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Supplementary Figure Legends 1-2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles

Supplementary Figure 1 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles

The lack of safe and efficient systemic gene delivery vectors has largely reduced the potential of gene therapy in the clinic. Previously, we have reported that polypropylenimine dendrimer PPIG3/DNA nanoparticles are capable of tumor transfection upon systemic administration in tumor-bearing mice. To be safely applicable in the clinic, it is crucial to investigate the colloidal stability of nanoparticles and to monitor the exact biodistribution of gene transfer in the whole body of the live subject. Our biophysical characterization shows that dendrimers, when complexed with DNA, are capable of forming spontaneously in solution a supramolecular assembly that possesses all the features required to diffuse in experimental tumors through the enhanced permeability and retention effect. We show that these nanoparticles are of sizes ranging from 33 to 286 nm depending on the DNA concentration, with a colloidal stable and well-organized fingerprint-like structure in which DNA molecules are condensed with an even periodicity of 2.8 nm. Whole-body nuclear imaging using small-animal nano-single-photon emission computed tomography/computer tomography scanner and the human Na/I symporter (NIS) as reporter gene shows unique and highly specific tumor targeting with no detection of gene transfer in any of the other tissues of tumor-bearing mice. Tumor-selective transgene expression was confirmed by quantitative reverse transcription-PCR at autopsy of scanned animals, whereas genomic PCR showed that the tumor sites are the predominant sites of nanoparticle accumulation. Considering that NIS imaging of transgene expression has been recently validated in humans, our data highlight the potential of these nanoparticles as a new formulation for cancer gene therapy. [Cancer Res 2009;69(6):2655–62]

Supplementary Figure 2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles

In this paper we define RAL2 – the second Regional Atmosphere and Land (RAL) science configuration for regional modelling. RAL2 uses the Unified Model (UM) as the basis for the atmosphere and the Joint UK Land Environment Simulator (JULES) for the land. RAL2 defines the science configuration of the dynamics and physics schemes of the atmosphere and land and builds on the baseline of RAL1. There are two RAL2 sub-releases, one for mid-latitudes (RAL2-M) and one for tropical regions (RAL2-T). We document the differences between them and where appropriate discuss how RAL2 relates to RAL1 and the corresponding configuration of the global forecasting model. Our results show an increase in medium and low cloud amounts in the mid-latitudes leading to improved cloud forecasts. The increase in cloud amount leads to a reduced diurnal cycle of screen temperature. There is also a reduction in the frequency of heavier precipitation rates. RAL2 is expected to be the last RAL science configuration with two sub-releases as research effort is focused on producing a single defined configuration of the model that performs effectively in all regions of the world.

Purpose The purpose of this opinion piece is to present a case for the potential of positive autoethnography (PosAE) as a new autoethnographic approach. Design/methodology/approach This work resulted from on-going discussions between the authors as to the practicalities and benefits of associating the qualitative approach of autoethnography with the field of positive psychology. Findings PosAE is proposed to encourage writers to actively reflect on the importance for themselves, and their readers, of including positive narrative elements, prospective visions and exploratory trajectories in their work. Research limitations/implications This research builds on existing research that has included positive psychology in autoethnography. As positive psychology is grounded in empirical research, the authors are suggesting that PosAE is allied to pragmatic autoethnography. Practical implications PosAE offers to facilitate positive thought, affect and strategies that could improve well-being. For example, some people struggling with serious health issues, and those helping them, may find it useful for articulating conditions and envisioning, even experiencing, positive change. Social implications With so many lives impacted by mental health issues globally, and with rapidly changing societies struggling to provide stability and purpose, an autoethnography that provides tools such as PERMA (Positive emotions, Engagement, Positive Relationships, Meaning, Accomplishments/Achievements) to communicate the positive seems timely. Originality/value To the best of the authors’ knowledge, this is the first time the creation of an autoethnographic approach explicitly linked to positive psychology has been proposed.

