The biological origin of linguistic diversity

In contrast with animal communication systems, diversity is characteristic of almost every aspect of human language. Languages variously employ tones, clicks, or manual signs to signal differences in meaning; some languages lack the noun-verb distinction (e.g., Straits Salish), whereas others have a proliferation of fine-grained syntactic categories (e.g., Tzeltal); and some languages do without morphology (e.g., Mandarin), while others pack a whole sentence into a single word (e.g., Cayuga). A challenge for evolutionary biology is to reconcile the diversity of languages with the high degree of biological uniformity of their speakers. Here, we model processes of language change and geographical dispersion and find a consistent pressure for flexible learning, irrespective of the language being spoken. This pressure arises because flexible learners can best cope with the observed high rates of linguistic change associated with divergent cultural evolution following human migration. Thus, rather than genetic adaptations for specific aspects of language, such as recursion, the coevolution of genes and fast-changing linguistic structure provides the biological basis for linguistic diversity. Only biological adaptations for flexible learning combined with cultural evolution can explain how each child has the potential to learn any human language

Hyperdoctrines and the Ontology of Stratified Semantics

I present a version of Kit Fine's stratified semantics for the logic RWQ and define a natural family of related structures called RW hyperdoctrines. After proving that RWQ is sound with respect to RW hyperdoctrines, we show how to construct, for each stratified model, a hyperdoctrine that verifies precisely the same sentences. Completeness of RWQ for hyperdoctrinal semantics then follows from completeness for stratified semantics, which is proved in an appendix. By examining the base category of RW hyperdoctrines, we find reason to be worried about the ontology of stratified models

Beyond the Insider—Outsider Perspective: The Study of Religion as a Study of Discourse Construction

This essay reflects on contemporary theorizing of religion which embodies an explicit critique of the imperial project, seeing that by most common consent the scholarly disciplinary field of religious studies (history of religion, phenomenology of religion, Religionswissenschaft) is a late nineteenth century invention that coincides with the emergence of anthropology and ethnography as epiphenomena of the colonial project (whether as Orientalism or as exoticism the Other is rendered manageable subjects). The scholarly study of religion is, therefore, simultaneously a study of the history of theory and concept formation, and the social, cultural, and political work performed by such study and theorizing. The metatheory of the study of religion is a main focus of the essay. Alongside that, the essay focuses more pointedly on the concept of discourse, and considers the extraordinary situation where the same methodological vocabulary that functions in religious studies also functions in critical theological studies, which relativizes the division of ‘insider’ and ‘outsider’ perspectives. Yet both are conventionally practised either in isolation from each other as distinct theoretical and disciplinary bounded/defined study fields, or—the other and almost direct opposite—religious studies being performed in the context of theological study, situated in and offered by theological faculties. An overview of recent debates in the field of religious studies serves to highlight the continued struggle to demarcate the boundaries between the study of religion and the study of theology—in some of the recent, very strident debates mainstream religious studies is labelled as nothing more than theology. This contribution, then, aims at a kind of metatheoretical reflection on the study of religion and theology both as discourses that serve mythmaking, identity formation, culturally strategic purposes. That is, from the discourse perspective that is proposed here, it is possible to move beyond the definitional divide between religious studies and theology—even beyond ‘religion’ itself—to focus on the mundanely material practices that constitute that which is called religion. In the way in which the terms are used it is clear that the terminologies themselves bear the imprint of historical social discourses that occasioned the rise of their use. This essay, then, is something of a metacritique of the language of the study of religion—beyond religion, and beyond the study of religion and theology

Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours

Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal–epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protease with antiangiogenic properties, in brain tissues. Using quantitative RT–polymerase chain reaction (PCR), high, equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22 high-grade gliomas) and four glioma cell lines indicated at least two-fold reduction in mRNA compared to normal whole brain in all neoplastic tissues, and no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%) cell lines. In contrast, differential expression of TSP1 and VEGF was seen in nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in the expression of these genes. Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in >77% tumours. Methylation-specific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of 24 brain tumours (a metastasis) and three out of four glioma cell lines suggesting an alternative mechanism of downregulation. These data suggest a role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis and local invasion

Genome Desertification in Eutherians: Can Gene Deserts Explain the Uneven Distribution of Genes in Placental Mammalian Genomes?

