Resolving issues of scaling for gramian-based input–output pairing methods

A key problem in process control is to decide which inputs should control which outputs. There are multiple ways to solve this problem, among them using gramian-based measures, which include the Hankel interaction index array, the participation matrix and the (Formula presented.) method. The gramian-based measures, however, have issues with input and output scaling. Generally, this is resolved by scaling all inputs and outputs to have equal range. However, we demonstrate how this can result in an incorrect pairing and examine alternative methods of scaling the gramian-based measures, using either row or column sums or by utilising the Sinkhorn-Knopp algorithm. To systematically analyse the benefits of the scaling schemes, a multiple-input multiple-output model generator is used to test the different schemes on a large number of systems. This assessment shows considerable benefits to be gained from the alternative scaling of the gramian-based measures, especially when using the Sinkhorn-Knopp algorithm

Resolving Issues of Scaling for Gramian Based Input-Output Pairing Methods

A key problem in process control is to decide which inputs should control which outputs. There are multiple ways to solve this problem, among them using gramian based measures, which include the Hankel interaction index array, the participation matrix and the $\Sigma_{2}$ method. The gramian based measures however have issues with input and output scaling. Generally, this is resolved by scaling all inputs and outputs to have equal range. However, we demonstrate how this can result in an incorrect pairing and examine alternative methods of scaling the gramian based measures, using either row or column sums, or by utilizing the Sinkhorn-Knopp algorithm. The benefits of these scaling strategies are first illustrated by applying them to the control structure selection for a heat exchanger network. Then, to more systematically analyze the benefits of the scaling schemes, a multiple input multiple output model generator is used to test the different schemes on a large number of systems. This, along with implementation of automatic controller tuning, allows for a statistical comparison of the scaling methods. This assessment shows considerable benefits to be gained from the alternative scaling of the gramian based measures, especially when using the Sinkhorn-Knopp algorithm. The use of this method also has the advantage that the results are completely independent of the original scaling of the inputs and outputs.Comment: 20 pages, 2 figure

Iodine Nutrition and Iodine Supplement Initiation in Association with Thyroid Function in Mildly-to-Moderately Iodine-Deficient Pregnant and Postpartum Women

Background Whereas the adverse effects of severe iodine deficiency during pregnancy are well documented, the effects of mild-to-moderate deficiency are not well established. Objectives We aimed to explore whether iodine nutrition and timing of iodine supplement initiation are associated with thyroid function in pregnant and postpartum women. Methods In this cohort study, 137 pregnant women were enrolled and followed up at gestational weeks (GWs) 18 and 36, and 3 and 6 mo postpartum. Thyroid function tests [thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)], urinary iodine and creatinine concentration (UIC:Cr), and iodine intake (including iodine supplement use) were measured at each time point. The associations between thyroid hormone concentrations and UIC:Cr, iodine intakes, and iodine supplement use were estimated using multiple generalized estimating equation models. Results The median UIC at GW18 was 94 μg/L, indicating mild-to-moderate iodine deficiency. UIC:Cr (β; 95% CI) per 100 μg/g was negatively associated with fT3 (−0.191; −0.331, −0.051) and fT4 (−0.756; −1.372, −0.141) concentrations. Iodine intake (β; 95% CI) per 100 μg/d was positively associated with TSH (0.099; 0.022, 0.177), and negatively associated with fT3 (−0.084; −0.0141, −0.027) and fT4 (−0.390; −0.599, −0.182) concentrations. Compared with no use of supplement, those initiating an iodine-containing supplement prepregnancy and continuing through pregnancy had lower TSH (estimated means) (1.35 compared with 1.68 mIU/L, P = 0.021), and higher fT3 (4.48 compared with 4.28 pmol/L, P = 0.035) and fT4 (15.2 compared with 14.4 pmol/L, P = 0.024) concentrations. Conclusions Lower iodine availability during pregnancy and postpartum was associated with lower TSH, and higher fT3 and fT4 concentrations. The use of an iodine-containing supplement that was initiated prepregnancy and continuing through pregnancy was associated with lower TSH, and higher fT3 and fT4 concentrations, which may suggest improved thyroid function. These findings support the notion that optimization of iodine intake should start before pregnancy. This trial was registered at clinicaltrials.gov as NCT02610959.publishedVersio

Infant iodine status and associations with maternal iodine nutrition, breastfeeding status and thyroid function

