The Tweet\u27s the Thing: Exploring the Intersection of Social Media and Broadway

In 2009 the little known Broadway musical Next to Normal rose to fame through the aid of an unprecedented Twitter campaign conducted by Situation Interactive, a digital marketing agency. The Next to Normal Twitter account gathered over one million followers throughout a six-week campaign in which the Situation Interactive team joined forces with the book writer and lyricist of Next to Normal to recreate the plot in one hundred and forty-character snippets. By analyzing the data collected the researcher cultivates a collection of best practices for running a successful Twitter marketing campaign for a live experience

Mapping the location of terrestrial impacts and extinctions onto the spiral arm structure of the Milky Way

High density regions within the spiral arms are expected to have profound effects on passing stars. Understanding of the potential effects on the Earth and our Solar System is dependent on a sufficient dynamic model of arm passage. Using a novel combination of data we derive a model of the timings of the Solar System through the spiral arms and the relationship to arm tracers such as methanol masers. This reveals that asteroid/comet impacts are significantly clustered near the spiral arms and within specific locations of an average arm structure. The end-Permian and end-Cretaceous extinctions are shown to be located within a small star formation region in two different arms. The start of the Solar System greater than 4.5 Ga occurs in the same region in a third arm. The model complements geo-chemical data in determining the relative importance of extra-Solar events in the diversification and extinction of life on Earth

Nonuniform ocean acidification and attenuation of the ocean carbon sink

Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 44 (2017): 8404–8413, doi:10.1002/2017GL074389.Surface ocean carbon chemistry is changing rapidly. Partial pressures of carbon dioxide gas (pCO2) are rising, pH levels are declining, and the ocean's buffer capacity is eroding. Regional differences in short-term pH trends primarily have been attributed to physical and biological processes; however, heterogeneous seawater carbonate chemistry may also be playing an important role. Here we use Surface Ocean CO2 Atlas Version 4 data to develop 12 month gridded climatologies of carbonate system variables and explore the coherent spatial patterns of ocean acidification and attenuation in the ocean carbon sink caused by rising atmospheric pCO2. High-latitude regions exhibit the highest pH and buffer capacity sensitivities to pCO2 increases, while the equatorial Pacific is uniquely insensitive due to a newly defined aqueous CO2 concentration effect. Importantly, dissimilar regional pH trends do not necessarily equate to dissimilar acidity ([H+]) trends, indicating that [H+] is a more useful metric of acidification.2018-02-1

Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome)

White-Sutton syndrome (WHSUS) is a recently-identified genetic disorder resulting from de novo heterozygous pathogenic variants in POGZ. Thus far, over 50 individuals have been reported worldwide, however phenotypic characterization and data regarding the natural history are still incomplete. Here we report the clinical features of 22 individuals with 21 unique loss of function POGZ variants. We observed a broad spectrum of intellectual disability and/or developmental delay with or without autism, and speech delay in all individuals. Other common problems included ocular abnormalities, hearing loss and gait abnormalities. A validated sleep disordered breathing questionnaire identified symptoms of obstructive sleep apnea in 4/12 (33%) individuals. A higher-than-expected proportion of cases also had gastrointestinal phenotypes, both functional and anatomical, as well as genitourinary anomalies. In line with previous publications, we observed an increased body mass index (BMI) z-score compared to the general population (mean 0.59, median 0.9; p 0.0253). Common facial features included microcephaly, broad forehead, midface hypoplasia, triangular mouth, broad nasal root and flat nasal bridge. Analysis of the Baylor Genetics clinical laboratory database revealed that POGZ variants were implicated in approximately 0.14% of cases who underwent clinical exome sequencing for neurological indications with or without involvement of other body systems. This study describes a greater allelic series and expands the phenotypic spectrum of this new syndromic form of intellectual disability and autism

Global perspectives on observing ocean boundary current systems

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Todd, R. E., Chavez, F. P., Clayton, S., Cravatte, S., Goes, M., Greco, M., Ling, X., Sprintall, J., Zilberman, N., V., Archer, M., Aristegui, J., Balmaseda, M., Bane, J. M., Baringer, M. O., Barth, J. A., Beal, L. M., Brandt, P., Calil, P. H. R., Campos, E., Centurioni, L. R., Chidichimo, M. P., Cirano, M., Cronin, M. F., Curchitser, E. N., Davis, R. E., Dengler, M., deYoung, B., Dong, S., Escribano, R., Fassbender, A. J., Fawcett, S. E., Feng, M., Goni, G. J., Gray, A. R., Gutierrez, D., Hebert, D., Hummels, R., Ito, S., Krug, M., Lacan, F., Laurindo, L., Lazar, A., Lee, C. M., Lengaigne, M., Levine, N. M., Middleton, J., Montes, I., Muglia, M., Nagai, T., Palevsky, H., I., Palter, J. B., Phillips, H. E., Piola, A., Plueddemann, A. J., Qiu, B., Rodrigues, R. R., Roughan, M., Rudnick, D. L., Rykaczewski, R. R., Saraceno, M., Seim, H., Sen Gupta, A., Shannon, L., Sloyan, B. M., Sutton, A. J., Thompson, L., van der Plas, A. K., Volkov, D., Wilkin, J., Zhang, D., & Zhang, L. Global perspectives on observing ocean boundary current systems. Frontiers in Marine Science, 6, (2010); 423, doi: 10.3389/fmars.2019.00423.Ocean boundary current systems are key components of the climate system, are home to highly productive ecosystems, and have numerous societal impacts. Establishment of a global network of boundary current observing systems is a critical part of ongoing development of the Global Ocean Observing System. The characteristics of boundary current systems are reviewed, focusing on scientific and societal motivations for sustained observing. Techniques currently used to observe boundary current systems are reviewed, followed by a census of the current state of boundary current observing systems globally. The next steps in the development of boundary current observing systems are considered, leading to several specific recommendations.RT was supported by The Andrew W. Mellon Foundation Endowed Fund for Innovative Research at WHOI. FC was supported by the David and Lucile Packard Foundation. MGo was funded by NSF and NOAA/AOML. XL was funded by China’s National Key Research and Development Projects (2016YFA0601803), the National Natural Science Foundation of China (41490641, 41521091, and U1606402), and the Qingdao National Laboratory for Marine Science and Technology (2017ASKJ01). JS was supported by NOAA’s Global Ocean Monitoring and Observing Program (Award NA15OAR4320071). DZ was partially funded by the Joint Institute for the Study of the Atmosphere and Ocean (JISAO) under NOAA Cooperative Agreement NA15OAR4320063. BS was supported by IMOS and CSIRO’s Decadal Climate Forecasting Project. We gratefully acknowledge the wide range of funding sources from many nations that have enabled the observations and analyses reviewed here

Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics

Culex quinquefasciatus (the southern house mosquito) is an important mosquito vector of viruses such as West Nile virus and St. Louis encephalitis virus, as well as of nematodes that cause lymphatic filariasis. C. quinquefasciatus is one species within the Culex pipiens species complex and can be found throughout tropical and temperate climates of the world. The ability of C. quinquefasciatus to take blood meals from birds, livestock, and humans contributes to its ability to vector pathogens between species. Here, we describe the genomic sequence of C. quinquefasciatus: Its repertoire of 18,883 protein-coding genes is 22% larger than that of Aedes aegypti and 52% larger than that of Anopheles gambiae with multiple gene-family expansions, including olfactory and gustatory receptors, salivary gland genes, and genes associated with xenobiotic detoxification

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes