An integrative skeletal and paleogenomic analysis of stature variation suggests relatively reduced health for early European farmers.

Human culture, biology, and health were shaped dramatically by the onset of agriculture ∼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared "predicted" genetic contributions to height from paleogenomic data and "achieved" adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (∼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets.

During infection, naive CD8(+) T cells differentiate into effector cells, which are armed to eliminate pathogens, and memory cells, which are poised to protect against reinfection. The transcriptional program that regulates terminal differentiation into short-lived effector-memory versus long-lived memory cells is not clearly defined. Through the use of mice expressing reporters for the DNA-binding inhibitors Id2 and Id3, we identified Id3(hi) precursors of long-lived memory cells before the peak of T cell population expansion or upregulation of cell-surface receptors that indicate memory potential. Deficiency in Id2 or Id3 resulted in loss of distinct CD8(+) effector and memory populations, which demonstrated unique roles for these inhibitors of E-protein transcription factors. Furthermore, cytokines altered the expression of Id2 and Id3 differently, which provides insight into how external cues influence gene expression.

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes.

BACKGROUND: Hansen's disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease's complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period. RESULTS: Here, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae's genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria. CONCLUSIONS: Our findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease's global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy's global history and can contribute to current models of M. leprae's worldwide dissemination, including interspecies transmissions.

Pneumocystis jirovecii Pneumonia in Patients With Metastatic Prostate Cancer on Corticosteroids for Malignant Spinal Cord Compression: Two Case Reports and a Guideline Review.

Pneumocystis jirovecii, formerly known as Pneumocystis carinii, is an atypical fungal pathogen best known for causing Pneumocystis jirovecii pneumonia (PCP). The epidemiology of PCP is changing such that patients without HIV infection now comprise the largest subset of individuals diagnosed with PCP. While those with hematologic malignancies and organ transplants are at greatest risk for non-HIV-related PCP, this review will focus on PCP in patients with solid tumors. They are at risk for PCP due to their chemotherapy regimens and use of steroids in the management of various complications of treatment, and possibly because of the immunosuppressive effect of the cancer itself. In particular, patients with solid tumors being treated for metastatic spinal cord compression are at great risk for PCP. Patients with solid tumors and PCP face greater mortality than those with HIV infection. Multiple reviews have attempted to describe the ideal regimen of corticosteroids for metastatic spinal cord compression, but there is little consensus. We present 2 cases of patients with metastatic spinal cord compression due to prostate cancer undergoing radiation therapy and treatment with corticosteroids. These cases highlight the difficulties in predicting the length of corticosteroid therapy and the dangers that patients face without appropriate prophylaxis. This article will also provide a review of the current guidelines for PCP prophylaxis in patients undergoing treatment for metastatic spinal cord compression. We recommend empiric treatment with trimethoprim-sulfamethoxazole or dapsone in those patients with a sulfa allergy in all patients with solid tumors when any high-dose steroids are started for the treatment of metastatic spinal cord compression. Further research is needed to assess the epidemiology of PCP in patients with solid tumors and additional trials are necessary to refine PCP prophylaxis.

Effect of Reader and Patient Parameters on the Performance of Last-Image-Hold for Fluoroscopic Grading of Vesicoureteric Reflux.

OBJECTIVE. The purpose of this study is to determine the effect of different reader and patient parameters on the degree of agreement and the rate of misclassification of vesicoureteric reflux grading on last-image-hold frames in relation to spot-exposed frames from voiding cystourethrography (VCUG) as well as to determine the nature of reflux misclassification on last-image-hold frames. MATERIALS AND METHODS. Blinded readers conducted a retrospective evaluation of last-image-hold and spot-exposed frames of the renal fossae from 191 sequential VCUG examinations performed during a five-year period. Kappa tests were used to determine the agreement between reflux gradings and to assess the impact of reader and patient parameters. Pearson product-moment correlations were used to evaluate the effect of patient parameters on reader level of certainty regarding reflux grading. RESULTS. We measured almost perfect overall agreement for more experienced readers and substantial overall agreement for less experienced readers. Point estimates of overall misclassification were less than 2% for more experienced readers and less than 4% for less experienced readers. The readers' level of certainty about reflux grading had a positive impact on agreement values and misclassification rates. Experienced readers' most common misclassification was assigning reflux a grade of 3 on a spot-exposed frame and a grade of 2 on an equivalent last-image-hold frame. Inexperienced readers' most common misclassification involved missing reflux altogether. CONCLUSION. Instances of grade 2 reflux on last-image-hold frames may warrant supplemental evaluation with spot-exposed frames. Otherwise, a reader's level of certainty regarding reflux grading on a last-image-hold frame may help determine whether a supplemental spot-exposed frame would be beneficial.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI.

