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BACKGROUND: The prevalence of atrial fibrillation(AF) and diabetes mellitus is rising to epidemic proportions. We aimed to assess the impact of diabetes on the management and outcomes of patients with AF.METHODS: The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. Outcomes of interest were as follows: i)rhythm control interventions; ii)quality of life; iii)healthcare resource utilisation; and iv)major adverse events.RESULTS: Of 11,028 patients with AF, the median age was 71 (63-77) years and 2537 (23.0%) had diabetes. Median follow-up was 24 months. Diabetes was related to increased use of anticoagulation but less rhythm control interventions. Using multivariable analysis, at 2-year follow-up, patients with diabetes were associated with greater levels of anxiety (p = 0.038) compared to those without diabetes. Overall, diabetes was associated with worse health during follow-up, as indicated by Health Utility Score and Visual Analogue Scale. Healthcare resource utilisation was greater with diabetes in terms of length of hospital stay (8.1 (±8.2) vs. 6.1 (±6.7) days); cardiology and internal medicine/general practitioner visits; and emergency room admissions. Diabetes was an independent risk factor of major adverse cardiovascular event (MACE; HR 1.26 [95% CI, 1.04-1.52]), all-cause mortality (HR 1.28 [95% CI, 1.08-1.52]), and cardiovascular mortality (HR 1.41 [95% CI, 1.09-1.83]).CONCLUSION: In this contemporary AF cohort, diabetes was present in 1 in 4 patients and it served as an independent risk factor for reduced quality of life, greater healthcare resource utilisation and excess MACE, all-cause mortality and cardiovascular mortality. There was increased use of anticoagulation therapy in diabetes but with less rhythm control interventions.

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

Detailed tests and analysis of ageing effects of high irradiation dose on Multi-Strip Multi-Gap Resistive Plate Counters based on low resistivity glass electrodes were performed. MSMGRPC efficiency and cluster size before irradiation are measured and compared with their values after irradiation in a high irradiation dose accessed at a multi-purpose irradiation facility of IFIN-HH based on $^{60}$Co source. The composition and properties of the deposited layers on the glass electrodes, studied based on a multitude of analysis methods, i.e. SEM, XPS, foil-ERDA, RBS, AFM and THz-TDS, are presented., Comment: 13 pages, 34 figures

The Keck Planet Imager and Characterizer (KPIC) is a purpose-built instrument for high-dispersion coronagraphy in the K and L bands on Keck. This instrument will provide the first high resolution (R>30,000) spectra of known directly imaged exoplanets and low-mass brown dwarf companions visible in the northern hemisphere. KPIC is developed in phases. Phase I is currently at Keck in the early operations stage, and the phase II upgrade will deploy in late 2021. The goal of phase II is to maximize the throughput for planet light and minimize the stellar leakage, hence reducing the exposure time needed to acquire spectra with a given signal-to- noise ratio. To achieve this, KPIC phase II exploits several innovative technologies that have not been combined this way before. These include a 1000-element deformable mirror for wavefront correction and speckle control, a set of lossless beam shaping optics to maximize coupling into the fiber, a pupil apodizer to suppress unwanted starlight, a pupil plane vortex mask to enable the acquisition of spectra at and within the diffraction limit, and an atmospheric dispersion compensator. These modules, when combined with the active fiber injection unit present in phase I, will make for a highly efficient exoplanet characterization platform. In this paper, we will present the final design of the optics and opto-mechanics and highlight some innovative solutions we implemented to facilitate all the new capabilities. We will provide an overview of the assembly and laboratory testing of the sub-modules and some of the results. Finally, we will outline the deployment timeline.

The Keck Planet Imager and Characterizer (KPIC) is a purpose-built instrument to demonstrate new tech- nological and instrumental concepts initially developed for the exoplanet direct imaging field. Located downstream of the current Keck II adaptive optic system, KPIC contains a fiber injection unit (FIU) capable of combining the high-contrast imaging capability of the adaptive optic system with the high dispersion spectroscopy capability of the current Keck high resolution infrared spectrograph (NIRSPEC). Deployed at Keck in September 2018, this instrument has already been used to acquire high resolution spectra (R < 35, 000) of multiple targets of interest. In the near term, it will be used to spectrally characterize known directly imaged exoplanets and low-mass brown dwarf companions visible in the northern hemisphere with a spectral resolution high enough to enable spin and planetary radial velocity measurements as well as Doppler imaging of atmospheric weather phenomena. Here we present the design of the FIU, the unique calibration procedures needed to operate a single-mode fiber instrument and the system performance.

Probiotics are live microorganisms, which when administered in adequate amounts, present a health benefit for the host. While the beneficial effects of probiotics on gastrointestinal function are generally well recognized, new animal research and clinical studies have found that alterations in gut microbial communities can have a broad range of effects throughout the body. Non-intestinal sites impacted include the immune, endocrine, cardiovascular and the central nervous system (CNS). In particular, there has been a growing interest and appreciation about the role that gut microbiota may play in affecting CNS-related function through the 'microbiota-gut-brain axis'. Emerging evidence suggests potential therapeutic benefits of probiotics in several CNS conditions, such as anxiety, depression, autism spectrum disorders and Parkinson's disease. There may also be some gender-specific variances in terms of probiotic mediated effects, with the gut microbiota shaping and being concurrently molded by the hormonal environment governing differences between the sexes. Probiotics may influence the ability of the gut microbiome to affect a variety of biological processes in the host, including neurotransmitter activity, vagal neurotransmission, generation of neuroactive metabolites and inflammatory response mediators. Some of these may engage in cross talk with host sex hormones, such as estrogens, which could be of relevance in relation to their effects on stress response and cognitive health. This raises the possibility of gender-specific variation with regards to the biological action of probiotics, including that on the endocrine and central nervous systems. In this review we aim to describe the current understanding in relation to the role and use of probiotics in microbiota-gut-brain axis-related dysfunction. Furthermore, we will address the conceptualization and classification of probiotics in the context of gender and lifespan as well as how restoring gut microbiota composition by clinical or dietary intervention can help in supporting health outcomes other than those related to the gastrointestinal tract. We also evaluate how these new learnings may impact industrial effort in probiotic research and the discovery and development of novel and more personalized, condition-specific, beneficial probiotic therapeutic agents.

