Molecular Characterization of Mycoplasma pneumoniae Isolates in the United States from 2012 to 2018.

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. There are limited data in the United States on the molecular epidemiological characteristics of M. pneumoniae We collected 446 M. pneumoniae-positive specimens from 9 states between August 2012 and October 2018. Culture, antimicrobial susceptibility testing, P1 subtyping, and multilocus VNTR (variable-number tandem repeats) analysis (MLVA) were performed to characterize the isolates. Macrolide-resistant M. pneumoniae (MRMp) was detected in 37 (8.3%) specimens. P1 subtype 2 (P1-2) was the predominant P1 subtype (59.8%). P1 subtype distribution did not change significantly chronologically or geographically. The macrolide resistance rate in P1 subtype 1 (P1-1) samples was significantly higher than that in P1-2 (12.9% versus 5.5%). Six P1-2 variants were identified, including two novel types, and variant 2c was predominant (64.6%). P1-2 variants were distributed significantly differently among geographic regions. Classical P1-2 was more frequent in lower respiratory tract specimens and had longer p1 trinucleotide repeats. Classical P1-2 was most common in MRMp (35.7%), while variant 2c was most common in macrolide-susceptible M. pneumoniae (67.5%). Fifteen MLVA types were identified; 3-5-6-2 (41.7%), 4-5-7-2 (35.3%), and 3-6-6-2 (16.6%) were the major types, and four MLVA clusters were delineated. The distribution of MLVA types varied significantly over time and geographic location. The predominant MLVA type switched from 4-5-7-2 to 3-5-6-2 in 2015. MLVA type was associated with P1 subtypes and P1-2 variant types but not with macrolide resistance. To investigate the M. pneumoniae genotype shift and its impact on clinical presentations, additional surveillance programs targeting more diverse populations and prolonged sampling times are required.

Objective quantification of vitreous haze on optical coherence tomography scans: no evidence for relationship between uveitis and inflammation in multiple sclerosis.

BACKGROUND AND PURPOSE: The occurrence of intermediate uveitis, which is characterized by the presence of vitreous haze (VH), in patients with multiple sclerosis (MS) may be a sign of coexistent inflammatory central nervous system (CNS) disease activity. Using an automated algorithm to quantify VH on optical coherence tomography (OCT) scans, the aim was to investigate whether VH in MS patients is associated with signs of inflammatory CNS disease activity. METHODS: Vitreous haze was quantified on OCT macular volume scans of 290 MS patients and 85 healthy controls (HCs). The relationship between VH and clinical, retinal OCT and magnetic resonance imaging parameters of inflammatory disease activity was investigated using generalized estimating equations. RESULTS: Mean VH scores did not differ between patients and HCs (P = 0.629). Six patients (2.1%) showed values higher than the highest of the controls by HCs. VH scores did not differ between the different disease types or between eyes with and without a history of optic neuritis (P = 0.132). VH was not associated with inner nuclear layer volume on OCT (P = 0.233), cerebral T2 lesion load on magnetic resonance imaging (P = 0.416) or the development of new relapses (P = 0.205). CONCLUSION: In this study, OCT-based automated VH estimation did not detect increased vitreous inflammation in MS patients compared to HCs and did not find an association with CNS inflammatory burden.

Psychological, social and everyday visual impact of diabetic macular oedema and diabetic retinopathy: a systematic review.

AIMS: To synthesize the evidence on the impact of diabetic retinopathy and diabetic macular oedema from the patient perspective. METHODS: A systematic literature review was conducted using MEDLINE Complete, PsycINFO, EMBASE and AMED. We included articles investigating the impact of the condition on quality of life, symptoms, visual functioning, activities of daily living, well-being, social functioning, and financial status. The studies evaluated were observational, including cross-sectional, prospective cohort and retrospective cohort designs. Outcome data were extracted and synthesized. RESULTS: Searches yielded 5114 publications. After screening, 85 studies were included, measuring the following outcomes: visual functioning (n=46); quality of life (n=22); well-being (n=16); functional status (n=5); work (n=4); and visual task performance (n=2). Diabetic retinopathy has a considerable impact on visual functioning and this is greater in people with greater disease severity. Diabetic retinopathy significantly limits activities including working, driving, walking and reading, and has the potential to have a negative impact on psychological well-being. CONCLUSIONS: Diabetic retinopathy is associated with poor self-reported visual functioning, well-being, and health-related quality of life. Ability to perform basic everyday tasks appears to diminish with disease severity. Some studies suggest impaired mobility and problems with work, but there are gaps in this evidence.

