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Study question Does the cause of subfertility affect any age-related changes observed in anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH)? Summary answer There was no significant effect of the cause of subfertility on AMH and FSH, however women with unexplained subfertility were significantly older than controls. What is known already Ovarian reserve and consequently female fecundity irreversibly diminish with age. Subfertility is an increasingly prevalent clinical presentation with a multitude of underlying pathologies. Ovarian reserve testing, including biomarkers, plays a crucial role in the management of subfertility, particularly in predicting ovarian response during in-vitro fertilisation (IVF) treatment. For some couples, no cause can be identified and their subfertility remains unexplained thus making prognosis and treatment challenging. It has been proposed that these couples may have an ovarian reserve at the extreme lower end of normal. Study design, size, duration: This clinical audit retrospectively investigated 864 subfertile healthy women who had undergone investigation at the Royal Derby Hospital fertility clinic. Data were collected in Excel including age, serum AMH, serum FSH if available, and subfertility diagnosis. The data were collected from a pre-existing database produced by a group of researchers pre–2016 at the Royal Derby Hospital. The researchers had access to pathology lab reports and computerised hospital records containing clinical details. Participants/materials, setting, methods: Subfertility diagnoses were categorised by cause: male factor and tubal factor were combined and served as a control group, oligo-anovulatory factor, endometriosis factor, and unexplained subfertility. If multiple factors were present, oligo-anovulation was taken as the presiding factor. One-way ANOVA using Minitab was used for statistical analysis to assess the effect of cause of subfertility on age, on AMH, and on FSH. For AMH and FSH, age was incorporated as a covariate. Main results and the role of chance AMH significantly decreased with age (p 0.05). Compared to the control group, FSH was lower in the unexplained, oligo-anovulatory, and endometriosis groups. However, after adjusting for age, the effect of cause of subfertility on FSH was not significant (R2(adj)=2.05%), p > 0.05). Limitations, reasons for caution The previous group of researchers may have exhibited selection bias and clinical interpretation during data collection. The study population was unevenly distributed across the different causes of subfertility. Only the effect of age was accounted for despite many factors being known to affect female fertility. Wider implications of the findings: Respective nomograms for AMH and FSH according to cause of subfertility provide a reference point for clinicians, especially to predict ovarian response during IVF treatment. Although AMH was not significantly lower in the unexplained group compared to the control group, the women were significantly older implying a lower ovarian reserve. Trial registration number Not applicable

Two comparable groups, each of which comprised 41 patients, were treated with long-acting phenprocoumon and short-acting acenocoumarol, respectively, for six months. When phenprocoumon was used, a significantly more stable anticoagulant effect was seen. This was reflected by a greater percentage of thrombotest values within the intended therapeutic zone ranging from 5 to 10% thrombotest activity, inclusive. Moreover, there was a difference in the facility with which patients could be kept in the therapeutic range: the number of alterations that had to be made in maintenance dose and control interval was less with phenprocoumon than with acenocoumarol.

In this study we compared the results of the acidified glycerol lysis test, the Pink test and the osmotic fragility test in 38 patients with hereditary spherocytosis and in healthy controls. The sensitivity of the acidified glycerol lysis test was 81.6% when performed within 3 h after blood collection. After incubating for 24 h, the sensitivity increased to 100% whereas the specificity remained maximal. Similar incubation did not improve the diagnostic utility of the Pink test. All patients, but none of the controls, showed a positive osmotic fragility test. It is concluded, because of sensitivity and specificity in this study, that the acidified glycerol lysis test after incubation and the osmotic fragility test are superior to the Pink test in detecting spherocytosis.

The vast majority of the pulsars detected by the Fermi Large Area Telescope (LAT) display spectra with exponential cutoffs falling in a narrow range around a few GeV. Early spectral modelling predicted spectral cutoff energies of up to 100 GeV. More modern studies estimated spectral cutoff energies in the 1-20 GeV range. It was therefore not expected that pulsars would be visible in the very-high-energy (VHE; >100 GeV) regime. The VERITAS detection (confirmed by MAGIC) of pulsed emission from the Crab pulsar up to 400 GeV (and now possibly up to 1 TeV) therefore raised important questions about our understanding of the electrodynamics and local environment of pulsars. H.E.S.S. has now detected pulsed emission from the Vela pulsar in the 20-120 GeV range, making this the second pulsar detected by a ground-based Cherenkov telescope. We will review the latest developments in VHE pulsar science, including an overview of recent observations and refinements to radiation models and magnetic field structures. This will assist us in interpreting the VHE emission detected from the Crab and Vela pulsars, and predicting the level of VHE emission expected from other pulsars, which will be very important for the upcoming CTA., 10 pages, 5 figures, "To appear in the Proceedings of the 3rd Annual Conference on High Energy Astrophysics in Southern Africa (HEASA2015), 18-20 June 2015, Johannesburg, South Africa, Eds. M. Boettcher, D. Buckley, S. Colafrancesco, P. Meintjes and S. Razzaque."

Objectives To develop a model to predict which newborns ≥34 weeks gestation with respiratory distress will die or will require prolonged (>3 days) assisted ventilation. Methods Retrospective cohort study using data from Northern California newborns ≥34 weeks gestation who presented with respiratory distress. We split the cohort into derivation and validation datasets. Bivariate and multivariate data analyses were performed on the derivation dataset. After developing a simple score on the derivation dataset, we applied it to the original as well as to a second validation dataset from Massachusetts. Results Of 2276 babies who met our initial eligibility criteria, 203 (9.3%) had the primary study outcome (assisted ventilation >3 days or death). A simple score based on gestational age, the lowest PaO 2 /FIO 2 , a variable combining lowest pH and highest PaCO 2 , and the lowest mean arterial blood pressure had excellent performance, with a c-statistic of 0.85 in the derivation dataset, 0.80 in the validation dataset, and 0.80 in the secondary validation dataset. Conclusions A simple objective score based on routinely collected physiologic predictors can predict respiratory outcomes in infants ≥34 weeks gestation with respiratory distress.