The Keck Planet Imager and Characterizer comprises of a series of upgrades to the Keck II adaptive optics system and instrument suite to improve the direct imaging and high resolution spectroscopy capabilities of the facility instruments NIRC2 and NIRSPEC, respectively. Phase I of KPIC includes a NIR pyramid wavefront sensor and a Fiber Injection Unit (FIU) to feed NIRSPEC with a single mode fiber, which have already been installed and are currently undergoing commissioning. KPIC will enable High Dispersion Coronagraphy (HDC) of directly imaged exoplanets for the first time, providing potentially improved detection significance and spectral characterization capabilities compared to direct imaging. In favorable cases, Doppler imaging, spin measurements, and molecule mapping are also possible. This science goal drives the development of phase II of KPIC, which is scheduled to be deployed in early 2020. Phase II optimizes the system throughput and contrast using a variety of additional submodules, including a 952 element deformable mirror, phase induced amplitude apodization lenses, an atmospheric dispersion compensator, multiple coronagraphs, a Zernike wavefront sensor, and multiple science ports. A testbed is being built in the Exoplanet Technology Lab at Caltech to characterize and test the design of each of these submodules before KPIC phase II is deployed to Keck. This paper presents an overview of the design of phase II and report on results from laboratory testing., 12 pages; 11 figures; to appear in Proceedings of the SPIE, Techniques and Instrumentation for Detection of Exoplanets IX, Vol. 11117

The Carbon Observatory Instrument Suite, or CARBO, consists of four carbon observing instruments sharing a common instrument bus, yet targeted for a particular wavelength band each with a unique science observation. They are: a) Instrument 1, wavelength centered at 756 nm for oxygen and solar-induced chlorophyll fluorescence (SIF) observations, b) Instrument 2, centered at 1629 nm, for carbon dioxide (CO2) and methane (CH4) observation, c) Instrument 3, centered at 2062 nm for carbon dioxide and d) Instrument 4, centered at 2328 for carbon monoxide (CO) and methane. From low-Earth orbit, these instruments have a field-of-view of 10 to 15 degrees, and a spatial resolution of 2 km square. These instruments have a spectral resolving power ranging from ten to twenty thousand, and can monitor columnaverage dry air mole fraction of carbon dioxide (XCO2) at 1.5 ppm, and methane (XCH4) at 7 ppb. These new instruments will advance the use of immersion grating technology in spectrometer instruments in order to reduce the size of the instrument, while improving performance. These compact, capable instruments are envisioned to be compatible with small satellites, yet modular to be configured to address the particular science questions at hand. Here we report on the current status of the instrument design and fabrication, focusing primarily on Instruments 1 and 2. We will describe the key science and engineering requirements and the instrument performance error budget. We will discuss the optical design with particular emphasis on the immersion grating, and the advantages this new technology affords compared to previous instruments. We will also discuss the status of the focal plane array and the detector electronics and housing. Finally, we report on a new approach – developed during this instrument design process - which enables simultaneous measurement of both orthogonal polarization states (S and P) over the field-of-view and optical bandpass. We believe this polarization sensing capability will enable science observations which were previously limited by instrumental and observational degeneracies. In particular: improved sensitivity to all species, better sensitivity to surface polarization effects, better constraints on aerosol scattering parameters, and superior discrimination of the vertical distribution of gases and aerosols.

Purpose Assessing cardiovascular risk in patients with acromegaly using traditional cardiovascular risk factors is inadequate. Endothelial dysfunction seems to be a much better indicator for assessing cardiovascular risk in acromegaly. The study aims to compare from this point of view two groups of patients, with hypertension and with acromegaly. Methods The first group consists of 54 patients with acromegaly and the second group of 64 hypertensive patients. Endothelial dysfunction was evaluated by the FMD method. The relationship between endothelial dysfunction, specific humoral markers of acromegaly and traditional cardiovascular risk factors was analysed in both groups. Results Although the presence of cardiovascular risk factors was statistically significantly higher in the group of hypertensives (the most important were age, blood pressure, glycemia, hypertriglyceridemia and SCORE), the presence of endothelial dysfunction was higher in the acromegaly group (61.10% vs. 32.10%, p=0.02). The best correlation with endothelial dysfunction in acromegaly group was the level of GH (28.9±28 vs. 11.7±10.3, p=0.003). Conclusions The presence of endothelial dysfunction in patients with acromegaly is highly dependent on the level of GH and traditional cardiovascular risk factors are less important. In these patients the cardiovascular risk should not be evaluated in the same way as in normal population.

Purpose: To assess the value of contrast-enhanced ultrasound (CEUS) for differentiating malignant from benign focal liver lesions (FLLs) and for diagnosing different FLL types. Material and Methods: CEUS performed in 14 Romanian centers was prospectively collected between February 2011 and June 2012. The inclusion criteria were: age > 18 years; patients diagnosed with 1 – 3 de novo FLLs on B-mode ultrasound; reference method (computed tomography (CT), magnetic resonance imaging (MRI) or biopsy) available; patient’s informed consent. FLL lesions were characterized during CEUS according to the European Federation of Societies for Ultrasound in Medicine and Biology guidelines. For statistical analysis, indeterminate FLLs at CEUS were rated as false classifications. Results: A total number of 536 cases were included in the final analysis, 344 malignant lesions (64.2 %) and 192 benign lesions (35.8 %). The reference method was: CT/MRI – 379 cases (70.7 %), pathological exam – 150 cases (27.9 %) and aspiration of liver abscesses – 7 cases (1.4 %). CEUS was conclusive in 89.3 % and inconclusive in 10.7 % of cases. To differentiate between malignant and benign FLLs, CEUS had 85.7 % sensitivity, 85.9 % specificity, 91.6 % positive predictive value, 77.1 % negative predictive value and 85.8 % accuracy. The CEUS accuracy for differentiation between malignant and benign liver lesions was similar in tumors with diameter ≤ 2 cm and those with diameter > 2 cm. Conclusion: CEUS represents a useful method in clinical practice for differentiating between malignant and benign FLLs detected on standard ultrasonography, and the results of this study are in concordance with previous multicenter studies: DEGUM (Germany) and STIC (France).

The genetic basis of host preference has been investigated in only a few species. It is relevant to important questions in evolutionary biology, including sympatric speciation, generalist versus specialist adaptation, and parasite-host co-evolution. Here we show that a major locus strongly influences host preference in Nasonia. Nasonia are parasitic wasps that utilize fly pupae; N. vitripennis is a generalist that parasitizes a diverse set of hosts whereas N. giraulti specializes on Protocalliphora (bird blowflies). In laboratory choice experiments using Protocalliphora and Sarcophaga (flesh flies), N. vitripennis shows a preference for Sarcophaga while N. giraulti shows a preference for Protocalliphora. Through a series of interspecies crosses we have introgressed a major locus affecting host preference from N. giraulti into N. vitripennis. The N. giraulti allele is dominant and greatly increases preference for Protocalliphora pupae in the introgression line relative to the recessive N. vitripennis allele. Through the utilization of a Nasonia genotyping microarray, we have identified the introgressed region as 16 megabases of chromosome 4, although a more complete analysis is necessary to determine the exact genetic architecture of host preference in the genus. To our knowledge, this is the first introgression of the host preference of one parasitoid species into another, as well as one of the few cases of introgression of a behavioral gene between species.

To maintain the required WFIRST Coronagraph starlight suppression performance in a realistic space environment, a low order wavefront sensing and control (LOWFS/C) subsystem is necessary. The LOWFS/C uses the rejected stellar light from coronagraph to sense and suppress the telescope pointing drift and jitter as well as the low order wavefront errors due to changes in thermal loading on the telescope and the rest of the observatory. In this paper we will present an overview of the low order wavefront sensing and control subsystem for the WFIRST Coronagraph. We will describe LOWFS/C’s Zernike wavefront sensor concept and control design, and present an overview of sensing performance analysis and modeling, predicted line-of-sight jitter suppression loop performance, as well as the low order wavefront error correction with the coronagraph’s deformable mirror. We will also report the LOWFS/C testbed design and the preliminary in-air test results, which show promising performance of the Zernike wavefront sensor and FSM feedback loop.

Human sporadic colorectal cancer is the result of a lengthy somatic evolutionary process facilitated by various forms of genomic instability. Such instability arises endogenously from mutations in genes whose role is to preserve genomic integrity, and exogenously from environmental agents that generate genomic damage. We have found that cigarette smoking shifts the genomic profiles and genomic instability patterns of colorectal carcinomas. The genomic profiles of 57 consecutive cancers were examined; 31 cases were current or former smokers and 26 were nonsmokers. Genome-wide allelotypes of 348 markers were examined, along with comparative genomic hybridization (CGH) on ordered BAC microarrays, microsatellite instability, and inter-(simple sequence repeat) polymerase chain reaction instability. Tumors from nonsmokers exhibited losses of heterozygosity, particularly on chromosomes 14 and 18, whereas tumors from smokers exhibited a more diffuse pattern of allelic losses. Tumors from smokers exhibited higher overall rates of loss of heterozygosity, but showed lower rates of background microsatellite instability (MSI-L). On BAC array CGH, higher levels of generalized amplifications and deletions were observed in tumors from smokers, differentially affecting male smokers. In the transforming growth factor-beta signaling pathway, MADH4 mutations were more common in tumors from smokers, whereas transforming growth factor-beta RII mutations were more common among nonsmokers.

We have measured genomic instability in invasive breast carcinomas and assessed the relationship of genomic instability to known tumor prognostic factors. DNAs from tumors and adjacent normal tissue of 18 breast cancer patients were subjected to inter-Simple Sequence Repeat (inter-SSR) PCR for quantitation of tumor genomic instability. Associations between genomic instability level and known breast cancer prognostic factors were evaluated using the Pearson Product Moment Correlation, the Kruskal-Wallis test of independent samples and the Mann-Whitney non-parametric test. Genomic instability was detected by inter-SSR PCR in over 90% of the breast tumors. The mean instability index was 3.08% (0-7.59%), approximately the same mean value observed in studies of colorectal and thyroid carcinomas. Significantly higher levels of instability were associated with tumors exhibiting necrosis. Genomic instability as measured is detected in the majority of breast cancers at levels comparable to other tumor types. Hypoxia, such as that observed in necrotic regions of tumors, has been associated with elevated genomic damage. We hypothesize that the higher levels of genomic instability detected in necrotic tumors is a consequence of hypoxia-associated DNA damage.

Nasonia consists of three closely related species of parasitoid wasps that are all infected with the endosymbiotic bacteria Wolbachia, a reproductive parasite common in arthropods. This situation presents the opportunity to compare patterns of variation in three associated genomes, Wolbachia and the nuclear and mitochondrial genomes of its host. Furthermore, although Nasonia wasps are emerging as a model for evolutionary and genetic studies, little is known about their genetic variability. Using amplified fragment length polymorphisms (AFLPs), all three species present a relatively high level of nuclear polymorphism and have different patterns of variation, with one of the species, Nasonia giraulti, being divided into two divergent subgroups. In each species, the mitochondrial pattern of variation is different from the nuclear pattern, possibly due to genetic hitchhiking of the mitochondria during (cytoplasmically inherited) Wolbachia sweeps. Mitochondria in Nasonia show a synonymous substitution rate approximately 10-15-fold higher than nuclear genes, probably reflecting an elevated mitochondrial mutation rate that is among the highest found in insects. Finally, all three species are doubly infected with their own strains of Wolbachia, one each from the two major supergroups (A and B). Sequence analysis reveals that each of the three Nasonia species acquired their A and B bacteria independently by horizontal transfer events from other insects with the exception of B type Wolbachia in N. longicornis and N. giraulti, which were acquired prior to speciation and then codiverged with the host. This represents one of the few clear-cut examples of codivergence of Wolbachia during host speciation.

