Optimization Under Uncertainty Using the Generalized Inverse Distribution Function

A framework for robust optimization under uncertainty based on the use of the generalized inverse distribution function (GIDF), also called quantile function, is here proposed. Compared to more classical approaches that rely on the usage of statistical moments as deterministic attributes that define the objectives of the optimization process, the inverse cumulative distribution function allows for the use of all the possible information available in the probabilistic domain. Furthermore, the use of a quantile based approach leads naturally to a multi-objective methodology which allows an a-posteriori selection of the candidate design based on risk/opportunity criteria defined by the designer. Finally, the error on the estimation of the objectives due to the resolution of the GIDF will be proven to be quantifiableComment: 20 pages, 25 figure

Clinical characteristics and premorbid variables in childhoodonset schizophrenia: a descriptive study of twelve cases from a schizophrenia founder population

Objective: To analyze clinical and demographic data of childhood-onset (12 years and younger) schizophrenia patients collected for a genetic study in schizophrenia, undertaken nationally in South Africa, using multiple parameters. Method: Patients with an onset of schizophrenia at 12 years or younger, were included. From the Diagnostic Interview for Genetic Studies (DIGS), patients’ information and summary report data was tabulated and analyzed. Specific subgroups were further compared. This sub-population of 12 subjects was further compared with a group of the adult sample. Results: Of the 12 patients recruited, prominent resultswere: male to female ratio of 1:1; all had insidious onset of psychosis; a third had all 3 multidimensional impairment (MDI) symptoms; all patients that received ADHD treatment had ADHD treatment failure; two thirds had milestone delay; 58% had birth complications; a third were predominantly bottle fed; 42% had family history of schizophrenia; a third had family history of other major psychiatric conditions; all patients had at least one non-psychotic deviant behaviour (NPDB); no patient used cannabis; alldelusions were paranoid; 92% had school achievement difficulty and a third had treatment resistance. Gender comparison included: earlier onset of psychosis in females; all females had aggression versus a third of males; more females had school achievement difficulty than males; males had more treatment resistance. Patients with MDI, compared to the sample average had: earlier onset of non-psychotic deviant behaviour; lower school drop-out rate; less social difficulty and no treatment resistance. Conclusion: The results compare well to previous research on this topic. The new concepts introduced by the present studyrequire further investigation

Irrigation scheduling research: South African experiences and future prospects

Many scheduling approaches have been developed with Water Research Commission funding over the past 4 decades and deployed with varying levels of success; 2 approaches have won prestigious international awards. Soil-based approaches which include measurement of matric potential (tensiometry), water content (neutron probes, capacitance sensors) and depth of wetting (wetting front detectors) have been relatively well accepted by farmers. Atmospheric-based approaches apply, through biophysical modelling of the soil-crop-atmosphere system, thermodynamic limits to the amount of water that can evaporate from a cropped surface under particular environmental conditions. Modelling approaches have been quite empirical or somewhat more mechanistic, generic or crop specific, with pre-programmed (e.g. irrigation calendars) or real-time output. Novel mechanisms have been developed to deliver recommendations to farmers, including resource-poor irrigators. Although general adoption of objective irrigation scheduling in South Africa is still low, the high cost of electricity and nitrogen, and scarcity of water is reviving the interest of consultants and irrigators in the application of these tools to use water more efficiently. Where adoption has been relatively high, intensive support and farmer-researcher-consultant interactions have been key contributing factors. We propose 4 avenues in the R&D domain to ensure responsible water utilisation. Firstly, there is a need to continue to advance existing soil-water measurement technology; and secondly, to further develop new and emerging technologies, like the use of remote sensing. Thirdly, the user-friendliness should be improved as should systems that support existing scheduling tools; and finally, we need to appreciate that farmers are intuitively adaptive managers, and we need to develop simple monitoring tools and conceptual frameworks that enable structured learning.Keywords: BEWAB; CANESIM; PUTU; SWB; wetting front detecto

Epilepsy Is a Risk Factor for Sudden Cardiac Arrest in the General Population

Background People with epilepsy are at increased risk for sudden death. The most prevalent cause of sudden death in the general population is sudden cardiac arrest (SCA) due to ventricular fibrillation (VF). SCA may contribute to the increased incidence of sudden death in people with epilepsy. We assessed whether the risk for SCA is increased in epilepsy by determining the risk for SCA among people with active epilepsy in a community-based study. Methods and Results This investigation was part of the Amsterdam Resuscitation Studies (ARREST) in the Netherlands. It was designed to assess SCA risk in the general population. All SCA cases in the study area were identified and matched to controls (by age, sex, and SCA date). A diagnosis of active epilepsy was ascertained in all cases and controls. Relative risk for SCA was estimated by calculating the adjusted odds ratios using conditional logistic regression (adjustment was made for known risk factors for SCA). We identified 1019 cases of SCA with ECG-documented VF, and matched them to 2834 controls. There were 12 people with active epilepsy among cases and 12 among controls. Epilepsy was associated with a three-fold increased risk for SCA (adjusted OR 2.9 [95%CI 1.1–8.0.], p = 0.034). The risk for SCA in epilepsy was particularly increased in young and females. Conclusion Epilepsy in the general population seems to be associated with an increased risk for SCA

