| 1. |
- Weinstein, John N., et al.
(author)
-
The cancer genome atlas pan-cancer analysis project
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
-
Journal article (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
|
|
| 2. |
- Stewart, Christopher J., et al.
(author)
-
Temporal development of the gut microbiome in early childhood from the TEDDY study
- 2018
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7728, s. 583-588
-
Journal article (peer-reviewed)abstract
- The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial–immune crosstalk during this time thought to be involved in the pathobiology of later life diseases1–9 such as persistent islet autoimmunity and type 1 diabetes10–12. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3–14), a transitional phase (months 15–30), and a stable phase (months 31–46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case–control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial–immune crosstalk for long-term health.
|
|
| 3. |
- Bhiwapurkar, M. K., et al.
(author)
-
Effect of magnitudes and directions (mono-axis and multi-axis) of whole body-vibration exposures and subjects postures on the sketching performance
- 2011
-
In: Proceedings of the Institution of mechanical engineers. Part F, journal of rail and rapid transit. - 0954-4097 .- 2041-3017. ; 225:F1, s. 71-83
-
Journal article (peer-reviewed)abstract
- Whole-body vibrations in trains are known to affect the performance of sedentary activities such as reading, writing, sketching, working on a computer, etc. The objective of the study was to investigate the extent of disturbance perceived in sketching task by seated subjects in two postures under mono-and multi-axis Gaussian random vibration environment. The study involved 21 healthy male subjects in the age group of 23-32 years. Random vibrations were generated both in mono-and multi-axial directions in the frequency range of 1-10 Hz at 0.5, 1.0, and 1.5 m/s(2) rms (root mean square) amplitude. The subjects were required to sketch given geometric figures such as a circle, triangle, rectangle, and square with the help of ball-point pen under given vibration stimuli in two postures (sketch pad on lap and sketch pad on table). The deviation in distortion with respect to the given figure is represented in terms of percentage distortion. The influence of vibrations on the sketching activity was investigated both subjectively and by two specifically designed objective methods, namely, RMS (root mean square methodology) and area methods. The judgements of perceived difficulty to sketch were rated using seven-point semantic judgement scale. The percentage distortion and difficulty in sketching activity increased with an increase in vibration magnitude. Both subjective evaluation and the RMS method revealed that the task was affected more while sketching on the table. The percentage distortion was affected similarly and maximum in all the vibration directions except for the vertical, while sketching difficulty was found to be higher only with longitudinal and multi-axis vibration direction. The subjective evaluation also revealed that there was no effect of the type of entity chosen on the sketching difficulty.
|
|
| 4. |
- Bhiwapurkar, M. K., et al.
(author)
-
Influence of Mono-axis Random Vibration on Reading Activity
- 2010
-
In: Industrial Health. - 0019-8366 .- 1880-8026. ; 48:5, s. 675-681
-
Journal article (peer-reviewed)abstract
- Recent studies on train passengers' activities found that many passengers were engaged in some form of work, e.g., reading and writing, while traveling by train. A majority of the passengers reported that their activities were disturbed by vibrations or motions during traveling. A laboratory study was therefore set up to study how low-frequency random vibrations influence the difficulty to read. The study involved 18 healthy male subjects of 23 to 32 yr of age group. Random vibrations were applied in the frequency range (1-10 Hz) at 0.5, 1.0 and 1.5 m/s(2) rms amplitude along three directions (longitudinal, lateral and vertical). The effect of vibration on reading activity was investigated by giving a word chain in two different font types (Times New Roman and Anal) and three different sizes (10, 12 and 14 points) of font for each type. Subjects performed reading tasks under two sitting positions (with backrest support and leaning over a table). The judgments of perceived difficulty to read were rated using 7-point discomfort judging scale. The result shows that reading difficulty increases with increasing vibration magnitudes and found to be maximum in longitudinal direction, but with leaning over a table position. In comparison with Times New Roman type and sizes of font, subjects perceived less difficulty with Anal type for all font sizes under all vibration magnitude.
|
|
| 5. |
- Guruswami, V., et al.