Objectives. The object of this study is to measure genomic instability in papillary thyroid cancer and correlate these measurements with known clinical prognosticators such as patient age, tumor size, histologic subtype, and three commonly used thyroid risk assessment indices. A secondary objective of this study was to use the measurements of genomic instability to estimate the number of mutational events present in the papillary thyroid cancer genome. Methods. Inter-simple sequence repeat polymerase chain reaction (ISSR-PCR) is a rapid and reproducible technique for quantitation of genomic instability, or the degree of genome alteration, in solid tumors. This includes quantitation of amplifications, deletions, translocations, and insertions. Twenty-eight papillary carcinomas were evaluated by ISSR-PCR. Results. Evaluation of 28 papillary carcinomas by ISSR-PCR demonstrated a wide range of genomic instability. Of the panel of clinicopathologic factors examined, only patient age was significantly associated with genomic instability. The mean genomic instability index value was greatest in the youngest age group, which was significantly different from the median value measured in the oldest age group (3.7, 2.5, respectively, p = .05). The mean value in the intermediate age group fell between the younger and older groups (3.1). By use of ISSR-PCR, we have calculated 15,000 individual genomic events as having occurred in each papillary tumor cell. Conclusions. Despite its generally indolent biologic behavior, papillary thyroid cancer exhibits a high degree of genomic instability comparable to that seen in colorectal cancer. These results suggest that elevated genomic instability, as measured by ISSR-PCR, may not be sufficient to enable thyroid tumor progression to less indolent disease and that this process is severely constrained by some additional essential factor such as the differentiated state of the tissue or the need to bring into play an additional form of genomic destabilization. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 825–832, 2003

We report on the status of PALM-3000, the second generation adaptive optics instrument for the 5.1 meter Hale telescope at Palomar Observatory. PALM-3000 was released as a facility class instrument in October 2011, and has since been used on the Hale telescope a total of over 250 nights. In the past year, the PALM-3000 team introduced several instrument upgrades, including the release of the 32x32 pupil sampling mode which allows for correction on fainter guide stars, the upgrade of wavefront sensor relay optics, the diagnosis and repair of hardware problems, and the release of software improvements. We describe the performance of the PALM-3000 instrument as a result of these upgrades, and provide on-sky results. In the 32x32 pupil sampling mode (15.8 cm per subaperture), we have achieved K-band strehl ratios as high as 11% on a 14.4 mv star, and in the 64x64 pupil sampling mode (8.1 cm per subaperture), we have achieved K-band strehl ratios as high as 86% on stars brighter than 7th m_v.

We present a new instrument, the "Stellar Double Coronagraph" (SDC), a flexible coronagraphic platform. Designed for Palomar Observatory's 200" Hale telescope, its two focal and pupil planes allow for a number of different observing configurations, including multiple vortex coronagraphs in series for improved contrast at small angles. We describe the motivation, design, observing modes, wavefront control approaches, data reduction pipeline, and early science results. We also discuss future directions for the instrument., Comment: 25 pages, 12 figures. Correspondence welcome. The published work is open access and differs trivially from the version posted here. The published version may be found at http://iopscience.iop.org/article/10.1088/1538-3873/128/965/075003/meta

Despite significant progress, the management of acute colonic obstruction still remains a challenging problem. The purpose of this study was represented by the evaluation of the clinical results of different techniques of resection for malignant colorectal (primary or staged) obstruction.We performed a non-randomized clinical study. 590 patients with malignant colorectal occlusion who underwent surgery treatment an 3rd Surgical Clinic Cluj-Napoca between 1996-2005 were included.Patients with large bowel obstruction underwent one-stage primary resection with anastomosis in 267 cases or staged interventions in 323 cases. The groups were matched in: age, sex, comorbidities, tumor staging, serum preoperative levels of hemoglobin and proteins. The analysis of mortality and morbidity following surgical treatment for large bowel obstruction returned no significant difference among the two groups (p0.05). Moreover, the presented results showed a higher incidence of mortality (11.45% vs 9.33 %), morbidity (25.38% vs 14.6%) and increased hospitalization period (p = 0.029) among the patients that undergone seriate resections.One stage primary resections with anastomosis of the large bowel can be performed safely in case of emergency whenever patient comorbidities and local conditions do not stand as major restrictions.

The Gemini Planet Imager is an extreme adaptive optics system that will employ an apodized-pupil coronagraph to make direct detections of faint companions of nearby stars to a contrast level of the 10(exp -7) within a few lambda/D of the parent star. Such high contrasts from the ground require exquisite wavefront sensing and control both for the AO system as well as for the coronagraph. Un-sensed non-common path phase and amplitude errors after the wavefront sensor dichroic but before the coronagraph would lead to speckles which would ultimately limit the contrast. The calibration wavefront system for GPI will measure the complex wavefront at the system pupil before the apodizer and provide slow phase corrections to the AO system to mitigate errors that would cause a loss in contrast. The calibration wavefront sensor instrument for GPI has been built. We will describe the instrument and its performance.

The calibration wavefront system for GPI will measure the complex wavefront at the apodized pupil and provide slow phase corrections to the AO system to mitigate against errors that would cause a loss in contrast. This talk describes both the low-order and high-order sensors in the calibration wavefront sensor and how the information is combined to form the wavefront estimate before the coronagraph. Expected performance for this wavefront sensor will also be described for typical observing scenarios. Finally, we will show labratory results from our calibration testbed that demonstrate the instrument performance at levels commensurate with those required on the GPI instrument.

Eukaryotic DNA-binding protein replication protein A (RPA) has a strand melting property that assists polymerases and helicases in resolving DNA secondary structures. Curiously, previous results suggested that human RPA (hRPA) promotes undesirable recombination by facilitating annealing of flaps produced transiently during DNA replication; however, the mechanism was not understood. We designed a series of substrates, representing displaced DNA flaps generated during maturation of Okazaki fragments, to investigate the strand annealing properties of RPA. Until cleaved by FEN1 (flap endonuclease 1), such flaps can initiate homologous recombination. hRPA inhibited annealing of strands lacking secondary structure but promoted annealing of structured strands. Apparently, both processes primarily derive from the strand melting properties of hRPA. These properties slowed the spontaneous annealing of unstructured single strands, which occurred efficiently without hRPA. However, structured strands without hRPA displayed very slow spontaneous annealing because of stable intramolecular hydrogen bonding. hRPA appeared to transiently melt the single strands so that they could bind to form double strands. In this way, melting ironically promoted annealing. Time course measurements in the presence of hRPA suggest that structured single strands achieve an equilibrium with double strands, a consequence of RPA driving both annealing and melting. Promotion of annealing reached a maximum at a specific hRPA concentration, presumably when all structured single-stranded DNA was melted. Results suggest that displaced flaps with secondary structure formed during Okazaki fragment maturation can be melted by hRPA and subsequently annealed to a complementary ectopic DNA site, forming recombination intermediates that can lead to genomic instability.

