The entangling side of the Unruh-Hawking effect

We show that the Unruh effect can create net quantum entanglement between inertial and accelerated observers depending on the choice of the inertial state. This striking result banishes the extended belief that the Unruh effect can only destroy entanglement and furthermore provides a new and unexpected source for finding experimental evidence of the Unruh and Hawking effects.Comment: 4 pages, 4 figures. Added Journal referenc

Evidence for dark matter in the inner Milky Way

The ubiquitous presence of dark matter in the universe is today a central tenet in modern cosmology and astrophysics. Ranging from the smallest galaxies to the observable universe, the evidence for dark matter is compelling in dwarfs, spiral galaxies, galaxy clusters as well as at cosmological scales. However, it has been historically difficult to pin down the dark matter contribution to the total mass density in the Milky Way, particularly in the innermost regions of the Galaxy and in the solar neighbourhood. Here we present an up-to-date compilation of Milky Way rotation curve measurements, and compare it with state-of-the-art baryonic mass distribution models. We show that current data strongly disfavour baryons as the sole contribution to the galactic mass budget, even inside the solar circle. Our findings demonstrate the existence of dark matter in the inner Galaxy while making no assumptions on its distribution. We anticipate that this result will compel new model-independent constraints on the dark matter local density and profile, thus reducing uncertainties on direct and indirect dark matter searches, and will shed new light on the structure and evolution of the Galaxy.Comment: First submitted version of letter published in Nature Physics on Febuary 9, 2015: http://www.nature.com/nphys/journal/vaop/ncurrent/full/nphys3237.htm

Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. METHODS: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.This work was supported by grants from Spanish Health Ministry (FIS) network RIRAAF (RD 07/0064).Ye

Plasmodium knowlesi Genome Sequences from Clinical Isolates Reveal Extensive Genomic Dimorphism.

Plasmodium knowlesi is a newly described zoonosis that causes malaria in the human population that can be severe and fatal. The study of P. knowlesi parasites from human clinical isolates is relatively new and, in order to obtain maximum information from patient sample collections, we explored the possibility of generating P. knowlesi genome sequences from archived clinical isolates. Our patient sample collection consisted of frozen whole blood samples that contained excessive human DNA contamination and, in that form, were not suitable for parasite genome sequencing. We developed a method to reduce the amount of human DNA in the thawed blood samples in preparation for high throughput parasite genome sequencing using Illumina HiSeq and MiSeq sequencing platforms. Seven of fifteen samples processed had sufficiently pure P. knowlesi DNA for whole genome sequencing. The reads were mapped to the P. knowlesi H strain reference genome and an average mapping of 90% was obtained. Genes with low coverage were removed leaving 4623 genes for subsequent analyses. Previously we identified a DNA sequence dimorphism on a small fragment of the P. knowlesi normocyte binding protein xa gene on chromosome 14. We used the genome data to assemble full-length Pknbpxa sequences and discovered that the dimorphism extended along the gene. An in-house algorithm was developed to detect SNP sites co-associating with the dimorphism. More than half of the P. knowlesi genome was dimorphic, involving genes on all chromosomes and suggesting that two distinct types of P. knowlesi infect the human population in Sarawak, Malaysian Borneo. We use P. knowlesi clinical samples to demonstrate that Plasmodium DNA from archived patient samples can produce high quality genome data. We show that analyses, of even small numbers of difficult clinical malaria isolates, can generate comprehensive genomic information that will improve our understanding of malaria parasite diversity and pathobiology

Traditional knowledge of wild edible plants used in the northwest of the Iberian Peninsula (Spain and Portugal): a comparative study

<p>Abstract</p> <p>Background</p> <p>We compare traditional knowledge and use of wild edible plants in six rural regions of the northwest of the Iberian Peninsula as follows: Campoo, Picos de Europa, Piloña, Sanabria and Caurel in Spain and Parque Natural de Montesinho in Portugal.</p> <p>Methods</p> <p>Data on the use of 97 species were collected through informed consent semi-structured interviews with local informants. A semi-quantitative approach was used to document the relative importance of each species and to indicate differences in selection criteria for consuming wild food species in the regions studied.</p> <p>Results and discussion</p> <p>The most significant species include many wild berries and nuts (e.g. <it>Castanea sativa, Rubus ulmifolius, Fragaria vesca</it>) and the most popular species in each food-category (e.g. fruits or herbs used to prepare liqueurs such as <it>Prunus spinosa</it>, vegetables such as <it>Rumex acetosa</it>, condiments such as <it>Origanum vulgare</it>, or plants used to prepare herbal teas such as <it>Chamaemelum nobile</it>). The most important species in the study area as a whole are consumed at five or all six of the survey sites.</p> <p>Conclusion</p> <p>Social, economic and cultural factors, such as poor communications, fads and direct contact with nature in everyday life should be taken into account in determining why some wild foods and traditional vegetables have been consumed, but others not. They may be even more important than biological factors such as richness and abundance of wild edible flora. Although most are no longer consumed, demand is growing for those regarded as local specialties that reflect regional identity.</p

