Development of ITER-relevant plasma control solutions at DIII-D

Humphreys, D.A.,Ferron, J.R.,Bakhtiari, M.,Blair, J.A.,In, Y.,Jackson, G.L.,Jhang, H.,Johnson, R.D.,Kim, J.S.,LaHaye, R.J.,Leuer, J.A.,Penaflor, B.G.,Schuster, E.,Walker, M.L.,Wang, H.,Welander, A.S. International Atomic Energy Agency 2007 Nuclear fusion Vol.47 No.8

<P>The requirements of the DIII-D physics program have led to the development of many operational control results with direct relevance to ITER. These include new algorithms for robust and sustained stabilization of neoclassical tearing modes with electron cyclotron current drive, model-based controllers for stabilization of the resistive wall mode in the presence of ELMs, coupled linear–nonlinear algorithms to provide good dynamic axisymmetric control while avoiding coil current limits, and adaptation of the DIII-D plasma control system (PCS) to operate next-generation superconducting tokamaks. Development of integrated plasma control (IPC), a systematic approach to model-based design and controller verification, has enabled successful experimental application of high reliability control algorithms requiring a minimum of machine operations time for testing and tuning. The DIII-D PCS hardware and software and its versions adapted for other devices can be connected to IPC simulations to confirm control function prior to experimental use. This capability has been important in control system implementation for tokamaks under construction and is expected to be critical for ITER.</P>

11q13 is a susceptibility locus for hormone receptor positive breast cancer

Lambrechts, Diether,Truong, Therese,Justenhoven, Christina,Humphreys, Manjeet K.,Wang, Jean,Hopper, John L.,Dite, Gillian S.,Apicella, Carmel,Southey, Melissa C.,Schmidt, Marjanka K.,Broeks, Annegien Wiley (John WileySons) 2012 Human mutation Vol.33 No.7

Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2

Ahmed, Shahana,Thomas, Gilles,Ghoussaini, Maya,Healey, Catherine S,Humphreys, Manjeet K,Platte, Radka,Morrison, Jonathan,Maranian, Melanie,Pooley, Karen A,Luben, Robert,Eccles, Diana,Evans, D Gareth,F Nature Publishing Group 2009 Nature genetics Vol.41 No.5

Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08–1.13, P = 4.1 × 10<SUP>−23</SUP>) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92–0.97, P = 1.4 × 10<SUP>−8</SUP>). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.

Oral cholera vaccine in cholera prevention and control, Malawi

M’bangombe, Maurice,Pezzoli, Lorenzo,Reeder, Bruce,Kabuluzi, Storn,Msyamboza, Kelias,Masuku, Humphreys,Ngwira, Bagrey,Cavailler, Philippe,Grandesso, Francesco,Palomares, Adriana,Beck, Namseon,Shaffer, World Health Organization 2018 Bulletin of the World Health Organization Vol.96 No.6

<P><B>Abstract</B></P><P><B>Problem</B></P><P>With limited global supplies of oral cholera vaccine, countries need to identify priority areas for vaccination while longer-term solutions, such as water and sanitation infrastructure, are being developed.</P><P><B>Approach</B></P><P>In 2017, Malawi integrated oral cholera vaccine into its national cholera control plan. The process started with a desk review and analysis of previous surveillance and risk factor data. At a consultative meeting, researchers, national health and water officials and representatives from nongovernmental and international organizations reviewed the data and local epidemiological knowledge to determine priority districts for oral cholera vaccination. The final stage was preparation of an application to the global oral cholera vaccine stockpile for non-emergency use.</P><P><B>Local setting</B></P><P>Malawi collects annual data on cholera and most districts have reported cases at least once since the 1970s.</P><P><B>Relevant changes</B></P><P>The government’s application for 3.2 million doses of vaccine to be provided over 20 months in 12 districts was accepted in April 2017. By April 2018, over 1 million doses had been administered in five districts. Continuing surveillance in districts showed that cholera outbreaks were notably absent in vaccinated high-risk areas, despite a national outbreak in 2017–2018.</P><P><B>Lessons learnt</B></P><P>Augmenting advanced mapping techniques with local information helped us extend priority areas beyond those identified as high-risk based on cholera incidence reported at the district level. Involvement of the water, sanitation and hygiene sectors is key to ensuring that short-term gains from cholera vaccine are backed by longer-term progress in reducing cholera transmission.</P>