OBJECTIVE: The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. MATERIALS AND METHODS: Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. RESULTS: Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. CONCLUSION: Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to perform biopsy.

MRI-Ultrasound Fusion Targeted Biopsy of Prostate Imaging Reporting and Data System Version 2 Category 5 Lesions Found False-Positive at Multiparametric Prostate MRI.

OBJECTIVE: The purpose of this study was to determine imaging and clinical features associated with Prostate Imaging Reporting and Data System (PI-RADS) category 5 lesions identified prospectively at multiparametric MRI (mpMRI) that were found benign at MRI-ultrasound fusion targeted biopsy. MATERIALS AND METHODS: Between January 2015 and July 2016, 325 men underwent prostate mpMRI followed by MRI-ultrasound fusion targeted biopsy of 420 lesions prospectively identified and assessed with PI-RADS version 2. The frequency of clinically significant prostate cancer (defined as Gleason score ≥ 7) among PI-RADS 5 lesions was determined. Lesions with benign pathologic results were retrospectively reassessed by three abdominal radiologists and categorized as concordant or discordant between mpMRI and biopsy results. Multivariate logistic regression was used to identify factors associated with benign disease. Bonferroni correction was used. RESULTS: Of the 98 PI-RADS 5 lesions identified in 89 patients, 18% (18/98) were benign, 10% (10/98) were Gleason 6 disease, and 71% (70/98) were clinically significant prostate cancer. Factors associated with benign disease at multivariate analysis were lower prostate-specific antigen density (odds ratio [OR], 0.88; p < 0.001) and apex (OR, 3.54; p = 0.001) or base (OR, 7.11; p = 0.012) location. On secondary review of the 18 lesions with benign pathologic results, 39% (7/18) were scored as benign prostatic hyperplasia nodules, 28% (5/18) as inflammatory changes, 5% (1/18) as normal anatomic structures, and 28% (5/18) as discordant with imaging findings. CONCLUSION: PI-RADS 5 lesions identified during routine clinical interpretation are associated with a high risk of clinically significant prostate cancer. A benign pathologic result was significantly correlated with lower prostate-specific antigen density and apex or base location and most commonly attributed to a benign prostatic hyperplasia nodule. Integration of these clinical features may improve the interpretation of high-risk lesions identified with mpMRI.

Role of MRI in the Use of an Absorbable Hydrogel Spacer in Men Undergoing Radiation Therapy for Prostate Cancer: What the Radiologist Needs to Know.

OBJECTIVE: Hydrogel spacers have a novel role in the treatment of low- and intermediate-risk prostate cancer with dose-escalated radiation therapy. Given the growing number of patients undergoing treatment with radiation therapy, the use of hydrogel spacers is expected to increase. The purpose of this article is to review what a radiologist needs to know about the imaging of hydrogel spacers, including MRI technique and appearance on CT and MRI. CONCLUSION: MRI has a critical role in the evaluation of hydrogel spacer placement and is used to facilitate contouring by the radiation oncologist. The radiologist should be familiar with the imaging appearance of hydrogel spacers on CT and MRI to avoid interpretation pitfalls and errors.

Immediate replacement of fishing with dairying by the earliest farmers of the Northeast Atlantic archipelagos.

The appearance of farming, from its inception in the Near East around 12 000 years ago, finally reached the northwestern extremes of Europe by the fourth millennium BC or shortly thereafter. Various models have been invoked to explain the Neolithization of northern Europe; however, resolving these different scenarios has proved problematic due to poor faunal preservation and the lack of specificity achievable for commonly applied proxies. Here, we present new multi-proxy evidence, which qualitatively and quantitatively maps subsistence change in the northeast Atlantic archipelagos from the Late Mesolithic into the Neolithic and beyond. A model involving significant retention of hunter-gatherer-fisher influences was tested against one of the dominant adoptions of farming using a novel suite of lipid biomarkers, including dihydroxy fatty acids, ω-(o-alkylphenyl)alkanoic acids and stable carbon isotope signatures of individual fatty acids preserved in cooking vessels. These new findings, together with archaeozoological and human skeletal collagen bulk stable carbon isotope proxies, unequivocally confirm rejection of marine resources by early farmers coinciding with the adoption of intensive dairy farming. This pattern of Neolithization contrasts markedly to that occurring contemporaneously in the Baltic, suggesting that geographically distinct ecological and cultural influences dictated the evolution of subsistence practices at this critical phase of European prehistory.

Significance of histology in determining management of lesions regrowing after radiosurgery.

