International journalism and the emergence of transnational publics: between cosmopolitan norms, the affirmation of identity and market forces

Much has been written about transnational public spheres, though our understanding of their shape and nature remains limited. Drawing on three alternative conceptions of newswork as public communication, this article explores the role of international journalists in shaping transnational publics. Based on a series of original interviews, it asks how journalists are oriented in their newswork (e.g. are they cosmopolitan or parochial in their orientation) and how they ‘imagine’ the public. It finds that interviewees imagine a polycentric transnational public and variously frame their work as giving voice to those affected by an issue (imagining the public as a cosmopolitan community of fate), performing and reaffirming a particular kind of identity and belonging (imagining the public as a nation) or pursuing audiences wherever they may be (imagining the public as the de facto audience)

In vivo quantification of photosensitizer fluorescence in the skin-fold observation chamber using dual-wavelength excitation and NIR imaging

A major challenge in biomedical optics is the accurate quantification of in vivo fluorescence images. Fluorescence imaging is often used to determine the pharmacokinetics of photosensitizers used for photodynamic therapy. Often, however, this type of imaging does not take into account differences in and changes to tissue volume and optical properties of the tissue under interrogation. To address this problem, a ratiometric quantification method was developed and applied to monitor photosensitizer meso-tetra (hydroxyphenyl) chlorin (mTHPC) pharmacokinetics in the rat skin-fold observation chamber. The method employs a combination of dual-wavelength excitation and dualwavelength detection. Excitation and detection wavelengths were selected in the NIR region. One excitation wavelength was chosen to be at the Q band of mTHPC, whereas the second excitation wavelength was close to its absorption minimum. Two fluorescence emission bands were used; one at the secondary fluorescence maximum of mTHPC centered on 720 nm, and one in a region of tissue autofluorescence. The first excitation wavelength was used to excite the mTHPC and autofluorescence and the second to excite only autofluorescence, so that this could be subtracted. Subsequently, the autofluorescence-corrected mTHPC image was divided by the autofluorescence signal to correct for variations in tissue optical properties. This correction algorithm in principle results in a linear relation between the corrected fluorescence and photosensitizer concentration. The limitations of the presented method and comparison with previously published and validated techniques are discussed

Temporal trends of molecular markers associated with artemether- lumefantrine tolerance/resistance in Bagamoyo district, Tanzania

Background: Development and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy (ACT) constitutes a major threat to recent global malaria control achievements. Surveillance of molecular markers could act as an early warning system of ACT-resistance before clinical treatment failures are apparent. The aim of this study was to analyse temporal trends of established genotypes associated with artemether-lumefantrine tolerance/resistance before and after its deployment as first-line treatment for uncomplicated malaria in Tanzania 2006. Methods: Single nucleotide polymorphisms in the P. falciparum multidrug resistance gene 1 (pfmdr1) N86Y, Y184F, D1246Y and P. falciparum chloroquine transporter gene (pfcrt) K76T were analysed from dried blood spots collected during six consecutive studies from children with uncomplicated P. falciparum malaria in Fukayosi village, Bagamoyo District, Tanzania, between 2004-2011. Results: There was a statistically significant yearly increase of pfmdr1 N86, 184F, D1246 and pfcrt K76 between 2006-2011 from 14% to 61% (yearly OR = 1.38 [95% CI 1.25-1.52] p \u3c 0.0001), 14% to 35% (OR = 1.17 [95% CI 1.07-1.30] p = 0.001), 54% to 85% (OR = 1.21 [95% CI 1.03-1.42] p = 0.016) and 49% to 85% (OR = 1.33 [95% CI 1.17-1.51] p \u3c 0.0001), respectively. Unlike for the pfmdr1 SNP, a significant increase of pfcrt K76 was observed already between 2004-2006, from 26% to 49% (OR = 1.68 [95% CI 1.17-2.40] p = 0.005). From 2006 to 2011 the pfmdr1 NFD haplotype increased from 10% to 37% (OR = 1.25 [95% CI 1.12-1.39] p \u3c 0.0001), whereas the YYY haplotype decreased from 31% to 6% (OR = 0.73 [95% CI 0.56-0.98] p = 0.018). All 390 successfully analysed samples had one copy of the pfmdr1 gene. Conclusion: The temporal selection of molecular markers associated with artemether-lumefantrine tolerance/resistance may represent an early warning sign of impaired future drug efficacy. This calls for stringent surveillance of artemether-lumefantrine efficacy in Tanzania and emphasizes the importance of molecular surveillance as a complement to standard in vivo trials. © 2013 Malmberg et al.; licensee BioMed Central Ltd

Community-acquired MRSA and pig-farming

BACKGROUND: Sporadic cases of CA-MRSA in persons without risk-factors for MRSA carriage are increasing. CASE PRESENTATION: We report a MRSA cluster among family members of a pig-farmer, his co-workers and his pigs. Initially a young mother was seen with mastitis due to MRSA. Six months later her baby daughter was admitted to the hospital with pneumococcal otitis. After staying five days in hospital, the baby was found to be MRSA positive. At that point it was decided to look for a possible source, such as other family members and house-hold animals, including pigs on the farm, since those were reported as a possible source of MRSA earlier. Swabs were taken from the throat and nares of family members and co-workers. A veterinarian obtained swabs from the nares, throat and perineum of 10 pigs. Swabs were cultured following a national protocol to detect MRSA that included the use of an enrichment broth. Animal and human strains were characterized by PFGE, spa-typing, MLST analysis, SSCmec, AGR typing, and the detection for PVL, LukM, and TSST toxin genes. Three family members, three co-workers, and 8 of the 10 pigs were MRSA positive. With the exception of the initial case (the mother) all persons were solely colonized, with no signs of clinical infections. After digestion with SmaI, none of the strains showed any bands using PFGE. All isolates belonged to spa type t108 and ST398. CONCLUSION: 1. This report clearly shows clonal spread and transmission between humans and pigs in the Netherlands. 2. MLST sequence type 398 might be of international importance as pig-MRSA, since this type was shown earlier to be present in epidemiologically unrelated French pigs and pig-farmers. 3. Research is needed to evaluate whether this is a local problem or a new source of MRSA, that puts the until now successful Search and Destroy policy of the Netherlands at risk

Development of 'synthetic lethal' strategies to target BRCA1-deficient breast cancer

Recent clinical trials demonstrating the efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of BRCA1-deficient breast cancer have provided support for the 'synthetic lethal' concept of targeted cancer therapeutics. A new study provides further preclinical validation of this concept by demonstrating that BRCA1-deficient mouse mammary tumor cells are selectively sensitive to an inhibitor of the polycomb gene EZH2. The development of polycomb gene inhibitors may provide a novel approach to selectively exploit the molecular alterations in BRCA1-deficient breast tumors

Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrolment decision making

For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials. STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials. We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy. Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes

Single neurons and networks in the mouse claustrum integrate input from widespread cortical sources

The claustrum is thought to be one of the most highly interconnected forebrain structures, but its organizing principles have yet to be fully explored at the level of single neurons. Here, we investigated the identity, connectivity, and activity of identified claustrum neurons in Mus musculus to understand how the structure’s unique convergence of input and divergence of output support binding information streams. We found that neurons in the claustrum communicate with each other across efferent projection-defined modules which were differentially innervated by sensory and frontal cortical areas. Individual claustrum neurons were responsive to inputs from more than one cortical region in a cell-type and projection-specific manner, particularly between areas of frontal cortex. In vivo imaging of claustrum axons revealed responses to both unimodal and multimodal sensory stimuli. Finally, chronic claustrum silencing specifically reduced animals’ sensitivity to multimodal stimuli. These findings support the view that the claustrum is a fundamentally integrative structure, consolidating information from around the cortex and redistributing it following local computations

Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa.In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO).After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2-3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02).One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure

Learning Priors for Bayesian Computations in the Nervous System

Our nervous system continuously combines new information from our senses with information it has acquired throughout life. Numerous studies have found that human subjects manage this by integrating their observations with their previous experience (priors) in a way that is close to the statistical optimum. However, little is known about the way the nervous system acquires or learns priors. Here we present results from experiments where the underlying distribution of target locations in an estimation task was switched, manipulating the prior subjects should use. Our experimental design allowed us to measure a subject's evolving prior while they learned. We confirm that through extensive practice subjects learn the correct prior for the task. We found that subjects can rapidly learn the mean of a new prior while the variance is learned more slowly and with a variable learning rate. In addition, we found that a Bayesian inference model could predict the time course of the observed learning while offering an intuitive explanation for the findings. The evidence suggests the nervous system continuously updates its priors to enable efficient behavior

The effect of high tibial osteotomy on the results of total knee arthroplasty: a matched case control study

BACKGROUND: We performed a matched case control study to assess the effect of prior high tibia valgus producing osteotomy on results and complications of total knee arthroplasty (TKA). METHODS: From 1996 until 2003 356 patients underwent all cemented primary total knee replacement in our institution. Twelve patients with a history of 14 HTO were identified and matched to a control group of 12 patients with 14 primary TKA without previous HTO. The match was made for gender, age, date of surgery, body mass index, aetiology and type of prosthesis. Clinical and radiographic outcome were evaluated after a median duration of follow-up of 3.7 years (minimum, 2.3 years). The SPSS program was used for statistical analyses. RESULTS: The index group had more perioperative blood loss and exposure difficulties with one tibial tuberosity osteotomy and three patients with lateral retinacular releases. No such procedures were needed in the control group. Mid-term HSS, KSS and WOMAC scores were less favourable for the index group, but these differences were not significant. The tibial slope of patients with prior HTO was significantly decreased after this procedure. The tibial posterior inclination angle was corrected during knee replacement but posterior inclination was significantly less compared to the control group. No deep infection or knee component loosening were seen in the group with prior HTO. CONCLUSION: We conclude that TKA after HTO seems to be technically more demanding than a primary knee arthroplasty, but clinical outcome was almost identical to a matched group that had no HTO previously