Switching waves in multi-level incoherently driven polariton condensates

We show theoretically that an open-dissipative polariton condensate confined within a trapping potential and driven by an incoherent pumping scheme gives rise to bistability between odd and even modes of the potential. Switching from one state to the other can be controlled via incoherent pulsing which becomes an important step towards construction of low-powered opto-electronic devices. The origin of the effect comes from modulational instability between odd and even states of the trapping potential governed by the nonlinear polariton-polariton interactions

Parity solitons in nonresonantly driven-dissipative condensate channels

We study analytically and numerically the condensation of a driven-dissipative exciton-polariton system using symmetric nonresonant pumping geometries. We show that the lowest condensation threshold solution carries a definite parity as a consequence of the symmetric excitation profile. At higher pump intensities competition between the two parities can result in critical quenching of one and saturation of the other. Using long pump channels, we show that the competition of the condensate parities gives rise to a different type of topologically stable defect propagating indefinitely along the condensate. The defects display repulsive interactions and are characterized by a sustained wavepacket carrying a pair of opposite parity domain walls in the condensate channel

The use of digital photographs for the diagnosis of hand osteoarthritis: the AGES-Reykjavik study

<p>Abstract</p> <p>Background</p> <p>The objective of the study was to standardize a method using digital photographs to diagnose and grade hand osteoarthritis (HOA), to compare it with radiographs and clinical examination with regard to prevalence and relation to symptoms, and finally to construct a simple shortened version suitable for use in very large studies, where a global estimate may be preferable.</p> <p>Methods</p> <p>High quality photographs with standard distance and hand positioning were analysed for the presence of HOA and subsequently compared with standard radiographs and clinical examination in 381 random participants in the AGES-Reykjavik Study, a large population study. The mean age of the participants was 76 years.</p> <p>Results</p> <p>Using the photographic method, the most commonly affected joints were the second DIP joints followed by the third DIP joints and second and third PIP joints. Both interobserver (ICC = 0.83) and intraobserver reading agreements (ICC = 0.89) were acceptable. On comparison with radiography and clinical examination, aggregate scores were significantly correlated (R_s0.35-0.69), more so in females (R_s0.53-0.72) than males. Hand pain in males showed very little association with HOA findings by the three methods but all methods showed a comparable moderate association with hand pain in females. The performance of photography in predicting pain on most days for at least a month in females was comparable to that of radiography and clinical examination (AUC 0.63 <it>p </it>= 0.004). Analysis of intermittent pain yielded similar results for in the DIP and PIP joints (OR 3.2-3.3, <it>p </it>< 0.01), but for the CMC1 joints, both radiography (OR 9.0, <it>p </it>< 0.0001), and clinical examination (OR 9.8, <it>p </it>< 0.0001), had higher predictive odds ratios for pain than photography (OR 3.6, <it>p </it>< 0.0001)., A shortened, rapidly performed form of reading photographs also showed a high degree of correlation with the other methods (R_s0.56-0.82).</p> <p>Conclusion</p> <p>High quality hand photographs can be used to diagnose and grade hand osteoarthritis. The method has the advantage of being inexpensive and easy to perform. By using a slightly simplified method of reading, it appears to be highly suitable for use in large studies.</p

The sequences of 150,119 genomes in the UK Biobank

Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data(1,2). Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank(3). This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.publishedVersio

Throat Infections are Associated with Exacerbation in a Substantial Proportion of Patients with Chronic Plaque Psoriasis

Streptococcal throat infections are known to trigger or exacerbate psoriasis, and several studies support the benefit of tonsillectomy. To evaluate the potential of tonsillectomy as a treatment, we used a retrospective study-specific questionnaire to assess the proportion of psoriasis patients with sore throat-associated psoriasis exacerbations. Our survey sampled 275 psoriasis patients. Of patients with plaque psoriasis, 42% reported sore throat-associated psoriasis exacerbations, and of patients with confirmed streptococcal infections, 72% reported aggravation. Notably, women and patients with early onset psoriasis were more likely to report psoriasis exacerbation after a sore throat (p&lt; 0.001, p = 0.046, respectively). Other psoriasis aggravation factors were more common in patients with sore throat-associated exacerbations (p &lt; 0.01). Of tonsillectomized patients, 49% reported subsequent improvement and had more frequent sore throat -associated aggravation of psoriasis than patients who did not improve after tonsillectomy (p=0.015). These findings suggest a closer association between sore throats, streptococcal throat infections and plaque psoriasis than reported previously

HLA-Cw6 homozygosity in plaque psoriasis is associated with streptococcal throat infections and pronounced improvement after tonsillectomy: A prospective case series.