Digisonde Portable Sounder 4 (DPS-4) ionospheric F-region drift measurements at the polar cap station Casey (110.5°E, 66.3°S geographic, 80.8°S corrected geomagnetic), Antarctica were used to derive the Casey 1997 (C97) regression model of Smith [Ionospheric F-region plasma convection at Casey – a southern polar cap station. PhD Thesis. La Trobe University, Australia, 1998]. F-region ionospheric convection velocities derived from C97 are compared with convection velocities derived from the application of E × B /B 2 at the geomagnetic latitude of Casey to the relatively new DICM and IZMEM/DMSP fully parameterized electric potential convection models of Papitashvili and Rich [J. Geophys. Res. 107 (A8) 1198, 2002]. Where the DICM model was constructed from satellite F-region ion drift observations from DMSP satellite data at 840 km, and the IZMEM/DMSP model was constructed using ground-magnetometer measurements and calibrated against DMSP ion data. A comparison between C97 and the new DICM and IZMEM/DMSP models was undertaken as a function of dipole tilt angle or season and for a range of IMF parameters. The initial results of the comparison between these experimental models for estimating F-region ionospheric convection drift velocities will be presented.

Digisonde Portable Sounder 4 (DPS-4) and Canadian Advanced Digital Ionosonde (CADI) digital ionosondes were operated concurrently at the polar cap station Casey (110.5°E, 66.3°S geographic, 81.0°S magnetic), Antarctica during 2000–2001. These two digital ionosondes employ different antenna arrays and digital signal processing techniques, yet nevertheless are closely related instruments. An interleaved operation schedule permitted continuous recording of ionograms. Both instruments have proved reliable in monitoring the ionosphere. This paper presents observations of background ionospheric irregularities in the E- and F-region polar cap ionosphere using these two different digital ionosondes. The comparison between DPS and CADI ionogram records enabled us to devise alternative operation modes for the CADI program at Casey. The DPS has since been relocated to the polar cusp station Davis (78.0°E, 68.6°S geographic, 74.6°S magnetic), Antarctica.

Digisonde Portable Sounder 4 (DPS-4) and Canadian Advanced Digital Ionosonde (CADI) digital ionosondes were operated concurrently at the polar cap station Casey (110.5°E, 66.3°S geographic, 81.0°S magnetic), Antarctica during 2000–2001. These two digital ionosondes employ different antenna arrays and digital signal processing techniques, yet nevertheless are closely related instruments. An interleaved operation schedule permitted concurrent recording of ionograms and E- and F-region ionospheric drift measurements. This paper presents observations of background ionospheric drift in the F-region polar cap ionosphere using these two different digital ionosondes. A preliminary comparison between DPS and CADI drift measurements revealed substantial differences between the vertical (Vz) and horizontal (Vh) drift velocities determined by the two digital ionosondes. The DPS has since been relocated to the polar cusp station Davis (78.0°E, 68.6°S geographic, 74.6°S magnetic), Antarctica.

The statistical occurrence of decametre-scale ionospheric irregularities, average line-of-sight (LOS) Doppler velocity, and Doppler spectral width in the sub-auroral, auroral, and polar cap ionosphere ( - 57°L to - 88°L) has been investigated using echoes recorded with the Tasman International Geospace Environment Radar (TIGER), a SuperDARN radar located on Bruny Island, Tasmania (147.2° E, 43.4° S geographic; - 54.6 °L). Results are shown for routine soundings made on the magnetic meridian beam 4 and the near zonal beam 15 during the sunspot maximum interval December 1999 to November 2000. Most echoes were observed in the nightside ionosphere, typically via 1.5-hop propagation near dusk and then via 0.5-hop propagation during pre-midnight to dawn. Peak occurrence rates on beam 4 were often > 60% near magnetic midnight and ~ - 70 °L. They increased and shifted equatorward and toward pre-midnight with increasing Kp (i.e. Bz southward). The occurrence rates remained very high for Kp > 4, de-spite enhanced D-region absorption due to particle precipitation. Average occurrence rates on beam 4 exhibited a relatively weak seasonal variation, consistent with known longitudinal variations in auroral zone magnetic activity (Basu, 1975). The average echo power was greatest between 23 and 07 MLT. Two populations of echoes were identified on both beams, those with low spectral width and a mode value of ~ 9 ms-1 (bin size of 2 ms-1) concentrated in the auroral and sub-auroral ionosphere (population A), and those with high spectral width and a mode value of ~ 70 ms-1 concentrated in the polar cap ionosphere (population B). The occurrence of population A echoes maximised post-midnight because of TIGER’s lower latitude, but the subset of the population A echoes observed near dusk had characteristics reminiscent of "dusk scatter" (Ruohoniemi et al., 1988). There was a dusk "bite out" of large spectral widths between ~ 15 and 21 MLT and poleward of - 67 °L, and a pre-dawn enhancement of large spectral widths between ~ 03 and 07 MLT, centred on ~ - 61 °L. The average LOS Doppler velocities revealed that frequent westward jets of plasma flow occurred equatorward of, but overlapping, the diffuse auroral oval in the pre-midnight sector.Key words. Ionosphere (auroral ionosphere; electric fields and currents, ionospheric irregularities)

Vertical geoelectric field measurements at Vostok, Antarctica ( 78.5° S , 107° E ; corrected geomagnetic latitude, 83.4°S) made during 1998 are compared with both Weimer (1996) and IZMEM (1994) model calculations of the solar-wind-induced, polar-cap potential differences with respect to the station. By investigating the correlations between these parameters for individual UT hours, we confirm and extend the diurnal range over which significant correlations have been obtained. Nineteen individual UT hours are significantly correlated with the Weimer model predictions and nine with the IZMEM model predictions. Diurnal variation in the slopes of the linear regressions allows us to comment on each model, demonstrating that Antarctic polar plateau geoelectric field measurements can be used to investigate polar convection. Seasonal variations in the diurnal electric field variations at Vostok are compared with the Carnegie global electric circuit diurnal curves, after allowance is made for the solar-wind-induced, polar-cap potential difference patterns.

A Lowell Digital Ionosonde (DPS-4) has been used at the Australian Antarctic polar cap station Casey (−80.6° CGM latitude) in a study of ionospheric polar cap patches. The instrument ran a series of campaigns consisting of 3-minute cycles of ionograms and drift velocity measurements during 1997–1999. Patches identified from group range and critical frequencies on the ionogram records were compared with drift measurements and other geophysical data sets. Correlations were observed with Total Electron Content derived from GPS satellite observations with a receiver also located at Casey. Comparisons with plasma drift velocities, (derived from DPS drift measurements), indicate that patches are often associated with apparent fluctuations in horizontal drift velocity. Peaks in the horizontal velocity appear to correlate with the patch edges. Possible explanations of these observations are discussed. This paper considers case studies of patch observations in April 1998.

Theory predicts that in the high-latitude southern hemisphere, southwest (SW) electric fields will produce convergent ion flow and thereby create thin sporadic E (Es)-layers at node heights > 120 km, whilst northwest (NW) fields will produce downward ion flow and create thicker Es-layers at heights < 110 km. To investigate this theory, Digisonde ionograms (giving the Es-occurrence) and drift measurements (giving electric field estimates) at two Antarctic stations were statistically analyzed. As previously found for the polar cap station Casey (81 degreesS magnetic), more of the Es-traces were associated with SW fields than NW fields. However, new results for the cusp station Zhongshan (73 degreesS) show that fewer Es-layers occur there, and NW fields play a slightly more important role than SW fields, similar to the results found at auroral latitudes in the northern hemisphere. To further our understanding of the occurrence distributions, we study the fluctuating properties of the electric fields at the two stations. It is found that the electric fields at Zhongshan fluctuate more than those at Casey. Thus we suggest that the field fluctuation is also an important consideration helping to explain the differences in the Es-occurrence at the two stations. This suggestion is confirmed by our numerical simulations which show that Es-layers are more effectively formed by steady SW fields than by steady NW fields, and less effectively by fluctuating SW fields than by fluctuating NW fields. (C) 2001 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

The influence of the interplanetary magnetic field (IMF) on the occurrence of sporadic E (Es)-layers in the southern polar cap ionosphere has been investigated. We statistically analysed ionogram and Doppler velocity observations made using a HF digital ionosonde located at Casey, Antarctica (66.3°S, 110.5°E; 81°S magnetic latitude) during the two summer campaign intervals 1 January to 18 February, and 1 November to 31 December 1997. The ionogram and Doppler velocity measurements were used to determine the Es-occurrence and electric field vectors (assuming E×B/B2 drift), respectively. Concurrent IMF data were obtained from measurements made on board the Wind spacecraft. First, the gross properties of the IMF dependence of Es-formation were obtained: the occurrence rate was higher for negative By and/or positive Bz, and lower for positive By and/or negative Bz. To reconcile these gross properties with the electric field theory of Es-layer formation, the detailed diurnal variation of both Es-occurrence and the ionospheric electric field were obtained for different orientations of the IMF. The main statistical results are that: (1) the By component mainly controls the occurrence of the midnight Es-layers through its influence on the corresponding South West electric field; and (2) the Bz component mainly controls the occurrence of the evening Es-layers. However, the change in the occurrence rate for evening Es-layers was not related to the strength of the associated North West and North East electric fields. The total occurrence of Es-layers depended more on By than on Bz, owing to the dominance of By-controlled midnight Es-layers in the occurrence distribution. Nevertheless, the dependence of Es-occurrence on Bz was important. We suggest that the increase in Es-occurrence for positive Bz might be explained by the intermittent production of lower F-region ionisation by polar showers and squalls, which also increase in frequency and intensity for positive Bz. The importance of metallic ion transport within the ionosphere is also considered.

Signatures of the ionospheric cusp in HF digital ionosonde measurements of plasma drift made at the polar cap station Casey, Antarctica (−80.8° geomagnetic latitude), are investigated. Measurements recorded during the campaign interval February 13–17, 1996, are considered in this case study because the summer dipole tilt effect, and an interplanetary magnetic field (IMF) northward condition on February 16, were favorable for the detection of the cusp at a higher than usual latitude. On February 14 and 15 the magnitude of the IMF was about 4–6 nT, and the station probably passed just poleward of the cusp. The most general signatures of the cusp were enhanced electric field and electric field turbulence shown by increased drift velocity and velocity scatter in the convection throat, respectively. Broadband, unstructured fluctuations in the geomagnetic field measured by magnetometers near to noon are well known to be a signature of cusp currents and were associated with the intervals of enhanced convection turbulence. A major cusp event occurred above Casey on February 16, when the magnitude of the IMF increased from about 5 to > 10 nT. Cusp signatures during this event included the drift velocity surging to large values just before and after an interval during which the F region echoes were lost because of an absence of F region ionization and the formation of electron density patches. The loss of echoes was only partly explained by increased absorption and scatter of the transmitted radio waves. Although the spectral width of Doppler peaks increased, this, by itself, was not a unique signature of the cusp because the obliquity of echoes also controlled the spectral width in our near-vertical interferometry. However, signatures of the cusp were easily recognized in digisonde data, and the cusp's location and dynamics can be monitored using digisondes.

The thermopheric oxygen λ630 nm emission has been observed using high-resolution Fabry–Perot spectrometers at Mawson (67.6°S, 62.9°E) and Davis (68.6°S, 78.0°E), Antarctica. A new technique, combining the results from the two instruments, is used to derive vector wind fields. The technique is described and applied to five nights of simultaneous cardinal point data obtained in 1997. Solar flux was low during this interval, typically F10.7=75. Of the five nights two were magnetically disturbed and three were quiet. The observations for the disturbed nights were compared to a TIEGCM model run and reasonable agreement was found in the first half of the night. On one of the disturbed nights a closed evening circulation cell and cross-polar jet could be identified in our data. On none of the nights was a morning circulation cell evident. Auroral imager data were used to locate the auroral oval. For several hours around magnetic midnight the auroral oval produces doldrums in the thermospheric winds that are not described by the model. Auroral doldrums are also seen on the quiet nights which otherwise maintain a flow approximately consistent with a pressure-gradient driver.