The increasing demand within the astronomy community for direct detection of extrasolar Jovian planets is driving the development of the next generation of ground-based, precision instruments like the Gemini Planet Imager (GPI). The precision and stability of the opto-mechanical components within GPI needed to achieve the required 10 -7 contrast will challenge the limits of design and material properties. This study examines the challenge of mounting small, high-precision mirrors (~1nm RMS WFE) for all gravity orientations, for 30°C temperature fluctuations and for vibration conditions typical of a cassegrain-mounted instrument on the Gemini telescopes. Various flexure-based mounting schemes, typically used for small optics (12 mm to 50 mm diameter), are considered in the context of the GPI opto-mechanical requirements. Through this study several candidate designs are selected for detailed investigation. The further design, analysis, and optimization of these candidate flexure designs are presented and evaluated against the relevant requirements. Special consideration and discussion is devoted to finite element analysis techniques and optimization procedures. Finally, the chosen flexure configuration is prescribed for the range of mirror sizes within GPI.

The calibration wavefront system for the Gemini Planet Imager (GPI) will measure the complex wavefront at the apodized pupil and provide slow phase errors to the AO system to mitigate against image plane speckles that would cause a loss in contrast. This talk describes both the low-order and high-order sensors in the calibration wavefront sensor and how the information is combined to form the wavefront estimate before the coronagraph. We will show laboratory results from our calibration testbed that demonstrate the subsystem performance at levels commensurate with those required on the final instrument.

The ATLAS Muon Spectrometer, currently in the installation phase, uses dedicated detectors to be able to trigger on high transverse momentum muons in the range 6 - 20 GeV/cResistive Plate Chambers (RPC) are equipping the Barrel region in the middle and outer station, while precision chambers (Monitored Drift Tubes, MDT) are present also in the inner layer. The RPCs have the required timing and spatial resolution of about 2 ns × 1 cm, to be able to associate the muon to the correct bunch crossing and provide the second coordinate measurements to the MDTs. In order to successfully commission the chambers, cosmic runs are taken to check and validate the readout and trigger chain, and cosmic rates are measured and compared against values obtained with a cosmic ray Montecarlo generator and full detector simulation. The first part of the detector under commission is the set of horizontal chambers positioned between the feet of the detector. The first results obtained in the ATLAS cavern will be presented. The first cosmic data taking collects signals from chambers arranged in six trigger towers, covering about one quarter of the full detector lenght. The experience gained on this small part of the detector will be very useful to define the commissioning work for the whole detector. © 2006 IEEE.

Genomic instability is a widespread and essential feature of the common adult-onset cancers. For solid tumors to arise, several key genes must become mutated (to generate growth, facilitate invasion, enlist nutrient supply, evade the immune response, avoid apoptosis, and so on) and this degree of mutation requires abnormally high mutation rates. To achieve such rates, genes whose normal role is to maintain genomic integrity become mutated, leading to ongoing genomic instability. Exogenous mutagens (carcinogens) additionally contribute to overall genomic damage, particularly in tobacco smokers. Genomic destabilization slowly leads to cancer as cells with mutations in genes advantageous for tumor development become selected, expand their populations, and evolve further. A considerable majority of human genes are involved in multicellular coordination and are not essential for maintaining the viability and reproductive potential of individual cells; thus, a window exists wherein an appropriate degree of genomic instability leads to tumor progression, as somatic evolution selects cells driven by self-interest. As with Darwinian evolution, such somatic evolution inherently leads to genomic diversity, seen clinically as tumor heterogeneity. Although genomic instability and the ensuing genomic heterogeneity render therapeutic targeting difficult, measurement of the degree and form of genomic instability has considerable potential as a clinical prognostic tool. Keywords: Aneuploidy; Arbitrarily primed PCR and Inter-(Simple Sequence Repeat) PCR; Intrachromosomal Instability; Microsatellite Instability; Spectral Karyotype (SKY)

Bloom syndrome is a familial genetic disorder associated with sunlight sensitivity and a high predisposition to cancers. The mutated gene, Bloom protein (BLM), encodes a DNA helicase that functions in genome maintenance via roles in recombination repair and resolution of recombination structures. We designed substrates representing illegitimate recombination intermediates formed when a displaced DNA flap generated during maturation of Okazaki fragments escapes cleavage by flap endonuclease-1 and anneals to a complementary ectopic DNA site. Results show that displaced, replication protein A (RPA)-coated flaps could readily bind and ligate at the complementary site to initiate recombination. RPA also displayed a strand-annealing activity that hastens the rate of recombination intermediate formation. BLM helicase activity could directly disrupt annealing at the ectopic site and promote flap endonuclease-1 cleavage. Additionally, BLM has its own strand-annealing and strand-exchange activities. RPA inhibited the BLM strand-annealing activity, thereby promoting helicase activity and complex dissolution. BLM strand exchange could readily dissociate invading flaps, e.g. in a D-loop, if the exchange step did not involve annealing of RPA-coated strands. Use of ATP to activate the helicase function did not aid flap displacement by exchange, suggesting that this is a helicase-independent mechanism of complex dissociation. When RPA could bind, it displayed its own strand-exchange activity. We interpret these results to explain how BLM is well equipped to deal with alternative recombination intermediate structures.

