Pool-BCGA: a parallelised generation-free genetic algorithm for the ab initio global optimisation of nanoalloy clusters.

The Birmingham cluster genetic algorithm is a package that performs global optimisations for homo- and bimetallic clusters based on either first principles methods or empirical potentials. Here, we present a new parallel implementation of the code which employs a pool strategy in order to eliminate sequential steps and significantly improve performance. The new approach meets all requirements of an evolutionary algorithm and contains the main features of the previous implementation. The performance of the pool genetic algorithm is tested using the Gupta potential for the global optimisation of the Au10Pd10 cluster, which demonstrates the high efficiency of the method. The new implementation is also used for the global optimisation of the Au10 and Au20 clusters directly at the density functional theory level.

Charge-induced dipole vs. relativistically enhanced covalent interactions in Ar-tagged Au-Ag tetramers and pentamers.

Vibrational spectra of Au(n)Ag(m)(+)⋅Ar(k) (n + m = 4, 5; k = 1-4) clusters are determined by far-infrared resonant multiple photon dissociation spectroscopy in the range ν̃=100-250 cm(-1). The experimental spectra are assigned using density functional theory for geometries obtained by the Birmingham cluster genetic algorithm. Putative global minimum candidates of the Ar complexes are generated by adding Ar atoms to the Au(n)Ag(m)(+) low energy isomers and subsequent local optimization. Differential Ar binding energies indicate exceptionally strong Au-Ar bonds in Au-rich clusters, leading to fundamental changes to the IR spectra. The stronger Ar binding is attributed to a relativistically enhanced covalent character of the Au-Ar bond, while in Au-rich species charge-induced dipole interactions overcompensate the relativistic affinity to Au. Moreover, not only the absolute composition but also the topologies are essential in the description of Ar binding to a certain cluster.

Three-dimensional atomic-scale structure of size-selected gold nanoclusters.

An unambiguous determination of the three-dimensional structure of nanoparticles is challenging. Electron tomography requires a series of images taken for many different specimen orientations. This approach is ideal for stable and stationary structures. But ultrasmall nanoparticles are intrinsically structurally unstable and may interact with the incident electron beam, constraining the electron beam density that can be used and the duration of the observation. Here we use aberration-corrected scanning transmission electron microscopy, coupled with simple imaging simulation, to determine with atomic resolution the size, three-dimensional shape, orientation and atomic arrangement of size-selected gold nanoclusters that are preformed in the gas phase and soft-landed on an amorphous carbon substrate. The structures of gold nanoclusters containing 3096 atoms can be identified with either Ino-decahedral, cuboctahedral or icosahedral geometries. Comparison with theoretical modelling of the system suggests that the structures are consistent with energetic considerations. The discovery that nanoscale gold particles function as active and selective catalysts for a variety of important chemical reactions has provoked much research interest in recent years. We believe that the detailed structure information we provide will help to unravel the role of these nanoclusters in size- and structure-specific catalytic reactions. We note that the technique will be of use in investigations of other supported ultrasmall metal cluster systems.

Communication: Global minimum search of Ag10⁺ with molecular beam optical spectroscopy.

The present study is focused on the optical properties of the Ag10⁺ cluster in the photon energy range ℏω = 1.9-4.4 eV. Absorption spectra are recorded by longitudinal molecular beam depletion spectroscopy and compared to optical response calculations using time-dependent density functional theory. Several cluster isomers obtained by the new pool-based parallel implementation of the Birmingham Cluster Genetic Algorithm, coupled with density functional theory, are used in excited state calculations. The experimental observations, together with additional simulations of ion mobilities for the several geometries found within this work using different models, clearly identify the ground state isomer of Ag10⁺ to be composed of two orthogonal interpenetrating pentagonal bipyramids, having overall D(2d) symmetry.

Optical and electronic properties of mixed Ag-Au tetramer cations.