In order to compare the possible influence of two absorbable suture materials on the formation of scar tissue, 26 women who had undergone reduction mammaplasty were the subjects of a randomized double blind clinical trial. In 26 women, who underwent a reduction mammaplasty, a prospective randomized double blind clinical trial was undertaken to compare the possible influence of two absorbable suture materials on the formation of scar tissue. The sutures under examination were Polyglecaprone 25 (Monocryl, Ethicon; Johnson & Johnson, Amersfoort, The Netherlands) and Polyglactine 910 (Vicryl Rapide, Ethicon; Johnson & Johnson, Amers-foort, The Netherlands). All scars were examined by one investigator after periods of 2 weeks, 3 months, and 1 year, to judge tissue reaction, redness and scar width. The monofilament Monocryl, which is absorbed more slowly and keeps its tensile strength longer than Vicryl Rapide, gave less tissue reaction initially and after periods of 3 months and 1 year produced significantly narrower scars than Vicryl Rapide.

The Dopplionogram was developed as a method of displaying Doppler shifts along the frequency axis of ionograms recorded using B-mode soundings of the Dynasonde, an early type of HF digital ionosonde. The basic idea of recording Doppler shifts in an ionogram format is applied and extended to the Doppler velocity mode of the Digisonde Portable Sounder-4 (DPS-4), a related and more recent type of digital ionosonde. In order to describe our mode of operation a Dopplionogram is redefined to mean a set of stepped-frequency soundings that yields a set of ionospheric Doppler shifts particular to the chosen transmission frequencies. Extension of the technique to include Doppler-sorted interferometry (DSI) analysis of the Doppler spectra facilitates a detailed analysis of ionospheric velocity variations in time and group height. This revitalized approach to DSI should prove useful for the study of ionospheric dynamics for which knowledge of the height profile of electric currents, drift velocity, and neutral winds is required. The technique is demonstrated using measurements of polar cap plasma winds obtained with a DPS-4 located at Casey, Antarctica (66.3°S, 110.5°E).

The seasonal, diurnal, and latitudinal variations of total electron content (TEC) were determined using Global Positioning System (GPS) satellite signals over approximately 5 days per month during almost half a sunspot cycle (July 1991 to June 1995) at Salisbury (latitude 34.77°S, longitude 138.63°E), South Australia. These are the only such extensive southern hemisphere data till 1995 that have been recorded and analyzed. A selection of the data is presented, discussed, and compared with other workers' observations. Examples of Australian Surveying and Land Information Group (AUSLlG) data in the Australian region are presented. Some model predictions for northern hemisphere ionospheric TEC are compared with the GPS southern hemisphere observations of the combined TEC of the ionosphere and protonosphere. (The two models employed are the international reference ionosphere (IRI-90) and the paramaterized ionospheric model (PIM)(version 1.4, February 1996)). They are considered to be global models, even though the IRJ model is based primarily, but not exclusively, on northern hemisphere TEC data, and PIM is based on a theoretical model and is thus not directly based on TEC data.

Ionospheric total electron content (TEC) and slab thickness (τ) have been determined for southern Australia from July 1991 to June 1995 using Global Positioning System (GPS) satellite reception and ionograms (at 5-min intervals) recorded at Salisbury, South Australia, and other Australian ionograms of the Ionospheric Prediction Service Radio and Space Services, Australian Department of Administrative Services. Seasonal, diurnal, and latitudinal variations in TEC and slab thickness are investigated. The removal of possible error sources in GPS measurements such as satellite and receiver biases is considered. Preliminary procedures are outlined in which protonospheric electron content is separated from GPS TEC measurements (up to 20,000 km height) by subtracting Navy Navigation Satellite System (NNSS) measurements (up to 1000 km height). Although slab thickness is substantially constant, there is a trend for increased values at times of reduced solar influence, such as when approaching sunspot minimum. A preliminary report is given of an extension of the current work at Salisbury by using Australian Surveying and Land Information Group GPS receivers at other Australian locations. A comparison is made between the experimental data and values derived from ionospheric models. The two models considered are the international reference ionosphere model (IRI90) and the parameterized ionospheric model ((PIM) version 1.4, February 1996). The GPS TEC measurements near solar minimum were consistently of the order of 5–10 TEC units greater than the model TEC predictions. This difference is attributed to the inclusion of protonospheric TEC in the GPS measurements but not in the model predictions.