In order to identify small regions of the genome whose specific copy number alteration is associated with high genomic instability in the form of overall genome-wide copy number aberrations, we have analyzed array-based comparative genomic hybridization (aCGH) data from 33 sporadic colorectal carcinomas. Copy number changes of a small number of specific regions were significantly correlated with elevated overall amplifications and deletions scattered throughout the entire genome. One significant region at 9q34 includes the c-ABL gene. Another region spanning 22q11-q13 includes the breakpoint cluster region (BCR) of the Philadelphia chromosome. Coordinate 22q11-q13 alterations were observed in 9 of 11 tumors with the 9q34 alteration. Additional regions on 1q and 14q were associated with overall genome-wide copy number changes, while copy number aberrations on chromosome 7p, 7q, and 13q21.1-q31.3 were found associated with this instability only in tumors from patients with a smoking history. Our analysis demonstrates there are a small number of regions of the genome where gain or loss is commonly associated with a tumor's overall level of copy number aberrations. Our finding BCR and ABL located within two of the instability-associated regions, and the involvement of these two regions occurring coordinately, suggests a system akin to the BCR-ABL translocation of CML may be involved in genomic instability in about one-third of human colorectal carcinomas.

Direct detection of exo-planets from the ground will become a reality with the advent of a new class of extreme-adaptive optics instruments that will come on-line within the next few years. In particular, the Gemini Observatory will be developing the Gemini Planet Imager (GPI) that will be used to make direct observations of young exo-planets. One major technical challenge in reaching the requisite high contrast at small angles is the sensing and control of residual wave front errors after the starlight suppression system. This paper will discuss the nature of this problem, and our approach to the sensing and control task. We will describe a laboratory experiment whose purpose is to provide a means of validating our sensing techniques and control algorithms. The experimental demonstration of sensing and control will be described. Finally, we will comment on the applicability of this technique to other similar high-contrast instruments.

Due to the huge interaction rates and the tough experimental environment of pp collisions at a centre-of-mass energy sqrt(s)=14 TeV and luminosities of up to 10^34cm^-2s^-1, one of the experimental challenges at the LHC is the triggering of interesting events. In the ATLAS experiment a three-level trigger system is foreseen for this purpose. The first-level trigger is implemented in custom hardware and has been designed to reduce the data rate from the initial bunch-crossing rate of 40MHz to around 75 kHz. Its event selection is based on information from the calorimeters and dedicated muon detectors. This article gives an overview over the full first-level trigger system including the Calorimeter Trigger, the Muon Trigger and the Central Trigger Processor. In addition, recent results are reported that have been obtained from test-beam studies performed at CERN where the full first-level trigger chain was established successfully for the first time and used to trigger the read-out of up to nine ATLAS sub-detector systems. Due to the huge interaction rates and the tough experimental environment of pp collisions at a centre-of-mass energy sqrt(s)=14TeV and luminosities of up to 10^34 cm^-2 s^-1, one of the experimental challenges at the LHC is the triggering of interesting events. In the ATLAS experiment a three-level trigger system is foreseen for this purpose. The first-level trigger is implemented in custom hardware and has been designed to reduce the data rate from the initial bunch-crossing rate of 40 MHz to around 75 kHz. Its event selection is based on information from the calorimeters and dedicated muon detectors. This article gives an overview over the full first-level trigger system including the Calorimeter Trigger, the Muon Trigger and the Central Trigger Processor. In addition, recent results are reported that have been obtained from test-beam studies performed at CERN where the full first-level trigger chain was established successfully for the first time and used to trigger the read-out of up to nine ATLAS sub-detector systems. Due to the huge interaction rates and the tough experimental environment of pp collisions at a centre-of-mass energy sqrt(s)=14TeV and luminosities of up to 10^34 cm^-2 s^-1, one of the experimental challenges at the LHC is the triggering of interesting events. In the ATLAS experiment a three-level trigger system is foreseen for this purpose. The first-level trigger is implemented in custom hardware and has been designed to reduce the data rate from the initial bunch-crossing rate of 40 MHz to around 75 kHz. Its event selection is based on information from the calorimeters and dedicated muon detectors. This article gives an overview over the full first-level trigger system including the Calorimeter Trigger, the Muon Trigger and the Central Trigger Processor. In addition, recent results are reported that have been obtained from test-beam studies performed at CERN where the full first-level trigger chain was established successfully for the first time and used to trigger the read-out of up to nine ATLAS sub-detector systems. Due to the huge interaction rates and the tough experimental environment of pp collisions at a centre-of-mass energy sqrt(s)=14TeV and luminosities of up to 10^34 cm^-2 s^-1, one of the experimental challenges at the LHC is the triggering of interesting events. In the ATLAS experiment a three-level trigger system is foreseen for this purpose. The first-level trigger is implemented in custom hardware and has been designed to reduce the data rate from the initial bunch-crossing rate of 40 MHz to around 75 kHz. Its event selection is based on information from the calorimeters and dedicated muon detectors. This article gives an overview over the full first-level trigger system including the Calorimeter Trigger, the Muon Trigger and the Central Trigger Processor. In addition, recent results are reported that have been obtained from test-beam studies performed at CERN where the full first-level trigger chain was established successfully for the first time and used to trigger the read-out of up to nine ATLAS sub-detector systems. Due to the huge interaction rates and the tough experimental environment of pp collisions at a centre-of-mass energy sqrt(s)=14TeV and luminosities of up to 10^34 cm^-2 s^-1, one of the experimental challenges at the LHC is the triggering of interesting events. In the ATLAS experiment a three-level trigger system is foreseen for this purpose. The first-level trigger is implemented in custom hardware and has been designed to reduce the data rate from the initial bunch-crossing rate of 40 MHz to around 75 kHz. Its event selection is based on information from the calorimeters and dedicated muon detectors. This article gives an overview over the full first-level trigger system including the Calorimeter Trigger, the Muon Trigger and the Central Trigger Processor. In addition, recent results are reported that have been obtained from test-beam studies performed at CERN where the full first-level trigger chain was established successfully for the first time and used to trigger the read-out of up to nine ATLAS sub-detector systems.

TPF-I has set for itself a host of challenging technical milestones along its path to demonstrating the feasibility of infrared nulling for planet detection Progress in each of these areas of technical development will be reviewed as well as progress in meeting the overarching technical milestones.

Infrared interferometric nulling is a promising technology for exoplanet detection. Nulling research for the Terrestrial Planet Finder Interferometer has been exploring a variety of interferometer architectures at the Jet Propulsion Laboratory (JPL).

