Supramolecular Self-Assembly as a Tool To Preserve the Electronic Purity of Perylene Diimide Chromophores.

Organic semiconductors are promising for efficient, printable optoelectronics. However, strong excited-state quenching due to uncontrolled aggregation limits their use in devices. We report on the self-assembly of a supramolecular pseudo-cube formed from six perylene diimides (PDIs). The rigid, shape-persistent cage sets the distance and orientation of the PDIs and suppresses intramolecular rotations and vibrations, leading to non-aggregated, monomer-like properties in solution and the solid state, in contrast to the fast fluorescence quenching in the free ligand. The stabilized excited state and electronic purity in the cage enables the observation of delayed fluorescence due to a bright excited multimer, acting as excited-state reservoir in a rare case of benign inter-chromophore interactions in the cage. We show that self-assembly provides a powerful tool for retaining and controlling the electronic properties of chromophores, and to bring molecular electronics devices within reach.

The ONETEP linear-scaling density functional theory program.

We present an overview of the onetep program for linear-scaling density functional theory (DFT) calculations with large basis set (plane-wave) accuracy on parallel computers. The DFT energy is computed from the density matrix, which is constructed from spatially localized orbitals we call Non-orthogonal Generalized Wannier Functions (NGWFs), expressed in terms of periodic sinc (psinc) functions. During the calculation, both the density matrix and the NGWFs are optimized with localization constraints. By taking advantage of localization, onetep is able to perform calculations including thousands of atoms with computational effort, which scales linearly with the number or atoms. The code has a large and diverse range of capabilities, explored in this paper, including different boundary conditions, various exchange-correlation functionals (with and without exact exchange), finite electronic temperature methods for metallic systems, methods for strongly correlated systems, molecular dynamics, vibrational calculations, time-dependent DFT, electronic transport, core loss spectroscopy, implicit solvation, quantum mechanical (QM)/molecular mechanical and QM-in-QM embedding, density of states calculations, distributed multipole analysis, and methods for partitioning charges and interactions between fragments. Calculations with onetep provide unique insights into large and complex systems that require an accurate atomic-level description, ranging from biomolecular to chemical, to materials, and to physical problems, as we show with a small selection of illustrative examples. onetep has always aimed to be at the cutting edge of method and software developments, and it serves as a platform for developing new methods of electronic structure simulation. We therefore conclude by describing some of the challenges and directions for its future developments and applications.

The relationship between meteorological variables and sporadic cases of Legionnaires' disease in residents of England and Wales.

We studied the timing of occurrence of 1676 sporadic, community-acquired cases of Legionnaires' disease in England and Wales between 1993 and 2008, in relation to temperature, relative humidity, rainfall, windspeed and ultraviolet light using a fixed-stratum case-crossover approach. The analysis was conducted using conditional logistic regression, with consideration of appropriate lag periods. There was evidence of an association between the risk of Legionnaires' disease and temperature with an apparently long time lag of 1-9 weeks [odds of disease at 95th vs. 75th centiles: 3·91, 95% confidence interval (CI) 2·06-7·40], and with rainfall at short time lags (of 2-10 days) (odds of disease at 75th vs. 50th centiles: 1·78, 95% CI 1·50-2·13). There was some evidence that the risk of disease in relation to high temperatures was greater at high relative humidities. A higher risk of Legionnaires' disease may be indicated by preceding periods of warmer wetter weather.

Enhancing Conductivity of Silver Nanowire Networks through Surface Engineering Using Bidentate Rigid Ligands.

Solution processable metallic nanomaterials present a convenient way to fabricate conductive structures, which are necessary in all electronic devices. However, they tend to require post-treatments to remove the bulky ligands around them to achieve high conductivity. In this work, we present a method to formulate a post-treatment free conductive silver nanowire ink by controlling the type of ligands around the silver nanowires. We found that bidentate ligands with a rigid molecular structure were effective in improving the conductivity of the silver nanowire networks as they could maximize the number of linkages between neighboring nanowires. In addition, DFT calculations also revealed that ligands with good LUMO to silver energy alignment were more effective. Because of these reasons, fumaric acid was found to be the most effective ligand and achieved a large reduction in sheet resistance of 70% or higher depending on the nanowire network density. The concepts elucidated from this study would also be applicable to other solution processable nanomaterials systems such as quantum dots for photovoltaics or LEDs which also require good charge transport being neighboring nanoparticles.