Adequate iodine nutrition during infancy is required for normal thyroid function and, subsequently, brain development. However, data on infant iodine status in the first year of life are scarce. This study aimed to describe infant iodine status and further explore its associations with maternal iodine nutrition, breast-feeding status and thyroid function. In this cohort study, 113 infants were followed up at ages 3, 6 and 11 months in Norway. Infant and maternal urinary iodine concentration (UIC), maternal iodine intake, breast milk iodine concentration (BMIC), breast-feeding status and infant thyroid function tests were measured. The median infant UIC was 82 µg/l at the age of 3 months and below the WHO cut-off of 100 µg/l. Infant UIC was adequate later in infancy (median 110 µg/l at ages 6 and 11 months). Infant UIC was associated positively with maternal UIC (β = 0·33, 95 % CI (0·12, 0·54)), maternal iodine intake (β = 0·30, 95 % CI (0·18, 0·42)) and BMIC (β = 0·46, 95 % CI (0·13, 0·79)). Breastfed infants had lower median UIC compared with formula-fed infants at ages 3 months (76 v. 190 µg/l) and 6 months (105 v. 315 µg/l). Neither infant UIC nor BMIC were associated with infant thyroid function tests. In conclusion, breastfed infants in Norway are at risk of insufficient iodine intake during the first months of life. Maternal iodine nutrition is important for providing sufficient iodine intake in infants, and awareness of promoting adequate iodine nutrition for lactating women should be prioritised.publishedVersio

Integrin α11β1 is expressed in breast cancer stroma and associates with aggressive tumor phenotypes

Cancer‐associated fibroblasts are essential modifiers of the tumor microenvironment. The collagen‐binding integrin α11β1 has been proposed to be upregulated in a pro‐tumorigenic subtype of cancer‐associated fibroblasts. Here, we analyzed the expression and clinical relevance of integrin α11β1 in a large breast cancer series using a novel antibody against the human integrin α11 chain. Several novel monoclonal antibodies against the integrin α11 subunit were tested for use on formalin‐fixed paraffin‐embedded tissues, and Ab 210F4B6A4 was eventually selected to investigate the immunohistochemical expression in 392 breast cancers using whole sections. mRNA data from METABRIC and co‐expression patterns of integrin α11 in relation to αSMA and cytokeratin‐14 were also investigated. Integrin α11 was expressed to varying degrees in spindle‐shaped cells in the stroma of 99% of invasive breast carcinomas. Integrin α11 co‐localized with αSMA in stromal cells, and with αSMA and cytokeratin‐14 in breast myoepithelium. High stromal integrin α11 expression (66% of cases) was associated with aggressive breast cancer features such as high histologic grade, increased tumor cell proliferation, ER negativity, HER2 positivity, and triple‐negative phenotype, but was not associated with breast cancer specific survival at protein or mRNA levels. In conclusion, high stromal integrin α11 expression was associated with aggressive breast cancer phenotypes.publishedVersio

Hypnosis as a treatment of chronic widespread pain in general practice: A randomized controlled pilot trial

<p>Abstract</p> <p>Background</p> <p>Hypnosis treatment in general practice is a rather new concept. This pilot study was performed to evaluate the effect of a standardized hypnosis treatment used in general practice for patients with chronic widespread pain (CWP).</p> <p>Methods</p> <p>The study was designed as a randomized control group-controlled study. Sixteen patients were randomized into a treatment group or a control group, each constituting eight patients. Seven patients in the treatment group completed the schedule. After the control period, five of the patients in the control group also received treatment, making a total of 12 patients having completed the treatment sessions. The intervention group went through a standardized hypnosis treatment with ten consecutive therapeutic sessions once a week, each lasting for about 30 minutes, focusing on ego-strengthening, relaxation, releasing muscular tension and increasing self-efficacy. A questionnaire was developed in order to calibrate the symptoms before and after the 10 weeks period, and the results were interpolated into a scale from 0 to 100, increasing numbers representing increasing suffering. Data were analyzed by means of T-tests.</p> <p>Results</p> <p>The treatment group improved from their symptoms, (change from 62.5 to 55.4), while the control group deteriorated, (change from 37.2 to 45.1), (p = 0,045). The 12 patients who completed the treatment showed a mean improvement from 51.5 to 41.6. (p = 0,046). One year later the corresponding result was 41.3, indicating a persisting improvement.</p> <p>Conclusion</p> <p>The study indicates that hypnosis treatment may have a positive effect on pain and quality of life for patients with chronic muscular pain. Considering the limited number of patients, more studies should be conducted to confirm the results.</p> <p>Trial Registration</p> <p>The study was registered in ClinicalTrials.gov and released 27.08.07 Reg nr NCT00521807 Approval Number: 05032001.</p

Thiopurine Enhanced ALL Maintenance (TEAM) : study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine/methotrexate-based maintenance therapy in pediatric and adult patients (0-45 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol

Background: A critical challenge in current acute lymphoblastic leukemia (ALL) therapy is treatment intensification in order to reduce the relapse rate in the subset of patients at the highest risk of relapse. The year-long maintenance phase is essential in relapse prevention. The Thiopurine Enhanced ALL Maintenance (TEAM) trial investigates a novel strategy for ALL maintenance. Methods: TEAM is a randomized phase 3 sub-protocol to the ALLTogether1 trial, which includes patients 0-45 years of age with newly diagnosed B-cell precursor or T-cell ALL, and stratified to the intermediate risk-high (IR-high) group, in 13 European countries. In the TEAM trial, the traditional methotrexate (MTX)/6-mercaptopurine (6MP) maintenance backbone (control arm) is supplemented with low dose (2.5-12.5 mg/m(2)/day) oral 6-thioguanine (6TG) (experimental arm), while the starting dose of 6MP is reduced from 75 to 50 mg/m(2)/day. A total of 778 patients will be included in TEAM during similar to 5 years. The study will close when the last included patient has been followed for 5 years from the end of induction therapy. The primary objective of the study is to significantly improve the disease-free survival (DFS) of IR-high ALL patients by adding 6TG to 6MP/MTX-based maintenance therapy. TEAM has 80% power to detect a 7% increase in 5-year DFS through a 50% reduction in relapse rate. DFS will be evaluated by intention-to-treat analysis. In addition to reducing relapse,TEAM may also reduce hepatotoxicity and hypoglycemia caused by high levels of methylated 6MP metabolites. Methotrexate/6MP metabolites will be monitored and low levels will be reported back to clinicians to identify potentially non-adherent patients. Discussion: TEAM provides a novel strategy for maintenance therapy in ALL with the potential of improving DFS through reducing relapse rate. Potential risk factors that have been considered include hepatic sinusoidal obstruction syndrome/nodular regenerative hyperplasia, second cancer, infection, and osteonecrosis. Metabolite monitoring can potentially increase treatment adherence in both treatment arms.Peer reviewe

Socialt kompetenta flickor och fysiskt aktiva pojkar : En studie om hur genus konstrueras i barnets plan för småbarnspedagogik

Denna magisteravhandling undersöker hur genus görs i den pedagogiska dokumentationen i småbarnspedagogiken. Grunderna för planen för småbarnspedagogik (Utbildningsstyrelsen, 2018) betonar en genussensitiv småbarnspedagogik, vilket innebär att könsbundna förväntningar inte ska få begränsa barnens valmöjligheter. En grundsyn är att genus konstrueras i vardagspraktiker (Walkerdine & Lucey, 1989). Detta sker bland annat i den pedagogiska dokumentationen genom att barn och deras aktiviteter kategoriseras utgående från rådande normer som styr pedagogernas uppfattningar om vad som är normalt respektive onormalt för barnen utifrån deras kön (Dahlberg m.fl., 2014). Avhandlingens syfte är att synliggöra hur genus görs i den pedagogiska dokumentationen inom småbarnspedagogiken. Avhandlingen utgår från följande forskningsfråga som formulerats med utgångspunkt i avhandlingens syfte: - Hur konstrueras genus i barnets plan för småbarnspedagogik? För att besvara denna forskningsfråga har kvalitativ metod använts med diskursanalys som forskningsansats. Avhandlingens datamaterial har bestått av cirka 30 barns planer för småbarnspedagogik. Materialet har samlats in genom dokumentinsamling från flera daghem i Svenskfinland. Barnens planer för småbarnspedagogik har analyserats med inspiration av Bolander och Fejes (2019) diskursanalytiska frågor. Resultatet presenteras i form av fyra diskurser som har utformats för att synliggöra hur genus konstrueras genom de beskrivningar av barnet som görs i barnets plan för småbarnspedagogik. Resultatet visar att flickors och pojkars intressen och färdigheter framställs som olika varandra. Detta synliggörs bland annat genom att pojkar uppmuntras till fysiska aktiviteter, medan flickor styrs till lugna lekar. Resultatet visar även att förväntningar på barnen är olika beroende på barnets kön. Sociala färdigheter i relation till andra barn och pedagoger värdesätts högt för flickor. Flickor förväntas utveckla en förmåga att lösa konfliktsituationer själva, i kombination med att deras socioemotionella färdigheter stöds. Pojkar förväntas å sin sida inte visa sig känsliga och framom att stödja pojkars socioemotionella färdigheter förväntas de utveckla mod nog för att verbalt kunna söka stöd av pedagoger i känslofyllda situationer. För att uppnå jämställdhet i småbarnspedagogiken behöver situationer i vardagen där barn bemöts olika utifrån deras kön synliggöras. Genom att utveckla en medvetenhet kring hur genus görs i den pedagogiska dokumentationen inom småbarnspedagogiken kan könsgränser utmanas och överskridas. På så sätt skapas möjligheter för barnen att göra val oavsett kön