안전한 환경을 제공하기 위한 바이오 봉쇄병실 설계 전략

마틱 조라나,험프리스 벤턴,오예인,임리사,드보스 제니퍼,Matic, Zorana,Humphreys, Benton,Oh, Yeinn,Lim, Lisa,DuBose, Jennifer 한국의료복지건축학회 2020 의료·복지 건축 Vol.26 No.2

NDVI derived from near-infrared-enabled digital cameras: Applicability across different plant functional types

Filippa, Gianluca,Cremonese, Edoardo,Migliavacca, Mirco,Galvagno, Marta,Sonnentag, Oliver,Humphreys, Elyn,Hufkens, Koen,Ryu, Youngryel,Verfaillie, Joseph,Morra di Cella, Umberto,Richardson, Andrew D. Elsevier 2018 Agricultural and forest meteorology Vol.249 No.-

<P><B>Abstract</B></P> <P>Time series of vegetation indices (e.g. normalized difference vegetation index [NDVI]) and color indices (e.g. green chromatic coordinate [<I>G</I> <SUB> <I>CC</I> </SUB>]) based on radiometric measurements are now available at different spatial and temporal scales ranging from weekly satellite observations to sub-hourly <I>in situ</I> measurements by means of near-surface remote sensing (e.g. spectral sensors or digital cameras). <I>In situ</I> measurements are essential for providing validation data for satellite-derived vegetation indices. In this study we used a recently developed method to calculate NDVI from near-infrared (NIR) enabled digital cameras (NDVI<SUB> <I>C</I> </SUB>) at 17 sites (for a total of 74 year-sites) encompassing six plant functional types (PFT) from the PhenoCam network.</P> <P>The seasonality of NDVI<SUB> <I>C</I> </SUB> was comparable to both NDVI measured by ground spectral sensors and by the moderate resolution imaging spectroradiometer (MODIS). We calculated site- and PFT-specific scaling factors to correct NDVI<SUB> <I>C</I> </SUB> values and recommend the use of site-specific NDVI from MODIS in order to scale NDVI<SUB> <I>C</I> </SUB>. We also compared <I>G</I> <SUB> <I>CC</I> </SUB> extracted from red-green-blue images to NDVI<SUB> <I>C</I> </SUB> and found PFT-dependent systematic differences in their seasonalities. During senescence, NDVI<SUB> <I>C</I> </SUB> lags behind <I>G</I> <SUB> <I>CC</I> </SUB> in deciduous broad-leaf forests and grasslands, suggesting that <I>G</I> <SUB> <I>CC</I> </SUB> is more sensitive to changes in leaf color and NDVI<SUB> <I>C</I> </SUB> is more sensitive to changes in leaf area. In evergreen forests, NDVI<SUB> <I>C</I> </SUB> peaks later than <I>G</I> <SUB> <I>CC</I> </SUB> in spring, probably tracking the processes of shoot elongation and new needle formation. Both <I>G</I> <SUB> <I>CC</I> </SUB> and NDVI<SUB> <I>C</I> </SUB> can be used as validation tools for the MODIS Land Cover Dynamics Product (MCD12Q2) for deciduous broad-leaf spring phenology, whereas NDVI<SUB> <I>C</I> </SUB> is more comparable than <I>G</I> <SUB> <I>CC</I> </SUB> with autumn phenology derived from MODIS. For evergreen forests, we found a poor relationship between MCD12Q2 and camera-derived phenology, highlighting the need for more work to better characterize the seasonality of both canopy structure and leaf biochemistry in those ecosystems.</P> <P>Our results demonstrate that NDVI<SUB> <I>C</I> </SUB> is in excellent agreement with NDVI obtained from spectral measurements, and that NDVI<SUB> <I>C</I> </SUB> and <I>G</I> <SUB> <I>CC</I> </SUB> can complement each other in describing ecosystem phenology. Additionally, NDVI<SUB> <I>C</I> </SUB> allows the detection of structural changes in the canopy that cannot be detected by visible-wavelength imagery.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We analyze 74 site-years of green chromatic coordinate (GCC) and camera NDVI data. </LI> <LI> Camera NDVI is comparable to traditional NDVI measurements. </LI> <LI> Camera NDVI and GCC can complement each other in describing ecosystem phenology. </LI> <LI> Both can be used as validation tools for satellite phenology products. </LI> </UL> </P>

