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Diabet. Med. 29, 776–783 (2012) Abstract Aims To develop and evaluate an image grading external quality assurance system for the Scottish Diabetic Retinopathy Screening Programme. Method A web-based image grading system was developed which closely matches the current Scottish national screening software. Two rounds of external quality assurance were run in autumn 2008 and spring 2010, each time using the same 100 images. Graders were compared with a consensus standard derived from the top-level graders’ results. After the first round, the centre lead clinicians and top-level graders reviewed the results and drew up guidance notes for the second round. Results Grader sensitivities ranged from 60.0 to 100% (median 92.5%) in 2008, and from 62.5 to 100% (median 92.5%) in 2010. Specificities ranged from 34.0 to 98.0% (median 86%) in 2008, and 54.0 to 100% (median 88%) in 2010. There was no difference in sensitivity between grader levels, but first-level graders had a significantly lower specificity than level-two and level-three graders. In 2008, one centre had a lower sensitivity but higher specificity than the majority of centres. Following the feedback from the first round, overall agreement improved in 2010 and there were no longer any significant differences between centres. Conclusions A useful educational tool has been developed for image grading external quality assurance.

We have used 2-DE for a time-course study of the changes in protein and phosphoprotein expression that occur immediately after fertilization in Solanum chacoense. The phosphorylation status of the detected proteins was determined with three methods: in vivo labeling, immunodetection, and phosphoprotein-specific staining. Using a pI range of 4-7, 262 phosphorylated proteins could be mapped to the 619 proteins detected by Sypro Ruby staining, representing 42% of the total proteins. Among these phosphoproteins, antibodies detected 184 proteins from which 78 were also detected with either of the other two methods (42%). Pro-Q Diamond phosphoprotein stain detected 111 proteins, of which 76 were also detected with either of the other two methods (68%). The 32P in vivo labeling method detected 90 spots from which 78 were also detected with either of other two methods (87%). On comparing before and after fertilization profiles, 38 proteins and phosphoproteins presented a reproducible change in their accumulation profiles. Among these, 24 spots were selected and analyzed by LC-MS/MS using a hybrid quadrupole-TOF (Q-TOF) instrument. Peptide data were searched against publicly available protein and EST databases, and the putative roles of the identified proteins in early fertilization events are discussed.

Proteome analysis of embryo and endosperm tissues from germinating tomato seed was conducted using 1-DE, 2-DE, and MS. Mobilization of the most abundant proteins, which showed similar profiles in the two tissues, occurred first in the endosperm. CBB R-250 staining of 2-DE gels revealed 352 and 369 major protein spots in the embryo and endosperm, respectively, at 0 h. Of these, 75 major spots were selected, excised, in-gel digested with trypsin, and analyzed by MALDI-TOF-MS and/or LC-ESI-Q/TOF-MS/MS. Peptide MS and MS/MS data were searched against publicly available protein and EST databases, and 47 proteins identified. Embryo-specific proteins included a BAC19.13 homologue, whereas four proteins specific to the endosperm were tomato mosaic virus coat proteins related to defense mechanisms. The most abundant proteins both in the embryo and endosperm were seed storage proteins, i.e., legumins (11 spots), vicilins (11 spots), albumin (2 spots). Housekeeping enzymes, actin-binding profilin, defense-related protein kinases, nonspecific lipid transfer protein, and proteins involved in general metabolism were also identified. The roles of some of the proteins identified in the embryo and endosperm are discussed in relation to seed germination in tomato.