Genomic instability in cancer is frequently described as being either chromosomal instability or microsatellite instability, although when events within chromosomes are monitored, extensive intrachromosomal instability is also found. Spectral karyotyping was used to visualize how extensively genomic instability gives rise to intratumor genomic heterogeneity in sporadic colorectal carcinomas. Two factors were then examined which might relate to intrachromosomal instability in colorectal cancers: the presence of the glutathione transferase-Ml gene to detoxify potential carcinogens, and the presence of activated ras which has been associated with chromosomal instability when first expressed. Intrachromosomal genomic instability was previously determined by inter-(simple sequence repeat) PCR (inter-SSR PCR) and by fractional allelic loss rate for 348 markers. GSTM1 status was determined for each of 49 tumors through use of specific PCR, and 28 of the tumors showed the GSTM1 null genotype. A significant association was found between GSTMl-null status and elevated inter-(simple sequence repeat) PCR instability. In contrast, no association was found with fractional allelic loss rate. The first exons of the K-ras and H-ras oncogenes were sequenced in 72 colorectal cancers; 19 of the tumors had a mutation in codon 12 of the K-ras gene (24.5%), but no H-ras mutations were found. A weak correlation (p=0.10) was observed between mutant K-ras and inter-(simple sequence repeat) PCR genomic instability, and no association existed with fractional allelic loss rate.

Wolbachia are widespread cytoplasmically inherited bacteria that induce various reproductive alterations in host arthropods, including cytoplasmic incompatibility (CI), an incompatibility between sperm and egg that typically results in embryonic death. CI has been invoked as a possible mechanism for reproductive isolation and speciation in arthropods, by restricting gene flow and promoting maintenance (and evolution) of genetic divergence between populations. Here we investigate patterns of Wolbachia infection and nuclear and mitochondrial differentiation in geographical populations of the birdnest blowfly Protocalliphora sialia . Blowflies in western North America are infected with two A-group Wolbachia , with some individuals singly and others doubly infected. Individuals in eastern North America mostly show single infections with a B-group Wolbachia. Populations in the Midwest are polymorphic for infections and show A- or B-group infection. There is a low level of mitochondrial divergence and perfect concordance of mitochondrial haplotype with infection type, suggesting that two Wolbachia -associated selective sweeps of the mitochondrion have occurred in this species. Amplified fragment length polymorphism analysis of nuclear genetic variation shows genetic differentiation between the eastern–Midwestern and western populations. Both Midwestern and eastern flies infected with A- Wolbachia show eastern nuclear genetic profiles. Current results therefore suggest that Wolbachia has not acted as a major barrier to gene flow between western and eastern–Midwestern populations, although some genetic differentiation between A- Wolbachia infected and B- Wolbachia infected individuals in eastern–Midwestern populations cannot be ruled out.

The StarLight mission aimed to place the first formation flying optical interferometer into space in year 2006. Utilizing two spacecraft to form a long baseline Michelson interferometer, it would measure white light fringes on a number of partially resolved stars of magnitudes >5 in the wavelength range 600 to 1000 nm. The interferometer baseline is variable between 30 and 125 m, and also has a fixed 1.3 m mode. The spacecraft are flown in a parabolic geometry which requires an optical delay line to build up more than 14 m of delay on one arm of the interferometer. To obtain high fringe visibility, starlight wavefront, pointing and intensity must be preserved through 22 reflections from mirrors and beamsplitters. The alignment of a total of 27 optics is maintained through careful thermal design and the use of two actuated mirrors on each arm. This paper describes the optical layout, including the beam combiner design which allows star tracking, optical system alignment and fringe formation on a single CCD. The effects of diffraction of the starlight transferred from a distant spacecraft and from optical surface imperfections are modeled. Other contributors to the visibility budget and the resulting variation of fringe visibility across the focal plane are discussed.

Wolbachia are widely distributed intracellular bacteria that cause a number of reproductive alterations in their eukaryotic hosts. Such alterations include the induction of parthenogenesis, feminization, cytoplasmic incompatibility, and male killing [1–11]. These important bacteria may play a role in rapid speciation in insects [12–14], and there is growing interest in their potential uses as tools for biological control and genetic manipulation of pests and disease vectors [15–16]. Here, we show recombination in the Wolbachia outer surface protein gene (wsp) between strains of Wolbachia. In addition, we find a possible ecological context for this recombination. Evidence indicates either genetic exchange between Wolbachia in a parasitoid wasp and in the fly that it parasitizes or horizontal transfer of Wolbachia between the parasitoid and the fly, followed by a recombination event. Results have important implications for the evolution of these bacteria and the potential use of Wolbachia in biological control.

Psychovisual examination methods detect macular changes better and more subtly then hitherto commonly used examination methods, in particular in dynamic investigations. The authors used this method in a series of investigations of diabetes, glaucoma and haemodialysis. The group is formed by 19 eyes of 16 patients with a first attack of central serous chorioretinopathy. Two thirds of the patients were treated by conservative methods, one third by photocoagulation with an argon laser. The observation period was 3 months to 13 years, the mean being 3.5 years. The control group was formed by a group of healthy subjects of corresponding age. The authors proved a statistically significant (5%) reduction of the contrast sensitivity at medium spatial frequencies (6 and 12 c/dg) in patients with one or several attacks of CSCHR. Statistically significant deterioration of colour discrimination (5%) was proved in patients with one attack of CSCHR in 20% of the patients. In patients with two or more attacks of the disease the authors recorded a statistically significant deterioration of colour discrimination (1%) in 44% of the patients. They did not reveal, using psychovisual examination methods, statistically significant differences between groups of patients treated conservatively or by laser. In all cases of impaired colour discrimination a disorder in the blue-yellow region was involved, i.e. in the region of retinal receptors.

The micro-arcsecond metrology testbed (MAM) is a high- precision long baseline interferometer inside a vibration- isolated vacuum tank. The instrument consists of an artificial star, a laser metrology system, and a single- baseline interferometer with a 1.8m baseline and a 5cm clear aperture. MAM's purpose is to demonstrate that the astrometric error budget specified for the Space Interferometry Mission can be met.

