Dornase alfa for cystic fibrosis.

BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. OBJECTIVES: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 12 October 2020. Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 08 February 2021. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence. MAIN RESULTS: The searches identified 74 trials, of which 19 (2565 participants) met our inclusion criteria. 15 trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years. Dornase alfa compared to placebo or no treatment Dornase alfa probably improved forced expiratory volume at one second (FEV1) at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed treatment may make little or no difference  in quality of life. Dornase alfa probably reduced the number of pulmonary exacerbations in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs. Dornase alfa: daily versus alternate day One cross-over trial (43 children) found little or no difference between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence). Dornase alfa compared to other medications that improve airway clearance Results for these comparisons were mixed. One trial (43 children) showed dornase alfa may lead to a greater improvement in FEV1 compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported little or no differences in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found dornase alfa may improve quality of life compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found little or no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence). When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show that, compared with placebo, therapy with dornase alfa may improve lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer, probably due to treatment. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.

Dornase alfa for cystic fibrosis.

BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. OBJECTIVES: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 23 April 2018.Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 07 June 2018. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence. MAIN RESULTS: The searches identified 69 trials, of which 19 (2565 participants) met our inclusion criteria. Fifteen trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Dornase alfa compared to placebo or no treatmentDornase alfa improved forced expiratory volume at one second at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed no difference between groups for changes in quality of life. There was a decrease in pulmonary exacerbations with dornase alfa in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.Dornase alfa: daily versus alternate dayOne cross-over trial (43 children) found no differences between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence).Dornase alfa compared to other medications that improve airway clearanceResults for these comparisons were mixed. One trial (43 children) showed a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported no difference in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found a difference in quality of life favouring dornase alfa when compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence).When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.

Dornase alfa for cystic fibrosis.

BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. OBJECTIVES: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 30 November 2015.Clinicaltrials.gov was also searched to identify unpublished or ongoing trials. Date of most recent search: 28 November 2015. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. MAIN RESULTS: The searches identified 54 trials, of which 19 (including a total of 2565 participants) met our inclusion criteria. Three additional papers examined the healthcare cost from one of the clinical trials. Fifteen trials compared dornase alfa to placebo or no dornase alfa treatment (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa with hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Compared to placebo, forced expiratory volume at one second improved in the intervention groups, with significant differences at one, three, six months and two years. There was also a significant improvement in lung clearance index at one month. There was a decrease in pulmonary exacerbations compared to placebo in trials of longer duration. The quality of the evidence from placebo-controlled trials was moderate to high for outcomes of lung function and pulmonary exacerbations. Limited, low quality evidence was available for changes in quality of life from baseline. One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.The results for trials comparing dornase alfa to other medications that improve airway clearance (hypertonic saline or mannitol) were mixed, with one trial showing a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline, and three trials finding no difference between medications. In the only trial to assess the combination of dornase alfa with another medication compared to dornase alone, there was no benefit seen with the combination of dornase alfa and mannitol. Evidence of dornase alfa compared to other medications was limited and the open-label design of the trials may have induced bias, therefore the quality of the evidence was judged to be low.Dornase alfa did not cause significantly more adverse effects, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to hyperosmolar agents in improving lung function.

Urban growth, climate change, and freshwater availability.

Nearly 3 billion additional urban dwellers are forecasted by 2050, an unprecedented wave of urban growth. While cities struggle to provide water to these new residents, they will also face equally unprecedented hydrologic changes due to global climate change. Here we use a detailed hydrologic model, demographic projections, and climate change scenarios to estimate per-capita water availability for major cities in the developing world, where urban growth is the fastest. We estimate the amount of water physically available near cities and do not account for problems with adequate water delivery or quality. Modeled results show that currently 150 million people live in cities with perennial water shortage, defined as having less than 100 L per person per day of sustainable surface and groundwater flow within their urban extent. By 2050, demographic growth will increase this figure to almost 1 billion people. Climate change will cause water shortage for an additional 100 million urbanites. Freshwater ecosystems in river basins with large populations of urbanites with insufficient water will likely experience flows insufficient to maintain ecological process. Freshwater fish populations will likely be impacted, an issue of special importance in regions such as India's Western Ghats, where there is both rapid urbanization and high levels of fish endemism. Cities in certain regions will struggle to find enough water for the needs of their residents and will need significant investment if they are to secure adequate water supplies and safeguard functioning freshwater ecosystems for future generations.

Demographic change and urban health: Towards a novel agenda for delivering sustainable and healthy cities for all.

The focus is on the demographic drivers and demographic implications of urban health and wellbeing in towns and cities across the globe. The aim is to identify key linkages between demographic change and urban health - subjects of two largely disparate fields of research and practice - with a view to informing arguments and advocacy for urban health while identifying research gaps and priorities. The core arguments are threefold. First, urban health advocates should express a globalized perspective on demographic processes, encompassing age-structural shifts in addition to population growth and decrease, and acknowledging their uneven spatial distributions within and between urban settings in different contexts. Second, advocates should recognize the dynamic and transformational effects that demographic forces will exert on economic and political systems in all urban settings. While demographic forces underpin the production of (intra)urban inequities in health, they also present opportunities to address those inequities. Third, a demographic perspective may help to extend urban health thinking and intervention beyond a biomedical model of disease, highlighting the need for a multi-generational view of the changing societal bases for urban health, and enjoining significant advances in how interested parties collect, manage, analyse, and use demographic data. Accordingly, opportunities are identified to increase the availability of granular and accurate data to enable evidence-informed action on the demographic/health nexus.

Mapping populations at risk: improving spatial demographic data for infectious disease modeling and metric derivation.

The use of Global Positioning Systems (GPS) and Geographical Information Systems (GIS) in disease surveys and reporting is becoming increasingly routine, enabling a better understanding of spatial epidemiology and the improvement of surveillance and control strategies. In turn, the greater availability of spatially referenced epidemiological data is driving the rapid expansion of disease mapping and spatial modeling methods, which are becoming increasingly detailed and sophisticated, with rigorous handling of uncertainties. This expansion has, however, not been matched by advancements in the development of spatial datasets of human population distribution that accompany disease maps or spatial models.Where risks are heterogeneous across population groups or space or dependent on transmission between individuals, spatial data on human population distributions and demographic structures are required to estimate infectious disease risks, burdens, and dynamics. The disease impact in terms of morbidity, mortality, and speed of spread varies substantially with demographic profiles, so that identifying the most exposed or affected populations becomes a key aspect of planning and targeting interventions. Subnational breakdowns of population counts by age and sex are routinely collected during national censuses and maintained in finer detail within microcensus data. Moreover, demographic and health surveys continue to collect representative and contemporary samples from clusters of communities in low-income countries where census data may be less detailed and not collected regularly. Together, these freely available datasets form a rich resource for quantifying and understanding the spatial variations in the sizes and distributions of those most at risk of disease in low income regions, yet at present, they remain unconnected data scattered across national statistical offices and websites.In this paper we discuss the deficiencies of existing spatial population datasets and their limitations on epidemiological analyses. We review sources of detailed, contemporary, freely available and relevant spatial demographic data focusing on low income regions where such data are often sparse and highlight the value of incorporating these through a set of examples of their application in disease studies. Moreover, the importance of acknowledging, measuring, and accounting for uncertainty in spatial demographic datasets is outlined. Finally, a strategy for building an open-access database of spatial demographic data that is tailored to epidemiological applications is put forward.

Structural Biology-Guided Design, Synthesis, and Biological Evaluation of Novel Insect Nicotinic Acetylcholine Receptor Orthosteric Modulators.