Aims To compare the respective performances of digital retinal imaging, fundus photography and slit-lamp biomicroscopy performed by trained optometrists, in screening for diabetic retinopathy. To assess the potential contribution of automated digital image analysis to a screening programme.Methods A group of 586 patients recruited from a diabetic clinic underwent three or four mydriatic screening methods for retinal examination. The respective performances of digital imaging (n = 586; graded manually), colour slides (n = 586; graded manually), and slit-lamp examination by specially trained optometrists (n = 485), were evaluated against a reference standard of slit-lamp biomicroscopy by ophthalmologists with a special interest in medical retina. The performance of automated grading of the digital images by computer was also assessed.Results Slit-lamp examination by optometrists for referable diabetic retinopathy achieved a sensitivity of 73% (52-88) and a specificity of 90% (87-93). Using two-field imaging, manual grading of red-free digital images achieved a sensitivity of 93% (82-98) and a specificity of 87% (84-90), and for colour slides, a sensitivity of 96% (87-100) and a specificity of 89% (86-91). Almost identical results were achieved for both methods with single macular field imaging. Digital imaging had a lower technical failure rate (4.4% of patients) than colour slide photography (11.9%). Applying an automated grading protocol to the digital images detected any retinopathy, with a sensitivity of 83% (77-89) and a specificity of 71% (66-75) and diabetic macular oedema with a sensitivity of 76% (53-92) and a specificity of 85% (82-88).Conclusions Both manual grading methods produced similar results whether using a one- or two-field protocol. Technical failures rates, and hence need for recall, were lower with digital imaging. One-field grading of fundus photographs appeared to be as effective as two-field. The optometrists achieved the lowest sensitivities but reported no technical failures. Automated grading of retinal images can improve efficiency of resource utilization in diabetic retinopathy screening.

We discuss eight trecento (fourteenth century) paintings containing depictions of astronomical events to reveal the revolutionary advances made in both astronomy and naturalistic painting in early Renaissance Italy, noting that an artistic interest in naturalism predisposed these pioneering painters to make their scientific observations. In turn, the convincing representations of their observations of astronomical phenomena in works of art rendered their paintings more believable, convincing. Padua was already a renowned center for mathematics and nascent astronomy (which was separating from astrology) when Enrico Scrovegni commissioned the famous Florentine artist Giotto di Bondone to decorate his lavish family chapel (circa 1301-1303). Giotto painted a flaming comet in lieu of the traditional Star of Bethlehem in the Adoration of the Magi scene. Moreover, he painted a historical apparition that he recently had observed with a great accuracy even by modern standards. Halley's Comet of 1301 (Olson, 1979). While we do not know the identity of the artist's theological advisor, we discuss the possibility that Pietro d'Abano, the Paduan medical doctor and "astronomer" who wrote on comets, might have been influential. We also compare Giotto's blazing comet with two others painted by the artist's shop in San Francesco at Assisi (before 1316) and account for the differences. In addition, we discuss Giotto's pupil, Taddeo Gaddi, reputed to have been partially blinded by a solar eclipse, whose calamity may find expression in his frescoes in Santa Croce, Florence (1328-30; 1338?). Giotto also influenced the Sienese painter Pietro Lorenzetti, two of whose Passion cycle frescoes at Assisi (1316-20) contain dazzling meteor showers that reveal the artist's observed astronomical phenomena, such as the "radiant" effect of meteor showers, first recorded by Alexander von Humboldt in 1799 and only accepted in the nineteenth century. Lorenzetti also painted sporadic, independent meteors, which do not emanate from the radiant. It is also significant that these artists observed differences between comets and meteors, facts that were not absolutely established until the eighteenth century. In addition we demonstrate that artistic and scientific visual acuity were part of the burgeoning empiricism of the fourteenth century, which eventually yielded modern observational astronomy.

Recent high hydrostatic pressure experiments have shown that incorporation of small amounts of nitrogen into conventional III–V compounds to form III–N–V alloys leads to splitting of the conduction band into two subbands. The downward shift of the lower subband edge is responsible for the observed, large reduction of the fundamental band gaps in III–N–V alloys. The observed effects were explained by an anticrossing interaction between the conduction band states close to the center of the Brillouin zone and localized nitrogen states. The interaction leads to a change in the nature of the fundamental from the indirect gap in GaP to a direct gap in GaNP. The predictions of the band anticrossing model of enlarged electron effective mass and enhanced donor activation efficiency were confirmed by experiments in GaInNAs alloys.

We study Ge solar cells with epitaxial GaInP windows for application as the third junction of GaInP/GaAs/Ge three-junction solar cells. We demonstrate Ge junctions with open-circuit voltages above 230 mV, fill factors above 65%, and internal quantum efficiencies of ∼90%. By varying separately the base and emitter contributions to the junction dark current, we deduce the factors limiting the performance of this device, and we project the improvement to the device performance that may be obtainable if key limiting factors such as the emitter surface-recombination velocity can be mitigated. Published in 2001 by John Wiley & Sons, Ltd.