RATIONALE: Shared symptoms and genetic architecture between COVID-19 and lung fibrosis suggests SARS-CoV-2 infection may lead to progressive lung damage.OBJECTIVES: The UKILD Post-COVID study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 based on risk strata.METHODS: The Post-HOSPitalisation COVID Study (PHOSP-COVID) was used for capture of routine and research follow-up within 240 days from discharge. Thoracic CTs linked by PHOSP-COVID identifiers were scored for percentage of residual lung abnormalities (ground glass opacities and reticulations). Risk factors in linked CT were estimated with Bayesian binomial regression and risk strata were generated. Numbers within strata were used to estimate post-hospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol driven research follow-up.MEASUREMENTS AND MAIN RESULTS: The interim cohort comprised 3700 people. Of 209 subjects with linked CTs (median 119 days, interquartile range 83-155), 166 people (79.4%) had >10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (RR 1·21 95%CrI 1·05; 1·40), percent predicted DLcoCONCLUSIONS: Residual lung abnormalities were estimated in up to 11% of people discharged following COVID-19 related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

In this paper we define RAL2 - the second "Regional Atmosphere and Land" (RAL) science configuration for regional modelling. RAL2 uses the Unified Model (UM) as the basis for the atmosphere and the Joint UK Land Environment Simulator (JULES) for the land. RAL2 defines the science configuration of the dynamics and physics schemes of the atmosphere and land and builds on the baseline of RAL1. There are two RAL2 sub-releases, one for mid-latitudes (RAL2-M) and one for tropical regions (RAL2-T). We document the differences between them and where appropriate discuss how RAL2 relates to RAL1 and the corresponding configuration of the global forecasting model. Our results show an increase in medium and low cloud amounts in the mid-latitudes leading to improved cloud forecasts. The increase in cloud amount leads to a reduced diurnal cycle of screen temperature. There is also a reduction in the frequency of heavier precipitation rates. RAL2 is expected to be the last RAL science configuration with two sub-releases as research effort is focused on producing a single defined configuration of the model that performs effectively in all regions of the world.

ObjectivesTo describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.DesignPopulation based study.Setting1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.Participants456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803).Main outcome measuresComparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.ResultsRelative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, PConclusionsGP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.

IntroductionThe COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD).Methods and analysisThe UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment.Ethics and disseminationAll contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals.ConclusionThis study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.

In this paper we define the first Regional Atmosphere and Land (RAL) science configuration for kilometre-scale modelling using the Unified Model (UM) as the basis for the atmosphere and the Joint UK Land Environment Simulator (JULES) for the land. RAL1 defines the science configuration of the dynamics and physics schemes of the atmosphere and land. This configuration will provide a model baseline for any future weather or climate model developments to be described against, and it is the intention that from this point forward significant changes to the system will be documented in the literature. This reproduces the process used for global configurations of the UM, which was first documented as a science configuration in 2011. While it is our goal to have a single defined configuration of the model that performs effectively in all regions, this has not yet been possible. Currently we define two sub-releases, one for mid-latitudes (RAL1-M) and one for tropical regions (RAL1-T). The differences between RAL1-M and RAL1-T are documented, and where appropriate we define how the model configuration relates to the corresponding configuration of the global forecasting model.

The impact of local climate conditions on air temperatures during a hot summer period over the United Kingdom in 2018 is studied using simple sensitivity experiments with a state‐of‐the‐art regional numerical weather prediction system. The experiments are designed to investigate the influence of sea surface temperature (SST) and soil moisture on the air temperatures over land. They involved applying changes to the analysed SST and soil moisture patterns with magnitudes consistent with the differences between forecast analysis and climatology. The results from daily 5‐day forecasts over an 11‐day period show that a 3°C reduction in SSTs reduces the simulated air temperatures averaged over all land points by just over 1°C. Moistening the soil while using the control SSTs reduces the temperatures by a little less than 1°C on average although this can be larger than 3°C locally. While the reduction in SST impacts the daily maximum and minimum temperatures to a similar extent, the increase in soil moisture had little impact on the daily minimum temperatures.