Brain metastases treated with stereotactic radiosurgery may show delayed enlargement on post-treatment imaging that is of ambiguous etiology. Histopathologic interpretation of brain specimens is often challenging due to the presence of significant radiation effects admixed with irradiated residual tumor of indeterminate viability. The purpose of this study was to assess the impact of histologic findings on clinical outcomes following resection of these lesions. Between 2004 and 2010, 690 patients with brain metastases were enrolled in a prospective gamma knife data repository, and lesions requiring excision were identified. Tissue specimens were divided into four groups based on the ratio of treatment related inflammatory changes (TRIC) to tumor cells, and subsequently patient outcomes were assessed. Of 2,583 metastases treated, 36 were excised due to symptomatic enlargement. Only TRIC, without residual evidence of tumor, was seen in 36 % (13/36) of specimens. Resection of these lesions resulted in 100 % local control in follow-up. Of the remaining 23 lesions that contained any viable-appearing tumor within the resected specimen, 8 recurred after resection. Lesions that enlarged in the first 6 months were more likely to contain higher amounts of residual tumor cells. Patients with even <2 % tumors cells on excision had significantly worse local control (75 vs. 100 %, p = 0.024) and survival (HR 0.27, p = 0.029) compared with those patients with exclusively TRIC. In summary, our findings underscore the importance of surgically obtaining tissue in a method that facilitates complete lesional interpretive histology in order to accurately guide ongoing patient management.

"Fact" and "fiction": enlivening health care education.

PURPOSE: This paper aims to demonstrate how close analysis of cultural narratives can be employed as effective pedagogical tools in the explication and critique of specific workplace issues relevant to health management education. DESIGN/METHODOLOGY/APPROACH: Two narratives have been selected to illustrate this point: the apparently "fictional" UK-based medical television drama series Bodies (2005-2006) and the apparently "factual" report of an Australian state government public inquiry into acute health care, the Garling Report. FINDINGS: Through their demonstration of how analyses of selected segments of these texts can be used in health management education, the authors conclude that the comparative analyses of ostensibly "fictional" and "factual" narratives allow for analysis and critique of the inadequacies of new public management (NPM) applied to the health care industry, leading to a greater understanding of wider ideological effects on public perceptions. PRACTICAL IMPLICATIONS: The authors argue that these understandings enliven students' learning experiences, and that such comparative analyses should be applied more widely across health management education to develop students' critical skills and openness to exploring alternative models. ORIGINALITY/VALUE: Comparative analysis of cultural texts is novel in health care education, and allows for the interrogation of ideology and its effects.

Human consumption of seaweed and freshwater aquatic plants in ancient Europe.

During the Mesolithic in Europe, there is widespread evidence for an increase in exploitation of aquatic resources. In contrast, the subsequent Neolithic is characterised by the spread of farming, land ownership, and full sedentism, which lead to the perception of marine resources subsequently representing marginal or famine food or being abandoned altogether even at the furthermost coastal limits of Europe. Here, we examine biomarkers extracted from human dental calculus, using sequential thermal desorption- and pyrolysis-GCMS, to report direct evidence for widespread consumption of seaweed and submerged aquatic and freshwater plants across Europe. Notably, evidence of consumption of these resources extends through the Neolithic transition to farming and into the Early Middle Ages, suggesting that these resources, now rarely eaten in Europe, only became marginal much more recently. Understanding ancient foodstuffs is crucial to reconstructing the past, while a better knowledge of local, forgotten resources is likewise important today.

Limited historical admixture between European wildcats and domestic cats.

Domestic cats were derived from the Near Eastern wildcat (Felis lybica), after which they dispersed with people into Europe. As they did so, it is possible that they interbred with the indigenous population of European wildcats (Felis silvestris). Gene flow between incoming domestic animals and closely related indigenous wild species has been previously demonstrated in other taxa, including pigs, sheep, goats, bees, chickens, and cattle. In the case of cats, a lack of nuclear, genome-wide data, particularly from Near Eastern wildcats, has made it difficult to either detect or quantify this possibility. To address these issues, we generated 75 ancient mitochondrial genomes, 14 ancient nuclear genomes, and 31 modern nuclear genomes from European and Near Eastern wildcats. Our results demonstrate that despite cohabitating for at least 2,000 years on the European mainland and in Britain, most modern domestic cats possessed less than 10% of their ancestry from European wildcats, and ancient European wildcats possessed little to no ancestry from domestic cats. The antiquity and strength of this reproductive isolation between introduced domestic cats and local wildcats was likely the result of behavioral and ecological differences. Intriguingly, this long-lasting reproductive isolation is currently being eroded in parts of the species' distribution as a result of anthropogenic activities.

Translabial Ultrasound: An Effective Modality for Evaluation of Midurethral Sling Revision.