Macrolide-Resistant Mycoplasma pneumoniae in the United States as Determined from a National Surveillance Program.

There are sparse data to indicate the extent that macrolide-resistant Mycoplasma pneumoniae (MRMp) occurs in the United States or its clinical significance. Between 2015 and 2018, hospitals in 8 states collected and stored respiratory specimens that tested positive for M. pneumoniae and sent them to the University of Alabama at Birmingham, where real-time PCR was performed for detection of 23S rRNA mutations known to confer macrolide resistance. MRMp was detected in 27 of 360 specimens (7.5%). MRMp prevalence was significantly higher in the South and East (18.3%) than in the West (2.1%). A2063G was the predominant 23S rRNA mutation detected. MICs for macrolide-susceptible M. pneumoniae (MSMp) were ≤0.008 µg/ml, whereas MICs for MRMp were 16 to 32 µg/ml. Patients with MRMp infection were more likely to have a history of immunodeficiency or malignancy. Otherwise, there were no other significant differences in the clinical features between patients infected with MRMp and those infected with MSMp, nor were there any differences in radiographic findings, hospitalization rates, viral coinfections, the mean duration of antimicrobial treatment, or clinical outcomes. There was no significant change in MRMp incidence over time or according to age, sex, race/ethnicity, or status as an inpatient or an outpatient. Patients with MRMp were more likely to have received a macrolide prior to presentation, and their treatment was more likely to have been changed to a fluoroquinolone after presentation. This is the first national surveillance program for M. pneumoniae in the United States. Additional surveillance is needed to assess the clinical significance of MRMp and to monitor changes in MRMp prevalence.

Revealing Color Forces with Transverse Polarized Electron Scattering.

The Spin Asymmetries of the Nucleon Experiment measured two double spin asymmetries using a polarized proton target and polarized electron beam at two beam energies, 4.7 and 5.9 GeV. A large-acceptance open-configuration detector package identified scattered electrons at 40° and covered a wide range in Bjorken x (0.3

In Vitro Activities of the Benzoquinolizine Fluoroquinolone Levonadifloxacin (WCK 771) and Other Antimicrobial Agents against Mycoplasmas and Ureaplasmas in Humans, Including Isolates with Defined Resistance Mechanisms.

Levonadifloxacin (WCK 771) was evaluated against 68 type strains and clinical isolates of Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma spp. in comparison with moxifloxacin, levofloxacin, tetracycline, and azithromycin or clindamycin. Levonadifloxacin MICs were ≤0.5 µg/ml for M. genitalium MIC90s were 1 µg/ml for M. hominis, 0.125 µg/ml for M. pneumoniae, and 2 µg/ml for Ureaplasma spp. Levonadifloxacin merits further study for treating infections caused by these organisms.

Optimizing OCT acquisition parameters for assessments of vitreous haze for application in uveitis.

Detection and evaluation of inflammatory activity in uveitis is essential to the management of the condition, and yet continues to be largely dependent on subjective clinical measures. Optical coherence tomography (OCT) measurement of vitreous activity is an alternative to clinical vitreous haze scoring and has passed a number of early validation studies. In this study we aimed to evaluate the impact of 'operator factors' on the variability of the technique as part of the validation process, and to help evaluate its suitability for 'real world' use. Vitreous haze index was calculated as a ratio between the reflectivity of the vitreous and of the outer retina in each scan. Different scanning conditions were tested and their effect on the measurement is reported. Our results show that the 'quantitative imaging' technique of OCT-measured vitreous activity had good reliability in normal subjects under a range of 'real world' conditions, such as when the operator changes the averaging value. The technique was however vulnerable to highly inaccurate focussing or abnormal downward displacement of the image. OCT-based quantification of vitreous activity is a promising alternative to current subjective clinical estimates, with sufficient 'tolerance' to be used in routine clinical practice as well as clinical trials.

A view on glaucoma--are we seeing it clearly?

Successful clinical management of glaucoma should not simply be about control of intraocular pressure, but must equate to correct decisions about intensifying treatment when patients are at risk of developing 'visual disability'. Yet little is known about what visual field defects, at different stages of glaucoma, specifically affect patients' abilities to perform everyday visual tasks. One way to do this is to measure patient performance in tasks in a lab setting. Another way is to ask patients themselves. The latter can be revealing and demystify views about how patients perceive the world. This short commentary highlights some of the current research in this area.