The influence of heart disease on characteristics, quality of life, use of health resources, and costs of COPD in primary care settings

<p>Abstract</p> <p>Background</p> <p>To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.</p> <p>Methods</p> <p>Epidemiologic, observational, and descriptive study (EPIDEPOC study). Patients ≥ 40 years of age with stable COPD attending primary care settings were included. Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected. Results were compared between patients with or without associated heart disease.</p> <p>Results</p> <p>A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males. When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease. Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease. Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases. The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05. Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.</p> <p>Conclusion</p> <p>Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease.</p

Performance indicators for clinical practice management in primary care in Portugal : consensus from a Delphi study

Early OnlineBackground: Performance indicators assessing the quality of medical care and linked to pay for performance may cause disagreement. Portuguese indicators included in recent health care reform are controversial. Objectives: To obtain consensus from opinion leaders in family medicine regarding the performance indicators for practice management used in the evaluation of Family Health Units in Portugal. Methods: Eighty-nine specialists in primary care were invited to answer the following question in an online Delphi study: 'Which performance indicators should be assessed regarding the organization and management of clinical practice in primary care in Portugal?' A Likert scale was used to evaluate validity, reliability, feasibility and sensitivity to change. Twenty-seven experts participated in the second round and achieved a high degree of consensus. Eight categories were created for analysis. Results: The experts suggested the use of existing indicators as well as new indicators. Thirty-nine indicators suggested by the experts are currently in use in Portugal. The assessment of the number of clinical acts performed, the number of administrative acts, and evaluation of the clinical demographic profile achieved a high degree of consensus. The expert panel suggested fifty new indicators. Five categories of these new indicators had a high degree of consensus, and three categories had a low degree of consensus. Conclusion: The expert panel recommended that performance indicators of practice management should first assess the quantity of clinical and administrative activities undertaken. These indicators must take into account the human and financial resources available to the clinic and its demographic context

Independent effect of prior exacerbation frequency and disease severity on the risk of future exacerbations of COPD: a retrospective cohort study

Few studies have researched the independent effect of COPD severity on the risk of future exacerbations adjusted by previous exacerbation frequency. We aimed to analyse the independent effect of COPD severity on the risk of exacerbations in the following year, and whether this effect was stronger or not than the effect of a previous history of exacerbations. We conducted a retrospective population-based cohort study including 900 patients with confirmed COPD. Exacerbation frequency was observed for the previous year and for the following year. Patients were defined as ‘Frequent Exacerbator’ (FE) phenotype if they suffered ?2 exacerbations in a year, and were categorised according to the severity of COPD (GOLD Grades 1–4). Odds ratios (ORs) were estimated by logistic regression adjusting for age, gender, smoking status, severity of COPD and being FE in the previous year. The main predictor of being FE among all grades of COPD severity was a history of frequent exacerbations in the previous year: adjusted OR 4.97; 95% confidence interval (CI) (3.54–6.97). COPD severity was associated with a higher risk of being FE: Crude OR GOLD Grade 4 3.86; 95% CI (1.50–9.93). However, this association diminished after adjusting for being FE in the previous year: adjusted OR 2.08; 95% CI (0.75–5.82). Our results support that a history of frequent exacerbations in the previous year is the most important independent predictor of exacerbations in the following year, also among the most severe COPD patients. Severity of COPD would be associated with a higher risk of exacerbations, but this effect would be partly determined by the exacerbations suffered in the previous year

Population-Attributable Risks for Ischemic Stroke in a Community in South Brazil: A Case-Control Study

Background: Risk factors for ischemic stroke are mostly known, but it is still unclear in most countries, what are their combined population-attributable risk percent (PAR%). In a case-control study the individual odds ratios (ORs) and the individual and combined PAR%, including risk factors not addressed in previous studies were estimated. Methods: Cases and controls were selected from patients attending to an emergency department. Cases were patients aged with 45 years or more with the first episode of ischemic stroke, characterized by a focal neurological deficit or change in the mental status occurring during the previous 24 hours. Controls, matched to cases by age and gender, were selected from patients without neurological complaints. Results: 133 cases and 272 controls were studied. Odds ratios for ischemic stroke were: atrial fibrillation (27.3; CI 95 % 7.5

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies