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Genotyping of thiopurine S-methyltransferase (TPMT) is recommended for predicting the adverse drug response of thiopurines. In the current study, a novel version of allele-specific PCR (AS-PCR), termed competitive real-time fluorescent AS-PCR (CRAS-PCR) was developed to analyze the TPMT*2 genotype in ethnic Chinese. This technique simultaneously uses wild-type and mutant allele-specific scorpion primers in a single reaction. To determine the optimal conditions for both traditional AS-PCR and CRAS-PCR, we used the Taguchi method, an engineering optimization process that balances the concentrations of all components using an orthogonal array rather than a factorial array. Instead of running up to 264 experiments with the conventional factorial method, the Taguchi method achieved the same optimization using only 16 experiments. The optimized CRAS-PCR system completely avoided non-specific amplification occurring in traditional AS-PCR and could be performed at much more relaxed reaction conditions at 1% sensitivity, similar to traditional AS-PCR. TPMT*2 genotyping of 240 clinical samples was consistent with published data. In conclusion, CRAS-PCR is a novel and robust genotyping method, and the Taguchi method is an effective tool for the optimization of molecular analysis techniques.
Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC.
We identified studies that examined the effect of BRAFV600E mutation on CRC within the PubMed, ISI Science Citation Index, and Embase databases. The effect of BRAFV600E on outcome parameters was estimated by odds ratios (ORs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model.
25 studies with a total of 11,955 CRC patients met inclusion criteria. The rate of BRAFV600 was 10.8% (1288/11955). The BRAFV600E mutation in CRC was associated with advanced TNM stage, poor differentiation, mucinous histology, microsatellite instability (MSI), CpG island methylator phenotype (CIMP). This mutation was also associated with female gender, older age, proximal colon, and mutL homolog 1 (MLH1) methylation.
This meta-analysis demonstrated that BRAFV600E mutation was significantly correlated with adverse pathological features of CRC and distinct clinical characteristics. These data suggest that BRAFV600E mutation could be used to supplement standard clinical and pathological staging for the better management of individual CRC patients, and could be considered as a poor prognostic marker for CRC.
The high-resolution melting curve analysis (HRMA) might be a good alternative method for rapid detection of BRAF mutations. However, the accuracy of HRMA in detection of BRAF mutations has not been systematically evaluated. We performed a systematic review and meta-analysis involving 1324 samples from 14 separate studies. The overall sensitivity of HRMA was 0.99 (95% confidence interval (CI) = 0.75–0.82), and the overall specificity was very high at 0.99 (95% CI = 0.94–0.98). The values for the pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 68.01 (95% CI = 25.33–182.64), 0.06 (95% CI = 0.03–0.11), and1263.76 (95% CI = 393.91–4064.39), respectively. The summary receiver operating characteristic curve for the same data shows an area of 1.00 and a Q* value of 0.97. The high sensitivity and specificity, simplicity, low cost, less labor or time and rapid turnaround make HRMA a good alternative method for rapid detection of BRAF mutations in the clinical practice.
The effects of traumatic spinal cord injury (SCI) on the changes in the central nervous system (CNS) over time may depend on the dynamic interaction between the structural integrity of the spinal cord and the capacity of the brain plasticity. Functional magnetic resonance imaging (fMRI) was used in a longitudinal study on five rhesus monkeys to observe cerebral activation during upper limb somatosensory tasks in healthy animals and after unilateral thoracic SCI. The changes in the spinal cord diameters were measured, and the correlations among time after the lesion, structural changes in the spinal cord, and primary somatosensory cortex (S1) reorganization were also determined. After SCI, activation of the upper limb in S1 shifted to the region which generally dominates the lower limb, and the rostral spinal cord transverse diameter adjacent to the lesion exhibited obvious atrophy, which reflects the SCI-induced changes in the CNS. A significant correlation was found among the time after the lesion, the spinal cord atrophy, and the degree of contralateral S1 reorganization. The results indicate the structural changes in the spinal cord and the dynamic reorganization of the cerebral activation following early SCI stage, which may help to further understand the neural plasticity in the CNS.
The cost of next-generation sequencing is now approaching that of early GWAS panels, but is still out of reach for large epidemiologic studies and the millions of rare variants expected poses challenges for distinguishing causal from non-causal variants. We review two types of designs for sequencing studies: two-phase designs for targeted follow-up of genomewide association studies using unrelated individuals; and family-based designs exploiting co-segregation for prioritizing variants and genes. Two-phase designs subsample subjects for sequencing from a larger case-control study jointly on the basis of their disease and carrier status; the discovered variants are then tested for association in the parent study. The analysis combines the full sequence data from the substudy with the more limited SNP data from the main study. We discuss various methods for selecting this subset of variants and describe the expected yield of true positive associations in the context of an on-going study of second breast cancers following radiotherapy. While the sharing of variants within families means that family-based designs are less efficient for discovery than sequencing unrelated individuals, the ability to exploit co-segregation of variants with disease within families helps distinguish causal from non-causal ones. Furthermore, by enriching for family history, the yield of causal variants can be improved and use of identity-by-descent information improves imputation of genotypes for other family members. We compare the relative efficiency of these designs with those using unrelated individuals for discovering and prioritizing variants or genes for testing association in larger studies. While associations can be tested with single variants, power is low for rare ones. Recent generalizations of burden or kernel tests for gene-level associations to family-based data are appealing. These approaches are illustrated in the context of a family-based study of colorectal cancer.
sequencing; two-phase sampling design; family-based study; rare variant association; breast neoplasms; colorectal cancer
This study focused on the effects of laser acupuncture (LA) and manual acupuncture (MA) at different acupoints on gastric motility and heart rate variability (HRV) simultaneously to elucidate the site specific effects of acupoints and the correlation between changes of gastric motility and low frequency/high frequency (LF/HF) ratio. Gastric motility and HRV were recorded before and during MA or LA. Stimulating PC-6 or ST-36 significantly enhanced gastric motility, while BL-21 caused no changes. In contrast, MA or LA at CV-12 significantly suppressed gastric motility. Stimulating PC-6 or ST-36 significantly increased heart rate (HR), while CV-12 or BL-21 induced no significant changes of HR. Stimulating PC-6 significantly increased LF/HF, while ST-36, CV-12, or BL-21 induced no significant effects. These results indicated that there was acupoint specificity in the effects of acupuncture on gastric motility and HRV. The stimulatory effect of MA and LA at PC-6 and ST-36 on HR was associated with sympathetic activity. The stimulatory effect of MA or LA at PC-6 or ST-36 on gastric motility was associated with vagal activity. Laser needle can be used as an alternative stimulation therapy.
The purpose of this study was to evaluate the influence of the duration of interstitial laser acupuncture therapy effects on neurovegetative and neurobioelectrical parameters like heart rate (HR), heart rate variability (HRV), and electroencephalogram (EEG). We investigated 6 male Sprague-Dawley rats. They underwent 10 min, 20 min, and 30 min interstitial laser acupuncture (in randomized order, with a break of at least 30 min between the different measurement conditions) at the acupoint Neiguan. HR changed significantly only during 20 min red laser stimulation, whereas 10 and 30 min stimulation did not induce significant changes. HRV did not change significantly during any of the different durations; however, an increase was found during 20 min irradiation. Neither the LF/HF ratio of HRV nor the integrated EEG showed significant changes. In this study, it could be experimentally proved that some effects of laser acupuncture are time dependent, and therefore the dosage, as well known from theory, also depends on the time factor. We could especially demonstrate that different treatment times lead to different effects on neurovegetative and neurobioelectrical parameters. Further studies are needed to verify or refute these results.
Identification of cytotoxic T lymphocyte (CTL) epitopes from additional tumor antigens is essential for the development of specific immunotherapy of malignant tumors. Neuritin, a recently discovered antigen overexpressed in astrocytoma, is considered to be a promising target for biological therapy. In the present study, we predicted and identified HLA-A2-restricted CTL epitopes from neuritin by using the following four-step procedure: (1) computer-based epitope prediction from the amino acid sequence of neuritin; (2) peptide-binding assay to determine the affinity of the predicted peptide with HLA-A2.1 molecule; (3) stimulation of primary T cell response against the predicted peptides in vitro; and (4) testing of the induced CTLs toward target cells expressing neuritin and HLA-A2.1. The results demonstrated that effectors induced by peptides of neuritin containing residues 13–21, 121–129 and 4–12 could specifically-secrete interferon-γ and lyse target cells. Our results indicate that these peptides are new HLA-A2.1-restricted CTL epitopes, and may serve as valuable tools for astrocytoma immunotherapy.
HLA-A*0201; Cytotoxic T lymphocyte; Epitopes; Neuritin
The aim of this study was to investigate the interrelation between splenic siderotic nodules, hypersplenism and liver function in patients with liver cirrhosis. The splenic enhanced susceptibility-weighted angiography (ESWAN) and conventional magnetic resonance images of 33 patients with liver cirrhosis were retrospectively studied and the ESWAN images were graded. The distribution and prevalence of the image grades for patients with and without hypersplenism were evaluated. In addition, the splenic volume and the distribution of Child-Pugh and albumin scores were compared between patients with and without siderotic nodules, and the correlation between splenic volume and the ESWAN image grades were evaluated in the patients with siderotic nodules. The ESWAN images revealed splenic siderotic nodules in 24 patients. The distribution and prevalence of the ESWAN image grades were demonstrated to be significantly different (P<0.001) between patients with and without hypersplenism. Furthermore, significant differences were observed between patients with and without siderotic nodules with regard to splenic volume and the distribution of Child-Pugh and serum albumin scores (P<0.001). No significant correlation was demonstrated between splenic volume and the ESWAN image grades (P>0.05). In conclusion, a higher prevalence of splenic siderotic nodules (72.7%) was observed using the ESWAN sequence, in comparison with results from previous studies, obtained using the T1-spoiled gradient echo sequence. The presence of splenic siderotic nodules was consistent with the occurrence of hypersplenism and was interrelated with reserved liver function.
spleen; siderotic nodules; magnetic resonance imaging; liver cirrhosis; hypersplenism; thrombocytopenia
We report here that a new superconducting phase with much higher Tc has been found in K intercalated FeSe compound with excess Fe. We successfully grew crystals by precisely controlling the starting amount of Fe. Besides the superconducting (SC) transition at ~30 K, we observed a sharp drop in resistivity and a kink in susceptibility at 44 K. By combining thermodynamic measurements with electron spin resonance (ESR), we demonstrate that this is a new SC transition. Structural analysis unambiguously reveals two phases coexisting in the crystals, which are responsible respectively for the SC transitions at 30 and 44 K. The structural experiments and first-principles calculations consistently indicate that the 44 K SC phase is close to a 122 structure, but with an unexpectedly large c-axis of 18.10 Å. We further find a novel monotonic dependence of the maximum Tc on the separation of neighbouring FeSe layers.
Severe asthma is associated with fixed airway obstruction attributable to inflammation, copious luminal mucus, and increased airway smooth muscle (ASM) mass. Paradoxically, studies demonstrated that the hypertrophic and hyperplastic ASM characteristic of severe asthma has reduced contractile capacity. We compared the G-protein–coupled receptor (GPCR)–induced Ca2+ mobilization and expression of GPCRs and signaling proteins related to procontractile signaling in ASM derived postmortem from subjects who died of nonrespiratory causes, with cells from subjects who died of asthma. Despite the increased or comparable expression of contraction-promoting GPCRs (bradykinin B2 or histamine H1 and protease-activated receptor 1, respectively) in asthmatic ASM cells relative to cells from healthy donors, asthmatic ASM cells exhibited reduced histamine-induced Ca2+ mobilization and comparable responses to bradykinin and thrombin, suggesting a postreceptor signaling defect. Accordingly, the expression of regulator of G-protein signaling–5 (RGS5), an inhibitor of ASM contraction, was increased in cultured, asthmatic ASM cells and in bronchial smooth muscle bundles of both human subjects with asthma and allergen-challenged mice, relative to those of healthy human subjects or naive mice. The overexpression of RGS5 impaired the release of Ca2+ to thrombin, histamine, and carbachol, and reduced the contraction of precision-cut lung slices to carbachol. These results suggest that increased RGS5 expression contributes to decreased myocyte shortening in severe and fatal asthma.
asthma; bronchial smooth muscle; signal transduction; G-protein–coupled receptors
To investigate the effects of melatonin on cellular proliferation and endogenous vascular endothelial growth factor (VEGF) expression in pancreatic carcinoma cells (PANC-1).
PANC-1 cells were cultured for this study. The secreted VEGF concentration in the culture medium was determined using ELISA method, VEGF production in the tumor cells was detected by immunocytochemistry, and VEGF mRNA expression was determined by RT-PCR.
Higher melatonin concentrations significantly inhibited cellular proliferation, with 1 mmol/L concentration exhibiting the highest inhibitory effect (P<0.01). VEGF concentrations in the cell culture supernatants and intra-cellules were all significantly reduced after melatonin (1 mmol/L) incubation (P<0.05). VEGF mRNA expression decreased markedly in a time-dependent manner during the observation period (P<0.05).
High melatonin concentrations markedly inhibited the proliferation of pancreatic carcinoma cells. The endogenous VEGF expression was also suppressed by melatonin incubation.
Melatonin; VEGF; pancreatic cancer
Chinese bayberry myrica rubra is a very popular fruit in southeastern China. In spite of its wide consumption, no allergies to this fruit have been reported previously. Here we report on a 40-year-old woman suffering from anaphylaxis to Chinese bayberry fruit. Prick-prick skin tests revealed strong reactions to fresh Chinese bayberry fruits as well as to peach, and weaker reactions to some other fruits including apple, melon, and banana. ImmunoCAP analysis revealed identical titers of specific IgE (4.3 kUA/L) to peach extract and its lipid transfer protein (LTP, rPru p 3), which was confirmed by detection of a 9 kD band following immunoblotting. Immunoblot analysis with Chinese bayberry extract gave bands of 22, 45, and 90 kD, but no 9 kD band was recognized. There was also no evidence of LTP recognition for loquat (36 kD) or melon (24 kD). This first report of a severe allergic reaction to Chinese bayberry fruit in a patient with LTP-mediated peach allergy indicates that other as yet unidentified non-pollen related fruit allergens are involved in this new severe fruit allergy.
Chinese bayberry; Fruit allergy; Anaphylaxis
In the title compound, C19H19ClO4, the dihedral angle between the mean planes of the benzene rings is 126.8 (1)°. Weak C—H⋯O interactions are observed.
This study was designed to determine the levels of survivin expression and identify its clinical significance as a prognostic factor for stage III non-small cell lung cancer (NSCLC). A total of 210 cases of stage III NSCLC were collected and the expression levels of survivin and vascular endothelial growth factor A (VEGF-A) in tumor tissues were investigated using immunohistochemistry (IHC). The medical records of the patients were reviewed to determine the association with clinical course. Of the 210 NSCLC tissues, 112 (53.3%) cases demonstrated positive expression of survivin protein. Coexpression of survivin and VEGF-A was identified. The 5-year survival rate of patients with positive survivin expression was significantly lower compared with the survivin-negative cancer patients (P<0.05). The expression of survivin in NSCLC correlated with tumor size. Survivin and VEGF-A were independent prognostic factors of stage III NSCLC. Survivin protein is a valuable marker of prognosis in stage III NSCLC patients.
survivin; VEGF-A; immunohistochemistry; prognostic marker
Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and increased mucous glands, which can lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we investigated whether the astragalus extract inhibits airway remodeling in a mouse asthma model and observed the effects of astragalus extract on the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway in ovalbumin-sensitized mice. Mice were sensitized and challenged by ovalbumin to establish a model of asthma. Treatments included the astragalus extract and budesonide. Lung tissues were obtained for hematoxylin and eosin staining and Periodic acid-Schiff staining after the final ovalbumin challenge. Levels of TGF-β1 were assessed by immunohistology and ELISA, levels of TGF-β1 mRNA were measured by RT-PCR, and levels of P-Smad2/3 and T-Smad2/3 were assessed by western blotting. Astragalus extract and budesonide reduced allergen-induced increases in the thickness of bronchial airway and mucous gland hypertrophy, goblet cell hyperplasia and collagen deposition. Levels of lung TGF-β1, TGF-β1 mRNA and P-Smad2/3 were significantly reduced in mice treated with astragalus extract and budesonide. Astragalus extract improved asthma airway remodeling by inhibiting the expression of the TGF-β1/Smad signaling pathway, and may be a potential drug for the treatment of patients with a severe asthma airway.
astragalus plant; airway remodeling; asthma; trans-forming growth factor-β1/Smad signaling pathway
Regulators of G-protein signaling (RGS) proteins are scaffolds that control diverse signaling pathways by modulating signalosome formation and by accelerating the GTPase activity of heterotrimeric G proteins. Although expression of many RGS proteins is relatively low in quiescent cells, transcriptional and post-translational responses to environmental cues regulate both their abundance and activity. We found previously that RGS13, one of the smallest RGS proteins in the family, inhibited cyclic AMP-dependent protein kinase (PKA)-induced gene expression through interactions with the transcription factor cAMP-response element-binding (CREB) protein. Here, we show that PKA activation also leads to increased steady-state RGS13 expression through RGS13 phosphorylation, which inhibits RGS13 protein degradation. RGS13 turnover was significantly reduced in cells stimulated with cAMP, which was reversed by expression of the PKA-specific inhibitory peptide PKI. RGS13 phosphorylation was diminished by mutation of an N-terminal Thr residue (T41) identified as a phosphorylation site by mass spectrometry. Mutation of Thr41 in RGS13 to Ala (T41A) reduced steady-state RGS13 levels and its ability to inhibit M2 muscarinic receptor-mediated Erk phosphorylation compared with wild-type RGS13 by attenuating the protective effect of cAMP on RGS13 degradation. RGS13 underwent ubiquitylation, indicating that it is a likely target of the proteasome. These studies are the first to demonstrate post-translational mechanisms controlling the expression of RGS13. Stabilization of RGS13 through PKA-mediated phosphorylation could enhance RGS13 functions, providing negative feedback regulation that promotes cellular desensitization.
RGS proteins; cAMP; protein kinase; phosphorylation
Oral squamous cell carcinoma (OSCC) has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases (CLNM) in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical-histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy (aRT) and strategies for follow-up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently.
oral squamous cell carcinoma; lymph node metastasis; contralateral neck metastasis; neck dissection; head and neck cancer
Helicobacter pylori persists deep in the human gastric mucus layer in a harsh, nutrient-poor environment. Survival under these conditions depends on the ability of this human pathogen to invoke starvation/stress responses when needed. Unlike many bacteria, H. pylori lacks starvation/stress-responding alternative sigma factors, suggesting an additional mechanism might have evolved in this bacterium. H. pylori produces polyphosphate, however, the role and target of polyphosphate during starvation/stress have not been identified. Here we show that polyphosphate accumulated during nutrient starvation directly targets transcriptional machinery by binding to the principal sigma factor in H. pylori, uncovering a novel mechanism in microbial stress response. A positively-charged-Lys-rich region at the NTD of the major sigma factor is identified as the binding region for polyphosphate (region P) in vivo and in vitro, revealing a new element in sigma 70 family proteins. This interaction is biologically significant because mutant strains defective in the interaction undergo premature cell death during starvation. We suggested that polyphosphate is a second messenger employed by H. pylori to mediate gene expression during starvation/stress. The putative “region P” is present in sigma factors of other human pathogens, suggesting that the uncovered interaction might be a general strategy employed by other pathogens.
Helicobacter pylori; Polyphosphate; Sigma factor; Stress responses; Bacterial gene regulation
AIM: To evaluate the esophageal motility and abnormal acid and bile reflux incidence in cirrhotic patients without esophageal varices (EV).
METHODS: Seventy-eight patients with liver cirrhosis without EV confirmed by upper gastroesophageal endoscopy and 30 healthy control volunteers were prospectively enrolled in this study. All the patients were evaluated using a modified protocol including Child-Pugh score, upper gastrointestinal endoscopy, esophageal manometry, simultaneous ambulatory 24-h esophageal pH and bilirubin monitoring. All the patients and volunteers accepted the manometric study.
RESULTS: In the liver cirrhosis group, lower esophageal sphincter pressure (LESP, 15.32 ± 2.91 mmHg), peristaltic amplitude (PA, 61.41 ± 10.52 mmHg), peristaltic duration (PD, 5.32 ± 1.22 s), and peristaltic velocity (PV, 5.22 ± 1.11 cm/s) were all significantly abnormal in comparison with those in the control group (P < 0.05), and LESP was negatively correlated with Child-Pugh score. The incidence of reflux esophagitis (RE) and pathologic reflux was 37.18% and 55.13%, respectively (vs control, P < 0.05). And the incidence of isolated abnormal acid reflux, bile reflux and mixed reflux was 12.82%, 14.10% and 28.21% in patients with liver cirrhosis without EV.
CONCLUSION: Cirrhotic patients without EV presented esophageal motor disorders and mixed acid and bile reflux was the main pattern; the cirrhosis itself was an important causative factor.
Gastroesophageal reflux disease; Liver cirrhosis; Esophageal varices; Esophageal manometry; pH; Bilirubin; Monitoring
C-X-C chemokine receptor type 4 (CXCR4) plays an important role in determining the metastatic potential of non-small cell lung cancer. In order to elucidate the effect and mechanism of CXCR4 in tumor angiogenesis we evaluated the clinical significance of CXCR4, phosphorylated signal transducer and activator of transcription 3 (P-STAT3), and vascular endothelial growth factor (VEGF) expression in patients with completely resected non-small cell lung cancer (NSCLC). A total of 208 cases of resected NSCLC were collected, and expression of CXCR4, P-STAT3 and VEGF-A in tumor tissue was investigated using immunohistochemistry (IHC). We reviewed the patient clinical records to determine the association of the expression of these proteins with the clinical course of the disease. Expression of CXCR4, P-STAT3 and VEGF-A was detected in 56.3, 46.2 and 51.9% of the samples, respectively. We observed co-expression between CXCR4, P-STAT3 and VEGF-A. Using multivariate analysis, the expression levels of CXCR4 and VEGF-A were identified as independent prognostic factors that affected overall survival. In conclusion, the results of this study suggest that CXCR4, P-STAT3 and VEGF-A expression may play a role in tumor progression and angiogenesis of NSCLC. However, further studies are needed to uncover the detailed mechanism that underlies the role of these proteins in NSCLC.
C-X-C chemokine receptor type 4; phosphorylated signal transducer and activator of transcription 3; vascular endothelial growth factor; immunohistochemistry; prognosis; non-small cell lung cancer
To define the genetic basis of arrhythmogenic right ventricular cardiomyopathy.
Arrhythmogenic right ventricular cardiomyopathy (ARVC), characterized by right ventricular fibrofatty replacement and arrhythmias, causes sudden death. Autosomal dominant Inheritance, reduced penetrance, and 7 desmosome-encoding causative genes are known. The basis of low penetrance is poorly understood.
ARVC probands and family members were enrolled, blood obtained, lymphoblastoid cell lines immortalized, DNA extracted, PCR amplification of desmosome-encoding genes performed, PCR products sequenced and diseased tissue samples studied for intercellular junction protein distribution using confocal immunofluorescence microscopy and antibodies against key proteins.
We identified 21 variants in plakophilin-2 (PKP2) in 38 of 198 probands (19%), including missense, nonsense, splice site, and deletion/insertion mutations. Pedigrees showed wide intra-familial variability (severe early-onset disease to asymptomatic individuals). In 9/38 probands, PKP2 variants were identified that were encoded in trans (compound heterozygosity). The 38 probands hosting PKP2 variants were screened for other desmosomal genes mutations; second variants (digenic heterozygosity) were identified in 16/38 subjects with PKP2 variants (42%) including desmoplakin (DSP, n=6), desmoglein-2 (DSG2, n=5), plakophilin-4 (PKP4, n=1), and desmocollin-2 (DSC2, n=1). Heterozygous mutations in non-PKP 2desmosomal genes occurred in 14/198 subjects (7%), including DSP (n=4), DSG2 (n=5), DSC2 (n=3), and junctional plakoglobin (JUP, n=2). All variants occurred in conserved regions; none were identified in 700 ethnic-matched controls.
Immunohistochemical analysis demonstrated abnormalities of protein architecture.
These data suggest that the genetic basis of ARVC includes reduced penetrance with compound and digenic heterozygosity. Disturbed junctional cytoarchitecture in subjects with desmosomal mutations confirms that ARVC is a disease of the desmosome and cell junction.
Arrhythmias; Cardiomyopathies; Desmosomes; Intercalated Disks; Genetic Mutations
AIM: To investigate the role of intestinal mucosal blood flow (IMBF) and motility in the damage of intestinal mucosal barrier in rats with traumatic brain injury.
METHODS: Sixty-four healthy male Wistar rats were divided randomly into two groups: traumatic brain injury (TBI) group (n = 32), rats with traumatic brain injury; and control group (n = 32), rats with sham-operation. Each group was divided into four subgroups (n = 8) as 6, 12, 24 and 48 h after operation. Intestinal motility was measured by the propulsion ratio of a semi-solid colored marker (carbon-ink). IMBF was measured with the laser-Doppler technique. Endotoxin and D-xylose levels in plasma were measured to evaluate the change of intestinal mucosal barrier function following TBI.
RESULTS: The level of endotoxin was significantly higher in TBI group than in the control group at each time point (0.382 ± 0.014 EU/mL vs 0.102 ± 0.007 EU/mL, 0.466 ± 0.018 EU/mL vs 0.114 ± 0.021 EU/mL, 0.478 ± 0.029 EU/mL vs 0.112 ± 0.018 EU/mL and 0.412 ± 0.036 EU/mL vs 0.108 ± 0.011 EU/mL, P < 0.05). D-xylose concentrations in plasma in TBI group were significantly higher than in the control group (6.68 ± 2.37 mmol/L vs 3.66 ± 1.07 mmol/L, 8.51 ± 2.69 mmol /L vs 3.15 ± 0.95 mmol/L, 11.68 ± 3.24 mmol/L vs 3.78 ± 1.12 mmol/L and 10.23 ± 2.83 mmol/L vs 3.34 ± 1.23 mmol/ L, P < 0.05). The IMBF in TBI group was significantly lower than that in the control group (38.5 ± 2.8 PU vs 45.6 ± 4.6 PU, 25.2 ± 3.1 PU vs 48.2 ± 5.3 PU, 21.5 ± 2.7 PU vs 44.9 ± 2.8 PU, 29. 4 ± 3.8 PU vs 46.7 ± 3.2 PU) (P < 0.05). Significant decelerations of intestinal propulsion ratio in TBI groups were found compared with the control group (0.48% ± 0.06% vs 0.62% ± 0.03%, 0.37% ± 0.05% vs 0.64% ± 0.01%, 0.39% ± 0.07% vs 0.63% ± 0.05% and 0.46% ± 0.03% vs 0.65% ± 0.02%) (P < 0.05).
CONCLUSION: The intestinal mucosal permeability is increased obviously in TBI rats. Decrease of intestinal motility and IMBF occur early in TBI, both are important pathogenic factors for stress-related damage of the intestinal mucosal barrier in TBI.
Traumatic brain injury; Intestinal mucosa barrier; Stress; Intestinal mucosa blood flow; Intestinal motility
asdA mutants of Gram-negative bacteria have an obligate requirement for diaminopimelic acid (DAP), which is an essential constituent of the peptidoglycan layer of the cell wall of these organisms. In environments deprived of DAP, i.e., animal tissues, they will undergo lysis. Deletion of the asdA gene has previously been exploited to develop antibiotic-sensitive strains of live attenuated recombinant bacterial vaccines. Introduction of an Asd+ plasmid into a ΔasdA mutant makes the bacterial strain plasmid-dependent. This dependence on the Asd+ plasmid vector creates a balanced-lethal complementation between the bacterial strain and the recombinant plasmid. E. ictaluri is an enteric Gram-negative fish pathogen that causes enteric septicemia in catfish. Because E. ictaluri is a nasal/oral invasive intracellular pathogen, this bacterium is a candidate to develop a bath/oral live recombinant attenuated Edwardsiella vaccine (RAEV) for the catfish aquaculture industry. As a first step to develop an antibiotic-sensitive RAEV strain, we characterized and deleted the E. ictaluri asdA gene. E. ictaluri ΔasdA01 mutants exhibit an absolute requirement for DAP to grow. The asdA gene of E. ictaluri was complemented by the asdA gene from Salmonella. Several Asd+ expression vectors with different origins of replication were transformed into E. ictaluri ΔasdA01. Asd+ vectors were compatible with the pEI1 and pEI2 E. ictaluri native plasmids. The balanced-lethal system was satisfactorily evaluated in vivo. Recombinant GFP, PspA, and LcrV proteins were synthesized by E. ictaluri ΔasdA01 harboring Asd+ plasmids. Here we constructed a balanced-lethal system, which is the first step to develop an antibiotic-sensitive RAEV for the aquaculture industry.
The cone beam CT (CBCT) guided radiation can reduce the systematic and random setup errors as compared to the skin-mark setup. However, the residual and intrafractional (RAIF) errors are still unknown. The purpose of this paper is to investigate the magnitude of RAIF errors and correction action levels needed in cone beam computed tomography (CBCT) guided accelerated partial breast irradiation (APBI).
Ten patients were enrolled in the prospective study of CBCT guided APBI. The postoperative tumor bed was irradiated with 38.5 Gy in 10 fractions over 5 days. Two cone-beam CT data sets were obtained with one before and one after the treatment delivery. The CBCT images were registered online to the planning CT images using the automatic algorithm followed by a fine manual adjustment. An action level of 3 mm, meaning that corrections were performed for translations exceeding 3 mm, was implemented in clinical treatments. Based on the acquired data, different correction action levels were simulated, and random RAIF errors, systematic RAIF errors and related margins before and after the treatments were determined for varying correction action levels.
A total of 75 pairs of CBCT data sets were analyzed. The systematic and random setup errors based on skin-mark setup prior to treatment delivery were 2.1 mm and 1.8 mm in the lateral (LR), 3.1 mm and 2.3 mm in the superior-inferior (SI), and 2.3 mm and 2.0 mm in the anterior-posterior (AP) directions. With the 3 mm correction action level, the systematic and random RAIF errors were 2.5 mm and 2.3 mm in the LR direction, 2.3 mm and 2.3 mm in the SI direction, and 2.3 mm and 2.2 mm in the AP direction after treatments delivery. Accordingly, the margins for correction action levels of 3 mm, 4 mm, 5 mm, 6 mm and no correction were 7.9 mm, 8.0 mm, 8.0 mm, 7.9 mm and 8.0 mm in the LR direction; 6.4 mm, 7.1 mm, 7.9 mm, 9.2 mm and 10.5 mm in the SI direction; 7.6 mm, 7.9 mm, 9.4 mm, 10.1 mm and 12.7 mm in the AP direction, respectively.
Residual and intrafractional errors can significantly affect the accuracy of image-guided APBI with nonplanar 3DCRT techniques. If a 10-mm CTV-PTV margin is applied, a correction action level of 5 mm or less is necessary so as to maintain the RAIF errors within 10 mm for more than 95% of fractions. Pre-treatment CBCT guidance is not a guarantee for safe delivery of the treatment despite its known benefits of reducing the initial setup errors. A patient position verification and correction during the treatment may be a method for the safe delivery.

domain: medical


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My credits include
AllMusic verified credits for Stewart Hidalgo:
- Mary Scholz
- Antelope Orion
- Allen Smart C1
- BAE 1073MP
- Avedis E27
- Shadow Hills Vandergraph
- Yamaha NS-10s
- Avantone MixcubesUA LA-610 MK II
Terms of Service
Mixing - 2 Revisions Per track. Additional revisions $15 each.
Allow 3-5 Days for turn around on Mixing and Editing
If extra production is required on tracks additional fees will be negotiated
Reviews of Stewart Hidalgo
I had my pop/rock project mixed by Stewart, and I was very satisfied with the way they turned out. He was patient, communicative, and professional, which were qualities that I had been looking for in a mixing engineer. I also liked that he understood the sound that I was going for, which strengthened my confidence in his abilities.
Stew is the best engineer hands down .. i travel miles to Santa Monica to go to him when there's plenty of engineers by where I live.. you wanna know why? cause my boy does good WORK
Stewart is a killer musician, engineer, and consummate professional. A lot of people get by just pressing record, but he pushed not only me, but himself making sure the music was brought to it's fullest potential. He was a great asset from all the way from the basic tracks to the mastering.
Stewart Hidalgo is extremely talented, extremely nice, and extremely patient. Especially that last part! I can't tell you how many times the poor man was willing to go back to make sure my insane conception of my ridiculously complex album (http://programmar.net/music/somaphone6/somaphone6.html) was spot on and sounding great. Hire him asap! : )
I had the pleasure of working with Stewart on a rock project (https://mattchanway.bandcamp.com) , where he handled the mixing, mastering, and also played bass. He is very professional and goes the extra mile to ensure projects are finished within deadlines and up to the client's expectations, both as a session musician and audio engineer.

domain: artistic


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Download MP3: Bigbrown X Piszy “Bless The Boy”
The Koroba master who took a break from the music scene after the hit single that causes alot of rave in Nigeria, ILERI
Bigbrown Aka Isoko boy comes back to the the scene with an inspiring Music “BLESS THE BOY”
And this time around he’s forcing up with the America based act Piszy
Y’all should cop this music below and share your thoughts….


|Min. Order (Square Meters)||FOB Price|
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Corrugated Core Material: It is made by using 0.2mm-0.5mm aluminum sheet rolled by a corrugating machine into a corrugated or trapezoidal shape, characterized by higher stiffness and compressive strength, light weight and so on.


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By Marc Pender
The biggest determination of life longevity is an active lifestyle vs a sedentary one and Diana Nyad is proving that. Diana will be swimming from Cuba to Florida come this June but if you thought that was amazing this is a woman who is over 60 years old. I first met Diana in Sint Maarten where she was training. She had just come off a 15 hour swim and was working out strength training when I met her. She is filled with vitality and inspiration. She hasn’t been swimming for 31 years but last year she completed a 24 hour swim off the coast of Florida which is just a warm up for her lifelong dream of being the first person to swim from Cuba to Florida without a shark cage. June will be the month to watch and with the help of CNN we all should be able to see her. Follow along and check out her website.

domain: news


Man Jailed for Misusing Lottery Profits
A man has been given a custodial sentence for the misuse of lottery profits.
Simon Rydings, a 50-year-old from Edinburgh, ran a lottery on behalf of a charity but was found to have deprived it of some £285,000. He has now been given three months in prison.
Edinburgh Man to Also Pay Compensation
Rydings was tasked with handling a fundraising lottery for Sheffield Hospitals Charity in South Yorkshire. After defrauding the organisation, he was given a three-month jail term and ordered to pay £1,000 in compensation to the charity, payable within 18 months of him leaving prison.
Mr. Rydings appeared at Birmingham Magistrates’ Court to answer charges. There, it was found that he had failed to pass on significant sums of money to the charity in terms of lottery proceeds, some £285,000 in total.
Gambling Commission Lead Prosecution
At the time of the offence, Rydings was employed as the Chief Executive Officer of gambling operator Capen Limited who held an external lottery manager licence.
Capen has its offices in London and now shows accounts as being overdue with Companies House. Their External Lottery Manager and Gambling Software licences registered with the Gambling Commission are now surrendered, both expiring in February 2024.
The Gambling Commission indeed prosecuted the case against Rydings. As it went on, Rydings eventually admitted the misuse of lottery proceeds set forth under the 2005 Gambling Act, the offences having been committed between 1st January 2018 and 31st March 2020.
For his part, Rydings told the court that he had since spent all of the money he took. He claims he needed the money on “other costs” running the business and that he now did not have the funds available to return all of the £285,000 he took.
UK Lotteries Must Be Run Primarily for Good Causes
While lottery wins can be heavily taxed around the world and remain private, in the UK, this is not the case. Not only are lottery winnings not taxed, but also any lottery existing and having been given a Gambling Commission licence must be run for good causes, including the National Lottery currently run by Camelot.
This was a point made strongly after the court case by the Commission’s executive director Helen Vann, who made it plain when speaking publicly that all lotteries must be run for charities. Vann pointed out that charities and other non-commercial entities who run lotteries tend to rely on the income they receive from the competitions to support their work in lieu of other income.
In this case, Simon Rydings, it was found by the court, failed in his role as CEO of a company holding a Gambling Commission licence and now must pay a heavy price.
The Commission is adamant that lottery players in the UK have the right to know that, whenever they buy a lottery ticket, that they are helping to support good causes. In the case of this type of lottery, they even know in advance what charity they are helping and should be confident that some of their money is ending up in the charity’s coffers.
Rydings denied the buyers of Sheffield Hospitals Charity lottery tickets that chance. He will now serve his three-month sentence in prison before assessments are made on how much of the £285,000 he took he can pay back to the charity.


Coleman 100 Quart Xtreme Marine Cooler
A must-have for fishermen, Coleman Xtreme Marine Coolers are designed specifically for use in the hot sun. UVGuard™ reflective colour additives protect the cooler, fighting against yellow discoloration and cracking caused by sun exposure. Combined with all of the Coleman Xtreme cooling-qualities, these coolers are perfect for outdoorsmen, fishermen, or a day at the beach!
- Capacity – Litres: 90 L
- Product Weight: 7.4 kg
- Insulation Material: PU
- Outer Case/ Inner Liner Material: HDPE
- Ice Retention: 5 Days
- Inner Dimensions (cm): 79 x 33 x 29
- Outer Dimensions (cm): 92 x 42 x 44
Additional Premium PU Insulation
Unlike other manufacturers, Coleman rigid coolers are insulated with Polyurethane insulation (PU). PU is a very dense and an excellent insulator filling the entire internal cavity of the cooler, leaving no air gaps and so improving its insulating efficiency. Extensive testing at Coleman has shown that cooling loss from rigid coolers is 30% through the top and also 30% through the base. Coleman's latest models feature increased insulation in these particular areas together with reduced insulation on the sides. The result of these changes is not only improved cooling performance but the reduction in exterior dimensions and the increase in internal volume.
A New Shape and Increased Efficiency
When a cooler comes in contact with a warm floor, heat is transferred directly from the floor to the cooler and reduces the cooler's efficiency. Coleman has included shaped feet into the design of its newer rigid cooler models separating the cooler base from the floor and increasing airflow. This flow of air acts as an additional form of insulation, slowing the transfer of heat from the floor and so improving the coolers performance. Additional research has also resulted in the rounding of the cooler’s corners, once again this change of shape has increased airflow and further enhanced their performance.
When a cooler comes in contact with a hot floor, heat is transferred directly to the cooler. If the cooler is lifted off of the ground, the heat is transferred through the air in the gap (air is a great insulator). Cooler have two integrated, rounded feet providing the perfect amount of space for air to flow. Research indicates that the most performance efficient shape for a cooler is spherical, as this is not practical we have angled the corners of selected models to further enhance performance.
Antimicrobial Liner - Resists Odour, Mold and Mildrew
The Antimicrobial additive is bonded in the material and there is no risk of it being scratched or washed off. It is very strong and won’t weak over time - it’s there for the life of the product. The Antimicrobial barrier ensures the product resists mold and mildew growth and it also blocks unpleasant odours from developing. It is totally safe. The active ingredient in the antimicrobial substance is also used in common dandruff shampoos and artificial food additives. Consumers come in contact with the substance daily and in some cases digest it without any ill effects. The Antimicrobial surface is environmentally and eco-friendly.


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Eating fish may make kids smarter and help them sleep
Ivy League researchers advise parents to incorporate fish into their children's diets after a study found a weekly fish regimen is linked with higher IQs and better sleep.
University of Pennsylvania researchers analyzed the IQs, fish-eating habits and sleeping patterns of more than 500 Chinese children aged 9 to 11. They found children who ate fish weekly scored nearly five points higher on IQ tests than those who never or seldom ate fish. Children who had fish sometimes had a roughly three-IQ-point advantage over those who didn't or rarely ate it.
The research team of Jianghong Liu, Jennifer Pinto-Martin, Alexandra Hanlon and Adrian Raine said the finding builds on existing research about the positive effects of Omega-3 fatty acids. Omega 3s, which are found in fish, have been tied to intelligence and sleep independently, but "they've never all been connected before," a university statement read.
Raine, a professor in the school's Penn Integrates Knowledge program, calls it a "double hit" of benefits. Liu, Pinto-Martin and Hanlon are part of the Penn School of Nursing.
The research, published Dec. 21 in the Nature journal Scientific Reports, also quizzed parents on their children's quality of sleep, including how often they wake in the middle of the night and "daytime sleepiness." It found, "increased fish consumption was associated with fewer disturbances of sleep."
Researcher Pinot-Martin said parents could give children fish as young as 10 months old and should start by about 2. For infants, she said, make sure the fish is finely chopped and has no bones.
"Introducing the taste early makes it more palatable," Pinot-Martin said. "It really has to be a concerted effort, especially in a culture where fish is not as commonly served or smelled."
The U.S. Food and Drug Administration suggests pregnant woman and children should eat anywhere from one to three servings of fish each week.
Follow Sean Rossman on Twitter: @SeanRossman


The Nigerian military is set to launch a nationwide operation to demand identity cards from citizens across the 36 States of Nigeria in what they tagged ”Operation Postive Identification”
‘Operation Positive Identification’ would see soldiers accosting citizens on the roads or streets and asking them to show means of identification on the spot.
Soldiers had been taking similar measures to differentiate citizens from terrorists in the North East of Nigeria where Boko Haram has been a menace. According to the Military, citizens in the North-east had been collaborating with soldiers to make the exercise successful by carrying with them valid identity documents.
Operation Positive Identification has been officially declared to begin from November 1st, 2019 and end December 23rd, 2019.
Citizens have been warned to carry a valid means of identification, especially voter’s card, national identity card, driver’s license, international passport, whenever they are going out to avoid being seen as criminally-minded by soldiers.Also, Citizens have been warned to dress responsibly and shun carrying Illegal or prohibited substances.


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Join us in creating community by supporting the Library’s free programs, resources & services – DONATE!
The Library will be CLOSED Monday, Feb. 17.
In 2020, resolve to step out of your familiar reading routine and travel to parts unknown through literature. We begin 2020 with one of the world’s newest and oldest languages – Modern Hebrew. Our second book is Dearest Anne by Judith Katzir, with Dalya Bilu (Translator). The discussion will be lead by Lani Ravin on Wednesday, January 22 at 6:30pm.
About the Book:
Explore books, rhymes and songs specially selected for tiny tots, followed by time to play and chat with other babies and their caregivers. Ages birth to 18 months.
Staff set-up: One table against wall next to door, several chairs along other walls. No tables or chairs in center of room.

domain: library


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Boil noodles according to package instructions.
Heat 1 T vegetable oil in wok or large saucepan.
Add cooked noodles and stir to begin heating them.
Push the noodles to one side of the wok and add another tablespoon vegetable oil to the other side.
Place carrot, garlic, scallions, and peas in the heated oil and stir. They should sizzle and become tender.
Stir noodles and vegetables together.
Add 1 T soy sauce and 3 T sesame oil. Stir.
Add salt to taste.
Once noodles and vegetables are thoroughly heated, serve!

domain: food


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A day after speculations that JD(U) might expel its president, Nitish Kumar from the party, Kumar on Friday has said that Sharad Yadav can take a walk. “He is free to go where he wants,” said Bihar chief minister.
Kumar was in Delhi today to meet Prime Minister, Narendra Modi and BJP chief, Amit Shah. This was their first in-person communication since Kumar dramatically formed his government in Bihar with BJP’s support. “The party has made a decision. He (Sharad Yadav) should accept it,” CM said.
Yadav refused to attend the oath-taking ceremony that saw Kumar being re-inducted as head of the state. Since then he issued daily recriminations alleging that Kumar has betrayed the people of Bihar.
Yadav was told yesterday by JD-U to watch his language. After a three-day tour of Bihar, Yadav said the CM runs a “sarkari” version of his party, while the real JD-U is to be found in masses.
“The political language being used by him is very objectionable and uncomfortable for the party president (Nitish Kumar) and the government (of Bihar). We will ask him to refrain from making statement which crosses limits,” said KC Tyagi, senior JD-U leader.


