Survival probabilities in time-dependent random walks

We analyze the dynamics of random walks in which the jumping probabilities are periodic {\it time-dependent} functions. In particular, we determine the survival probability of biased walkers who are drifted towards an absorbing boundary. The typical life-time of the walkers is found to decrease with an increment of the oscillation amplitude of the jumping probabilities. We discuss the applicability of the results in the context of complex adaptive systems.Comment: 4 pages, 3 figure

Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system.

Targeted recombination was carried out to select mouse hepatitis viruses (MHVs) in a defined genetic background, containing an MHV-JHM spike gene encoding either three heptad repeat 1 (HR1) substitutions (Q1067H, Q1094H, and L1114R) or L1114R alone. The recombinant virus, which expresses spike with the three substitutions, was nonfusogenic at neutral pH. Its replication was significantly inhibited by lysosomotropic agents, and it was highly neuroattenuated in vivo. In contrast, the recombinant expressing spike with L1114R alone mediated cell-to-cell fusion at neutral pH and replicated efficiently despite the presence of lysosomotropic agents; however, it still caused only subclinical morbidity and no mortality in animals. Thus, both recombinant viruses were highly attenuated and expressed viral antigen which was restricted to the olfactory bulbs and was markedly absent from other regions of the brains at 5 days postinfection. These data demonstrate that amino acid substitutions, in particular L1114R, within HR1 of the JHM spike reduced the ability of MHV to spread in the central nervous system. Furthermore, the requirements for low pH for fusion and viral entry are not prerequisites for the highly attenuated phenotype

The rise and fall of viticulture in the Late Antique Negev Highlands reconstructed from archaeobotanical and ceramic data.

The international scope of the Mediterranean wine trade in Late Antiquity raises important questions concerning sustainability in an ancient international economy and offers a valuable historical precedent to modern globalization. Such questions involve the role of intercontinental commerce in maintaining sustainable production within important supply regions and the vulnerability of peripheral regions believed to have been especially sensitive to environmental and political disturbances. We provide archaeobotanical evidence from trash mounds at three sites in the central Negev Desert, Israel, unraveling the rise and fall of viticulture over the second to eighth centuries of the common era (CE). Using quantitative ceramic data obtained in the same archaeological contexts, we further investigate connections between Negev viticulture and circum-Mediterranean trade. Our findings demonstrate interrelated growth in viticulture and involvement in Mediterranean trade reaching what appears to be a commercial scale in the fourth to mid-sixth centuries. Following a mid-sixth century peak, decline of this system is evident in the mid- to late sixth century, nearly a century before the Islamic conquest. These findings closely correspond with other archaeological evidence for social, economic, and urban growth in the fourth century and decline centered on the mid-sixth century. Contracting markets were a likely proximate cause for the decline; possible triggers include climate change, plague, and wider sociopolitical developments. In long-term historical perspective, the unprecedented commercial florescence of the Late Antique Negev appears to have been unsustainable, reverting to an age-old pattern of smaller-scale settlement and survival-subsistence strategies within a time frame of about two centuries

Detection and Molecular Characterization of 9000-Year-Old Mycobacterium tuberculosis from a Neolithic Settlement in the Eastern Mediterranean

Background: Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis. It has no environmental reservoir and is believed to have co-evolved with its host over millennia. This is supported by skeletal evidence of the disease in early humans, and inferred from M. tuberculosis genomic analysis. Direct examination of ancient human remains for M. tuberculosis biomarkers should aid our understanding of the nature of prehistoric tuberculosis and the host/pathogen relationship.Methodology/Principal Findings: We used conventional PCR to examine bone samples with typical tuberculosis lesions from a woman and infant, who were buried together in the now submerged site of Atlit-Yam in the Eastern Mediterranean, dating from 9250-8160 years ago. Rigorous precautions were taken to prevent contamination, and independent centers were used to confirm authenticity of findings. DNA from five M. tuberculosis genetic loci was detected and had characteristics consistent with extant genetic lineages. High performance liquid chromatography was used as an independent method of verification and it directly detected mycolic acid lipid biomarkers, specific for the M. tuberculosis complex.Conclusions/Significance: Human tuberculosis was confirmed by morphological and molecular methods in a population living in one of the first villages with evidence of agriculture and animal domestication. The widespread use of animals was not a source of infection but may have supported a denser human population that facilitated transmission of the tubercle bacillus. The similarity of the M. tuberculosis genetic signature with those of today gives support to the theory of a long-term co-existence of host and pathogen

Orphan crops of archaeology-based crop history research

Agrobiodiversity is central to sustainable farming worldwide. Cultivation, conservation and reintroduction of diverse plant species, including ‘forgotten’ and ‘underutilized’ crops, contribute to global agrobiodiversity, living ecosystems and sustainable food production. Such efforts benefit from traditional and historical knowledge of crop plants' evolutionary and cultural trajectories. This review is a first attempt at systematically gauging species representativeness in studies of archaeological plant remains. Results indicate that, in addition to discipline-specific methodological sources of bias, modern agricultural biases may replicate themselves in crop history research and influence understandings of ‘forgotten crops’. Recognizing these biases is an initial stride towards rectifying them and promoting agrobiodiversity in both research and practical applications. Summary: So-called ‘forgotten’ or ‘orphan’ crops are an important component of strategies aimed at preserving and promoting biodiversity. Knowledge of historical cultivation, usage, and geographic and evolutionary trajectories of plants, that is, crop history research, is important for the long-term success of such efforts. However, research biases in the crops chosen for study may present hurdles. This review attempts to systematically identify patterns in crop species representativeness within archaeology-based crop history research. A meta-analysis and synthesis of archaeobotanical evidence (and lack thereof) is presented for 268 species known to have been cultivated for food prior to 1492 CE from the Mediterranean region to South Asia. We identified 39 genera with known crop plants in this geographical and historical context that are currently absent from its archaeobotanical record, constituting ‘orphan’ crops of archaeobotany. In addition, a worldwide synthesis of crop species studied using geometric morphometric, archaeogenetic and stable isotope analyses of archaeological plant remains is presented, and biases in the species represented in these disciplines are discussed. Both disciplinary methodological biases and economic agenda-based biases affecting species representativeness in crop history research are apparent. This study also highlights the limited geographic diffusion of most crops and the potential for deeper historical perspectives on how crops become marginalized and ‘forgotten’

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs