Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in ...Hong Kong, Malaysia, and Thailand, the prevalence of patients with ⩾ 1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia.
A multicenter study was conducted to evaluate the diagnostic performance and the time to identifcation of the Verigene Blood Culture Test, the BC-GP and BC-GN assays, to identify both Gram-positive ...and Gram-negative bacteria and their drug resistance determinants directly from positive blood cultures collected in Hong Kong.
A total of 364 blood cultures were prospectively collected from four public hospitals, in which 114 and 250 cultures yielded Gram-positive and Gram-negative bacteria, and were tested with the BC-GP and BC-GN assay respectively. The overall identification agreement for Gram-positive and Gram-negative bacteria were 89.6% and 90.5% in monomicrobial cultures and 62.5% and 53.6% in polymicrobial cultures, respectively. The sensitivities for most genus/species achieved at least 80% except Enterococcus spp. (60%), K.oxytoca (0%), K.pneumoniae (69.2%), whereas the specificities for all targets ranged from 98.9% to 100%. Of note, 50% (7/14) cultures containing K.pneumoniae that were missed by the BC-GN assay were subsequently identified as K.variicola. Approximately 5.5% (20/364) cultures contained non-target organisms, of which Aeromonas spp. accounted for 25% and are of particular concern. For drug resistance determination, the Verigene test showed 100% sensitivity for identification of MRSA, VRE and carbapenem resistant Acinetobacter, and 84.4% for ESBL-producing Enterobacteriaceae based on the positive detection of mecA, vanA, blaOXA and blaCTXM respectively.
Overall, the Verigene test provided acceptable accuracy for identification of bacteria and resistance markers with a range of turnaround time 40.5 to 99.2 h faster than conventional methods in our region.
How and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a ...mechanism for binding stimulus features across sensory modalities. Here, we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex via the phase of the local field potential is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis.
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•Visual stimuli can shape how auditory cortical neurons respond to sound mixtures•Temporal coherence between senses enhances sound features of a bound multisensory object•Visual stimuli elicit changes in the phase of the local field potential in auditory cortex•Vision-induced phase effects are lost when visual cortex is reversibly silenced
Atilgan et al. demonstrate that temporal coherence between auditory and visual stimuli shapes the representation of a sound scene in auditory cortex. Auditory cortex is identified as a site of multisensory binding, with inputs from visual cortex underpinning these effects.
Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular ...mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial-mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by β-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of β-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.
Older patients with chronic diseases often take multiple prescription drugs, increasing their risk of adverse health events. However, polypharmacy remains ill-defined.
To investigate the impact of ...number of drugs prescribed on potentially inappropriate medication (PIM) and the associated risk factors in older outpatients with chronic diseases.
Retrospective cross-sectional study.
We retrospectively assessed 780 older patients (mean, 75.5 ± 7.1 years) with long-term (≥ 28 days) prescriptions for chronic diseases at the geriatric clinics of a university hospital from January to June 2012 using the Screening Tool of Older Person's potentially inappropriate Prescriptions (STOPP). Clinical information for each patient was analyzed. Logistic regression and receiver operating characteristic curve (ROC) analyses were performed; number needed to harm (NNH) was also estimated.
According to STOPP criteria, 302 patients (39%) had at least one PIM. Multivariate analysis revealed that PIM risk was associated with the number of medications prescribed (P < 0.001) and the presence of cardiovascular (P < 0.001) or gastrointestinal disease (P = 0.003). The estimated area under the ROC for the number of medications needed to predict PIM risk was 0.680 (P < 0.001) with the optimal cut-off value of five medications. After adjusting covariates, patients prescribed ≥ 5 drugs adjusted odds ratio (OR) = 5.4; adjusted NNH = 4.25; P < 0.001 and those prescribed 4 drugs (adjusted OR = 3.5; adjusted NNH = 6.88; P = 0.003) had significantly higher PIM risk than those prescribed ≤ 2 drugs.
The number of prescribed medications can be an index of PIM risk in older patients with chronic diseases. Clinicians should suspect high PIM risk in older outpatients with ≥ 5 prescriptions.
Abstract Background and aims Abdominal aortic calcification (AC) has been reported to be associated with cardiovascular disease (CVD) in hemodialysis patients but is rarely discussed in peritoneal ...dialysis (PD) patients. We examined the independent predictors and predictive power for survival of AC in prevalent PD patients. Methods and Results AC was detected by computed tomography (CT) and represented as the percentage of the total aortic cross-section area affected by AC (%AC). The predictors of %AC ≥15 were examined by multiple logistic regression analysis. Cox proportional hazard analysis was used to determine the hazard ratios associated with high %AC. A total of 183 PD patients were recruited to receive CT scans and divided into group 1 (%AC < 15, n = 97), group 2 (%AC ≥ 15, n = 41), and group 3 (diabetic patients, n = 45). Group 1 patients had lower osteoprotegerin (OPG) levels than group 2 patients (798 ± 378 vs. 1308 ± 1350 pg/mL, p < 0.05). The independent predictors for %AC ≥ 15 included the atherogenic index, OPG, and C-reactive protein (CRP). The age-adjusted hazard ratios associated with %AC ≥15 were 3.46 ( p = 0.043) for mortality and 1.90 ( p = 0.007) for hospitalization. Conclusions %AC can predict mortality and morbidity in non-diabetic PD patients, and 15% is a good cut-off value for such predictions. There are complex associations among mineral metabolism, inflammation, and dyslipidemia in the pathogenesis of AC.
To investigate the risk factors for acute GVHD (aGVHD), based on NIH consensus criteria (NCC), we evaluated 775 patients who underwent allogeneic transplantation. Of them, 346 patients developed ...aGVHD by NCC, in whom we also analyzed factors affecting aGVHD-specific survival. The cumulative incidence of aGVHD was 44.7%, consisting of classic aGVHD (n=320) and late-onset (n=26). Multivariate analyses revealed that younger age (P=0.015), unrelated donors (P=0.004) and acute leukemia compared with other hematologic malignancies (P=0.005) were significant risk factors for aGVHD, whereas PBSCs showed no association (P=0.720). Multivariate analyses, with only aGVHD patients, revealed that late-onset aGVHD had superior aGVHD-specific survival to classic aGVHD (P=0.044), and identified the association of visceral organ involvement (P=0.002), severity of aGVHD at onset (P=0.035) and advanced disease status (P<0.001) with inferior aGVHD-specific survival. In conclusion, this study demonstrates the risk and prognostic factors for aGVHD by NCC with some differences with the previous reports that were based on old criteria. The difference in the risk factors according to different criteria will give insights about the pathophysiology of GVHD. The better prognosis of late-onset aGVHD than of classic aGVHD raises the necessity for prospective trials with a large cohort focusing on the onset time.
This paper reports on several substorms observed under northward interplanetary magnetic field (IMF) conditions, the intensity of which was at least as significant as that of typical substorms under ...moderately southward IMF conditions. Such northward IMF periods were identified during the recovery phase of three strong storms. In the case of each storm, two or more substorms occurred successively, being separated by ∼1.8–5 h, while the IMF condition continued persistently northward. The substorms are clearly evidenced by auroral and other complementary observations. For the most intense substorms, the auroral breakup occurred at the magnetic latitude of ∼58°, and for the others it was between 60° and 65°. The polar cap size prior to each onset was substantial despite the northward IMF conditions. The auroral expansion following each onset lasted from a few up to several magnetic local time hours and exhibited a clear poleward expansion feature. For most of the events studied, geosynchronous magnetic dipolarizations preceded by field stretching and/or energetic particle injections occurred. The occurrence of such (intense) substorms implies that a certain (large) amount of energy remains in the tail even under northward IMF conditions. The occurrence of two or more successive substorms further implies that even after the release of a certain amount of energy triggered by the substorm, the tail can still have a substantial amount of energy left, which can be released by a subsequent substorm(s). We conjecture that an intense substorm during a northward IMF period can be expected when such a period belongs to the recovery phase of an intense storm mainly because of large energy loading done by preceding southward IMF Bz during the storm's main (and some early recovery) phase. In addition we argue that substorm energy can also be supplied by other mechanisms of the solar wind–magnetosphere coupling under northward IMF conditions such as dayside reconnection in the presence of a substantial IMF By component.
Cancer outcomes vary widely among different countries. However, comparisons of cost-effectiveness and cost-efficiency of different systems are complex because the incidences of different cancers vary ...across countries and their chances of cure also differ substantially. We aim to propose a new standardized method for global comparison and to explore its relationship with economic indicators.
Cancer statistics from all 184 countries and 27 cancers listed in GLOBOCAN 2012 were analyzed. The complement of age-standardized mortality/incidence ratio 1 - (ASM/ASI) was taken as the proxy relative survival (RS). Accounting for various country-specific cancer patterns, the cancer site-standardized proxy RS (proxy SS-RS) of individual countries were calculated by weighting the proportion of specific cancer sites as compared with the global pattern of incidence. Economic indicators of different countries listed by the World Bank were correlated with corresponding proxy SS-RS.
Substantial variation in site-specific survival and new case distribution supported the use of proxy SS-RS, which ranged from 0.124 to 0.622 (median 0.359). The median total health expenditure per capita (HEpc) increased from US$44 for countries with proxy SS-RS < 0.25, to US$4643 for countries with proxy SS-RS ≥0.55. Results from logarithmic regression model showed exponential increase in total HEpc for better outcome. The expenditure varied widely among different strata, with the widest difference observed among countries with SS-RS ≥0.55 (total HEpc US$1412-$9361).
Similar to age-standardization, cancer site-standardization adjusted for variation in pattern of cancer incidence provides the best available and feasible strategies for comparing cancer survivals across countries globally. Furthermore, cancer outcome correlated significantly with economic indicators and the amount of HEpc escalated exponentially. Our findings call for more in-depth studies applying cancer-site standardization to provide essential data for sharing of experience and urgent actions by policy makers to develop comprehensive and financially sustainable cancer plan for greater equity.
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