BACKGROUND: Weight loss among older patients is a severe problem, associated with an increased incidence of infections, decubiti, and death. Megestrol acetate (MA) causes weight gain in cachectic cancer and AIDS patients, but its effects in older cachectic patients are unknown. OBJECTIVE: To compare the effects of MA oral suspension (O.S.), 800 mg/day, versus placebo on weight in geriatric nursing home patients with weight loss or low body weight. DESIGN: Twelve-week, randomized, double-blind, placebo-controlled trial with a 13-week follow-up period. SETTING: Veterans Administration Medical Center (VMAC) nursing home. PATIENTS: Nursing home patients with weight loss of ≥5% of usual body weight over the past 3 months, or body weight 20% below their ideal body weight. INTERVENTIONS: Patients were randomly assigned to receive placebo or MA 800 mg/day for 12 weeks and were then followed for 13 weeks off treatment. MEASUREMENTS: Primary outcome was measured by weight and appetite change. Secondary outcome measures included sense of well-being, enjoyment of life, change in depression scale, laboratory nutrition parameters, energy intake counts, body composition, and adverse events. RESULTS: At 12 weeks there were no significant differences in weight gain between treatment groups, whereas MA-treated patients reported significantly greater improvement in appetite, enjoyment of life, and well-being. Body composition was not statistically different between the two groups. At Week 25 (3 months after treatment), 61.9% of MA-treated patients had gained ≥1.82 kg (4 lbs) compared to 21.7% of placebo patients. CONCLUSIONS: In geriatric patients with weight loss or low body weight MA improves appetite and well-being after 12 weeks of treatment. During the 3 months of MA treatment, there was no statistically significant weight gain (≥4 lbs). Three months after treatment, weight gain (≥4 lbs) was significantly increased in MA-treated patients. J Am Geriatr Soc 48: 485–492, 2000.

We report pressure studies of conductivity, photoconductivity and Hall effect in Si doped GaAs0.986N0.014. We observed that pressure causes an unusually large reduction of the electron mobility in this compound (factor of 2.5 in the pressure range 0 to 2 GPa). We also measured the pressure coefficient of the energy gap and we found it, in agreement with previous reports, to be reduced by almost 40% compared to that of GaAs. These results can be successfully explained by a recently proposed, phenomenological model based on the concept of an anticrossing interaction between localized N-related states (resonant with the conduction band) and conduction band states. This model explains well the reduction of the pressure coefficient of the bandgap and predicts an enhancement of the effective mass of GaAs1—xNx. The decrease of electron mobility observed in the present study is in agreement with this latter prediction.

Elevated methylglyoxal (MG) levels have been reported in insulin-resistance syndrome. The present study investigated whether MG, a highly reactive metabolite of glucose, induced structural and functional changes of insulin. Incubation of human insulin with MG in vitro yielded MG-insulin adducts, as evidenced by additional peaks observed on mass spectrometric (MS) analysis of the incubates. Tandem MS analysis of insulin B-chain adducts confirmed attachment of MG at an arginine residue. [3H]-2-deoxyglucose uptake by 3T3-L1 adipocytes was significantly and concentration-dependently decreased after the treatment with MG-insulin adducts, in comparison with the effect of native insulin at the same concentrations. A significant decrease of glucose uptake induced by MG-insulin adducts was also observed in L8 skeletal muscle cells. MG alone had no effect on glucose uptake or the transcriptional expression of insulin receptor. Unlike native insulin, MG-insulin adducts did not inhibit insulin release from pancreatic beta-cells. The degradation of MG-insulin through liver cells was also decreased. In conclusion, MG modifies insulin by attaching to internal arginine residue in beta-chain of insulin. The formation of this MG-insulin adduct decreases insulin-mediated glucose uptake, impairs autocrine control of insulin secretion, and decreases insulin clearance. These structural and functional abnormalities of insulin molecule may contribute to the pathogenesis of insulin resistance.

Using time-resolved small-signal exciton absorption bleaching at low temperature, the optical transition energies from all three valence bands in spontaneously-ordered GaInP have been measured with high accuracy. The origin of the bleaching signal and the contributions of binding energy are discussed. With three measured energies from each sample, all parameters in the quasi-cubic perturbation model can be fitted. Good agreement is obtained with a spin–orbit splitting parameter of 103 meV, nearly independent of the degree of ordering. The ratio of bandgap reduction to crystal-field splitting parameter is found to be 2.7, slightly higher than in previous works. This difference is attributed to a more accurate determination of light-hole-like bandgap energy.

A two-dimensional diffraction grating for phonons is described. It scatters thermal phonons strongly when their dominant wavelength is equal to the grating's lattice constant. Through measurements of the Kapitza resistance between the silicon crystal carrying the grating and liquid helium, it is shown that the scattering by the grating is predominantly coherent, as expected for phonon diffraction.

Summary The problem of testing the Hardy-Weinberg law when data are sampled from several populations with different allele frequencies is considered. An Odds-ratio representation of disequilibrium is proposed. This ration is assumed to be constant across strata, an assumption that seems more reasonalbe than that of previous authors of a constant difference in true and expected (undre equilibrium) heterozygote proportions. A score-type test which optimally combines information from the separate strata is then drived using the theory of unbiased estimating equations. Simulations show that the new test has greater power than previously proposed tests when the disequilibrium ratio is constant across strata. The method is applied to glyoxable genotype data form populations in India.

A magnesium aluminosilicate glass-ceramic (Corning Code 9606) has been heat-treated at 900°, 1010°, 1200°, and 1260°C for up to 90 min., and the effect on the thermal conductivity between 30 and 300 K has been studied. It has been shown that the large increase of the thermal conductivity which results from the ceramming occurs predominantly when crystalline cordierite forms. At 1260°C, heat treatment for only 20 min leads to a thermal conductivity identical to that measured for commercial 9606, which has been cerammed for 8 h at the same temperature. This observation provides further evidence for the usefulness of commercial 9606 as a thermal conductivity standard. Measurements of the specific heats of Code 9606 before and after ceramming have been reviewed and have been found to be close to that of crystalline SiO2 above ∼ 30 K, regardless of the state of ceramming. A review has also been made of thermal conductivity and specific heat of several ZrTiO4 nucleated lithium aluminosilicate glass-ceramics at various states of ceramming. The thermal conductivity of these glass-ceramics seems to be sufficiently independent of chemical composition as well as of the degree of crystallization to warrant a recommended curve for this class of glass-ceramics.

One hundred thirty-seven V.A. patients were randomized to one of three treatment groups to evaluate the efficacy of biphasic calcium phosphate (BCP) ceramic in the treatment of periodontal osseous defects. This material was tested against both autogenous bone implant and open flap curettage procedures. Baseline probing attachment level, Navy plaque index, and gingival index were recorded for all patients. These parameters were monitored for 3 years. At the end of this period, 101 patients had completed the study. Although the plaque and gingival indices steadily increased with time, there were no statistically significant differences among the treatment groups. Patients in the ceramic group had a gain in attachment level of 1.0 mm; those in the curettage group, 0.9 mm; and 0.4 mm for those in the bone implant group. Although the BCP patients had a greater gain, the difference was not statistically significant. In this veteran population, not only did BCP patients fail to outperform those in the control groups, all three treatment groups were similarly ineffective.

Using cervical smears obtained as part of routine gynaecological examinations, a retrospective study of the effects of the drug tamoxifen on squamous epithelial maturation of the cervix of post-menopausal women being treated for advanced breast cancer was made. The degree of squamous epithelial maturation was quantitated by using the Maturation Index and the Maturation Value. Although tamoxifen is a synthetic, non-steroidal compound classified as anti-oestrogenic, the findings indicate that this drug commonly produces a level of squamous maturation indicative of oestrogenic stimulation in Papanicolaou stained cervical smears from post-menopausal patients receiving this drug. Knowledge of the oestrogenic effect of tamoxifen in the cervix can obviate clinical concern about endometrial carcinoma.

Varicella zoster virus (VZV) infection involving the posterior segment of the eye after fludarabine treatment has not previously been described. Two patients, who had completed fludarabine treatment 3 and 18 months previously, presented with visual loss that had been preceded by a recent history of cutaneous zoster. The use of the polymerase chain reaction (PCR) for VZV DNA from ocular specimens allowed rapid confirmation of clinical diagnosis and treatment with a good outcome in one patient. With the increasing use of fludarabine and other purine analogues, an awareness of such complications is important because of their potentially sight-threatening consequences.

A 56-year-old male complained of chronic oral ulcers. Initial workup revealed diffuse alveolar bone destruction and other systemic disturbances including diabetes insipidus. Biopsy suggested histiocytosis X and further tests verified the diagnosis. A clinical differential diagnosis is developed, follow-up is presented and the entities comprising histiocytosis X are discussed.

A previously untransfused 20-year-old man presented with a seven day history of malaise, fatigue, jaundice, dark urine and splenomegaly. Hemolytic anemia was indicated by a hemoglobin of 8.7 mg/dl, reticulocyte count 8 per cent, Lactic dehydrogenase 389 iu/L, bilirubin 4.3 mg/dl (direct 0.1 mg/dl), and undetectable haptoglobins. Tests for nonimmunologic mediated hemolytic anemia were negative. The direct antiglobulin test (DAT) was repeatedly negative with polyspecific, anti-IgG, -IgA, -IgM and anti-C3 antisera. The patient's serum contained a weak anti-I, anti-E strongly reactive by indirect antiglobulin test (IAT) and an antibody reactive against all cells tested. The latter antibody reacted weakly by the IAT but strongly against enzyme-treated cells (Titer 160). Eluates from the patient's red blood cells only reacted with E+ red blood cells. The patient typed E negative. He was treated for warm autoimmune hemolytic anemia (AIHA) with high doses of prednisone. By the twelfth day his response allowed the medication to be tapered and by one month from the onset of treatment laboratory studies had returned to normal. The DAT remained negative, however, following recovery, anti-E could not be eluted from the red blood cells. Anti-E remained in his serum and the titer of the enzyme reactive antibody had decreased to 16. It is suggested that the anti-“E-like” antibody may represent auto anti-Hr preferentially reacting with E+ red blood cells. A unique feature in the case is the presence of a specific antibody eluted from cells that appear to lack that antigen in a DAT-negative patient with AIHA.

A method, combining the standardization of radiographs with consistent radiopaque marker placement using a controlled force, is presented. Ten adult volunteers with healthy mouths were selected. Customized radiographic film holders were fabricated consisting of a plastic stent of the maxillary or mandibular arches to which a radiographic bite-block was attached. An orthodontic stainless steel tube was added and placed so that the radiographic marker could be guided repeatedly to the base of the sulcus in the same position. The radiographs were exposed using a self-adhesive grid on the periapical film. To document repeatability, measurements using the device were obtained at different time intervals: twice-a-week for the first, third, and fifth week for a total of six measurements for each volunteer. Results showed that the mean vertical and horizontal dimensions were nearly constant across the study period. The device had been shown to be accurate and enabled placement of a radiographic marker to repeatedly reach the same position in the sulcus with a good degree of precision.

Fiber-supplemented breads, prepared by replacing 7.5% of the hard wheat flour with field pea, flax or sunflower hulls, wheat bran or microcrystalline cellulose, were evaluated for breadmaking characteristics and physiological effects on rats. Cellulose-supplemented dough and bread resembled the straight-grade wheat bread while pea hull and wheat bran breads were similar to whole wheat bread. Flax and sunflower hulls had adverse effects on dough mixograph properties, loaf volume and crumb characteristics while sunflower hulls also contributed grittiness and aftertaste in taste panel evaluations. The fiber-supplemented breads, when fed to weanling rats, gave similar feed consumptions, weight gains and serum cholesterol levels as rats fed the whole wheat bread. Pea hulls increased daily fecal weight and, with coarse sunflower hulls, decreased dry matter digestibility. Fine wheat bran and fine sunflower hulls in the bread diets were associated with low fecal weight, low fecal volume, high fecal density and high digestibility of dry matter.

The “Hander,” new Type 52 oil expeller was evaluated to determine its performance in expressing sunflower oil for use in diesel engines. Strain gauges were mounted on the barrel of the expeller and were used to give a relative indication of barrel pressure. Relative barrel pressure was then used as the independent variable in determining performance. Filterability of four commercial sunflower oils and blends of these oils with No. 2 diesel fuel were determined at various temperatures and pressures. Oil extraction efficiency ranged from ca. 56% to 84% at low and high relative barrel pressures, respectively. The greatest oil extraction rate was 12.3 kg/hr at a feed rate of 40 kg/hr with an extraction efficiency of ca. 80%. Dewaxed sunflower oils and blends filtered much better than nondewaxed oils and their blends. Increasing temperature, pressure and percentage of diesel fuel in the blends increased filterability of dewaxed sunflower oil.