The Micro Arcsecond Metrology Testbed (MAM) is a laboratory- based, long baseline, white-light interferometer inside a vibration-isolated vacuum tank. The single baseline, high precision interferometer will be able to observe a translating, artificial star at a distance of 10.74 meters with 5 μ as accuracy. The MAM testbed consists of an artificial star, laser metrology and a high precision interferometer. This paper addresses the design and characteristics of the interferometer. The interferometer functions include both angle- and optical-path tracking. The optics are arranged to from dispersed fringes in a channeled spectrum on a charge coupled device and a true white-light fringe on an avalanche photodiode, while at the same time producing guide spots for angle tracking.

This paper describes the design and performance of a brassboard astrometric beam combiner. The beam combiner was developed as part of the JPL Interferometry Technology Program . The purpose of this program is to test out design concepts in hardware that will eventually be used for the Space Interferometry Mission. The label brassboard implies that the beam combiner is flight-like in terms of fit and function. The beam combiner met its design performance except for fringe visibility. Although it has not been environmentally tested as an assembly, the beam combiner was designed to survive the appropriate thermal and vibration tests.

Background: Venous thromboembolism represents the third cause of cardiovascular disease after coronary artery disease and stroke with remarkable complications and high recurrence rate. Up to 50% of the new cases of venous thromboembolism are idiopathic, and patients with this condition require special care and follow up. Thrombophilic factors have a prevalence of 25 to 50% in patients with unprovoked forms of thromboembolism. Objectives: As there are not clear statistics regarding this problem in Romania, the aim of the study was to determine the prevalence of idiopathic venous thromboembolism in a group of patients with venous thromboembolism, the frequency of thrombophilia and to study the risk factors which action simultaneously. Methods: The study was performed in two emergency hospitals from Bucharest, Romania on patients with venous thromboembolism. CT scans were used to confirm pulmonary embolism and venous ultrasonography to confirm venous thrombosis. In the absence of trigger factors patients were tested for thrombophilia. Results: 176 patients were included. 112 cases (63.64%) were unprovoked (idiopathic) and only 64 (36.36%) were provoked (secondary). Idiopathic venous thromboembolism was more frequent in males, the differences between sexes being statistically significant (p

In 14 patients (7 men and 7 women), mean age 48 and 50 years resp. with chronic renal failure, having regular dialyzation treatment for more than 10 years (2 patients more than 20 years) the authors made ophthalmological and psychophysiological examinations in order to assess complications after prolonged dialysis. In three patients dialysis was discontinued while a graft was functional. In addition to known complications, calcification of the conjunctiva, osmotic cataract and retinal changes and changes of the optic disc the authors detected also changes of the visual field, contrast sensitivity and colour differentiation. They revealed changes of contrast differentiation in all spatial frequencies with a maximum in medium and upper frequencies. They revealed in more than 60% disorders of colour differentiation with a maximum in the blue-yellow and blue area of the spectrum. Ophthalmic complications the frequency of which is declining only rare by endanger the function of the eye.

The authors investigated a group of 42 patients (84 eyes) with primary glaucoma of the open angle and with glaucoma of a low tension. In addition to the basic examination they applied in all patients fluorescent angiography focused on the papilla of the optic nerve, static computer threshold perimetry using a Humphrey Field Analyzer, strategy 30-2, examination of the colour sense (Farnsworth-Munsell 100 HUE test and the desaturated HUE test with computer analysis) and examination of contrast sensitivity by means of the Cambridge low contrast test. They describe the results in the initial stage of an at least 5-year study. In patients aged 41-50 years (n = 10) they found small paracentral scotomas in the visual field in 90% and arcuate scotomas in 10%, minor absolute defects of filling of the papilla in 85%, in 15% only relative defects. In patients aged 51-60 years (n = 15) they revealed acute scotomas in 73% and marked quadrant losses in 27%. Changes in the fluoroangiogram were more marked than in the former groups. In patients aged 61-71 years (n = 15) the changes were analogous. Defects of colour sense of the blue-yellow area were recorded in 63 eyes. Changes of the colour sense and absolute defects of filling in fluorescent angiography correlated with the degree and site of affection of the visual field and the patient's age in primary open angle glaucoma. Conversely, in glaucoma with normal tension the values of colour sense remained normal even when the visual field was affected.

Sepsis was induced in male rats by injections of live Escherichia coli No. 4 (or E. coli No. 3) and Bacteroides fragilis organisms into a preformed subcutaneous abscess. Body weight, food and water intake, and cardiac output were measured daily. After 1, 2, or 3 weeks, animals were sacrificed, and blood, liver, and muscle were collected for measurements of plasma glucose and carnitine, mitochondrial respiratory activity, mitochondrial cytochrome concentrations, and tissue adenine nucleotides. Compared with sham controls, no significant differences were found in state 3 respiratory activities of liver mitochondria isolated from rats with moderate (no weight loss, cardiac output increased to 150% of control) or severe (0.5% weight loss/day, cardiac output increased to 200% of control) sepsis at any time. After 1 week of severe, but not moderate, sepsis, pyruvate-supported respiration in muscle mitochondria was significantly decreased, while branched-chain ketoacid and beta-hydroxybutyrate-supported respiration remained unchanged. After 2 weeks of severe, but not moderate, sepsis, beta-hydroxybutyrate and branched-chain ketoacid oxidation increased severalfold; pyruvate utilization remained depressed. Severe or moderate sepsis did not uncouple mitochondrial respiration at any time. Total muscle carnitine concentration was significantly decreased after long-term but not short-term severe sepsis. Severe short-term sepsis caused a significant increase in liver short-chain acyl and total carnitines. Muscle energy charge was unaltered by either moderate or severe sepsis. These results represent the first demonstration of sepsis-induced fuel shifts at the mitochondrial level in muscle: Severe hyperdynamic sepsis is characterized by the reduced ability of muscle mitochondria to utilize pyruvate with a simultaneous increase in branched-chain ketoacid and ketone body utilization. These changes were not observed in liver mitochondria.

The authors examined 41 eyes of 22 compensated type I diabetics 1 - 2 years after laser photocoagulation, using an automatic static perimeter Peritest. One fifth of the investigated patients had marked changes - DR20. The patients are not aware of the diminution of the visual field. Even the most extensive diminution of the visual field in this group did not restrict the ability to drive motor vehicles.