Efficiently Computing Excitations of Complex Systems: Linear-Scaling Time-Dependent Embedded Mean-Field Theory in Implicit Solvent.

Quantum embedding schemes have the potential to significantly reduce the computational cost of first-principles calculations while maintaining accuracy, particularly for calculations of electronic excitations in complex systems. In this work, I combine time-dependent embedded mean field theory (TD-EMFT) with linear-scaling density functional theory and implicit solvation models, extending previous work within the ONETEP code. This provides a way to perform multilevel calculations of electronic excitations on very large systems, where long-range environmental effects, both quantum and classical in nature, are important. I demonstrate the power of this method by performing simulations on a variety of systems, including a molecular dimer, a chromophore in solution, and a doped molecular crystal. This work paves the way for high accuracy calculations to be performed on large-scale systems that were previously beyond the reach of quantum embedding schemes.

Accurate and Efficient Computation of Optical Absorption Spectra of Molecular Crystals: The Case of the Polymorphs of ROY.

When calculating the optical absorption spectra of molecular crystals from first principles, the influence of the crystalline environment on the excitations is of significant importance. For such systems, however, methods to describe the excitations accurately can be computationally prohibitive due to the relatively large system sizes involved. In this work, we demonstrate a method that allows optical absorption spectra to be computed both efficiently and at high accuracy. Our approach is based on the spectral warping method successfully applied to molecules in solvent. It involves calculating the absorption spectrum of a supercell of the full molecular crystal using semi-local time-dependent density functional theory (TDDFT), before warping the spectrum using a transformation derived from smaller-scale semi-local and hybrid TDDFT calculations on isolated dimers. We demonstrate the power of this method on three polymorphs of the well-known color polymorphic compound ROY and find that it outperforms both small-scale hybrid TDDFT dimer calculations and large-scale semi-local TDDFT supercell calculations, when compared to the experiment.

Travel-associated Legionnaires disease in Europe in 2008.

In 2008, the European Surveillance Scheme for Travel Associated Legionnaires Disease (EWGLINET) received reports of 866 cases of travel-associated Legionnaires disease, 42 of whom were reported to have died. 824 of the cases were classified as confirmed and 42 were presumptive. As in previous years, a very low proportion of clinical isolates were obtained (63 cases, 7.3%). Males outnumbered females by 2.8:1 in the 2008 dataset and had a median age of 60 years compared with women, whose median age was 63 years. Travel outside Europe was reported for 12% of the cases. The scheme identified 108 new clusters in 2008. Sixteen were located in countries outside EWGLINET and 38 (35.2%) involved only one case from each reporting country, and would not ordinarily have been detected by national surveillance schemes alone. The largest cluster (six cases) was associated with travel to Spain. The 108 clusters were associated with 144 environmental investigations, 35 of which were at re-offending sites, (sites which had previously been investigated and where additional cases had subsequently occurred). At 61 (42.1%) of the sites Legionella species were detected. The names of 12 sites were published on the EWGLINET website.

Legionnaires disease in Europe 2007-2008.

Each spring, countries that participate in the European Surveillance Scheme for Travel Associated Legionnaires Disease (EWGLINET) are requested to submit their annual dataset of all cases of Legionnaires disease in residents of their country with onset of illness in the preceding year. These data have been collected annually since 1994 and are used to analyse epidemiological and microbiological trends within and between countries over time. This paper presents an overview of the data collected for 2007 and 2008. A total of 5,907 cases were reported by 33 countries in 2007 and 5,960 cases by 34 countries in 2008, a similar two-year total to that recorded in 2005 and 2006 [1]. The only countries with a major difference in case numbers between 2007 and 2008 were Russia, due to a large outbreak in 2007, and Italy where cases increased by 256 in 2008 mainly due to an increase in community-acquired infections. The 779 reported deaths give a two-year case fatality rate of 6.6%. Some 243 outbreaks or clusters were detected, 150 of which were linked to travel-associated infections. As in previous years, the overall main method of diagnosis was by urinary antigen detection and the proportion of cases diagnosed by culture remained low at 8.8%, although isolation rates by country ranged from under 1% to over 40%.