In this paper challenges associated with a new generation of Computer Science students are examined. The mode of education in tertiary institutes has progressed slowly while the needs of students have changed rapidly in an increasingly technological world. The major learning paradigms and learning theories within these paradigms are studied to find a suitable strategy for educating modern students. These paradigms include Behaviourism, Constructivism, Humanism and Cogntivism. Social Learning theory and Elaboration theory are two theories that are further examined and a survey is done to determine how these strategies will be received by students. The results and findings are evaluated and indicate that students are fairly receptive to a method that incorporates both Social Learning theory and Elaboration theory, but that some aspects of all paradigms need to be implemented to create a balanced and effective strategy with technology as foundation., {"references":["A. K. Beerman, \"Computer-based Multimedia: New Directions in\nTeaching and Learning.\" Department of Food Science and Nutrition, pp.\n15-18, 28 June, 1996.","D. Tapscott, Growing up digital: The rise of the Net Generation. New\nYork: McGraw-Hill, 1998.","D. G. Oblinger and J. L. Oblinger, Educating the Net Generation, Date\nof access: 28 February 2012.\nhttp://www.educause.edu/ir/library/pdf/pub7101.pdf, 2005.","M. Prensky, \"Digital Natives, Digital Immigrants\" On The Horizon, vol.\n9, no. 5, October, 2001.","S. Bennett, K. Maton and L. Kervin, \"The 'Digital Natives' debate: A\ncritical review of the evidence.\" British Journal of Educational\nTechnology, vol. 39 no. 5, 2008.","G. E. Kennedy, T. S. Judd, A. Churchward and K. Gray, \"First year\nstudents' experiences with technology: Are they really digital natives?\"\nAustralian Journal of Educational Technology, vol. 24, no. 1, pp.108-\n122, 2008.","J. B. Caruso and G. Salaway, The ECAR Study of Undergraduate\nStudents and Information Technology, EDUCAUSE, 2008.","H. Thinyane, \"Are digital natives a world-wide phenomenon? An\nInvestigation into South African Students' use and experience with\ntechnology.\" Computers & Education, vol. 55, pp. 406-414, 2010.","T. Kramlinger and T. Huberty, \"Behaviorism Versus Humanism\" , pp.\n41-45. December 1990.\n[10] N. Friessen, \"Mind and Machine: Eithical and epistemological\nimplications for research.\" AI & Society, vol. 25, no. 1, pp. 83 - 92, 9\nDecember 2009.\n[11] B. F. Skinner, The Technology of Teaching, New York: Appleton-\nCentury-Crofts, 1968.\n[12] B. F. Skinner, \"Teaching Machines.\" Science, pp. 969-977, 1958.\n[13] C. Guey, Y. Chengand S. Shibata, \"A Triarchal instruction model:\nintegration of principles from Behaviorism, Cognitivism and\nHumanism.\" Procedia - Social and Behavioral Sciences, vol. 9, pp.\n105-118, 2010.\n[14] H. L. Petri and M. 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Squire, \"Design-Based Research: Putting a stake in the\nground.\" The Journal of the learning sciences, vol. 13, no. 1, pp. 1-14,\n2004.\n[22] P. Cobb, J. Confrey, A. Disessa, R. Lehrer, and L. Schauble, \"Design\nExperiments in Educational Research.\" Educational Researcher, vol.\n32, no. 1, pp. 9-13, Jan/Feb 2003.\n[23] A. Collins, D. Joseph and K. Bielaczyc, \"Design Research: Theoretical\nand Methodological Issues.\" The Journal of the learning sciences, vol.\n13, no. 1, pp. 15-42, 2004.\n[24] A. Collins, \"Towards a design science of education.\" in E. Scanlon, and\nT. O'Shea, eds. New directions in educational technology, Berlin:\nSpringer. pp. 15-22, 1992.\n[25] W. Huitt, Humanism and open education. Date of access: 8 August\n2012. http://www.edpsycinteractive.org/topics/affect/humed.html, 2009.\n[26] N. Gage, and D. Berliner, Educational Psychology. Boston: Houghton,\nMifflin, 1991.\n[27] G. R. Taylor, Practical application of Social Learning theories in\neducating young African-American Males. Lanham: University Press of\nAmerica, 2003.\n[28] A. Bandura, \"Social Cognitive theory.\" in R. Vasta, ed. Annals of child\ndevelopment, Greenwich: JAI Press, vol. 6, pp. 1-60, 1989.\n[29] A. Bandura, Social foundations of thought and action: A social cognitive\ntheory. Prentice-Hall, 1986.\n[30] R. Wood and A. Bandura, \"Social Cognitive Theory of organizational\nManagement.\" The Academy of Management review, vol. 14, no. 3, pp.\n361-384, July 1989.\n[31] A. Bandura, \"Social cognitive theory of moral thought and action.\" in\nW. M. Kurtines and J. L. Gerwitz, eds. Handbook of moral behaviour\nand development, Hillsdale: Erlbaum, vol. 1, pp. 45-103 1991.\n[32] C. M. Reigeluth, Instructional-Design Theories and models. Mahwah:\nLawrence Erlbaum, 1999.\n[33] G. Morrison, S. Ross, E. Kemp and H. Kalman, Designing Effective\nInstruction. Chennai: Wiley and Sons, 2004.\n[34] R. 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An analysis of the different methods of treating residual flexion deformity at the PIP joint level after digital fasciectomy in 75 PIP joints has shown that gentle passive manipulation alone gives better results with fewer complications than more aggressive surgical intervention.

Ru and RuO 2 have recently been introduced as electrode materials for integrated ferroelectric capacitors. Compared with Pt electrodes, they present the advantage of a higher endurance of the capacitor under repeated pulse switching. The stresses in sputter-deposited Ru bottom and top electrodes and in PbZr 0.4 Ti 0.6 O 3 films deposited using organometallic chemical vapor deposition have been studied in the asdeposited state and in-situ during annealing treatments. It was observed that an annealing treatment of the Ru/PbZr 0.4 Ti 0.6 O 3 /Ru stack influences the stress in the PbZr 0.4 Ti 0.6 O 3 film.

A preliminary analysis was made of ionospheric slab thickness, τ, and total electron content, TEC, for southern Australia using GPS satellite measurements. It was found that at mid-latitudes τ has similar overall diurnal, seasonal and latitudinal variations in the southern hemisphere as in the northern hemisphere. However, there are appreciable differences between τ in the two hemispheres which would justify appropriate modifications to ionospheric models based on northern hemisphere data before being applied confidently to the southern hemisphere. The usefulness of GPS satellites together with ionosondes over a spread of latitudes was demonstrated in determining long-term variations of TEC and τ over a large area. It was concluded that as few as four GPS receivers could provide TEC for the whole of Australia in real-time, though approximately six receivers in convenient locations would be required in practice.

Ionospheric slab thickness was determined for Southern Australia from July 1991 to June 1993 for approximately 50 hours per month using GPS satellite reception and ionograms (at 5-minute intervals) recorded at Salisbury, South Australia, and other Australian ionograms. Seasonal, diurnal and latitudinal variations of slab thickness are shown to be similar in the northern and southern hemispheres; however, there are appreciable differences which justify the use of southern hemisphere data in ionospheric modelling.

Bone cements should have the ability to chemically bond to both bone and surgical metals, exhibit no chemical or thermal necrosis, and have no significant shrinkage or exotherm upon setting. Taking these properties into consideration, glass polyalkenoate cements (GPCs) have potential as bone cements. GPCs are formed by the reaction between an ion-leachable glass and an aqueous solution of polyacrylic acid (PAA) [1] and have proven antibacterial and cariostatic properties [2], which are related to their ability to release beneficial amounts of ions over time [3, 4]. The GPCs can be formulated to release ions that can have a therapeutic benefit in a chosen application such as fluoride release in dental applications [5], which assists in the prevention of secondary caries [6]. Recently, GPCs have been formulated with zinc (Zn) replacing Al; a more biologically acceptable ion [7]. The authors have previously shown that GPCs based on a glass phase containing both Zn and silver (Ag) have the ability to release ions which are antibacterial against both Staphylococcus aureus (Oxford strain) [8] and Pseudomonas aeruginosa (a clinical isolate) [9, 10] in vitro and methicillin-resistant S. aureus (MRSA) both in vitro and in vivo [11]. The authors have also shown that their cements have the ability to inhibit proliferation of a biofilm of P. aeruginosa (PA01) [9]. The objective of the study reported herein is to build on the authors previous publications in order to determine if increases in Ag content of the glass phase of these cements will result in a concomitant increase in antibacterial efficacy of the resultant Ag-Zn GPCs formulated from them.

The authors have previously shown that it is possible to incorporate silver into a soda-zinc-silicate glass and subsequently form a glass polyalkenoate cement from it. The objective of the research described herein is to determine if incremental increases in the silver content of these glass polyalkenoate cements will increase their antibacterial efficacy against gram-positive and gram-negative bacteria using the accepted spread plate method. Four glass polyalkenoate cements were formulated; three contained increasing amounts of silver incorporated into them (cements A, B, and C, containing 0.33 mol%, 0.66 mol%, and 0.99 mol% silver, respectively) and a fourth contained no silver, which acted as a control (control cement). The handling properties of the glass polyalkenoate cements were evaluated, where working times were around 2 min and setting times ranged from 1 h 17 min to 2 h 41 min. Inductively coupled plasma atomic emission spectroscopy was employed to determine silver ion release with cement maturation for up to 14 days. The majority of silver ions were released within the first 24 h, with up to 2 mg/L cumulative ion release recorded up to 14 days. The antibacterial properties of the coatings were evaluated against Staphylococcus aureus and Pseudomonas aeruginosa bacteria. The silver-glass polyalkenoate cements exhibited antibacterial effect against both bacterial strains. The maximum inhibition zones recorded against S. aureus was 14.8 mm (SD ± 1.11) and against P. aeruginosa was 20.6 mm (SD ± 0.81). Cement B had a greater antibacterial effect compared to cement A, however, cements B and C had comparable antibacterial effects after 14 days even though cement C contained 0.33 mol% more silver than B. This indicates that by increasing the silver content in these cements, the antibacterial efficacy increases to a point, but there is a threshold where further silver ion release does not increase the antibacterial effect.

We describe a 1-year-old boy with a rare de novo 46,XY/47,XY,+ i(5p) mosaicism (ratios 28/3 in peripheral blood lymphocytes and 2/12 in skin fibroblasts). The boy, born after a pregnancy of 34 weeks, had lung hypoplasia, persistent hypotonia, and postnatal growth failure. Craniofacial anomalies were also present. His clinical manifestations correspond to those described in trisomy 5p patients. Prenatal diagnosis on maternal age indication had shown normal male chromosomes in 16 cells in the short term culture of a chorionic villus sampling. Retrospectively, 1 out of 217 cells in this culture showed the i(5p). Several mechanisms could have resulted in the formation of this 46/47, + i(5p) mosaic. Postzygotic local incorrect ligation during chromatid replication, followed by a second replication offers an attractive model on theoretical grounds since it needs only one step to explain both isochromosome formation and mosaicism. Differences between the various tissues in selection pressure on cells with the isochromosome might explain the different ratios of mosaicism found. (C) 1993 Wiley-Liss, Inc.

A 4-year-old mentally retarded girl had congenital depigmentations of ventrolateral parts of the chest, abdomen, and legs. She also showed dysmorphic features of the head, thorax, and extremities, a pigmented ring in both irises, and a hernia of the left obliquus muscle. Cytogenetic investigations revealed deletion of chromosome 4 for the long arm segment q12-q21. The typical depigmentations, reported in four other patients with a similar chromosomal deletion, correspond with those in the autosomal dominant piebald trait. Mutations in the Kit protooncogene (mapped to the chromosome (4q11-4q1 2 region) have been found in patients affected with this dominant disorder. Piebaldism in children with developmental delay and dysmorphic features should alert the physician to the possibility of a deletion of the long arm of chromosome 4.

In northwest European countries maternal age is increasing. This will lead to an increase of the prevalence of Down syndrome conceptuses. Meanwhile, the increased use of prenatal cytogenetic diagnosis (PCD) will lead to a decrease in the prevalence of Down syndrome among livebirths. We were interested to know what the result of these two opposite developments would be in the near future, and we describe here a model to quantify these processes and the resulting livebirth prevalence of Down syndrome. The model is demonstrated for The Netherlands from 1992 to 2001. The predicted livebirth prevalence for The Netherlands in 1992 is 1.36 per 1000. Demographic factors will cause an increase to 1.76 per 1000 in 2001 with present indications for PCD and a utilization ratio of 50%. An increase of the utilization ratio to 90% in 2001 will lead to a prevalence of 1.22 per 1000, a little less than the present prevalence. Alternative screening programs, including maternal serum screening, could lead to a further decrease of the livebirth prevalence. The model described here can be used for evaluation of the consequences of alternative forms of Down syndrome screening.A model for predicting the prevalence of Down syndrome among future live births was applied to data from the Netherlands between 1992 and 2001. Concern has been raised about this issue since Down syndrome is associated with increased maternal age, and maternal age has been rising throughout northwestern Europe. The model was based on maternal age specific Down syndrome risk, local demographic factors, age distribution of females, age specific fertility rate, trends in age specific fertility rate, expected impact of prenatal diagnosis, type of screening, utilization ratio of screening program, and utilization ratio of selective abortion. Models applied 2 alternatives: 1) screening according to the present list of indications in the Netherlands, and 2) screening based on assessment of alpha fetoprotein, human gonadotrophin, and maternal age. The prenatal cytogenetic diagnosis (PCD) for Down syndrome in which the pregnancy was terminated was determined as 9.3% (registered cases in 19 European regions between 1980 and 1986. The PCD utilization ratio for all women aged 36 years and older was set at 50% in 1989, and 20% of nonusers were assumed to have a utilization ratio of 4.2% or 7.6%. In the Netherlands, all women aged 36 years and over have access to a diagnostic test for Down syndrome. Data on the maternal age specific risk of Down syndrome was taken from estimates by Cuckle et al. (based on empirical data from the US, the UK, Sweden, Australia, and Belgium). The assumption was that 98% of pregnancies with a prenatal diagnosis of trisomy 21 would be terminated for all screening programs. The prediction of Down syndrome for 1992 was estimated at 1.36/1000 at 50% PCD utilization and 1.76/1000 in 2001. For 90% utilization, Down syndrome prevalence would be 1.07/1000 in 2001. For 90% utilization, Down syndrome prevalence would be 1.07/1000 in 1992 and 1.22/1000 in 2001. If serum screening was used at 50% utilization, the prevalence would be 1.09/1000 in 1992 and 1.44/1000 in 2001. With 90% utilization and serum screening, the Down syndrome prevalence would be .63/1000 in 1992 and .75/1000 in 2001. The actual live birth prevalence of Down syndrome in the Netherlands was 1.16 between 1981 and 1986. Since discussion was devoted to current and possible future operations of screening programs.