In recent years, a growing partnership has emerged between the Met Office and the designated U.S. national centers for expertise in severe weather research and forecasting, that is, the National Oceanic and Atmospheric Administration (NOAA) National Severe Storms Laboratory (NSSL) and the NOAA Storm Prediction Center (SPC). The driving force behind this partnership is a compelling set of mutual interests related to predicting and understanding high-impact weather and using high-resolution numerical weather prediction models as foundational tools to explore these interests.The forum for this collaborative activity is the NOAA Hazardous Weather Testbed, where annual Spring Forecasting Experiments (SFEs) are conducted by NSSL and SPC. For the last decade, NSSL and SPC have used these experiments to find ways that high-resolution models can help achieve greater success in the prediction of tornadoes, large hail, and damaging winds. Beginning in 2012, the Met Office became a contributing partner in annual SFEs, bringing complementary expertise in the use of convection-allowing models, derived in their case from a parallel decadelong effort to use these models to advance prediction of flash floods associated with heavy thunderstorms.The collaboration between NSSL, SPC, and the Met Office has been enthusiastic and productive, driven by strong mutual interests at a grassroots level and generous institutional support from the parent government agencies. In this article, a historical background is provided, motivations for collaborative activities are emphasized, and preliminary results are highlighted.

In this paper we define the first "Regional Atmosphere and Land" (RAL) science configuration for kilometre scale modelling using the UM and JULES. "RAL1" defines the science configuration of the dynamics and physics schemes of the atmosphere and land. This configuration will provide a model baseline for any future weather or climate model developments to be described against and it is the intention that from this point forward significant changes to the system will be documented in literature. This is reproducing the process used for global configurations of the UM which was first documented as a science configuration in 2011. While it is our goal to have a single defined configuration of the model that performs effectively in all regions, this has not yet been possible. Currently we define two sub-releases, one for mid-latitudes (RAL1-M) and one for tropical regions (RAL1-T). The differences between RAL1-M and RAL1-T are documented and where appropriate, we define how the model configuration relates to the corresponding configuration of the global forecasting model.

A limitation of the Met Office operational data assimilation scheme is that surface-sensitive infrared satellite sounding channels cannot be used during daytime periods where numerical weather prediction (NWP) model background land surface temperature (LST) biases are greater than 2 K in magnitude. The Met Office Unified Model (UM) has a significant cold LST bias in semi-arid regions when compared with satellite observations; a range of UM configurations were assessed with different model resolutions, land surface cover datasets and bare soil parameterisations. UM LST biases were evaluated at global resolution and in a limited area model (LAM) at a 2.2 km resolution over the SALSTICE (Semi-Arid Land Surface Temperature and IASI Calibration Experiment) experimental domain in south-eastern Arizona. This validation is in conjunction with eddy-covariance flux tower measurements. LST biases in the Global Atmosphere/Land 3.1 (GA/L3.1) configuration were largest in the mid-morning with respect to Moderate Resolution Imaging Spectroradiometer (MODIS) Terra (-13.6±2.8 K at the Kendall Grassland site). The diurnal cycle of LST in Global Atmosphere/Land 6.1 (GA/L6.1) showed a significant improvement relative to GA/L3.1 with the cold LST biases reduced to -1.4±2.7 K and -3.6±3.0 K for Terra and Aqua overpasses, respectively. The higher-resolution LAM showed added value over the global configurations. The spatial distribution of the LST biases relative to MODIS and the modelled bare soil cover fraction were found to be moderately correlated (0.61±0.08) during the daytime, which suggests that regions of cold LST bias are associated with low bare soil cover fraction. Coefficients of correlation with the shrub surface fractions followed the same trend as the bare soil cover fraction, although with a less significant correlation (0.36±0.09), and indicated that the sparse vegetation canopies in south-eastern Arizona are not well represented in UM ancillary datasets. The x component of the orographic slope was positively correlated with the LST bias (0.41±0.05 for MODIS Aqua) and identified that regions of cold model LST bias are found on easterly slopes, and regions of warm model LST bias are found on westerly slopes. An overestimate in the modelled turbulent heat and moisture fluxes at the eddy-covariance flux sites was found to be coincident with an underestimate in the ground heat flux.

Very little has been published on the subject of solitary laughter. Yet it appears quite possible that it is experienced by a large majority of people. A pilot study I have recently undertaken involving participants of numerous nationalities, as well as searches through literature and across the Internet, suggest that solitary laughter, while not as common as social instances of laughing, is a widespread human behaviour. It is even accorded special value by some. Seeking to encourage further research into the subject, this article discusses research and examines the forces that have militated against a more thorough research engagement with solitary laughter. It argues that a primary factor may be a pervasive assumption among influential scholars that laughter is an essentially social phenomenon and that laughing in solitude may be explained away as “vicarious” or “pseudo” socialising. Doubt is cast here upon that assumption. It is argued that while the reductionism at work in the extremely broad application of a social hypothesis may be theoretically attractive, it belies the diverse, evolving operations of both laughter and humour; this may be unnecessarily, if unwittingly, restricting the field of enquiry. Solitary laughter is a significant, complex behaviour and worthy of attention in its own right.

A limitation of the Met Office operational data assimilation scheme is that surface-sensitive infrared satellite sounding channels cannot be used during daytime periods where Numerical Weather Prediction (NWP) model background land surface temperature (LST) biases are greater than 2 K. The Met Office Unified Model (UM) has a significant cold LST bias in semi-arid regions when compared with satellite observations. UM LST biases were evaluated at global resolution and in a Limited Area Models (LAM) at 2.2 km resolution over the SALSTICE (Semi-Arid Land Surface Temperature and IASI Calibration Experiment) experimental domain in southeastern Arizona. This validation is in conjunction with eddy-covariance flux tower measurements. LST biases in the Global Atmosphere/Land 3.1 (GA/L3.1) configuration were largest in the mid-morning with respect to Terra (−13.6 ± 2.8 K at the Kendall Grassland site). The diurnal cycle of LST in Global Atmosphere/Land 6.1 (GA/L6.1) showed a significant improvement relative to GA/L3.1. The higher resolution LAM showed added value over the global configurations. The spatial distribution of the LST biases relative to Moderate Resolution Imaging Spectroradiometer (MODIS) and the modelled bare soil cover fraction were found to be moderately correlated (0.61 ± 0.08) during the daytime, which suggests that regions of cold LST bias are associated with low bare soil cover fraction. Coefficients of correlation with the shrub surface fractions followed the same trend as the bare soil cover fraction although with a less significant correlation (0.36 ± 0.09), and indicate that the sparse vegetation canopies in southeastern Arizona are not well represented in UM ancillary datasets. The x-component of the orographic slope was positively correlated with the LST bias (0.35 ± 0.06) and identified that regions of cold model LST bias are found on easterly slopes and regions of warm model LST bias are found on westerly slopes. An overestimate in the modelled turbulent heat and moisture fluxes at the eddy-covariance flux sites was found to be coincident with an underestimate in the ground heat flux.

We compare measurements of the turbulent and radiative surface energy fluxes from an automatic weather station (AWS) on Larsen C Ice Shelf, Antarctica with corresponding fluxes from three high-resolution atmospheric models over a 1 month period during austral summer. All three models produce a reasonable simulation of the (relatively small) turbulent energy fluxes at the AWS site. However, biases in the modeled radiative fluxes, which dominate the surface energy budget, are significant. There is a significant positive bias in net shortwave radiation in all three models, together with a corresponding negative bias in net longwave radiation. In two of the models, the longwave bias only partially offsets the positive shortwave bias, leading to an excessive amount of energy available for heating and melting the surface, while, in the third, the negative longwave bias exceeds the positive shortwave bias, leading to a deficiency in calculated surface melt. Biases in shortwave and longwave radiation are anticorrelated, suggesting that they both result from the models simulating too little cloud (or clouds that are too optically thin). We conclude that, while these models may be able to provide some useful information on surface energy fluxes, absolute values of modeled melt rate are significantly biased and should be used with caution. Efforts to improve model simulation of melt should initially focus on the radiative fluxes and, in particular, on the simulation of the clouds that control these fluxes.

The provision of weather forecasts for the London Olympic and Paralympic Games in 2012 offered the opportunity for the Met Office to accelerate the transition to operations of several advanced numerical modeling capabilities and to demonstrate their performance to external scientists. It was also an event that captured public interest, providing an opportunity to educate and build trust in the weather forecasting enterprise in the United Kingdom and beyond. The baseline NWP guidance for the duration of the Olympic Games came from three main configurations of the Met Office Unified Model: global 25-km deterministic, North Atlantic/Europe 18-km ensemble, and U.K. 1.5-km deterministic. The advanced capabilities demonstrated during the Olympic Games consisted of a rapid-update hourly cycle of a 1.5-km grid length configuration for the southern United Kingdom using four-dimensional variational data assimilation (4D-Var) and enhanced observations; a 2.2-km grid length U.K. ensemble; a 333-m grid length configur...

During winter much of the Antarctic coast is susceptible to severe and hazardous strong-wind events (SWEs) associated with the enhancement of katabatic winds by synoptic weather systems. In this study a SWE that occurred at Mawson, East Antarctica, involving a hurricane force wind speed of ∼39 m s−1 is simulated by the Met Office Unified Model at high horizontal resolutions with grid lengths between 12 and 1.5 km. It is shown that all the simulations capture the qualitative evolution of the SWE but underestimate its peak wind speed. The extent of the underestimate is dependent on horizontal resolution, with the 4 and 1.5 km (12 km) models underforecasting the peak wind speed by around 15% (36%). In addition to a strengthening of the katabatic flow, the simulated low-level cyclonic winds associated with the depression responsible for the SWE caused the formation of a barrier-type jet parallel to the coast, resulting in strong wind convergence/interaction at the coastline and suggesting a strong topographic influence on the dynamics responsible for SWE formation. Moreover, it suggests that Mawson is influenced by small-scale gravity waves that formed in response to the stronger winds, and that representation of this was particularly sensitive to horizontal resolution. Additional experiments suggest that the Met Office Unified Model simulation of the SWE is most sensitive to the representation of turbulent mixing under stable conditions. This study is important to identify shortcomings in the performance of the Met Office Unified Model near Antarctica's coastal regions as well as to improve understanding of the processes responsible for SWEs.

Previously unknown foehn jets have been identified to the east of the Antarctic Peninsula (AP) above the Larsen C Ice Shelf. These jets have major implications for the east coast of the AP, a region of rapid climatic warming and where two large sections of ice shelf have collapsed in recent years.\ud \ud During three foehn events across the AP, leeside warming and drying is seen in new aircraft observations and simulated well by the Met Office Unified Model (MetUM) at ∼1.5 km grid spacing. In case A, weak southwesterly flow and an elevated upwind inversion characterise a highly nonlinear flow regime with upwind flow blocking. In case C strong northwesterly winds characterise a relatively linear case with little upwind flow blocking. Case B resides somewhere between the two in flow regime linearity.\ud \ud The foehn jets – apparent in aircraft observations where available and MetUM simulations of all three cases – are mesoscale features (up to 60 km in width) originating from the mouths of leeside inlets. Through back trajectory analysis they are identified as a type of gap flow. In cases A and B the jets are distinct, being strongly accelerated relative to the background flow, and confined to low levels above the Larsen C Ice Shelf. They resemble the ‘shallow foehn’ of the Alps. Case C resembles a case of ‘deep foehn’, with the jets less distinct. The foehn jets are considerably cooler and moister relative to adjacent regions of calmer foehn air. This is due to a dampened foehn effect in the jet regions: in case A the jets have lower upwind source regions, and in the more linear case C there is less diabatic warming and precipitation along jet trajectories due to the reduced orographic uplift across the mountain passes.

While there are certainly funnier writers than Milan Kundera, probably no major modern author of fiction has pursued the subjects of humor and laughter as persistently and thoroughly as the writer o? Laughable Loves, The Joke and The Book of Laughter and Forgetting. It is ironic then that at the very beginning of his extended treatise on modern aesthetics, Testaments Betrayed (199$), Kundera observes, "If I were asked the most common cause of misunderstanding between my readers and me, I would not hesitate: humor" (6). The entire book then becomes in a sense a clarification of his position on the subject, but not before he has articulated what is at stake for him in all this by referencing Octavio Paz's assertion that "Humor is the great invention of the modern spirit" and by claiming that this humor's birth, coinciding with that of the novel in Rabelais and Cervantes, is absolutely fundamental to modern European culture (5).

In an experiment carried out by Aurnou and Olson [J. Fluid Mech. 430, 283 (2001)] thermal convection in a liquid gallium layer in the presence of a uniform vertical magnetic field was investigated. The critical Rayleigh number at the onset of magnetoconvection was determined as a function of the Chandrasekhar number Q (the ratio of the Lorentz force to the viscous force) and the Taylor number Ta (the squared ratio of the Coriolis force to the viscous force). In the experimental apparatus, the upper and lower boundaries of the liquid gallium layer were electrically conducting copper plate walls. This paper presents a study of the effect of electrically conducting walls on rotating magnetoconvection. It is shown that the electrical properties of the walls have significant effects on the characteristics of rotating magnetoconvection when both the Chandrasekhar number Q and the Taylor number Ta are sufficiently large. It is demonstrated that, as a consequence of the electrically conducting walls, oscillatory ...

here is no question that in the latter decades of the twentieth century X philosophical, literary, and cultural studies were infected with some thing of a comic spirit. Postmodernism was identified with and through images of play, energy, and movement that sought to ceaselessly and joyfully throw into crisis our faith in the permanence of structures. The only thing that would be permanent now was the need for change that the ascendancy of desire itself as a cosmological principle was driving. Here, of course, postmodernist theory revealed its continuity with, and indeed its debt to, high modernist dynamism?most conspicuously, Nietzsche's Dionysianism, Bergson's quasi mystical ?lan vital, and Freud's "energo-economics." Thus when Derrida announced the triumph of "becoming," of endless desiring and jouissance, through his linguistic concepts of signifying force and diff?rance, it was in Nietzsche that he found inspiration: "we must affirm this, in the sense in which Nietzsche puts affirmation into play, in a certain laughter and a cer tain step of the dance."2 Desire and play were inseparable, and laughter was the privileged icon?the transcendental signifier, if you like?of that unruly force that drove us.

Laughter has achieved special significance within some of the more radical postmodern, and especially poststructuralist, discourses as an icon of liberated desire. Yet there is a sense in which laughter is anything but the expression of libidinal force, in which it can be seen to reflect a momentary subversion of desire. To understand this, poststructuralist linguistic theory itself can be employed (against itself), because in the linguistic philosophy of Jacques Derrida in particular there is a unique acknowledgment of the temporal dimension of communication and thought, and of the relationship of this to human desire. Such a model of communication provides insights into the way in which laughter is produced through the subversion of the human experience of temporality — and of desire, an effect of delayed satisfaction. The present article draws widely on the comic theoretical heritage, seeking to synthesize existing theories into a time-based model of how, and why, laughter is produced.