We present experimental and theoretical studies of the optical response of mixed Ag(n)Au(+)(4-n) (n=1-3) clusters in the photon energy range ℏω = 1.9-3.5 eV. Absorption spectra are recorded by a newly built longitudinal molecular beam depletion spectroscopy apparatus providing lower limits to absolute photodissociation cross sections. The experimental data are compared to optical response calculations in the framework of long-range corrected time-dependent density functional theory with initial cluster geometries obtained by the unbiased Birmingham Cluster Genetic Algorithm coupled with density functional theory. Experiments and excited state calculations shed light on the structural and electronic properties of the mixed Ag-Au tetramer cations.

Influence of spin-orbit effects on structures and dielectric properties of neutral lead clusters.

Combining molecular beam electric deflection experiments and global optimization techniques has proven to be a powerful tool for resolving equilibrium structures of neutral metal and semiconductor clusters. Herein, we present electric molecular beam deflection experiments on PbN (N = 7-18) clusters. Promising structures are generated using the unbiased Birmingham Cluster Genetic Algorithm approach based on density functional theory. The structures are further relaxed within the framework of two-component density functional theory taking scalar relativistic and spin orbit effects into account. Quantum chemical results are used to model electric molecular beam deflection profiles based on molecular dynamics calculations. Comparison of measured and simulated beam profiles allows the assignment of equilibrium structures for the most cluster sizes in the examined range for the first time. Neutral lead clusters adopt mainly spherical geometries and resemble the structures of lead cluster cations apart from Pb10. Their growth pattern deviates strongly from the one observed for tin and germanium clusters.

Evaluation of photodissociation spectroscopy as a structure elucidation tool for isolated clusters: a case study of Ag4(+) and Au4(+).

Resolving the structure of clusters in the gas phase often requires the comparison of experimental data to quantum chemical calculations. Herein, we present the variation of a straightforward approach, in which photodissociation spectra of isolated clusters are compared to optical response calculations in order to elucidate cluster structures. Our absorption spectra were measured using a newly built longitudinal beam depletion spectroscopy apparatus and recorded in the photon energy range hω = 1.9-3.5 eV. Cluster geometries were obtained using the unbiased Birmingham Cluster Genetic Algorithm coupled with density functional theory, while the optical response was calculated in the framework of time-dependent density functional theory. Experiments and excited state calculations are in excellent agreement using long-range corrected exchange correlation functionals for both ground and excited state calculations. Our methodology indicates a contribution of Y shaped Au4(+) whereas for Ag4(+) only the ground state isomer has to be considered to explain the experimental absorption spectrum. Our extended methodology shows two nearly degenerate isomers of Au4(+) probably being present in the molecular beam and therefore shows promise for the further structure determination of pure and binary transition-metal clusters.

Configuration of microbially synthesized Pd-Au nanoparticles studied by STEM-based techniques.

Bimetallic Pd-Au particles synthesized using Desulfovibrio desulfuricans bacteria are characterized using scanning transmission electron microscopy (STEM) with a high-angle annular dark field (HAADF) detector combined with energy dispersive x-ray (EDX) silicon drift detector (SDD) elemental mapping and plasmon electron energy-loss spectroscopy (EELS). When combined with EDX, theoretical considerations or EELS, the atomic-number contrast (Z-contrast) provided by HAADF-STEM is effective in characterizing the compositional configuration of the bimetallic nanoparticles. Homogeneous mixing and complex segregations have been found for different particles in this work. The EELS study has also found different behaviours corresponding to surface plasmon resonances in different regions of a single particle due to its heterogeneity and anisotropy. HAADF-STEM tomography has been performed to obtain three-dimensional (3D) visualization of the nanoparticles.

Agreement and reasons for disagreement between photographic and hospital biomicroscopy grading of diabetic retinopathy.