To investigate the incidence of scalp metastases in high-risk breast cancer patients in order to assess whether caution is warranted with scalp cooling during adjuvant therapy.Observational study.The incidence of scalp metastases and the disease course were studied in 885 very well evaluated high-risk breast cancer patients. These patients, who had at least four positive axillary lymph nodes, were treated in a randomised study with either classical chemotherapy, or the same chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (the so-called N4+ study).After a median follow up of 110 months, 403 of the 885 patients (46%) had relapsed or developed metastases. 25 patients (3%) had developed skin metastasis; 4 of these patients (0.5%) had developed hairy scalp metastasis. The scalp metastases always occurred at the same time as or later than metastases elsewhere.Scalp metastases occur with a very low frequency and not as the first sign of metastatic disease. It is therefore unlikely that scalp cooling (to prevent baldness) decreases the local working of chemotherapy to such an extent that the risk of scalp metastases increases.

In order to gain more insight into the association between alpha-fetoprotein (AFP) and fetal chromosomal disorders, especially Down's syndrome, we measured AFP in fetal serum, amniotic fluid, and maternal serum at cordocentesis. We compared the concentration and gradient of AFP in these three compartments. Our data confirm earlier findings on second-trimester fetal serum AFP concentration. The results indicate that low maternal serum AFP in pregnancies with fetal chromosomal disorders could result from an impaired fetal kidney function as well as from impaired membrane or placental passage of AFP, rather than from reduced fetal AFP production.

We report the result of investigations from 20 families with 72 carriers of the paracentric inversion inv(11)(q21q23) in the Netherlands. There is no increase in the rate of spontaneous abortions among carriers of the inversion or their partners. Also, so far, there are no children with recombinant chromosomes arising from the inversion. It is doubtful whether prenatal diagnosis would be helpful to carriers of this inversion. The results of the genealogy study and geographical distribution are discussed; it is suggested that all the families have arisen from a single mutation.

A population-based series of patients with cancer is likely to comprise more patients with serious co-morbidity than clinical trials because of restrictive eligibility criteria for the latter. Since co-morbidity may influence decision-making, we studied the age-specific prevalence of co-morbidity and its relationship to applied treatment. Data on all 194 patients with Hodgkin's disease (HD) and on 904 patients with non-Hodgkin's lymphoma (NHL) diagnosed between 1993 and 1996 were derived from the Eindhoven Cancer Registry. In the age-group below 60 years, 87% of patients with HD and 80% with NHL did not have a co-morbid condition. The prevalence of serious co-morbidity was 56% for patients with Hodgkin's disease who were 60 years and over and 43% and 61% for non Hodgkin patients who were 60-69 years and 70 years and over, respectively. The most common co-morbid conditions were cardiovascular disease (18%), hypertension (13%), chronic obstructive pulmonary disease (COPD; 13%), and diabetes mellitus (10%) for elderly Hodgkin's patients. For non-Hodgkin's patients of 60-69 years and 70 years and over, cardiovascular disease (15 and 22%, respectively), hypertension (14 and 14%, respectively), COPD (6 and 10% respectively), and diabetes mellitus (8 and 10%, respectively) were the most prevalent co-morbid conditions. The presence of co-morbidity was not related to stage or grade of disease at diagnosis. In the presence of co-morbidity, 50% less chemotherapy was administered to elderly patients with Hodgkin's disease and 10-15% less to elderly patients with non-Hodgkin's lymphoma. The presence of co-morbidity was associated with a decreased overall survival within the first 4 months after diagnosis in both Hodgkin's disease and non-Hodgkin's lymphoma for all age-groups. In conclusion, serious co-morbidity was found for more than half of all lymphoma patients who were 60 years and older. Elderly patients with serious co-morbidity received chemotherapy less often, which is likely to affect survival adversely, as was indicated by a decreased survival within the first 4 months after diagnosis.

Since prolonged remission can be induced in the majority of patients with Hodgkin's disease (HD), treatment-related mortality and morbidity have emerged. We investigated whether awareness of toxicity diminished treatment-related mortality for unselected patients treated between 1972 and 1993 in general hospitals in the southeastern Netherlands. We also estimated the prevalence of treatment-related morbidity among patients treated in the 1980s. Data were collected on all 345 HD patients registered in the Eindhoven Cancer Registry between 1972 and 1993. Medical records and histology were reviewed; follow-up ended in 1994. Administration of MOPP chemotherapy decreased, and there was a shift from total nodal irradiation to less extended low-dose radiotherapy. For cured patients the 10-year relative survival improved from 84% in the 1970s to 90% in the 1980s, which is reflected by a decline in excess mortality from 16% to 10%. The 10-year relative mortality risk due to secondary malignancies decreased from 4.3 (95% CI, 1.2-7.4) to 3.0 (CI 0.2-5.8), which is also reflected by a decline in the 10-year cumulative incidence for all cancers from 10% to 5%. However, the relative risk of late cardiovascular death, which is closely related to previous irradiation, barely changed, as shown by a decrease from 2.4 (CI 0.4-4.5) to 2.2 (CI.0-4.7). HD survivors profited less from the sharp decline in cardiovascular mortality observed for the general population. Among patients, the prevalence of serious treatment-related morbidity 5 years or more after initial diagnosis was 34%. In conclusion, modest decline in excess mortality among cured HD patients was observed in the 1980s, as reflected by a decrease in mortality due to second malignancies. However, late mortality, especially due to radiation-related cardiovascular disease, is still substantial. About one third of HD survivors suffer radiation-induced sequelae. Clinical trials to find ways to minimize iatrogenic complications are important.