The development of novel and safe insecticides remains an important need for a growing world population to protect crops and animal and human health. New chemotypes modulating the insect nicotinic acetylcholine receptors have been recently brought to the agricultural market, yet with limited understanding of their molecular interactions at their target receptor. Herein, we disclose the first crystal structures of these insecticides, namely, sulfoxaflor, flupyradifurone, triflumezopyrim, flupyrimin, and the experimental compound, dicloromezotiaz, in a double-mutated acetylcholine-binding protein which mimics the insect-ion-channel orthosteric site. Enabled by these findings, we discovered novel pharmacophores with a related mode of action, and we describe herein their design, synthesis, and biological evaluation.

Roundtable on Urban Living Environment Research (RULER).

For 18 months in 2009-2010, the Rockefeller Foundation provided support to establish the Roundtable on Urban Living Environment Research (RULER). Composed of leading experts in population health measurement from a variety of disciplines, sectors, and continents, RULER met for the purpose of reviewing existing methods of measurement for urban health in the context of recent reports from UN agencies on health inequities in urban settings. The audience for this report was identified as international, national, and local governing bodies; civil society; and donor agencies. The goal of the report was to identify gaps in measurement that must be filled in order to assess and evaluate population health in urban settings, especially in informal settlements (or slums) in low- and middle-income countries. Care must be taken to integrate recommendations with existing platforms (e.g., Health Metrics Network, the Institute for Health Metrics and Evaluation) that could incorporate, mature, and sustain efforts to address these gaps and promote effective data for healthy urban management. RULER noted that these existing platforms focus primarily on health outcomes and systems, mainly at the national level. Although substantial reviews of health outcomes and health service measures had been conducted elsewhere, such reviews covered these in an aggregate and perhaps misleading way. For example, some spatial aspects of health inequities, such as those pointed to in the 2008 report from the WHO's Commission on the Social Determinants of Health, received limited attention. If RULER were to focus on health inequities in the urban environment, access to disaggregated data was a priority. RULER observed that some urban health metrics were already available, if not always appreciated and utilized in ongoing efforts (e.g., census data with granular data on households, water, and sanitation but with little attention paid to the spatial dimensions of these data). Other less obvious elements had not exploited the gains realized in spatial measurement technology and techniques (e.g., defining geographic and social urban informal settlement boundaries, classification of population-based amenities and hazards, and innovative spatial measurement of local governance for health). In summary, the RULER team identified three major areas for enhancing measurement to motivate action for urban health-namely, disaggregation of geographic areas for intra-urban risk assessment and action, measures for both social environment and governance, and measures for a better understanding of the implications of the physical (e.g., climate) and built environment for health. The challenge of addressing these elements in resource-poor settings was acknowledged, as was the intensely political nature of urban health metrics. The RULER team went further to identify existing global health metrics structures that could serve as platforms for more granular metrics specific for urban settings.

Global Harmonization of Urbanization Measures: Proceed with Care.

By 2050, two-thirds of the world's population is expected to be living in cities and towns, a marked increase from today's level of 55 percent. If the general trend is unmistakable, efforts to measure it precisely have been beset with difficulties: the criteria defining urban areas, cities and towns differ from one country to the next and can also change over time for any given country. The past decade has seen great progress toward the long-awaited goal of scientifically comparable urbanization measures, thanks to the combined efforts of multiple disciplines. These efforts have been organized around what is termed the "statistical urbanization" concept, whereby urban areas are defined by population density, contiguity and total population size. Data derived from remote-sensing methods can now supply a variety of spatial proxies for urban areas defined in this way. However, it remains to be understood how such proxies complement, or depart from, meaningful country-specific alternatives. In this paper, we investigate finely resolved population census and satellite-derived data for the United States, Mexico and India, three countries with widely varying conceptions of urban places and long histories of debate and refinement of their national criteria. At the extremes of the urban-rural continuum, we find evidence of generally good agreement between the national and remote sensing-derived measures (albeit with variation by country), but identify significant disagreements in the middle ranges where today's urban policies are often focused.