AIMS: To compare agreement level and identify reasons for disagreement between grading of mydriatic digital photographs in a diabetic retinopathy screening service and hospital eye service biomicroscopy grading. METHODS: Structured examination findings leading to automatically calculated National Screening Committee grades recorded on an electronic medical record system in the hospital eye service at the first clinic visit after diabetic retinopathy screening service referral between April 2006 and November 2007 were retrospectively compared with the grade at the screening visit that prompted referral. In cases of disagreement, screening images were reviewed. RESULTS: Data on 452 eyes (226 patients) were analysed. For retinopathy, hospital eye service slit-lamp biomicroscopy grades were: R0 (no diabetic retinopathy) in 63 eyes; R1 (background retinopathy) in 251 eyes; R2 (pre-proliferative) in 129 eyes and R3 (proliferative) in nine eyes. Diabetic retinopathy screening service grades were in agreement in 350 eyes (77.4%), showed a lower grade in 59 eyes and a higher grade in 43. Agreement was moderate (κ=0.60). The most common reason for disagreement was overgrading of R1 by clinicians. Hospital eye service biomicroscopy maculopathy grades were: M0 (no maculopathy) in 366 eyes and M1 (maculopathy) in 86 eyes. Diabetic retinopathy screening service grades were in agreement in 327 eyes (72.3%), showed a lower grading in five eyes and a higher grade in 120 eyes. Agreement was moderate (κ=0.41). The commonest cause for disagreement was clinicians failing to identify fine macular exudates. CONCLUSIONS: This study of routine clinical services demonstrates moderate agreement between non-medical grading of mydriatic digital retinal photography images and hospital slit-lamp biomicroscopy grading of patients referred with diabetic retinopathy. The majority of errors in grading were attributable to errors by hospital doctors, usually in the direction of under-grading which could be a potential source of clinical risk if treatment is delayed.

Cytotoxic T-lymphocyte-associated antigen 4 antibody-induced colitis and its management with infliximab.

Anti-CTLA-4 antibodies are human monoclonal antibodies previously studied in the treatment of metastatic melanoma (MM). CTLA-4 is an inhibitory receptor on cytotoxic T cells, blockade of which will activate T cells allowing them to attack malignant cells. Normal host cells may also be affected, and immune-mediated enterocolitis can occur. This is a prospective observational study on the use of corticosteroids and infliximab in the treatment of patients with immune-mediated colitis secondary to anti-CTLA-4 antibody treatment of MM. Five patients presented with colitis after medication administration. Patients were treated with high-dose corticosteroids for 1 week, but diarrhea did not completely abate in any of them. They were then treated successfully with infliximab. One patient had recurrence of symptoms and responded to repeat treatment with infliximab. Patients who develop immune-mediated colitis after administration of anti-CTLA-4 antibodies have previously been reported to respond to corticosteroids, but in our study, all required treatment with infliximab.

The Royal College of Ophthalmologists' National Ophthalmology Database Study of cataract surgery. Report 5: Clinical outcome and risk factors for posterior capsule rupture and visual acuity loss following cataract surgery in patients aged 90 years and older.

BACKGROUND: Older age is commonly associated with an increased risk of surgical complications and comparatively poor outcomes. PURPOSE: To report cataract surgery outcomes and risk indicators for patients aged 90 years and older. METHODS: Data collected as part of routine cataract care in 34 centres contributing to the United Kingdom Royal College of Ophthalmologists' National Ophthalmology Database (NOD) were analysed. Very elderly people undergoing cataract surgery were profiled in terms of demographics, pre- and postoperative best-measured visual acuity (VA), ocular co-morbidities, intraoperative posterior capsule rupture (PCR) or vitreous loss or both, and risk indicators for operative PCR and adverse VA outcome. RESULTS: 25,856 cataract operations in 19,166 people of 90 years or older between 2000 and 2014 are reported. Preoperative VA was available for 82.4% eyes, being 0.30 LogMAR or better in 21.5%. Postoperative VA was available for 61.8% eyes, being 0.30 LogMAR or better in 74.4%. For those without ocular co-morbidity, postoperative VA was 0.30 LogMAR or better in 84.7%. Various co-morbidities were present in 49% and contributed to an adverse VA outcome. PCR data were available for all operations and occurred in 2.7%. Significant risk indicators for PCR included pseudoexfoliation/phakodonesis, mature cataract, smaller pupil and worse preoperative VA. CONCLUSIONS: Slightly poorer cataract surgery outcome results were noted in patients of 90 years or older, more so in patients with ocular co-morbidity which was highly prevalent. However, surgeons should not be deterred from offering cataract surgery to the very elderly as successful visual rehabilitation remains achievable.

Cataract surgery patient-reported outcome measures: a head-to-head comparison of the psychometric performance and patient acceptability of the Cat-PROM5 and Catquest-9SF self-report questionnaires.

Background Cataract surgery is the most frequently undertaken NHS surgical procedure. Visual acuity (VA) provides a poor indication of visual difficulty in a complex visual world. In the absence of a suitable outcome metric, recent efforts have been directed towards the development of a cataract patient-reported outcome measure (PROM) of sufficient brevity, precision, and responsiveness to be implementable in routine high volume clinical services.Aim To compare and contrast the two most promising candidate PROMs for routine cataract surgery.Method The psychometric performance and patient acceptability of the recently UK developed five-item Cat-PROM5 questionnaire was compared with the English translation of the Swedish nine-item Catquest-9SF using Rasch-based performance metrics and qualitative semistructured interviews.Results Rasch-based performance was assessed in 822 typical NHS cataract surgery patients across four centres in England. Both questionnaires demonstrated good to excellent performance for all metrics assessed, including Person Reliability Indices of 0.90 (Cat-PROM5) and 0.88 (Catquest-9SF), responsiveness to surgery (Cohen's standardized effect size) of 1.45 SD (Cat-PROM5) and 1.47 SD (Catquest-9SF) and they were highly correlated with each other (R=0.85). Qualitative assessments confirmed that both questionnaires were acceptable to patients, including in the presence of ocular comorbidities. Preferences were expressed for the shorter Cat-PROM5, which allowed patients to map their own issues to the questions as opposed to the more restrictive specific scenarios of Catquest-9SF.Conclusion The recently UK developed Cat-PROM5 cataract surgery questionnaire is shorter, with performance and patient acceptability at least as good or better than the previous 'best of class' Catquest-9SF instrument.

Cat-PROM5: a brief psychometrically robust self-report questionnaire instrument for cataract surgery.

PurposeTo develop a short, psychometrically robust and responsive cataract patient reported outcome measure suitable for use in high-volume surgical environments.MethodsA prospective study in which participants completed development versions of questionnaires exploring the quality of their eyesight using items harvested from two existing United Kingdom developed parent questionnaires. Participants were 822 patients awaiting cataract surgery recruited from 4 cataract surgical centres based in the UK. Exclusion criteria were other visually significant comorbidities and age <50 years. An iterative multi-stage process of evaluation using Rasch and factor analyses with sequential item reduction was undertaken.ResultsA definitive item set of just five items delivered performance in accordance with the requirements of the Rasch model: no threshold disordering, no misfitting items, Rasch-based reliability 0.90, person separation 2.98, Cronbach's α 0.89, good targeting of questions to patients with cataract with pre-operative item mean -0.41 logits and absence of significant floor or ceiling effects, minor deviations of item invariance, and confirmed unidimensionality. The test-re-test repeatability intra-class correlation coefficient was 0.89 with excellent responsiveness to surgery, Cohen's d -1.45 SD. Rasch calibration values are provided for Cat-PROM5 users.ConclusionsA psychometrically robust and highly responsive five-item cataract surgery patient reported outcome measure has been developed, which is suitable for use in high-volume cataract surgical services.

Appropriateness of quality standards for meaningful intercentre comparisons of aflibercept service provision for neovascular age-related macular degeneration.

PurposeReal-world data give different information on health-care delivery compared with randomised controlled trials. We aimed to evaluate the appropriateness of possible quality standards for intersite comparisons of outcomes of providing Aflibercept for neovascular age-related macular degeneration (nAMD) in clinical practice.Patients and methodsRetrospective data analysis from an electronic medical record. A consecutive series of treatment-naive patients initiated on aflibercept for nAMD, in the UK from March 2013 to October 2015. Age, visual acuity (VA) at baseline and 1 year, and injection episodes were remotely extracted in an anonymised format.ResultsThe mean baseline VA was 54.3 letters, ranging from 51.3 to 58.1 between different centres, in 5620 eyes taken from 12 centres. Out of these, 3360 were initiated on treatment more than a year before. The percentage with <35 letters at baseline was 19.9-3% and that with >70 letters was 24.8-10.7%. Eyes with ≥70 letters at 1 year ranged from 20.2 to 42.9% and those with <35 ranged from 4.5 to 21.6% across different sites. Injection rates in 1 year varied from 5.5 to 8.6, and data available at 1 year also varied from 82.3 to 46.4%.ConclusionsSignificant variation was found between sites attempting to provide the same therapeutic regime. For fair comparisons between sites, we recommend that both VA measures and process measures, such as injection numbers, retention rates, and discharge policies, are used. More work is required to explain the differences. Such real-world data are not generated in the same way as a randomised clinical trial, and maybe best used to help improve service provision.