Are rates of vision loss in patients in English glaucoma clinics slowing down over time? Trends from a decade of data.

PURPOSE: To examine changes in rates of visual field (VF) progression in patients attending a sample of glaucoma clinics in England between 1999 and 2012. METHODS: An archive of 473 252 Humphrey VFs recorded across the UK was retrospectively examined. Distribution of rates recorded in the first half of the decade was compared with the second. The relationship between age and severity of MD loss at baseline with rates of loss and frequency of testing was examined. RESULTS: VF series from 18 926 eyes were analysed. Median rate of MD loss for the period before and after 2003 was -0.11 and -0.06 dB/year, respectively, but the proportion of eyes with medium or fast rates of MD loss remained constant. Median rate of MD loss in older (>70 years) eyes was faster than that observed in younger (<60 years) eyes (-0.21 compared with -0.01 dB/year). Median rate of loss did not vary with severity of MD loss at baseline. Frequency of testing, typically carried out annually, did not vary by age, rate of loss or disease severity. CONCLUSIONS: VFs of eyes treated in the first half of the decade deteriorated more rapidly than those in the second half. Several factors might explain these differences but average effects were small and there was no reduction in the proportion of rapidly progressing eyes over the decade. Older age and, to a lesser extent, worse VF damage at diagnosis are indicators for faster VF loss in clinics, but frequency of VF testing was similar for all patients.

Longitudinal target-spin asymmetries for deeply virtual compton scattering.

A measurement of the electroproduction of photons off protons in the deeply inelastic regime was performed at Jefferson Lab using a nearly 6 GeV electron beam, a longitudinally polarized proton target, and the CEBAF Large Acceptance Spectrometer. Target-spin asymmetries for ep→e^{'}p^{'}γ events, which arise from the interference of the deeply virtual Compton scattering and the Bethe-Heitler processes, were extracted over the widest kinematics in Q^{2}, x_{B}, t, and ϕ, for 166 four-dimensional bins. In the framework of generalized parton distributions, at leading twist the t dependence of these asymmetries provides insight into the spatial distribution of the axial charge of the proton, which appears to be concentrated in its center. These results also bring important and necessary constraints for the existing parametrizations of chiral-even generalized parton distributions.

Portsmouth visual field database: an audit of glaucoma progression.

AIM: To explore visual field (VF) progression in a cohort of secondary care-treated glaucoma and ocular hypertensive (OHT) patients. METHODS: We extracted VFs from our database drawn from our normal clinical practice. VF series from 4177 eyes from 2208 patients who had five or more VFs were obtained, the 'better' eye was selected and the rate of VF progression was calculated using mean deviation (MD) data. RESULTS: The median rate of progression for the whole sample was -0.1 dB/year (interquartile range (IQR) -4 to 0 dB/year) over a median of 6.7 years (IQR 4.9-8.7). Of 2208 patients, 477 (21.2%) progressed at > -0.5 dB/year; 46 (2.1%) progressed at >-2.0 dB/year. Of those with a 'final MD' of worse than -10 dB (N=244) in their better eye; 14.0% were 'fast progressors' (>-2 dB/year), 33.7% 'moderate progressors' (-1 to -2 dB/year), and 28.8% 'slow progressors' (-0.3 dB to -1 dB/year). Of those with 'initial MD' better than -3 dB and those with worse than -3 dB, 31/1679 (1.8%) and 213/529 (40.3%) respectively, had a final MD of worse than -10 dB. CONCLUSION: Fast progressors, while important, are relatively rare. Moderate and slow progressors make up the majority of the progressing population within this data set. The risk of significant visual loss is much higher in those with initial damage. With increasing life expectancy, moderate and slow progressors may become increasingly clinically important.

Surveillance for ocular hypertension: an evidence synthesis and economic evaluation.

OBJECTIVES: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways. DESIGN: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model. SETTING: Primary and secondary care. PARTICIPANTS: Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences). INTERVENTIONS: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community. MAIN OUTCOME MEASURES: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs). RESULTS: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence. LIMITATIONS: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates. CONCLUSIONS: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment. FUNDING: The National Institute for Health Research Health Technology Assessment Programme.

Probing quark-gluon interactions with transverse polarized scattering.

We have extracted QCD matrix elements from our data on doubly polarized inelastic scattering of electrons on nuclei. We find the higher twist matrix element d˜2, which arises strictly from quark-gluon interactions, to be unambiguously nonzero. The data also reveal an isospin dependence of higher twist effects if we assume that the Burkhardt-Cottingham sum rule is valid. The fundamental Bjorken sum rule obtained from the a0 matrix element is satisfied at our low momentum transfer.