Urban Family Planning in Low- and Middle-Income Countries: A Critical Scoping Review.

Health agendas for low- and middle-income countries (LMICs) should embrace and afford greater priority to urban family planning to help achieve a number of the global Sustainable Development Goals. The urgency of doing so is heightened by emerging evidence of urban fertility stalls and reversals in some sub-Saharan African contexts as well as the significance of natural increase over migration in driving rapid urban growth. Moreover, there is new evidence from evaluations of large programmatic interventions focused on urban family planning that suggest ways to inform future programmes and policies that are adapted to local contexts. We present the key dimensions and challenges of urban growth in LMICs, offer a critical scoping review of recent research findings on urban family planning and fertility dynamics, and highlight priorities for future research.

Applying the Crystalline Sponge Method to Agrochemicals: Obtaining X-ray Structures of the Fungicide Metalaxyl-M and Herbicide S-Metolachlor.

The crystalline sponge method is a technique that provides the ability to elucidate the absolute structure of noncrystalline or hard to crystallize compounds through single-crystal X-ray diffraction by removing the need to obtain crystals of the target compound. In this study the crystalline sponges {[(ZnX2)3(2,4,6-tris(4-pyridyl)-1,3,5-trazine)2].x(solvent)} n (X = I, Br) were used to obtain X-ray structures of the agrochemical active ingredients metalaxyl-M and S-metolachlor. The effect of the temperature used during guest uptake and the influence of changing the host framework ZnX2 nodes on guest encapsulation were investigated. Additionally, three compounds containing chemical fragments similar to those of metalaxyl-M and S-metolachlor (phenylacetaldehyde, N-ethyl-o-toluidine, and methyl phenylacetate) were also encapsulated. This allowed for the effect of guest size on the position that guests occupy within the host frameworks to be examined. The disorder experienced by the guest compounds was documented, and an analysis of the intermolecular host-guest interactions (CH···π and π ···π) used for guest ordering within the host frameworks was also undertaken in this study.

NEMO oligomerization and its ubiquitin-binding properties.

The IKK [IkappaB (inhibitory kappaB) kinase] complex is a key regulatory component of NF-kappaB (nuclear factor kappaB) activation and is responsible for mediating the degradation of IkappaB, thereby allowing nuclear translocation of NF-kappaB and transcription of target genes. NEMO (NF-kappaB essential modulator), the regulatory subunit of the IKK complex, plays a pivotal role in this process by integrating upstream signals, in particular the recognition of polyubiquitin chains, and relaying these to the activation of IKKalpha and IKKbeta, the catalytic subunits of the IKK complex. The oligomeric state of NEMO is controversial and the mechanism by which it regulates activation of the IKK complex is poorly understood. Using a combination of hydrodynamic techniques we now show that apo-NEMO is a highly elongated, dimeric protein that is in weak equilibrium with a tetrameric assembly. Interaction with peptides derived from IKKbeta disrupts formation of the tetrameric NEMO complex, indicating that interaction with IKKalpha and IKKbeta and tetramerization are mutually exclusive. Furthermore, we show that NEMO binds to linear di-ubiquitin with a stoichiometry of one molecule of di-ubiquitin per NEMO dimer. This stoichiometry is preserved in a construct comprising the second coiled-coil region and the leucine zipper and in one that essentially spans the full-length protein. However, our data show that at high di-ubiquitin concentrations a second weaker binding site becomes apparent, implying that two different NEMO-di-ubiquitin complexes are formed during the IKK activation process. We propose that the role of these two complexes is to provide a threshold for activation, thereby ensuring sufficient specificity during NF-kappaB signalling.

The heterogeneity and change in the urban structure of metropolitan areas in the United States, 1990-2010.