Second-year visual acuity outcomes of nAMD patients treated with aflibercept: data analysis from the UK Aflibercept Users Group.

PurposeTo audit the visual acuity (VA) outcomes achieved at the end of year two in 17 UK centres, which followed the year 1 VIEW protocol in year 1, but a variable approach in year 2 for aflibercept for neovascular macular degeneration (nAMD).Patients and methodsRetrospective data analysis, from an electronic medical record, of a consecutive series of treatment-naive nAMD patients who received aflibercept for 2 consecutive years, having followed the VIEW protocol in year one, defined as eyes having received 7 or 8 injections from baseline.ResultsThe mean number of intravitreal injections (IVI)s during year 2 was 3.7 in 1180 eyes (1083 patients). The mean baseline VA of the whole cohort was 56.3 ETDRS letters, improving to 61.3 at 1 year (+5) and 59.1 (+2.8) at the end of year 2. The mean VA letter score at the end of year 2, stratified by number of IVIs into three groups was as follows: group A, 57.3 (gain of +1.7) (44% of eyes (/=6 IVIs)). Even though there were VA gains in the three groups over the 2-years, there was a drop in VA in year one to two. Eyes that received >/=6 IVIs (group C) had a smaller reduction of VA during year 2 than those which received

The UK Neovascular AMD Database Report 3: inter-centre variation in visual acuity outcomes and establishing real-world measures of care.

PurposeInternational variations in visual acuity (VA) outcomes of eyes treated for neovascular age-related macular degeneration (nAMD) are well-documented, but intra-country inter-centre regional variations are not known. These data are important for national quality outcome indicators. We aimed to determine intra-country and inter-centre regional variations in outcomes for treatment of nAMD.Patients and methodsProspective multicentre national database study of 13 UK centres that treated patients according to a set protocol (three loading doses, followed by Pro-Re-Nata retreatment). A total of 5811 treatment naive eyes of 5205 patients received a total of 36 206 ranibizumab injections over 12 months.ResultsMean starting VA between centres varied from 48.9 to 59.9 ETDRS letters. Mean inter-centre VA change from baseline to 12 months varied from +6.9 letters to -0.6 letters (mean of +2.5 letters). The proportion of eyes achieving VA of 70 letters or more varied between 21.9 and 48.7% at 12 months. Median number of injections (visits) at each centre varied from 5 to 8 (9 to 12), with an overall median of 6 (11). Age, starting VA, number of injections, and visits, but not gender were significantly associated with variation in these VA outcomes (P<0.01). Significant variation between centres persisted even after adjusting for these factors.ConclusionThere are modest differences in VA outcomes between centres in the UK. These differences are influenced, but not completely explained, by factors such as patient age, starting VA, number of injections, and visits. These data provide an indication of the VA outcomes that are achievable in real-world settings.

The Royal College of Ophthalmologists' National Ophthalmology Database study of cataract surgery: report 1, visual outcomes and complications.