Travel-associated Legionnaires disease in Europe in 2009.

A total of 818 cases of Legionnaires' disease with onset of illness in 2009 were reported from 22 European and two non-European countries to the European Surveillance Scheme for Travel-Associated Legionnaires' Disease (EWGLINET). This is a decrease of 52 cases compared with 2008 and 129 fewer than in 2007 - the peak year of reporting to date. A total of 794 (97.1%) cases were reported as confirmed and 24 as presumptive cases. Outcome of illness was reported for 561 (68.6%) cases. Of these cases 28 (5%) were reported to have died. More than half, of the cases in 2009 (n=469, 57.3%) were reported within 20 days of symptom onset. Cases visited 53 countries and were infected in all months of the year, with a peak in September (n=146). By country of residence of the cases, the United Kingdom (UK) reported the highest number of cases (n=173). Italy reported the second highest number of cases (n=169) and was also the country associated with the most cases by country of infection (n=209). A total of 88 new clusters (75 in Europe and 13 outside Europe) were detected in 2009 and were associated with 196 cases. The largest cluster occurred in Italy and involved seven cases. Without the scheme's international database, thirty three (37.5%) of the newly detected clusters would not have been identified. In 49 of the accommodation sites with clusters of cases, environmental samples were found to be positive for Legionella spp. Details of 10 sites were published on the European Working Group for Legionella Infections (EWGLI) website for failure to return information on the status of environmental investigations.

Characteristics of reoffending accommodation sites in Europe with clusters of Legionnaires disease, 2003-2007.

Between 2003 and 2007, 21% (n=100/477) of accommodation sites linked to clusters of two or more cases of Legionnaires' disease that were investigated by the European Surveillance Scheme for Travel-Associated Legionnaires' Disease (EWGLINET) went on to be associated with at least one further case, despite reporting that satisfactory control measures had been implemented at the time the cluster was first detected. This paper examines these sites (termed reoffenders) in order to determine whether they share any characteristics that may have contributed to the reoffence. All investigations conducted at cluster sites between 2003 and 2007 were included in the analysis, giving a total of 615 investigations conducted at 477 sites. Every country that investigated more than three cluster sites had to deal with at least one reoffence, and one site reoffended five times. The cases involved in the cluster that stayed elsewhere during their incubation periods could be used to help assess the probability of exposure, and therefore the risk, posed by particular cluster sites. A more extensive investigation and control regime may be needed in some instances to better control the risk of Legionnaires' disease at an accommodation site.

Combining Embedded Mean-Field Theory with Linear-Scaling Density-Functional Theory.

We demonstrate the capability of embedded mean-field theory (EMFT) within the linear-scaling density-functional-theory code ONETEP, which enables DFT-in-DFT quantum embedding calculations on systems containing thousands of atoms at a fraction of the cost of a full calculation. We perform simulations on a wide range of systems from molecules to complex nanostructures to demonstrate the performance of our implementation with respect to accuracy and efficiency. This work paves the way for the application of this class of quantum embedding method to large-scale systems that are beyond the reach of existing implementations.

Can syndromic thresholds provide early warning of national influenza outbreaks?

BACKGROUND: Influenza incidence thresholds are used to help predict the likely impact of influenza and inform health professionals and the public of current activity. We evaluate the potential of syndromic data (calls to a UK health helpline NHS Direct) to provide early warning of national influenza outbreaks. METHODS: Time series of NHS Direct calls concerning 'cold/flu' and fever syndromes for England and Wales were compared against influenza-like-illness clinical incidence data and laboratory reports of influenza. Poisson regression models were used to derive NHS Direct thresholds. The early warning potential of thresholds was evaluated retrospectively for 2002-06 and prospectively for winter 2006-07. RESULTS: NHS Direct 'cold/flu' and fever calls generally rose and peaked at the same time as clinical and laboratory influenza data. We derived a national 'cold/flu' threshold of 1.2% of total calls and a fever (5-14 years) threshold of 9%. An initial lower fever threshold of 7.7% was discarded as it produced false alarms. Thresholds provided 2 weeks advanced warning of seasonal influenza activity during three of the four winters studied retrospectively, and 6 days advance warning during prospective evaluation. CONCLUSION: Syndromic thresholds based on NHS Direct data provide advance warning of influenza circulating in the community. We recommend that age-group specific thresholds be developed for other clinical influenza surveillance systems in the UK and elsewhere.