Selective, non-covalent conjugation of synthetic peptides with recombinant proteins mediated by host-guest chemistry.

The combination of potent chemical moieties with biologically active proteins is key to some of today's most innovative therapeutic drugs. In order to obviate any chemical modification of the proteins, we present a novel and powerful strategy for the selective conjugation of recombinant protein domains with synthetically derived peptides via a cucurbit[8]uril host-guest chemistry approach.We thank Alexandra Rieck, Isabelle Sermadiras, Benjamin Kemp and Jennifer Spooner for help with the expression and purification of the Fc and Tn3 domains, Jefferson Revell and Jacky Metcalfe for help with the synthesis of modified peptides and Christel Veyssier for help with the light scattering experiments. RJG was supported by the MedImmune postdoctoral program. SS was supported by ERC Starting Investigator grant ASPiRe (No. 240629).This is the final version of the article. It first appeared from Royal Society of Chemistry via http://dx.doi.org/10.1039/C6CC00405

Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer

Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand–foot syndrome and a combination of grade 1–2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity

Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years

Ankylosing spondylitis (AS) is a chronic rheumatic disease associated with spinal inflammation that subsequently leads to progression of structural damage and loss of function. The fully human anti-tumor necrosis factor (anti-TNF) antibody adalimumab reduces the signs and symptoms and improves overall quality of life in patients with active AS; these benefits have been maintained through 2 years of treatment. Our objective was to compare the progression of structural damage in the spine in patients with AS treated with adalimumab for up to 2 years versus patients who had not received TNF antagonist therapy. Radiographs from patients with AS who received adalimumab 40 mg every other week subcutaneously were pooled from the Adalimumab Trial Evaluating Long-Term Efficacy and Safety for Ankylosing Spondylitis (ATLAS) study and a Canadian AS study (M03-606). Radiographic progression from baseline to 2 years in the spine of adalimumab-treated patients from these two studies (adalimumab cohort, n = 307) was compared with an historic anti-TNF-naïve cohort (Outcome in AS International Study [OASIS], n = 169) using the modified Stoke AS Spine Score (mSASSS) method. mSASSS results were not significantly different between the adalimumab cohort and the OASIS cohort, based on baseline and 2-year radiographs. Mean changes in mSASSS from baseline to 2 years were 0.9 for the OASIS cohort and 0.8 for the adalimumab cohort (P = 0.771), indicating similar radiographic progression in both groups. When results for patients in the OASIS cohort who met the baseline disease activity criteria for the ATLAS and Canadian studies (OASIS-Eligible cohort) were analyzed, there was no significant difference in mean change in mSASSS from baseline to 2 years between OASIS-Eligible patients and adalimumab-treated patients; the mean changes in mSASSS were 0.9 for the OASIS-Eligible cohort and 0.8 for the adalimumab cohort (P = 0.744). Two years of treatment with adalimumab did not slow radiographic progression in patients with AS, as assessed by the mSASSS scoring system, when compared with radiographic data from patients naïve to TNF antagonist therap

Cardiac magnetic resonance imaging analysis in STEMI: quantitative or still visual?

Cardiovascular Aspects of Radiolog

Giving voters what they want? Party orientation perceptions and preferences in the British electorate

Some of the most important propositions in the political marketing literature hinge on assumptions about the electorate. In particular, voters are presumed to react in different ways to different orientations or postures. Yet there are theoretical reasons for questioning some of these assumptions, and certainly they have seldom been empirically tested. Here, we focus on one prominent example of political marketing research: Lees-Marshment’s orientations’ model. We investigate how the public reacts to product and market orientation, whether they see a trade-off between the two (a point in dispute among political marketing scholars), and whether partisans differ from non-partisan voters by being more inclined to value product over market orientation. Evidence from two mass sample surveys of the British public (both conducted online by YouGov) demonstrates important heterogeneity within the electorate, casts doubt on the core assumptions underlying some political marketing arguments and raises broader questions about what voters are looking for in a party