AIMS: To describe the outcomes of cataract surgery in the United Kingdom. METHODS: Anonymised data on 180 114 eyes from 127 685 patients undergoing cataract surgery between August 2006 and November 2010 were collected prospectively from 28 sites. Outcome measures included intraoperative and postoperative complication rates, and preoperative and postoperative visual acuities. RESULTS: Median age at first eye surgery was 77.1 years, 36.9% cases had ocular co-pathology and 41.0% patients underwent cataract surgery on both eyes. Preoperative visual acuity was 0.30 logMAR or better in 32.0% first eyes and 47.7% second eyes. Postoperative best-measured visual acuity was 0.00 and 0.30 logMAR or better in 50.8 and 94.6% eyes without ocular co-pathology, and 32.5 and 79.9% in eyes with co-pathology. For eyes without co-pathology, postoperative uncorrected distance visual acuity was 0.00 and 0.30 logMAR or better in 27.3 and 80.9% eyes. Posterior capsule rupture or vitreous loss or both occurred in 1.95% cases, and was associated with a 42 times higher risk of retinal detachment surgery within 3 months and an eight times higher risk of endophthalmitis. CONCLUSION: These results provide updated data for the benchmarking of cataract surgery. Visual outcomes, and the rate of posterior capsule rupture or vitreous loss or both appear stable over the past decade.

The Royal College of Ophthalmologists' National Ophthalmology Database Study of cataract surgery: report 2, relationships of axial length with ocular copathology, preoperative visual acuity, and posterior capsule rupture.

PURPOSE: To describe the relationships of axial length with ocular copathology, preoperative visual acuity, and posterior capsule rupture rates in patients undergoing cataract surgery.DesignThe Royal College of Ophthalmologists' National Ophthalmology Database (NOD) study. METHODS: Anonymised data on 180 114 eyes from 127 685 patients undergoing cataract surgery between August 2006 and November 2010 were collected prospectively from 28 sites. Data parameters included: demographics, biometry, ocular copathology, visual acuity measurements, and surgical complications including posterior capsule rupture, or vitreous loss or both (PCR). RESULTS: Consultant surgeons performed a higher proportion of operations on eyes whose axial length were at the extremes. Glaucoma and age related macular degeneration were more common in eyes with shorter axial lengths, whilst previous vitrectomy was associated with longer axial lengths. Eyes with brunescent or white cataracts or amblyopia were more common at both axial length extremes. Preoperative visual acuities were similar for eyes with axial length measurements up to approximately 28 mm and worse for eyes with longer axial length measurements. PCR rates showed little change with axial length (overall mean 1.95%, 95% CI: 1.89 to 2.01%), except for a borderline increase in eyes with axial length <20.0 mm where rates were 3.6% (95% CI: 2.0 to 6.3%). The likelihood of PCR in eyes with axial length <20.0 mm was 1.88 times higher than those of ≥20.0 mm (P=0.0373). CONCLUSION: Rates of ocular comorbidities vary by axial length. PCR rates in eyes with very short or long axial lengths were lower than expected.

Prevalence and incidence of blindness and other degrees of sight impairment in patients treated for neovascular age-related macular degeneration in a well-defined region of the United Kingdom.

AIMS: This study aimed to evaluate the incidence and prevalence of blindness, sight impairment, and other visual acuity (VA) states in patients receiving ranibizumab for neovascular age-related macular degeneration (nAMD) in Gloucestershire. METHODS: Serial VA and injection data for all treatment-naive patients receiving their first intravitreal injections of ranibizumab for nAMD in the Gloucestershire National Health Service Ophthalmology department between 2008 and 2010 were extracted from an electronic medical record system. RESULTS: The prevalence of blindness (VA in the better-seeing eye ≤25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters) at the time of first intravitreal injection was 0.8%, increasing to 3.5% after 3 years. The prevalence of sight impairment (VA in the better-seeing eye 26-39 ETDRS letters) increased from 4.1% at baseline to 5.5% after 3 years. The incidence of initiating ranibizumab treatment for nAMD in people aged ≥50 years in Gloucestershire was 111 people per 100 000 population in 2009, and 97 people in 2010. The incidence of patients meeting the visual criteria for blindness and sight impairment registration from treated nAMD in people aged ≥50 years in Gloucestershire was 3.5 and 9.7 people, respectively per 100 000 population in 2010. CONCLUSION: This is the first real-world study on the incidence and prevalence of eligibility for blindness and sight impairment registration in treated nAMD in the UK based on VA data. The incidence and prevalence of eligibility for certification of blindness or sight impairment in patients treated with ranibizumab for nAMD is low in Gloucestershire, with only 3.6% of the incident population progressing to blindness in 2010.