(author)
-
Super-polylogarithmic hypergraph coloring hardness via low-degree long codes
- 2014
-
In: Proceedings of the Annual ACM Symposium on Theory of Computing. - New York, NY, USA : ACM. - 9781450327107 ; , s. 614-623
-
Conference paper (peer-reviewed)abstract
- We prove improved inapproximability results for hypergraph coloring using the low-degree polynomial code (aka, the"short code" of Barak et. al. [FOCS 2012]) and the techniques pro-posed by Dinur and Guruswami [FOCS 2013] to incorporatethis code for inapproximability results. In particular, we prove quasi-NP-hardness of the following problems on n-vertex hypergraphs: • Coloring a 2-colorable 8-uniform hypergraph with 2 2Ω(√log log n) colors. • Coloring a 4-colorable 4-uniform hypergraph with 22Ω(√ log log n) colors. • Coloring a 3-colorable 3-uniform hypergraph with (log n) Ω(1√ log log log n) colors. In each of these cases, the hardness results obtained are (at least) superpolynomially stronger (if not exponentially stronger as in the third case) than what was previously known for the respective cases. In fact, prior to this result, (log n)O(1) colors was the strongest quantitative bound on the number of colors ruled out by inapproximability results for O(1)-colorable hypergraphs. The fundamental bottleneck in obtaining coloring in approximability results using the low-degree long code was a ultipartite structural restriction in the PCP construction of Dinur-Guruswami. We are able to get around this restriction by simulating the multipartite structure implicitly by querying just one partition (albeit requiring 8 queries), which yields our result for 2-colorable 8-uniform hypergraphs. The result for 4-colorable 4-uniform hypergraphs is obtained via a "query doubling" method exploiting additional properties of the 8-query test. For 3-colorable 3-uniform hyper-graphs, we exploit the ternary domain to design a test with an additive (as opposed to multiplicative) noise function, and analyze its efficacy in killing high weight Fourier coefficients via the pseudorandom properties of an associated quadratic form. The latter step involves extending the key algebraic ingredient of Dinur-Guruswami concerning testing binary Reed-Muller codes to the ternary alphabet.
|
|
| 6. |
|
|
| 7. |
- Herrick, Ariane L, et al.
(author)
-
Treatment outcome in early diffuse cutaneous systemic sclerosis : The European Scleroderma Observational Study (ESOS)
- 2017
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:7, s. 1207-1218
-
Journal article (peer-reviewed)abstract
- Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
|
|
| 8. |
- Olausson, Josefin, 1983, et al.
(author)
-
Optimization of cerebrospinal fluid microbial DNA metagenomic sequencing diagnostics
- 2022
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
-
Journal article (peer-reviewed)abstract
- Infection in the central nervous system is a severe condition associated with high morbidity and mortality. Despite ample testing, the majority of encephalitis and meningitis cases remain undiagnosed. Metagenomic sequencing of cerebrospinal fluid has emerged as an unbiased approach to identify rare microbes and novel pathogens. However, several major hurdles remain, including establishment of individual limits of detection, removal of false positives and implementation of universal controls. Twenty-one cerebrospinal fluid samples, in which a known pathogen had been positively identified by available clinical techniques, were subjected to metagenomic DNA sequencing. Fourteen samples contained minute levels of Epstein-Barr virus. The detection threshold for each sample was calculated by using the total leukocyte content in the sample and environmental contaminants found in the bioinformatic classifiers. Virus sequences were detected in all ten samples, in which more than one read was expected according to the calculations. Conversely, no viral reads were detected in seven out of eight samples, in which less than one read was expected according to the calculations. False positive pathogens of computational or environmental origin were readily identified, by using a commonly available cell control. For bacteria, additional filters including a comparison between classifiers removed the remaining false positives and alleviated pathogen identification. Here we show a generalizable method for identification of pathogen species using DNA metagenomic sequencing. The choice of bioinformatic method mainly affected the efficiency of pathogen identification, but not the sensitivity of detection. Identification of pathogens requires multiple filtering steps including read distribution, sequence diversity and complementary verification of pathogen reads.
|
|
| 9. |
- Peytrignet, Sébastien, et al.
(author)
-
Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.
- 2018
-
In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 57:2, s. 370-381
-
Journal article (peer-reviewed)abstract
- Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined.The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001).The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.
|
|
| 10. |
- Younes, George, et al.
(author)
-
X-Ray Burst and Persistent Emission Properties of the Magnetar SGR 1830-0645 in Outburst
- 2022
-
In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 924:2
-
Journal article (peer-reviewed)abstract
- We report on NICER X-ray monitoring of the magnetar SGR 1830-0645 covering 223 days following its 2020 October outburst, as well as Chandra and radio observations. We present the most accurate spin ephemerides of the source so far: nu = 0.096008680(2) Hz, = -6.2(1) x 10(-14) Hz s(-1), and significant second and third frequency derivative terms indicative of nonnegligible timing noise. The phase-averaged 0.8-7 keV spectrum is well fit with a double-blackbody (BB) model throughout the campaign. The BB temperatures remain constant at 0.46 and 1.2 keV. The areas and flux of each component decreased by a factor of 6, initially through a steep decay trend lasting about 46 days, followed by a shallow long-term one. The pulse shape in the same energy range is initially complex, exhibiting three distinct peaks, yet with clear continuous evolution throughout the outburst toward a simpler, single-pulse shape. The rms pulsed fraction is high and increases from about 40% to 50%. We find no dependence of pulse shape or fraction on energy. These results suggest that multiple hot spots, possibly possessing temperature gradients, emerged at outburst onset and shrank as the outburst decayed. We detect 84 faint bursts with NICER, having a strong preference for occurring close to the surface emission pulse maximum-the first time this phenomenon is detected in such a large burst sample. This likely implies a very low altitude for the burst emission region and a triggering mechanism connected to the surface active zone. Finally, our radio observations at several epochs and multiple frequencies reveal no evidence of pulsed or burst-like radio emission.
|
|