The importance of the subclassification of nodular sclerosing Hodgkin's disease (NSHD) according to the British National Lymphoma Investigation Group (BNLI) criteria, which had an independent prognostic value for 90 unselected patients diagnosed in our region in the period 1972-83, is still equivocal. Because survival of patients with Hodgkin's disease improved in our region during the period 1972-92 and because treatment may modify prognostic factors, we re-evaluated the prognostic value of NSHD subclassification up to 1993. A registry-based study was performed with data on all 345 Hodgkin patients diagnosed in the period 1972-92. Available histology was reviewed. The prognostic value of nodular sclerosis (NS) grading was evaluated for two periods, 1972-80 and 1981-92, designated as the seventies and the eighties, respectively. NSHD was diagnosed in 57% (n = 195) of all registered cases of Hodgkin's disease, 17 of which could not be evaluated. NS stage I (NSI; 73%) and NS stage II (NSII; 27%) patients exhibited the same distribution of stage during both periods; NSII patients were older than NSI patients in the seventies. NSII patients presented with an elevated ESR and B symptoms more frequently during the eighties and subsequently received combined modality therapy more often. The crude 5-year survival rate for grade I v grade II NSHD was 85% v 38% (P < 0.05) for the seventies and 84% v 83% for the eighties. Subclassification of NSHD was not an independent prognostic factor after adjustment for age, stage, gender, B symptoms and ESR, though it remained of independent prognostic value when ESR was left out of the Cox model. The most important factors adversely influencing survival were advanced age, advanced stage and male gender. The independent prognostic value of the subclassification of NSHD has disappeared, as reflected by the clearly improved survival of NSII patients, probably due to more intensive treatment in the eighties, whereas survival of NSI patients did not changes.

In Hodgkin's disease DNA aneuploidy is not a prognostic factor. However, the prognostic significance of DNA content in Hodgkin's disease may be missed by either intratumor DNA heterogeneity or DNA analysis of limited samples. For flow cytometry usually one section of 40-60 microns is used for the analysis. In breast cancer this proved to be insufficient. In Hodgkin's disease no data are available. Therefore, we examined if analysis of more sections does increase the yield of aneuploidy. Archival, formalin-fixed, parafin embedded tissues were used. From 13 patients four sections of 50 microns could be analysed for DNA content. In 12 of 13 patients the results were consistent in all four sections of one patient case; seven diploid, four aneuploid and one multiploid. In one case ploidy status changed: two sections were diploid and two were aneuploid. The DNA-index of the aneuploid samples ranged from 0.75 to 1.38 and varied from 0.02 to 0.14 within one case. The S-phase fraction remained constant within all evaluable cases (sd: 0.5-1.5%), except for one (sd: 4.7%). In conclusion, in Hodgkin's disease the ploidy status of the first section can be regarded to represent the whole tissue sample. Therefore, the absence of prognostic value of ploidy status is not explained by sampling errors in tissues analysed.

Paraffin-embedded lymph nodes from patients with Hodgkin's disease were examined for flow cytometric DNA content. In order to increase the sensitivity of the assay we tried to enrich for the neoplastic cells by bivariate analysis using a polyclonal anti-nucleolar antibody (AN-AB) and the forward scatter (FSC). DNA aneuploidy was found to be present in 67 of all 137 cases (49%), in 24 cases only demonstrable by dual-parameter analysis. The DNA index varied from 0.69 to 1.89 with a total of 22 hypo-diploid cases. The number of aneuploid nuclei exceeded the expected frequency of Reed-Sternberg (RS) and Hodgkin (H) cells in most of the analysed specimens. In conclusion, flow cytometry in Hodgkin's disease appears to give useful informatipn regarding the ploidy status and evidence has been provided that the malignant cell population in Hodgkin's disease is not limited to the classical RS/H cells.

A 70,XXX,+18 karyotype was found by chorionic villus sampling, while the fetal fibroblast culture of the affected fetus revealed a 47,XX,+18 karyotype. From several possible mechanisms, we assume that a second gamete fusion occurred after the first cell division of the zygote. According to this interpretation, the mosaicism arose in very early pregnancy (at the two-cell stage). This discrepancy can therefore be explained by selection pressure, due to the differentiation processes in the embryonic tissues.

Over the years several methods for evaluating mediastinal involvement in Hodgkin's disease have been applied to chest radiographs and conflicting results have been reported. In a retrospective study of 104 patients we evaluated interobserver variability inassessing mediastinal involvement and investigated various cut-off points for mediastinal size as to their ability to identify patients with high- and low-risk for recurrence. For mediastinal involvement the concordance rate for two reviewing radiologists was 94% ( 98 104 ) and compared with prior assessment by outside radiologists the concordance rates were 90% ( 94 104 ) and 88% ( 92 104 ), respectively. A good correlation between the reviewing radiologists was found for the quantitative evaluation of mediastinal diameter and thoracic ratios. ROC curves and relative risk figures were used to investigate the various cut-off points for mediastinal width and for the ratios of the maximal mediastinal diameter to the chest diameter at Th 5–6 (M1) and to the chest diameter at the widest thoracic level (M2). Neither the ROC curve analysis nor the use of relative risk figures revealed a cut-off point clearly more accurate in predicting recurrence. In conclusion, our results do not suggest that interobserver variability in mediastinal assessment, differences in the method of mediastinal measurement, or the cut-off points applied to mediastinal width can explain the discrepancies in the reported data on the prognostic value of mediastinal width in Hodgkin's disease, but rather factors such as patient selection and differences in treatment given may be responsible.

The usefulness of the pre-incubated acidified glycerol lysis test (AGLT), a laboratory test for spherocytosis, has been investigated in a selected hospital population of 348 patients with haemolytic and non-haemolytic anaemia. The AGLT was positive in 58 out of 59 patients with hereditary spherocytosis. In all 32 patients with other types of hereditary haemolytic anaemia the AGLT was normal or equivocal, but clearly different from spherocytosis. Adults with a positive AGLT, but without hereditary spherocytosis, had auto-immune haemolytic anaemia, myelodysplastic syndrome or were pregnant women. In newborn infants the AGLT was positive, in the first week of life, in those babies having hereditary spherocytosis or immune haemolysis due to blood group incompatibility; no positive AGLT results were seen if no haematological explanation for neonatal hyperbilirubinaemia could be found. At the optimal cut-off point the sensitivity of the AGLT for hereditary spherocytosis was 98.3% and the specificity 91.1%, under the most unfavourable conditions. The AGLT is a very useful and simple test for the diagnosis of hereditary spherocytosis.