Development of a competency framework for optometrists with a specialist interest in glaucoma.

PURPOSE: To develop a competency framework, using a modified Delphi methodology, for optometrists with a specialist interest in glaucoma, which would provide a basis for training and accreditation. METHODS: A modified iterative Delphi technique was used using a 16-member panel consisting almost exclusively of sub-specialist optometrists and ophthalmologists. The first round involved scoring the relevance of a draft series of competencies using a 9-point Likert scale with a free-text option to modify any competency or suggest additional competencies. The revised framework was subjected to a second round of scoring and free-text comment. The Delphi process was followed by a face-to-face structured workshop to debate and agree the final framework. The version of the framework agreed at the workshop was sent out for a 4-month period of external stakeholder validation. RESULTS: There was a 100% response to round 1 and an 94% response to round 2. All panel members attended the workshop. The final version of the competency framework was validated by a subsequent stakeholder consultation and contained 19 competencies for the diagnosis of glaucoma and 7 further competencies for monitoring and treatment. CONCLUSIONS: Application of a consensus methodology consisting of a modified Delphi technique allowed the development of a competency framework for glaucoma specialisation by optometrists. This will help to shape the development of a speciality curriculum and potentially could be adapted for other healthcare professionals.

Measurement of single- and double-spin asymmetries in deep inelastic pion electroproduction with a longitudinally polarized target.

We report the first measurement of the transverse momentum dependence of double-spin asymmetries in semi-inclusive production of pions in deep-inelastic scattering off the longitudinally polarized proton. Data have been obtained using a polarized electron beam of 5.7 GeV with the CLAS detector at the Jefferson Lab (JLab). Modulations of single spin asymmetries over the azimuthal angle between lepton scattering and hadron production planes ϕ have been measured over a wide kinematic range in Bjorken x and virtual photon squared four-momentum Q2. A significant nonzero sin2ϕ single spin asymmetry was observed for the first time indicating strong spin-orbit correlations for transversely polarized quarks in the longitudinally polarized proton.

Precise measurement of the neutron magnetic form factor G(M)n in the few-GeV2 region.

The neutron elastic magnetic form factor was extracted from quasielastic electron scattering on deuterium over the range Q;{2}=1.0-4.8 GeV2 with the CLAS detector at Jefferson Lab. High precision was achieved with a ratio technique and a simultaneous in situ calibration of the neutron detection efficiency. Neutrons were detected with electromagnetic calorimeters and time-of-flight scintillators at two beam energies. The dipole parametrization gives a good description of the data.

Measurement of direct f0(980) photoproduction on the proton.

We report on the results of the first measurement of exclusive f_{0}(980) meson photoproduction on protons for E_{gamma}=3.0-3.8 GeV and -t=0.4-1.0 GeV2. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility. The resonance was detected via its decay in the pi;{+}pi;{-} channel by performing a partial wave analysis of the reaction gammap-->ppi;{+}pi;{-}. Clear evidence of the f_{0}(980) meson was found in the interference between P and S waves at M_{pi;{+}pi;{-}} approximately 1 GeV. The S-wave differential cross section integrated in the mass range of the f_{0}(980) was found to be a factor of about 50 smaller than the cross section for the rho meson. This is the first time the f_{0}(980) meson has been measured in a photoproduction experiment.

Search for the photoexcitation of exotic mesons in the pi+pi+pi- system.

A search for exotic mesons in the pi;{+}pi;{+}pi;{-} system photoproduced by the charge exchange reaction gammap-->pi;{+}pi;{+}pi;{-}(n) was carried out by the CLAS Collaboration at Jefferson Lab. A tagged-photon beam with energies in the 4.8 to 5.4 GeV range, produced through bremsstrahlung from a 5.744 GeV electron beam, was incident on a liquid-hydrogen target. A partial wave analysis was performed on a sample of 83 000 events, the highest such statistics to date in this reaction at these energies. The main objective of this study was to look for the photoproduction of an exotic J;{PC}=1;{-+} resonant state in the 1 to 2 GeV mass range. Our partial wave analysis shows production of the a_{2}(1320) and the pi_{2}(1670) mesons, but no evidence for the a_{1}(1260), nor the pi_{1}(1600) exotic state at the expected levels. An upper limit of 13.5 nb is determined for the exotic pi_{1}(1600) cross section, less than 2% of the a_{2}(1320) production.