Vasijas para la fiesta y la fama: producción artesanal en un centro urbano huari

Excavaciones recientes en el sitio de Conchopata, en el valle de Ayacucho, sugieren que el sector sur de este gran centro urbano puede haber servido, por lo menos durante una fase de su ocupación, como un área residencial-artesanal donde se produjo cerámica de elite y doméstica. Los trabajos en este sitio han sacado a luz cientos de herramientas relacionadas con la producción alfarera, incluyendo alisadores, moldes y azadas de andesita de uso múltiple, así como varias áreas de quema de cerámica en forma de pozo o en área abierta ubicadas directamente encima de los pisos y las "ofrendas" del Horizonte Medio.En este trabajo se analizan la distribución espacial y los contextos de las herramientas utilizadas en la producción alfarera, de las áreas de quema y de las «ofrendas» en espacios arquitectónicos, patios y estructuras en forma de "D". Se concluye que los alfareros de Conchopata vivieron y trabajaron en esta parte del asentamiento, que eran bastante especializados y que, probablemente, pertenecieron a familias que produjeron cerámica para el uso diario y ceremonial en talleres ubicados dentro de sus grandes viviendas o adyacentes a ellas. Esta forma de producción alfarera no comparte rasgos con los modelos tradicionales de organización de la producción, sino que parece reflejar un nuevo tipo de organización de producción andina en el corazón del imperio Huari.Pottery for Celebration and Fame: Ceramic Artisan Production in a Huari Urban CenterRecent excavations at the Huari site of Conchopata have suggested that the southern sector of the large urban center may have served, at least during one occupation phase, as a residential-artisan area where elite and utilitarian pottery was made. This site has yielded hundreds of tools associated with pottery production, including polishers, molds, and multipurpose andesite hoes, along with several firing pit kilns and firing areas as well as the so-called Huari Middle Horizon ceramic "offerings".In this paper, we examine the spatial distribution and contexts of pottery-making tools, firing areas, and "offerings" within the architecturally defined rooms, plazas, and D-shaped structures. We conclude that the potters of Conchopata both lived and worked in this part of the settlement. They were highly specialized potters who likely belonged to the elite households and produced pottery and other ceramic objects for ceremonial and domestic purposes in workshops that were located inside, or adjacent, to large household compounds. This form of pottery production does not fit traditional organizational models, but instead appears to reflect a new type of craft production arrangement in the Huari imperial heartland

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca(2+) o) homeostasis. To elucidate the role of AP2σ2 in Ca(2+) o regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2σ2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2σ2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype-phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2σ2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2σ2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2σ2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Kinesiophobia in patients with non-traumatic arm, neck and shoulder complaints: a prospective cohort study in general practice

BACKGROUND: Complaints of arm, neck and shoulder are common in Western societies. Of those consulting a general practitioner (GP) with non-traumatic arm, neck or shoulder complaints, about 50% do not recover within 6 months.Kinesiophobia (also known as fear of movement/(re)injury) may also play a role in these complaints, as it may lead to avoidance behaviour resulting in hypervigilance to bodily sensations, followed by disability, disuse and depression. However, in relation to arm, neck and shoulder complaints little is known about kinesiophobia and its associated variables.Therefore this study aimed to: describe the degree of kinesiophobia in patients with non-traumatic complaints of arm, neck and shoulder in general practice; to determine whether mean scores of kinesiophobia change over time in non-recovered patients; and to evaluate variables associated with kinesiophobia at baseline. METHODS: In this prospective cohort study set in general practice, consulters with a first or new episode of non-traumatic arm, neck or shoulder complaints (aged 18-64 years) entered the cohort. Baseline data were collected on kinesiophobia using the Tampa Scale for Kinesiophobia, the 13-item adjusted version: TSK-AV, and on patient-, complaint-, and psychosocial variables using self-administered questionnaires. The mean TSK-AV score was calculated. In non-recovered patients the follow-up TSK-AV scores at 6 and 12 months were analyzed with the general linear mixed model. Variables associated with kinesiophobia at baseline were evaluated using multivariate linear regression analyses. RESULTS: The mean TSK-AV score at baseline was 24.8 [SD: 6.2]. Among non-recovered patients the mean TSK-AV score at baseline was 26.1 [SD: 6.6], which remained unchanged over 12- months follow-up period. The strongest associations with kinesiophobia were catastrophizing, disability, and comorbidity of musculoskeletal complaints. Additionally, having a shoulder complaint, low social support, high somatization and high distress contributed to the kinesiophobia score. CONCLUSION: The mean TSK-AV score in our population seems comparable to those in other populations in primary care.In patients who did not recover during the 12- month follow-up, the degree of kinesiophobia remained unchanged during this time period.The variables associated with kinesiophobia at baseline appear to be in line with the fear-avoidance model

Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk

DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P <7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.Peer reviewe

Training future generations to deliver evidence-based conservation and ecosystem management

1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis. 2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice. 3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses. 4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.Peer reviewe