While the population of the United States has been predominantly urban for nearly 100 years, periodic transformations of the concepts and measures that define urban places and population have taken place, complicating over-time comparisons. We compare and combine data series of officially-designated urban areas, 1990-2010, at the census block-level within Metropolitan Statistical Areas (MSAs) with a satellite-derived consistent series on built-up area from the Global Human Settlement Layer to create urban classes that characterize urban structure and provide estimates of land and population. We find considerable heterogeneity in urban form across MSAs, even among those of similar population size, indicating the inherent difficulties in urban definitions. Over time, we observe slightly declining population densities and increasing land and population in areas captured only by census definitions or low built-up densities, constrained by the geography of place. Nevertheless, deriving urban proxies from satellite-derived built-up areas is promising for future efforts to create spatio-temporally consistent measures for urban land to guide urban demographic change analysis.

Urbanization in India: Population and Urban Classification Grids for 2011.

India is the world's most populous country, yet also one of the least urban. It has long been known that India's official estimates of urban percentages conflict with estimates derived from alternative conceptions of urbanization. To date, however, the detailed spatial and settlement boundary data needed to analyze and reconcile these differences have not been available. This paper presents gridded estimates of population at a resolution of 1 km along with two spatial renderings of urban areas-one based on the official tabulations of population and settlement types (i.e., statutory towns, outgrowths, and census towns) and the other on remotely-sensed measures of built-up land derived from the Global Human Settlement Layer. We also cross-classified the census data and the remotely-sensed data to construct a hybrid representation of the continuum of urban settlement. In their spatial detail, these materials go well beyond what has previously been available in the public domain, and thereby provide an empirical basis for comparison among competing conceptual models of urbanization.

Using sexually transmitted infection biomarkers to validate reporting of sexual behavior within a randomized, experimental evaluation of interviewing methods.

This paper examines the reporting of sexual and other risk behaviors within a randomized experiment using a computerized versus face-to-face interview mode. Biomarkers for sexually transmitted infection (STI) were used to validate self-reported behavior by interview mode. As part of a parent study evaluating home versus clinic screening and diagnosis for STIs, 818 women aged 18-40 years were recruited in 2004 at or near a primary care clinic in São Paulo, Brazil, and were randomized to a face-to-face interview or audio computer-assisted self-interviewing. Ninety-six percent of participants were tested for chlamydia, gonorrhea, and trichomoniasis. Reporting of STI risk behavior was consistently higher with the computerized mode of interview. Stronger associations between risk behaviors and STI were found with the computerized interview after controlling for sociodemographic factors. These results were obtained by using logistic regression approaches, as well as statistical methods that address potential residual confounding and covariate endogeneity. Furthermore, STI-positive participants were more likely than STI-negative participants to underreport risk behavior in the face-to-face interview. Results strongly suggest that computerized interviewing provides more accurate and reliable behavioral data. The analyses also confirm the benefits of using data on prevalent STIs for externally validating behavioral reporting.

Understanding urbanization: A study of census and satellite-derived urban classes in the United States, 1990-2010.

Most of future population growth will take place in the world's cities and towns. Yet, there is no well-established, consistent way to measure either urban land or people. Even census-based urban concepts and measures undergo frequent revision, impeding rigorous comparisons over time and place. This study presents a new spatial approach to derive consistent urban proxies for the US. It compares census-designated urban blocks with proxies for land-based classifications of built-up areas derived from time-series of the Global Human Settlement Layer (GHSL) for 1990-2010. This comparison provides a new way to understand urban structure and its changes: Most land that is more than 50% built-up, and people living on such land, are officially classified as urban. However, 30% of the census-designated urban population and land is located in less built-up areas that can be characterized as mainly suburban and peri-urban in nature. Such insights are important starting points for a new urban research program: creating globally and temporally consistent proxies to guide modelling of urban change.

Scalable total synthesis and comprehensive structure-activity relationship studies of the phytotoxin coronatine.

