Investigation of the MOST channel conductance in weak inversion

The drain-source conductance of several MOS transistors has been studied as a function of the silicon surface-potential ψs in the weak and intermediate inversion region, under the condition of quasi-thermal equilibrium at room temperature. The silicon surface conductance per square ifG(in□ has been measured to vary exponentially with qψs/kT in weak inversion for excess minority carrier densities extending over the range 105-1011 cm−2. The exponential behaviour of G□ vs. qψs/kT appeared to be insensitive for the presence of interface states, when distributed around peak values as large (As) 6 × 1011/cm2 eV at ≈ 200 meV energy distance from midgap.\ud \ud Garrett and Brattain predicted theoretically that the excess minority carrier surface charge for weak inversion should also be an exponential function of qψs/kT, we conclude that the minority carrier mobility remains constant over the entire weak inversion region.\ud \ud A refined version of the low frequency CV method the so-called ‘split’ CV method has been introduced, which allows a simple determination of the charge trapped in interface states in weak and intermediate inversion as well as a determination of the bulk dope density

Interface studies of the MOS-structure by transfer-admittance measurements

The transfer-admittance of n- and p-channel MOS transistors has been measured under the condition of a uniform channel. These MOS transistors all showed a measurable “slow interface state drift” <0·1–0·2 V. The transfer-susceptance has been found to show a significant peak value in moderate inversion. Over the entire moderate and strong inversion region the transfer-susceptance remains constant as a function of the measurement frequency ω between 1·6 Hz and 2 × 104 Hz, while the transfer-conductance varies almost like ln ω. Furthermore the transfer-susceptance shows a linear relationship with the variation of the transfer-conductance per frequency decade. The paper shows that these phenomena can be well explained by assuming a tunneling of channel charge carriers into electron states in the oxide. Also the temperature behaviour of the transfer-admittance does not seem to be in conflict with this tunnel model. More than the CV measuring method the measurement of the transfer-admittance allows an investigation of the interaction between mobile inversion layer charge carriers, and interface states in the condition of moderate inversion (5 × 1010-5 × 1011 electrons cm−2). The measuring method might therefore find application in the investigation of charge trapping in CCD devices. As a pertinent result the density of oxide states having time constants between 6 × 10−1 sec and 1·6 × 10−5 sec appears to increase to values of about 1011 per cm2V as the interface state energy approaches the conduction and valence band edge energies within a distance of 70 meV

The measurement of interface state charge in the MOS system

A simple method of measuring charge in surface states as a function of the surfacepotential in MOS transistor or MOS capacitors is proposed.\ud \ud A constant d.c. current is fed into the gate of an MOS transistor and with the help of an operational amplifier, the gate voltage Vg with respect to the bulk is plotted as a function of gate charge Qg. The gate charge as a function of the surfacepotential φs can be directly read off from the Vg-Qg curve.\ud \ud As the silicon charge Qs(φs) is known from the literature the surface state charge can be easily determined as a function of φs. The method is illustrated with measurements on n-type and p-type MOS transistors. Finally the accuracy of the charge measuring method is discussed and a comparison with other interface state charge measuring methods is made from which the charge measuring method evolves as a method, attractive for its simplicity

Evaluating future urbanisation patterns in the Netherlands

Although the Netherlands is one of the most densely populated countries, two thirds of the land area are still under agricultural use. Major socio-economic changes are however expected for the agricultural sector. The increasing globalisation of economic relations in agriculture and the possible reduction of European price support to farmers are examples of such developments that may affect agricultural land use. At the same time other land use functions put increasing pressure on rural land in order to accommodate housing, employment, recreation and water storage. The present study takes a closer look at the expected spatial developments and simulates possible future land use patterns by using an economics based land use model. Two opposing scenarios of anticipated land use change are used to illustrate the possible extremes of future land use configurations. These scenarios vary both in their quantitative and qualitative description of the projected changes. The simulation of low-density residential areas in green areas will illustrate this approach. The development of these new rural living areas is currently a sensitive topic in the public debate on urbanisation. The simulated urbanisation patterns are evaluated in terms of their impact on spatial policy related issues through the application of newly developed indicators. For decades the Dutch government has strived for compact forms of urbanisation in order to preserve the remaining stretches of open space. The applied metrics of land use change will therefor focus on the concentration of urbanisation and the fragmentation of open space. The findings of this study may be especially interesting now Dutch spatial policy seems to be on the brink of loosening its traditional grip on spatial planning.