ABSTRACT: Midurethral sling (MUS) surgical procedures, in which a polypropylene synthetic mesh graft is transvaginally placed to support the urethra and manage stress urinary incontinence (SUI), is commonly performed ( Urology. 2013;82(1):38-41; Radiology. 2018;289(3):728-729). Within 10 years of sling placement, about 1 in 20 women undergo subsequent surgery to revise their mesh, in which the mesh is cut or partially excised ( Obstet Gynecol . 2019;133:1099-1108). Translabial ultrasound (TLUS) has been described as a sensitive technique for viewing MUS, although few studies have evaluated its ability to view surgically revised MUS ( Radiology . 2018;289(3):721-727). Understanding the anatomy of the MUS is critical to urologists and urogynecologists striving to optimize management of patients presenting with lower urinary tract symptoms and history of MUS. To assess the clinical utility and reliability of TLUS as a diagnostic tool in its detection of MUS discontinuity, we conducted a retrospective analysis on patients who underwent TLUS at a tertiary care center between September 2017 and May 2020 for indication of lower urinary tract symptoms and history of MUS placement. Performance of TLUS was evaluated by comparing findings with operative or clinical records. Among the 81 women included, detection of MUS revision, which was defined as a discontinuity in sling material, had a sensitivity of 84.6% and specificity of 97.1%. Translabial ultrasound is an inexpensive, nonirradiating, and noninvasive modality that is effective at visualizing MUSs. It is a reliable identifier of previous MUS revision, in which it detects a midline discontinuity of the hyperechoic mesh with an average 10 mm gap.

Defining Soft Tissue: Bitmap Printing of Soft Tissue for Surgical Planning.

Nearly all applications of 3D printing for surgical planning have been limited to bony structures and simple morphological descriptions of complex organs due to the fundamental limitations in accuracy, quality, and efficiency of the current modeling paradigms and technologies. Current approaches have largely ignored the constitution of soft tissue critical to most surgical specialties where multiple high-resolution variations transition gradually across the interior of the volume. Differences in the scales of organization related to unique organs require special attention to capture fine features critical to surgical procedures. We present a six-material bitmap printing technique for creating 3D models directly from medical images, which are superior in spatial and contrast resolution to current 3D modeling methods, and contain previously unachievable spatial fidelity for soft tissue differentiation. A retrospective exempt IRB was obtained for all data through the Colorado Multiple Institution Review Board #21-3128.

Solid Pseudopapillary Neoplasm: A Single Institutional Case Series of a Rare Pancreatic Tumor.

Purpose: Solid pseudopapillary neoplasms (SPN) are rare pancreatic cystic neoplasms with low malignant potential that tend to occur in young women. Due to the rarity of this disease, there are few large case series in the literature, and the exact pathophysiology remains unknown. In this article, we aim to share our institutional experience. Methods: Retrospective clinical data collection and analysis was performed on all patients with a diagnosis of SPN at the University of Colorado Hospital and Children's Hospital of Colorado (n = 28). Results: Twenty-eight patients were diagnosed with SPN during the study period. The median age was 21.5 years, and the majority of patients were female (89.3%) and Caucasian (60.7%). Six patients were diagnosed incidentally (21.4%). The majority of tumors were in the pancreatic tail (46.4%), and most underwent distal pancreatectomy (64.3%). The mean tumor size was 5.4 cm, and R0 resection was achieved in 25 patients (89.3%). Ten patients underwent laparoscopic resection (35.7%). The median hospital length of stay was 8.5 days, and postoperative complication rate was 39.3%. Median follow-up was 41 months, with 78.6% of patients alive without evidence of disease, while 2 patients were lost to follow-up. Two patients developed recurrence/metastases, which were resected; both are alive without evidence of disease. Conclusion: SPN are rare pancreatic tumors diagnosed most frequently in young women. Surgical resection is the mainstay of treatment, and outcomes are excellent if complete resection is achieved. Predictors of malignant disease are inconsistent in current literature. Considerations should be made for a minimally invasive approach in patients with SPN. Multidisciplinary clinics may be helpful in the diagnosis, management, and surveillance of pancreatic cystic lesions, with major potential for the advanced practitioner role.

Neolithic culinary traditions revealed by cereal, milk and meat lipids in pottery from Scottish crannogs.

Cereal cultivation in Britain dates back to ca. 4000 BCE, probably introduced by migrant farmers from continental Europe. Widespread evidence for livestock appears in the archaeozoological record, also reflected by ubiquitous dairy lipids in pottery organic residues. However, despite archaeobotanical evidence for domesticated plants (such as cereals), organic residue evidence has been near-absent. Our approach, targeting low-abundance cereal-specific markers, has now revealed evidence for cereals (indicating wheat) in Neolithic pottery from Scottish 'crannogs', dating to ca. 3600 - 3300 BCE. Their association with dairy products suggests cereals may have been regularly prepared together as a milk-based gruel. We also observed a strong association between the occurrence of dairy products and smaller-mouthed vessels. Here, we demonstrate that cereal-specific markers can survive in cooking pots for millennia, revealing the consumption of specific cereals (wheat) that are virtually absent from the archaeobotanical record for this region and illuminating culinary traditions among early farming communities.