Single-cell western blotting.

To measure cell-to-cell variation in protein-mediated functions, we developed an approach to conduct ∼10(3) concurrent single-cell western blots (scWesterns) in ∼4 h. A microscope slide supporting a 30-μm-thick photoactive polyacrylamide gel enables western blotting: settling of single cells into microwells, lysis in situ, gel electrophoresis, photoinitiated blotting to immobilize proteins and antibody probing. We applied this scWestern method to monitor single-cell differentiation of rat neural stem cells and responses to mitogen stimulation. The scWestern quantified target proteins even with off-target antibody binding, multiplexed to 11 protein targets per single cell with detection thresholds of <30,000 molecules, and supported analyses of low starting cell numbers (∼200) when integrated with FACS. The scWestern overcomes limitations of antibody fidelity and sensitivity in other single-cell protein analysis methods and constitutes a versatile tool for the study of complex cell populations at single-cell resolution

Identification of integrative and conjugative elements in pathogenic and commensal Neisseriaceae spp. via genomic distributions of DNA uptake sequence dialects

Mobile genetic elements (MGEs) are key factors responsible for dissemination of virulence determinants and antimicrobial-resistance genes amongst pathogenic bacteria. Conjugative MGEs are notable for their high gene loads donated per transfer event, broad host ranges and phylogenetic ubiquity amongst prokaryotes, with the subclass of chromosomally inserted integrative and conjugative elements (ICEs) being particularly abundant. The focus on a small number of model systems has biased the study of ICEs towards those conferring readily selectable phenotypes to host cells, whereas the identification and characterization of integrated cryptic elements remains challenging. Even though antimicrobial resistance and horizontally acquired virulence genes are major factors aggravating neisserial infection, conjugative MGEs of Neisseria gonorrhoeae and Neisseria meningitidis remain poorly characterized. Using a phenotype-independent approach based on atypical distributions of DNA uptake sequences (DUSs) in MGEs relative to the chromosomal background, we have identified two groups of chromosomally integrated conjugative elements in Neisseria: one found almost exclusively in pathogenic species possibly deriving from the genus Kingella, the other belonging to a group of Neisseria mucosa-like commensals. The former element appears to enable transfer of traditionally gonococcal-specific loci such as the virulence-associated toxin–antitoxin system fitAB to N. meningitidis chromosomes, whilst the circular form of the latter possesses a unique attachment site (attP) sequence seemingly adapted to exploit DUS motifs as chromosomal integration sites. In addition to validating the use of DUS distributions in Neisseriaceae MGE identification, the >170 identified ICE sequences provide a valuable resource for future studies of ICE evolution and host adaptation

Dynamics of viscoelastic membranes

We determine both the in-plane and out-of-plane dynamics of viscoelastic membranes separating two viscous fluids in order to understand microrheological studies of such membranes. We demonstrate the general viscoelastic signatures in the dynamics of shear, bending, and compression modes. We also find a screening of the otherwise two-dimensional character of the response to point forces due to the presence of solvent. Finally, we show that there is a linear, hydrodynamic coupling between the in-plane compression modes of the membrane and the out-of-plane bending modes in the case where the membrane separates two different fluids or environments

Leadership, creativity, and innovation:A critical review and practical recommendations

Leadership is a key predictor of employee, team, and organizational creativity and innovation. Research in this area holds great promise for the development of intriguing theory and impactful policy implications, but only if empirical studies are conducted rigorously. In the current paper, we report a comprehensive review of a large number of empirical studies (N = 195) exploring leadership and workplace creativity and innovation. Using this article cache, we conducted a number of systematic analyses and built narrative arguments documenting observed trends in five areas. First, we review and offer improved definitions of creativity and innovation. Second, we conduct a systematic review of the main effects of leadership upon creativity and innovation and the variables assumed to moderate these effects. Third, we conduct a systematic review of mediating variables. Fourth, we examine whether the study designs commonly employed are suitable to estimate the causal models central to the field. Fifth, we conduct a critical review of the creativity and innovation measures used, noting that most are sub-optimal. Within these sections, we present a number of taxonomies that organize extant research, highlight understudied areas, and serve as a guide for future variable selection. We conclude by highlighting key suggestions for future research that we hope will reorient the field and improve the rigour of future research such that we can build more reliable and useful theories and policy recommendations

Using emergency department syndromic surveillance to investigate the impact of a national vaccination program: A retrospective observational study

BackgroundRotavirus infection is a common cause of gastroenteritis in children worldwide, with a high mortality burden in developing countries, particularly during the first two years of life. Rotavirus vaccination was introduced into the United Kingdom childhood vaccination schedule in July 2013, with high coverage (>90%) achieved by June 2016. We used an emergency department (ED) syndromic surveillance system to assess the impact of the rotavirus vaccination programme, specifically through the demonstration of any immediate and continuing impact on ED gastroenteritis visits in England.MethodsThis retrospective, observational study used syndromic surveillance data collected from 3 EDs in the two years before (July 2011-June 2013) and 3 years post (July 2013-June 2016) introduction of rotavirus vaccination. The weekly levels of ED visits for gastroenteritis (by age group and in total) during the period before rotavirus vaccination was first described alongside the findings of laboratory surveillance of rotavirus during the same period. An interrupted time-series analysis was then performed to demonstrate the impact of rotavirus vaccination introduction on gastroenteritis ED visit levels.ResultsDuring the two years before vaccine introduction ED visits for gastroenteritis in total and for the 0-4 years age group were seen to rise and fall in line with the seasonal rotavirus increases reported by laboratory surveillance. ED gastroenteritis visits by young children were lower in the three years following introduction of rotavirus vaccination (reduced from 8% of visits to 6% of visits). These attendance levels in young children (0-4years) remained higher than in older age groups, however the previously large seasonal increases in children were greatly reduced, from peaks of 16% to 3-10% of ED visits per week.ConclusionsED syndromic surveillance demonstrated a reduction in gastroenteritis visits following rotavirus vaccine introduction. This work establishes ED syndromic surveillance as a platform for rapid impact assessment of future vaccine programmes

Retrospective Observational Study of Atypical Winter Respiratory Illness Season Using Real-Time Syndromic Surveillance, England, 2014-15

During winter 2014–15, England experienced severe strains on acute health services. We investigated whether syndromic surveillance could contribute to understanding of the unusually high level of healthcare needs. We compared trends for several respiratory syndromic indicators from that winter to historical baselines. Cumulative and mean incidence rates were compared by winter and age group. All-age influenza-like illness was at expected levels; however, severe asthma and pneumonia levels were above those expected. Across several respiratory indicators, cumulative incidence rates during 2014–15 were similar to those of previous years, but higher for older persons; we saw increased rates of acute respiratory disease, including influenza like illness, severe asthma, and pneumonia, in the 65–74- and >75-year age groups. Age group–specific statistical algorithms may provide insights into the burden on health services and improve early warning in future winters

Observation of the topological Anderson insulator in disordered atomic wires

Topology and disorder have deep connections and a rich combined influence on quantum transport. In order to probe these connections, we synthesized one-dimensional chiral symmetric wires with controllable disorder via spectroscopic Hamiltonian engineering, based on the laser-driven coupling of discrete momentum states of ultracold atoms. We characterize the system's topology through measurement of the mean chiral displacement of the bulk density extracted from quench dynamics. We find evidence for the topological Anderson insulator phase, in which the band structure of an otherwise trivial wire is driven topological by the presence of added disorder. In addition, we observed the robustness of topological wires to weak disorder and measured the transition to a trivial phase in the presence of strong disorder. Atomic interactions in this quantum simulation platform will enable future realizations of strongly interacting topological fluids.Comment: 6 pages, 3 figures; 9 pages of supplementary material

The influence of a major sporting event upon emergency department attendances; A retrospective cross-national European study

Major sporting events may influence attendance levels at hospital emergency departments (ED). Previous research has focussed on the impact of single games, or wins/losses for specific teams/countries, limiting wider generalisations. Here we explore the impact of the Euro 2016 football championships on ED attendances across four participating nations (England, France, Northern Ireland, Wales), using a single methodology. Match days were found to have no significant impact upon daily ED attendances levels. Focussing upon hourly attendances, ED attendances across all countries in the four hour pre-match period were statistically significantly lower than would be expected (OR 0.97, 95% CI 0.94–0.99) and further reduced during matches (OR 0.94, 95% CI 0.91–0.97). In the 4 hour post-match period there was no significant increase in attendances (OR 1.01, 95% CI 0.99–1.04). However, these impacts were highly variable between individual matches: for example in the 4 hour period following the final, involving France, the number of ED attendances in France increased significantly (OR 1.27, 95% CI 1.13–1.42). Overall our results indicate relatively small impacts of major sporting events upon ED attendances. The heterogeneity observed makes it difficult for health providers to predict how major sporting events may affect ED attendances but supports the future development of compatible systems in different countries to support cross-border public health surveillance

Impact of the national rotavirus vaccination programme on acute gastroenteritis in England and associated costs averted.

BACKGROUND: Introduction of infant oral rotavirus vaccination in the UK in July 2013 has resulted in decreased hospitalisations and Emergency Department (ED) visits for acute gastroenteritis (AGE), for both adults and children. We investigated reductions in AGE incidence seen in primary care in the two years after vaccine introduction, and estimated the healthcare costs averted across healthcare settings in the first year of the vaccination programme. METHODS: We used primary care data from the Clinical Practice Research Datalink and age-stratified time-series analyses to derive adjusted incidence rate ratios (IRRa) for AGE in the first two years of the post-vaccination era (July 2013-April 2015) compared to the pre-vaccination era (July 2008-June 2013). We estimated cases averted among children aged <5years in the first year of the vaccination programme by comparing observed numbers of AGE cases in 2013-2014 to numbers predicted from the time-series models. We then estimated the healthcare costs averted for general practice consultations, ED visits and hospitalisations. RESULTS: In general practice, AGE rates in infants (the target group for vaccination) decreased by 15% overall after vaccine introduction (IRRa=0.85; 95%CI=0.76-0.95), and by 41% in the months of historically high rotavirus circulation (IRRa=0.59; 95%CI=0.53-0.66). Rates also decreased in other young children and to a lesser degree in older individuals, indicating herd immunity. Across all three settings (general practice, EDs, and hospitalisations) an estimated 87,376 (95% prediction interval: 62,588-113,561) AGE visits by children aged <5years were averted in 2013-14, associated with an estimated £12.5million (9,209-16,198) reduction in healthcare costs. CONCLUSIONS: The marked decreases in the general practice AGE burden after rotavirus vaccine introduction mirror decreases seen in other UK healthcare settings. Overall, these decreases are associated with substantial averted healthcare costs

Corrections to the Saffman-Delbruck mobility for membrane bound proteins

Recent experiments by Y. Gambin et al. [PNAS 103, 2098 (2006)] have called into question the applicability of the Saffman-Delbruck diffusivity for proteins embedded in the lipid bilayers. We present a simple argument to account for this observation that should be generically valid for a large class of transmembrane and membrane bound proteins. Whenever the protein-lipid interactions locally deform the membrane, that deformation generates new hydrodynamic stresses on the protein-membrane complex leading to a suppression of its mobility. We show that this suppression depends on the protein size in a manner consistent with the work of Y. Gambin et al.Comment: 3 pages, 1 figur