Thermal instabilities in the form of oscillatory magnetoconvection representing diffusively modified Alfven waves in an electrically-conducting Benard fluid layer of rigid walls in the presence of a vertical magnetic field are investigated. Emphasis of the article is on the transition from a nearly undamped Alfven wave to diffusively modified Alfven waves, and on the effect of physically realisable magnetic field boundary conditions on magnetoconvection. It is found that the extra magnetic dissipation in the magnetic Hartmann boundary layers can enhance oscillatory magnetoconvection in the form of strongly modified Alfven waves. Oscillatory magnetoconvection produced solely by the Alfven wave mechanism can be the most unstable mode even in the presence of a strong viscous effect. This article also represents the first study on the effect of an electrically conducting wall on magnetoconvection which is associated with a nonlinear eigenvalue problem. We find that the electrically perfectly conducting condit...

While the body, time and space are fundamental to human experience, comparatively little attention has been given to the connections between them. Here scholars from a wide range of disciplines explore important themes of embodied life in time and space across cultures, activities and bodymind states. Motivated by a common desire to deepen and extend our comprehension of these phenomena and the connections and conversations between them, this book emerged from intense inter-disciplinary dialogue during the 1st Global Conferences on Time, Space and the Body and Body Horror. A plenitude of theoretical approaches and media are deployed to investigate assumptions and pose problems, to creatively deconstruct and reconstruct the terms through which experience is rendered meaningful, pleasurable, and functional. These investigations, pursued through various research methods in fields of the arts, social and psychological sciences and humanities, invite readers into a genuinely pluralistic conversation around the most basic and profound aspects of being.

Following the disbanding of the Soviet Union in 1991, the government of Kyrgyzstan was unable to maintain the previous level of health services. To revitalize the health services, the Ministry of Health (MOH) first focused on improving their immunization services, including the immunization component of the Health Management Information System (HMIS). Secondly, to increase immunization coverage, the MOH set as a priority the elimination of prescribing false contraindications to immunization. To accomplish both goals, the MOH updated the national immunization policies and established a more effective structure for managing immunization services. To support the MOH, the US Agency for International Development (USAID) Resources for Child Health (REACH) and Basic Support for Institutionalizing Child Survival (BASICS) projects provided technical assistance through a resident coordinator and consultants, and by organizing an international seminar. The improvements extended beyond systems and forms, but, instead, emphasized monitoring by the frontline health worker and supervising the quality of health information. To accomplish their objectives, the MOH appointed a Working Group to define the problems, revise record-keeping procedures, and develop monitoring tools. This group, representing both national and local levels, was composed of MOH epidemiologists, paediatricians and a management information specialist. To reduce the burden of excessive record-keeping and reporting requirements, the Working Group identified four key indicators for the service delivery level: (1) DPT3 immunization coverage rates for children less than 1 year of age; (2) contraindication rates for DPT; (3) usage of DPT vaccine; and (4) daily refrigerator temperatures. Additional indicators were included at district and provincial levels. After a successful 1-year trial, the MOH implemented the revised HMIS nationally. Not only did the quality of the information system improve, but the new approach provided visible evidence, from facility to national levels, that the MOH was approaching their objective of reducing contraindication rates for DPT immunizations to 5% or less, and that vaccine wastage could be substantially reduced. The project demonstrated that giving health workers the basic epidemiologic skills to monitor their own work measurably improved the quality of the data, and by acquiring the new skills, the workers developed a sense of pride in their work.Following the disbanding of the Soviet Union in 1991, the government of Kyrgyzstan was unable to maintain the previous level of health services. To revitalize the health services, the Ministry of Health (MOH) first focused on improving their immunization services, including the immunization component of the Health Management Information System (HMIS). Secondly, to increase immunization coverage, the MOH set as a priority the elimination of prescribing false contraindications to immunization. To accomplish their objectives, the MOH appointed a Working Group to define the problems, revise record-keeping procedures, and develop monitoring tools. To reduce the burden of excessive record-keeping and reporting requirements, the working group identified four key indicators for the services delivery level: 1) diphtheria, pertussis, tetanus (DPT) immunization coverage rates for children less than 1 year of age; 2) contraindication rates for DPT; 3) usage of DPT vaccine; and 4) daily refrigerator temperature. After a successful 1-year trial, the MOH implemented the revised HMIS nationally. Not only did the quality of the information system improve, but also the new approach provided visible evidence that the MOH was approaching its objectives. The project demonstrated that giving health workers the basic epidemiological skills to monitor their own work measurably improved the quality of the data, and by acquiring the new skills, the workers developed a sense of pride in their work.

