that language is an integral component of modern symbolic thought, the archeological evidence clearly supports the basic tenet of the MP. But the associated proposition, that language was externalized in an independent event that followed its initial appearance as a conduit to internal thought, is much more debatable.

Melanoma and melanoma in-situ diagnosis after excision of atypical intraepidermal melanocytic proliferation: A retrospective cross-sectional analysis.

BACKGROUND: There is little evidence to guide surgical management of biopsies yielding the histologic descriptor atypical intraepidermal melanocytic proliferation (AIMP). OBJECTIVE: Determine frequency of and factors associated with melanoma and melanoma in-situ (MIS) diagnoses after excision of AIMP and evaluate margins used to completely excise AIMP. METHODS: Retrospective, cross-sectional study of 1127 biopsies reported as AIMP and subsequently excised within one academic institution. RESULTS: Melanoma (in situ, stage 1A) was diagnosed after excision in 8.2% (92/1127) of AIMP samples. Characteristics associated with melanoma/MIS diagnosis included age 60-79 years (odds ratio [OR] 8.1, 95% confidence interval [CI] 2.5-26.2), age ≥80 years (OR 7.2, 95% CI 1.7-31.5), head/neck location (OR 4.9, 95% CI 3.1-7.7), clinical lesion partially biopsied (OR 11.0, 95% CI 6.7-18.1), and lesion extending to deep biopsy margin (OR 15.1, 95% CI 1.7-136.0). Average ± standard deviation surgical margin used to excise AIMP lesions was 4.5 ± 1.8 mm. LIMITATIONS: Single-site, retrospective, observational study; interobserver variability across dermatopathologists. CONCLUSION: Dermatologists and pathologists can endeavor to avoid ambiguous melanocytic designations whenever possible through excisional biopsy technique, interdisciplinary communication, and ancillary studies. In the event of AIMP biopsy, physicians should consider the term a histologic description rather than a diagnosis, and, during surgical planning, use clinicopathologic correlation while bearing in mind factors that might predict true melanoma/MIS.

The story of life: critical insights from evolutionary biology.

The notion that humans, in all their complexity, are merely an evolutionary accident, an insignificant speck in a boundless cosmos, is deeply unsatisfying for most nonscientists and fails to resonate with their life experience. What, then, can evolutionary biology ultimately tell us about the meaning of our lives? In conversation with Steve Paulson, executive producer and host of To the Best of Our Knowledge, paleoanthropologists Melanie Lee Chang and Ian Tattersall, and paleontologist Simon Conway Morris share their insights on these competing concepts and explain how meaning and purpose can be gleaned from the remarkable story of life itself.

Evolution and inevitability.

Questions not only about the nature of evolution but also about the vastness of the Universe are addressed, as are speculations about the nature of life had evolution taken another route or on other planets.