Natural phytotoxins are valuable starting points for agrochemical design. Acting as a jasmonate agonist, coronatine represents an attractive herbicidal lead with novel mode of action, and has been an important synthetic target for agrochemical development. However, both restricted access to quantities of coronatine and a lack of a suitably scalable and flexible synthetic approach to its constituent natural product components, coronafacic and coronamic acids, has frustrated development of this target. Here, we report gram-scale production of coronafacic acid that allows a comprehensive structure-activity relationship study of this target. Biological assessment of a >120 member library combined with computational studies have revealed the key determinants of potency, rationalising hypotheses held for decades, and allowing future rational design of new herbicidal leads based on this template.

Clinical correlations and pulmonary function at 8 years of age after severe neonatal respiratory failure.

OBJECTIVES: The aim of this study was to determine the pulmonary sequelae of severe neonatal respiratory failure. STUDY DESIGN: This was a multicenter, prospective study. Fifty-four survivors of neonatal respiratory failure (oxygenation indices >25 on two occasions), completed pulmonary function testing at 8 years of age. Thirty-one (57%) received extracorporeal membrane oxygenation (ECMO). Pulmonary outcome was based on spirometry and lung volume data. Pulmonary outcome for each diagnostic and treatment group is reported as mean and as percent predicted. Individually subjects were also classified based on spirometry, as either normal, obstructed (defined as forced expiratory volume (FEV(1)) in 1 sec:forced vital capacity (FVC) of <80 % predicted, or with reduced FVC (FCV of <80% predicted) with normal FEV(1)/FVC. Risk for adverse outcome was determined using univariate analysis. RESULTS: Mean FVC, FEV(1) and FEV(25-75) were reduced in the total cohort. The reduction was greatest in the subgroup with CDH and the group treated with ECMO. Assessed individually, 54% of subjects had normal spirometry and lung volumes, 19% airflow obstruction, and 27% reduced FVC. Poorer pulmonary outcome was linked to ECMO, congenital diaphragmatic hernia (CDH), birth weight for gestational age <10th percentile, duration of hospitalization, or need for prolonged supplemental oxygen. CONCLUSION: Neonates with severe respiratory failure due to CDH or needing ECMO and small for gestation are at increased risk of poorer pulmonary outcome and require close follow-up.

Single-crystal X-ray diffraction and NMR crystallography of a 1:1 cocrystal of dithianon and pyrimethanil.

A single-crystal X-ray diffraction structure of a 1:1 cocrystal of two fungicides, namely dithianon (DI) and pyrimethanil (PM), is reported [systematic name: 5,10-dioxo-5H,10H-naphtho[2,3-b][1,4]dithiine-2,3-dicarbonitrile-4,6-dimethyl-N-phenylpyrimidin-2-amine (1/1), C14H4N2O2S2·C12H13N2]. Following an NMR crystallography approach, experimental solid-state magic angle spinning (MAS) NMR spectra are presented together with GIPAW (gauge-including projector augmented wave) calculations of NMR chemical shieldings. Specifically, experimental 1H and 13C chemical shifts are determined from two-dimensional 1H-13C MAS NMR correlation spectra recorded with short and longer contact times so as to probe one-bond C-H connectivities and longer-range C...H proximities, whereas H...H proximities are identified in a 1H double-quantum (DQ) MAS NMR spectrum. The performing of separate GIPAW calculations for the full periodic crystal structure and for isolated molecules allows the determination of the change in chemical shift upon going from an isolated molecule to the full crystal structure. For the 1H NMR chemical shifts, changes of 3.6 and 2.0 ppm correspond to intermolecular N-H...O and C-H...O hydrogen bonding, while changes of -2.7 and -1.5 ppm are due to ring current effects associated with C-H...π interactions. Even though there is a close intermolecular S...O distance of 3.10 Å, it is of note that the molecule-to-crystal chemical shifts for the involved sulfur or oxygen nuclei are small.