To access publisher's full text version of this article click on the hyperlink belowBACKGROUND: Carriage of the HLA-Cw*0602 allele is associated with a particular set of clinical features and treatment responses in psoriasis. Tonsillectomy can improve psoriasis. OBJECTIVES: We sought to evaluate whether HLA-Cw*0602 predicts a favorable outcome after tonsillectomy of patients with psoriasis. METHODS: This prospective case series followed up 28 tonsillectomized patients with plaque psoriasis for 24 months. The Psoriasis Area and Severity Index, Psoriasis Disability Index, and Psoriasis Life Stress Inventory were used for assessment. Tonsils were swabbed for bacteria and patients genotyped for HLA-Cw*0602. RESULTS: After tonsillectomy, HLA-Cw*0602 homozygotes showed significantly more improvement, compared with heterozygous and HLA-Cw*0602-negative patients. Thus, Psoriasis Area and Severity Index score was reduced by 82% in the homozygous patients compared with 42% and 31%, respectively (P < .001), Psoriasis Disability Index score improved by 87% compared with 38% and 41%, respectively (P < .001), and Psoriasis Life Stress Inventory score was 82% reduced compared with 60% and 54%, respectively (P < .001). The homozygotes more often had psoriasis onset associated with a throat infection (P = .007) and an increased frequency of streptococcal throat infections per lifetime (P = .038). LIMITATIONS: Few patients were included and some data were retrospective. CONCLUSIONS: Homozygous HLA-Cw*0602 carriage in plaque psoriasis may predict a favorable outcome after tonsillectomy.Icelandic Research Fund Landspitali University Hospital Research Fund United States Department of Health & Human Services National Institutes of Health (NIH) - USA National Psoriasis Foundation USA Babcock Memorial Trust United States Department of Health & Human Services National Institutes of Health (NIH) - USA A. Alfred Taubman Medical Research Institute Doris Duke Charitable Foundation Gran

Tumour diploidy and survival in breast cancer patients with BRCA2 mutations.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageIt is not well known to what extent carrying a BRCA2 mutation affects the survival of women with breast cancer and prognostic factors among BRCA2-positive women warrant investigation. Using a record linkage approach we compared the long-term survival in carriers and noncarriers of an inherited BRCA2 founder mutation (999del5), and sought to identify prognostic factors among the BRCA2 mutation-positive subset, including markers of genetic instability (aneuploidy) and mitotic activity (S-phase fraction). We established the genetic status of 2,967 Icelandic breast cancer patients (215 mutation carriers and 2,752 noncarriers) diagnosed from 1955 to 2004, representing 72 % of all cases diagnosed in the country during this period. Tumour ploidy and S-phase fraction were assessed on tumour cells by DNA flow cytometry. Prognostic factors were assessed blindly with respect to mutation status. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival by BRCA2 status, using Cox regression. After a median follow-up of 9.5 years, BRCA2 mutation carriers had a higher risk of death from breast cancer than noncarriers (HR 1.64, 95 % CI 1.24-2.16, p < 0.001). The risk increase was restricted to women with diploid tumours (HR 3.03, 95 % CI 1.91-4.79, p < 0.001). Among breast cancer patients with aneuploid tumours, survival of carriers was similar to that of noncarriers (HR 0.76, 95 % CI 0.41-1.41, p = 0.38). Increased tumour size and a positive nodal status predicted worse prognosis in all patients, whereas the highly correlated prognostic factors diploidy, low proliferative activity and a positive estrogen receptor status had reverse effects in mutation carriers and noncarriers. Breast cancer patients who carry the Icelandic founder BRCA2 mutation have inferior long-term survival than noncarriers, but the adverse prognosis is restricted to mutation carriers with diploid, slowly proliferating tumours.Icelandic Cancer Society US Army Medical Research Acquisition Activity DAMD17-97-1-7002 DAMD17-99-1-921

Association of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin.

To access publisher's full text version of this article click on the hyperlink belowMost pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population. Genotype information on 43 641 cancer patients and 370 971 control subjects from Iceland, the Netherlands, and the United States was used to assess the cancer risk profiles of K3326* and BRCA2 999del5. BRCA2 expression was assessed using RNAseq data from blood (n = 2233), as well as 52 tissues reported in the GTEx database. The cancer risks associated with K3326* are fundamentally different from those associated with 999del5. We report for the first time an association between K3326* and small cell lung cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.35 to 3.16) and squamous cell carcinoma of the skin (OR = 1.69, 95% CI = 1.26 to 2.26). Individuals homozygous for K3326* reach old age and have children. Unlike BRCA2 999del5, the K3326* allele does not affect the level of BRCA2 transcripts, and the allele is expressed to the same extent as the wild-type allele. K3326* associates primarily with cancers that have strong environmental genotoxic risk factors. Expression of the K3326* allele suggests that a variant protein may be made that retains the DNA repair capabilities important to hormone-responsive tissues but may be less efficient in responding to genotoxic stress.deCODE genetics/Amgen American Cancer Society National Institutes of Health National Cancer Institut