Wind flow and turbulence within the urban canopy layer can influence the heating and ventilation of buildings, affecting the health and comfort of pedestrians, commuters and building occupants. In addition, the predictive capability of pollutant dispersion models is heavily dependent on wind flow models. For that reason, well-validated microscale models are needed for the simulation of wind fields within built-up urban microenvironments. To address this need, an inter-comparison study of several such models was carried out within the European research network ATREUS. This work was conducted as part of an evaluation study for microscale numerical models, so they could be further implemented to provide reliable wind fields for building energy simulation and pollutant dispersion codes. Four computational fluid dynamics (CFD) models (CHENSI, MIMO, VADIS and FLUENT) were applied to reduced-scale single-block buildings, for which quality-assured and fully documented experimental data were obtained. Simulated wind and turbulence fields around two surface-mounted cubes of different dimensions and wall roughness were compared against experimental data produced in the wind tunnels of the Meteorological Institute of Hamburg University under different inflow and boundary conditions. The models reproduced reasonably well the general flow patterns around the single-block buildings, although over-predictions of the turbulent kinetic energy were observed near stagnation points in the upwind impingement region. Certain discrepancies between the CFD models were also identified and interpreted. Finally, some general recommendations for CFD model evaluation and use in environmental applications are presented.

In August and September 1977 a discrete cluster of 27 serologically or pathologically confirmed cases of Legionnaires' disease, plus six highly presumptive cases were identified in the area of Kingsport, Tennessee. Three patients died. Most patients manifested severe pneumonia and fever; no mild or asymptomatic disease forms were recognized despite intensive case-finding efforts. Illness was epidemiologically associated with residing, visiting, or working in one geographic area of Kingsport, residence there being the factor most strongly associated. Although the attack rate for area residents was 0.64%, the randomly determined prevalence of serologic reactors was 5.2%, which is not significantly different from that in a nonimplicated control neighborhood. The epidemic did not correlate temporally with any identified environmental or demographic event. No source of the bacterium was found either by a detailed case-control study of area associations or by bacterial isolation from sentinel guinea pigs or environmental specimens. There was no evidence of person-to-person spread.

An outbreak of acute histoplasmosis occurred among 42 people who gathered for two days in May 1977 to cut and clear a fallen oak tree near Nashville (Williamson County), Tennessee. Thirty-two (76 per cent) of the participants had serologic evidence of infection; 20 (48 per cent) had acute pulmonary disease and of these, three required hospitalization. Frequent symptoms of acute pulmonary disease included fever, malaise, chest pain, headache, cough, myalgia, weight loss (≥ 5 pounds) and stomach cramps. Chest roentgenograms revealed abnormalities in 87 per cent of the ill participants. The disease developed in two dogs that were also present at the activities. Illness began an average of 14 days after exposure. Risk of illness was associated with sawing the tree, and loading wood and bark into a truck, as well as the length of the time spent near the tree. Tests for fungal antibodies in serum obtained from the participants and community controls, (those who lived in the county but did not have symptoms of respiratory illness) were used to establish criteria for serologic diagnosis. Immunodiffusion tests with initial serum samples were most useful for diagnosis; the presence of an M precipitin band was 75 per cent sensitive and was 97 per cent specific as judged by data from community controls. Similarly, the mycelial form antigen Histoplasma capsulatum complement fixation test at a titer ≥ 1:8 was 55 per cent sensitive and 97 per cent specific, and the yeast-form antigen complement fixation test at a titer of ⩾ 1:16 was 75 per cent sensitive and 77 per cent specific. When serum obtained four weeks after exposure (one to two weeks after onset of symptoms) was compared with serum obtained eight weeks after exposure, a fourfold increase in complement fixation antibodies was detected in 28 per cent of those infected.