Modelling the fragmentation of open space. A framework for assessing the impact of land use change on open space

The Netherlands is one of the most densely populated countries in the world and urban functions are constantly claiming more space. This continuing urbanisation has lead to a growing concern for the preservation of open space. A loss of open space does not only mean a fragmentation of ecosystems or (potential) animal habitat but also affects the geographical, historical and cultural qualities of the landscape. The preservation of open space is an important theme in the spatial planning of the Netherlands. The Dutch government strives to keep the total volume of open space at a reasonable high level and tries to avoid the fragmentation of open space. The present research deals with the modelling of future land use and will focus more specifically on the fragmentation of open space. A GIS-oriented land use model will be used to study this subject. Assessing the impact of land use change on open space calls for a thorough definition of open space that takes into account the shape and size characteristics of various land use functions. This definition is strongly related to the policy context that introduces the concept of open space. In the Dutch, anthropocentric practice open space does not necessarily refer to large natural areas with high ecological values, but it rather relates to large areas with relatively few buildings. This might for example exclude wooded areas that do not offer panoramic views. Single objects (high voltage or television masts) can also severely affect the individual experience of open space. GIS-technology allows for a quantitative implementation of the concept of open space. It furthermore facilitates the spatial analysis of the impact of land use changes. Different simulations from land use models will be assessed both in terms of a total loss in the volume of open space and the localised impact in terms of fragmentation. To study the latter impact a methodology will be developed that will adopt experiences from spatial ecological research on habitat fragmentation.

Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis

Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93–80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage

Formalin fixation for optimal concordance of programmed death-ligand 1 immunostaining between cytologic and histologic specimens from patients with non-small cell lung cancer

Background Immunohistochemical staining of programmed death-ligand 1 (PD-L1) is used to determine which patients with non-small cell lung cancer (NSCLC) may benefit most from immunotherapy. Therapeutic management of many patients with NSCLC is based on cytology instead of histology. In this study, concordance of PD-L1 immunostaining between cytology cell blocks and their histologic counterparts was analyzed. Furthermore, the effect of various fixatives and fixation times on PD-L1 immunoreactivity was studied. Methods Paired histologic and cytologic samples from 67 patients with NSCLC were collected by performing fine-needle aspiration on pneumonectomy/lobectomy specimens. Formalin-fixed, agar-based or CytoLyt/PreservCyt-fixed Cellient cell blocks were prepared. Sections from cell blocks and tissue blocks were stained with SP263 (standardized assay) and 22C3 (laboratory-developed test) antibodies. PD-L1 scores were compared between histology and cytology. In addition, immunostaining was compared between PD-L1-expressing human cell lines fixed in various fixatives at increasing increments in fixation duration. Results Agar cell blocks and tissue blocks showed substantial agreement (kappa = 0.70 and kappa = 0.67, respectively), whereas fair-to-moderate agreement was found between Cellient cell blocks and histology (kappa = 0.28 and kappa = 0.49, respectively). Cell lines fixed in various alcohol-based fixatives showed less PD-L1 immunoreactivity compared with those fixed in formalin. In contrast to SP263, additional formalin fixation after alcohol fixation resulted in preserved staining intensity using the 22C3 laboratory-developed test and the 22C3 pharmDx assay. Conclusions Performing PD-L1 staining on cytologic specimens fixed in alcohol-based fixatives could result in false-negative immunostaining results, whereas fixation in formalin leads to higher and more histology-concordant PD-L1 immunostaining. The deleterious effect of alcohol fixation could be reversed to some degree by postfixation in formalin

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)