Implementing a finite-state off-normal and fault response system for disruption avoidance in tokamaks

Eidietis, N.W.,Choi, W.,Hahn, S.H.,Humphreys, D.A.,Sammuli, B.S.,Walker, M.L. International Atomic Energy Agency 2018 Nuclear fusion Vol.58 No.5

<P>A finite-state off-normal and fault response (ONFR) system is presented that provides the supervisory logic for comprehensive disruption avoidance and machine protection in tokamaks. Robust event handling is critical for ITER and future large tokamaks, where plasma parameters will necessarily approach stability limits and many systems will operate near their engineering limits. Events can be classified as off-normal plasmas events, e.g. neoclassical tearing modes or vertical displacements events, or faults, e.g. coil power supply failures. The ONFR system presented provides four critical features of a robust event handling system: sequential responses to cascading events, event recovery, simultaneous handling of multiple events and actuator prioritization. The finite-state logic is implemented in Matlab<SUP>®</SUP>/Stateflow<SUP>®</SUP> to allow rapid development and testing in an easily understood graphical format before automated export to the real-time plasma control system code. Experimental demonstrations of the ONFR algorithm on the DIII-D and KSTAR tokamaks are presented. In the most complex demonstration, the ONFR algorithm asynchronously applies ‘catch and subdue’ electron cyclotron current drive (ECCD) injection scheme to suppress a virulent 2/1 neoclassical tearing mode, subsequently shuts down ECCD for machine protection when the plasma becomes over-dense, and enables rotating 3D field entrainment of the ensuing locked mode to allow a safe rampdown, all in the same discharge without user intervention. When multiple ONFR states are active simultaneously and requesting the same actuator (e.g. neutral beam injection or gyrotrons), actuator prioritization is accomplished by sorting the pre-assigned priority values of each active ONFR state and giving complete control of the actuator to the state with highest priority. This early experience makes evident that additional research is required to develop an improved actuator sharing protocol, as well as a methodology to minimize the number and topological complexity of states as the finite-state ONFR system is scaled to a large, highly constrained device like ITER.</P>

Genome-wide association analysis identifies three new breast cancer susceptibility loci

Ghoussaini, Maya,Fletcher, Olivia,Michailidou, Kyriaki,Turnbull, Clare,Schmidt, Marjanka K,Dicks, Ed,Dennis, Joe,Wang, Qin,Humphreys, Manjeet K,Luccarini, Craig,Baynes, Caroline,Conroy, Don,Maranian, Nature Publishing Group, a division of Macmillan P 2012 Nature genetics Vol.44 No.3

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ??% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ??0,000 cases and ??8,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 ? 10<SUP>??35</SUP>), 12q24 (rs1292011; P = 4.3 ? 10<SUP>??19</SUP>) and 21q21 (rs2823093; P = 1.1 ? 10<SUP>??12</SUP>). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

Five polymorphisms and breast cancer risk: results from the Breast Cancer Association Consortium.

Gaudet, Mia M,Milne, Roger L,Cox, Angela,Camp, Nicola J,Goode, Ellen L,Humphreys, Manjeet K,Dunning, Alison M,Morrison, Jonathan,Giles, Graham G,Severi, Gianluca,Baglietto, Laura,English, Dallas R,Cou American Association for Cancer Research 2009 Cancer Epidemiology, Biomarkers & Prevention Vol.18 No.5

<P>Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent.</P>

Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls

Zheng, Wei,Zhang, Ben,Cai, Qiuyin,Sung, Hyuna,Michailidou, Kyriaki,Shi, Jiajun,Choi, Ji-Yeob,Long, Jirong,Dennis, Joe,Humphreys, Manjeet K.,Wang, Qin,Lu, Wei,Gao, Yu-Tang,Li, Chun,Cai, Hui,Park, Sue K Oxford University Press 2013 Human Molecular Genetics Vol.22 No.12

<P>In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at <I>P</I> < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at <I>P</I> < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ∼10% of excess familial risk of breast cancer in Asian populations.</P>