The evolution of genome size as well as structure and organization of genomes belongs among the key questions of genome biology. Here we show, based on a comparative analysis of 30 genomes, that there is generally a tight correlation between the number of genes per chromosome and the length of the respective chromosome in eukaryotic genomes. The surprising exceptions to this pattern are placental mammalian genomes. We identify the number and, more importantly, the uneven distribution of gene deserts among chromosomes, i.e., long (>500 kb) stretches of DNA that do not encode for genes, as the main contributing factor for the observed anomaly of eutherian genomes. Gene-rich placental mammalian chromosomes have smaller proportions of gene deserts and vice versa. We show that the uneven distribution of gene deserts is a derived character state of eutherians. The functional and evolutionary significance of this particular feature of eutherian genomes remains to be explained

Options for early breast cancer follow-up in primary and secondary care : a systematic review

Background Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer. Method A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions. Results Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival. Conclusions Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed

The Class of All Natural Implicative Expansions of Kleene’s Strong Logic Functionally Equivalent to Łukasiewicz’s 3-Valued Logic Ł3

25 p.We consider the logics determined by the set of all natural implicative expansions of Kleene’s strong 3-valued matrix (with both only one and two designated values) and select the class of all logics functionally equivalent to Łukasiewicz’s 3-valued logic Ł3. The concept of a “natural implicative matrix” is based upon the notion of a “natural conditional” defined in Tomova (Rep Math Log 47:173–182, 2012).S

The safety of over-the-counter niacin. A randomized placebo-controlled trial [ISRCTN18054903]

BACKGROUND: Niacin is widely available over the counter (OTC). We sought to determine the safety of 500 mg immediate release niacin, when healthy individuals use them as directed. METHODS: 51 female and 17 male healthy volunteers (mean age 27 years SD 4.4) participated in a randomized placebo-controlled blinded trial of a single dose of an OTC, immediate-release niacin 500 mg (n = 33), or a single dose of placebo (n = 35) on an empty stomach. The outcomes measured were self-reported incidence of flushing and other adverse effects. RESULTS: 33 volunteers on niacin (100%) and 1 volunteer on placebo (3%) flushed (relative risk 35, 95% confidence interval (CI) 6.8–194.7). Mean time to flushing on niacin was 18.2 min (95% CI: 12.7–23.6); mean duration of flushing was 75.4 min (95% CI: 62.5–88.2). Other adverse effects occurred commonly in the niacin group: chills (51.5% vs. 0%, P < .0001), generalized pruritus (75% vs. 0%, P = <.001), gastrointestinal upset (30% vs. 3%, P = .005), and cutaneous tingling (30% vs. 0%, P = <.001). Six participants did not tolerate the adverse effects of niacin and 3 required medical attention. CONCLUSION: Clinicians counseling patients about niacin should alert patients not only about flushing but also about gastrointestinal symptoms, the most severe in this study. They should not trust that patients would receive information about these side effects or their prevention (with aspirin) from the OTC packet insert

Expression of tumour-specific antigens underlies cancer immunoediting

Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack1, 2. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is thereby enhanced in immune-compromised mice, whereas the capacity for such tumours to grow after transplantation into wild-type mice is reduced2, 3. However, many questions about the process of cancer immunoediting remain unanswered, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours4. Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour-specific-antigen expression in immune surveillance, and potentially, immunotherapy.National Institutes of Health (U.S.) (Grant 1 U54 CA126515-01)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051)Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship AwardJohnD. Proctor FoundationDaniel K. Ludwig Schola

A population based time series analysis of asthma hospitalisations in Ontario, Canada: 1988 to 2000

BACKGROUND: Asthma is a common yet incompletely understood health problem associated with a high morbidity burden. A wide variety of seasonally variable environmental stimuli such as viruses and air pollution are believed to influence asthma morbidity. This study set out to examine the seasonal patterns of asthma hospitalisations in relation to age and gender for the province of Ontario over a period of 12 years. METHODS: A retrospective, population-based study design was used to assess temporal patterns in hospitalisations for asthma from April 1, 1988 to March 31, 2000. Approximately 14 million residents of Ontario eligible for universal healthcare coverage during this time were included for analysis. Time series analyses were conducted on monthly aggregations of hospitalisations. RESULTS: There is strong evidence of an autumn peak and summer trough seasonal pattern occurring every year over the 12-year period (Fisher-Kappa (FK) = 23.93, p > 0.01; Bartlett Kolmogorov Smirnov (BKS) = 0.459, p < 0.01). This pattern was observed in both sexes. However, young males (0–4 years) were hospitalised at two to three times the rate of females of the same age. Rates were much lower in the older age groups. A downward trend in asthma hospitalisations was observed in the total population over the twelve-year period (beta = -0.980, p < 0.01). CONCLUSIONS: A clear and consistent seasonal pattern was observed in this study for asthma hospitalisations. These findings have important implications for the development of effective management and prevention strategies