Travel-associated Legionnaires disease in Europe in 2007.

Nine hundred and forty six cases of travel-associated Legionnaires disease were reported to the European Surveillance Scheme for Travel Associated Legionnaires Disease (EWGLINET) with onset during 2007; 890 were confirmed and 56 were presumptive. Twenty eight cases died, giving a case fatality rate of 3.0%. 8.2% of cases were diagnosed by culture, an important increase from 5.2% in 2006. One hundred and twelve new clusters were identified; the largest involved nine cases. Sixteen of these clusters (14.3%) occurred in countries outside EWGLINET, and three involved cruise ships. Twenty nine of the new clusters (25.9%) would not have been detected without the EWGLINET scheme. A total of 151 investigations were conducted in Europe, 42 of which were conducted at re-offending sites (where additional cases had onset after a report was received to say that investigations and control measures had been satisfactorily conducted). The names of 13 accommodation sites were published on the European Working Group for Legionella Infections (EWGLI) website; 11 of these were situated in Turkey.

Travel-associated Legionnaires disease in Europe: 2006.

Twenty countries reported 921 cases of travel-associated Legionnaires' disease to EWGLINET (the European Surveillance Scheme for Travel-Associated Legionnaires' Disease) with onset during 2006; 875 confirmed and 46 presumptive. Thirty three cases died, giving a case fatality rate of 3.6%. Of the 124 new clusters detected in 2006, 43 would not have been identified without the EWGLINET scheme. A total of 146 investigations were conducted at cluster sites according to the standards of the EWGLINET investigation guidelines; 111 of these investigations were associated with the new clusters while 35 investigations were associated with re-offending sites (where additional cases had onset after a report was received to say that investigations and control measures had been satisfactorily conducted). The names of four accommodation sites were published on the EWGLI website. Overall, there has been an upwards trend in case numbers since the scheme was founded, which has implications for the work load of public health authorities across Europe and for the tour industry. Despite this increasing pressure on public health authorities, environmental investigations are being conducted in a timely manner.

Immunogenicity and safety of an indigenously developed DTPw hepatitis B combination vaccine in Indian infants.

OBJECTIVE: To evaluate the safety and immunogenicity of an indigenous hepatitis B, diphtheria, tetanus and B. pertussis tetravalent vaccine (Shantetra) in comparison with Tritanrix HBTM in healthy Indian infants. DESIGN: Multicentric, randomized, single blind intention-to-treat study with 12-18 weeks of follow up period. SETTING: 5 out patient departments at tertiary care referral centers across India. PARTICIPANTS: 151 infants were randomized in a 2:1 ratio to recruit 101 in the Shantetra and 50 in the Tritanrix HBTM groups respectively. A total of 136 subjects completed the study. No patients were withdrawn from the study due to any adverse effects. INTERVENTIONS: Recruited subjects were randomized to receive three doses of either of the two DTPw-Hepatitis B combination vaccines as per the EPI schedule. MAIN OUTCOME MEASURES: Monitoring the humoral immune response (seroconversion rates) induced by each antigenic component three to six weeks after the last dose of vaccine in both the groups. RESULTS: Seroprotective immune response was observed in 98.9% subjects for diphtheria, tetanus and hepatitis B components in the Shantetra group as compared to 95.5% subjects in the Tritanrix HB group. Anti pertussis antibody response was seen in 89% and 91.1% in the Shantetra and Tritanrix HB groups, respectively. The commonly observed adverse events in both the groups were, pain at injection site, mild fever and transient crying. CONCLUSION: The safety and immunogenicity of indigenously developed DTPwHepatitis B combination vaccine was demonstrated in the present study.

Comparison of clinical and environmental isolates of Legionella pneumophila obtained in the UK over 19 years.

Between January 1980 and December 1998, 3458 cases of Legionnaires' disease were reported to the national surveillance scheme in England and Wales. Of these, 463 (13.4%) were reported as proven by culture and isolation of Legionella spp., with 96.3% being Legionella pneumophila. Serogroup (Sgp), monoclonal antibody (mAb) subgrouping and restriction fragment length polymorphism (RFLP) analysis data were obtained for 321 (69.3%) of these, of which 284 were classified as being unrelated to any other isolate in the study. Typing data were also available for 117 unrelated environmental isolates of L. pneumophila obtained from England and Wales, giving a total of 401 unrelated isolates in the study. Of the clinical isolates, 88.0% were Sgp1, compared with only 42.7% of environmental isolates (p <0.001); 79.6% of clinical isolates were subgrouped as mAb2+, compared with only 12.8% of environmental isolates (p <0.001). RFLP typing identified 67 types among the 401 isolates, with clinical isolates showing significantly less diversity than environmental isolates (index of diversity (IOD) 0.944 vs. 0.958; p <0.05), with three RFLP types (1, 5 and 14) accounting for 40.0% of all clinical isolates. Combining the phenotypic and genotypic data resulted in 173 distinct phenons, with clinical isolates showing significantly less diversity than environmental isolates (IOD 0.964 vs. 0.996; p <0.01). Three phenons accounted for 30% of all clinical isolates. These data strongly suggest that some strains of L. pneumophila are more likely to cause human infection than would be expected from their distribution in the environment.

Legionnaires disease in Europe: 2005-2006.

Once a year, every country that participates in the European Surveillance Scheme for Travel Associated Legionnaires' Disease (EWGLINET) is asked to submit a dataset comprising all cases of Legionnaires' disease (not only travel-associated) with date of onset in the previous year. This paper presents the data collected for 2005 and 2006. In this period, 11,980 cases were reported by 35 countries, showing a continued increase compared with earlier years. 214 outbreaks or clusters were reported, involving 1028 cases. 377 cases died, giving a case fatality rate of 6.6%. The highest incidence rates in both years were recorded in Spain, while six countries reported a rate of less than one case per million population in at least one of the years. Incidence rates by age group were included in the dataset for the first time, showing an increase of the overall rate with age. Main method of diagnosis was the urinary antigen test (76.0%), whilst the percentage of cases diagnosed by culture fell from 10.0% in previous years to 8.9% in 2005-2006.

What is the probability of successive cases of Legionnaires' disease occurring in European hotels?

BACKGROUND: Public health officials will normally take action at accommodation sites following an association with a cluster of cases of Legionnaires' disease. This paper seeks to determine the likelihood of such a cluster occurring at a site once it has been associated with a single case of the disease, and therefore whether more should be done at sites following individual cases. METHODS: Information for UK residents reported to the EWGLINET system between 1993 and 2000 was included in a dataset. The size and country of hotel visited by the cases were divided into six country groups (France, Italy, Spain, Turkey, other Europe and other World), and eight size groups (<20 rooms, 20-49, 50-99, 100-199, 200-299, 300-399, 400-499, 500+). The data were investigated using Cox proportional hazards regression to model the probability of at least one further case following the first. RESULTS: The dataset comprised 793 cases that had stayed at 605 sites in 51 countries between 1993 and the end of 2000. This included 605 cases that were the first case associated with a site, and 188 subsequent cases. Following the first case, 16.6% of sites were associated with at least one subsequent case during the period under study. The probability of a subsequent case occurring within 6 months of the first varied by country and size group, with some combinations returning a probability >30%; the probability of a subsequent case occurring within 2 years of the first reached over 50% in some instances. CONCLUSIONS: There may be support for early intervention at some accommodation sites following a first case of Legionnaires' disease, in specific country and size groups.

The impact of new guidelines in Europe for the control and prevention of travel-associated Legionnaires' disease.

On 1 July 2002, EWGLINET introduced European guidelines for the control and prevention of travel-associated legionnaires' disease. This paper presents the results gathered by the surveillance scheme during the first two and a half years of the operation of the guidelines (to the end of 2004). Two hundred and thirty-seven new clusters and 70 cluster updates were identified. Investigations at 146 sites returned positive samples for legionella, and the proportion of positive sites reached over 60% in 2004. Thirty-four cluster sites were reported to have been investigated satisfactorily, but have gone on to be associated with subsequent cases ('repeater sites'). Fifty-one sites were published on the European Working Group for Legionella Infections (EWGLI) website; the publication states that EWGLINET cannot be confident that the sites have adequate control measures in place. The operation of the guidelines is discussed, and the situation in Turkey highlighted as a particular success.