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Presenting: the brass family! Philadelphia Orchestra musician Matt Vaughn will guide the audience through this regal instrument family.
Yannick Nézet-Séguin has made the first principal musician appointment of his tenure and it’s a welcome and familiar face: Nitzan Haroz has returned as principal trombone.
“I feel delighted and honored to be joining The Philadelphia Orchestra for the second time in my life. My colleagues here are like family to me and I missed playing with them a lot,” says Haroz, adding, “I couldn't have chosen a more exciting season to come back! I can't wait to play Strauss's Alpine Symphony and Mahler’s Second Symphony again. They are magnificent pieces with fabulous parts for the brass and they don't come around as often unfortunately!”
“It is a wonderful moment to welcome Nitzan Haroz back to The Philadelphia Orchestra,” says Nézet-Séguin. “We already made great music together during my time as music director designate, and I look forward to the return of his outstanding artistry to enrich our unique Philadelphia sound.”
The Israeli-born Haroz was principal trombone with The Philadelphia Orchestra from 1995 to 2012. He spent the past two years in the same position with the Los Angeles Philharmonic; prior to Philadelphia he played with the New York Philharmonic, the Israel Symphony and Opera Orchestra, the Israel Defense Forces Orchestra, and the Jerusalem Symphony.
“Playing with the LA Phil under Maestro Gustavo Dudamel was indeed a treat,” says Haroz. “The orchestra is great, the hall is wonderful. ... I am very fortunate to have experienced playing with three of the leading orchestras in the U.S. as well as the orchestras in Israel. It only expands one’s horizon to play with different orchestras. You are forced to adapt and adjust your style of playing according to the ensemble and that makes you a richer musician. Every orchestra I played with has a unique quality, style, and history. I keep learning from the musicians around me and try to be the best musician I can be.”
A return to Philadelphia was the clear next step on the horizon. In addition to missing his friends and colleagues here, Haroz’s three children are in Philadelphia. First, though, he had to audition.
“Auditioning for my old position was scary,” Haroz says. “It was draining emotionally and there was obviously no guarantee that I would win this job again. I had to compete against some of the finest trombone players and I knew that they had a very good chance—and reason—to win, not any less than me. Playing in front of your colleagues in a situation like this is a humbling experience. You want to impress them, prove yourself, and show that you're good enough. That can be nerve racking!”
Haroz survived the audition by thinking about his kids: “I thought about them before each piece I played. I chose one child to think about before I played and then played the excerpt for them. It helped me focus and conquer the fear.”
Returning to Philadelphia also means resuming his position on the faculty at the Curtis Institute of Music. “I had fantastic students there,” says Haroz. “The ties between The Philadelphia Orchestra and Curtis have been strong for years. It is an honor for me to be on their faculty again.”
Haroz’s first concert will be the first concert of the season, September 26, which includes the brass-showcasing Strauss. (“I can’t wait!” he says.) In addition to the Alpine Symphony (Sept. 26-28) and Mahler’s Symphony No. 2 (Oct. 30-Nov. 2), Haroz says he’s also looking forward to Mahler’s Fifth Symphony (March 26-28) (“Yes, I love Mahler ...”); Brahms’s Third (Dec. 4-6) and Fourth (Nov. 21 & 22) symphonies; Prokofiev’s Symphony No. 5 (Feb. 12 & 13); Dvořák’s Eighth Symphony (Nov. 13-15); and Rachmaninoff’s Symphony No. 2 (Jan. 22 & 23).
“There are so many other fantastic works this season,” he adds. Mostly, though, he’s happy to again be a Philadelphian.
“Playing with The Philadelphia Orchestra is a rare and precious gift,” says Haroz. “Every member of this orchestra is a singer on their instrument. I strive to be one too. It is, in my opinion, one of the reasons why we sound the way we do. I have often felt emotional enough to cry during concerts here, more then anywhere else. It's hard to describe how it feels to be part of this group again, I am very lucky.”
Photo by Linnea Lenkus


Shop owners concerned over duration of Mandai redevelopment project
Traders who have relocated their shops are concerned about how much duration it will take for the redevelopment process
Pune Municipal Corporation (PMC) and Maha-Metro jointly will be spending ₹11.68 crores for redevelopment work of Mahatma Phule Mandai. However, traders who have relocated their shops are concerned about how much duration it will take for the redevelopment process.
When HT reporter visited the area on Tuesday, it was found that people who have already shifted their shops are already waiting to return to their old places.
Shabbir Shaikh who runs wholesale and retail vegetable business said, “Initially, we were told that metro station work will go on till December 2022, now it has been pushed to March 2023. If they plan to redevelop the complete area then it will take more time. After relocating to Raviwar Peth, my business has already suffered. I hope whatever redevelopment work authorities are planning, should get over with the metro station work.”
A fruit seller, Dheeraj Paygude hopes to move back to the old place at the earliest.
“I hope PMC and MahaMetro get the work done in the promised time-frame,” he said.
The work of the metro underground station at Mahatma Phule Mandai is progressing briskly.
Kasba Peth, Sukharwar Peth and Budhwar Peth have a large number of historical monuments, such as Lal Mahal, Shaniwar Wada, Nana Wada, Vishram Bagh Wada, Kasba Ganapati and Tambadi Jogeshwari, Dagdushet Ganapati, Trishund Ganapati, Tulshibagh etc.
PMC and Pune Metro have drafted a plan to connect all these places and provide information about them through a ‘heritage walk’.
PMC commissioner Vikram Kumar and Pune Metro, director (works) Atul Gadgil have signed a MoU in this regard.
“Our first priority is to complete the metro station work. Once we are at an advanced stage, the redevelopment work of the Mandai area will commence. We are expecting it to be finished by march 2023,” Gadgil said.
Brijesh Dixit, managing director of MahaMetro said, “Apart from metro stations, we will be developing the area surrounding the stations. With PMC’s cooperation, the development plan of Mahatma Phule Mandai area has been prepared. The proposal will overhaul the look of this area. The entire Mahatma Phule Mandai will be made pedestrian friendly.”


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A Holistic Cloud-Enabled Robotics System for Real-Time Video Tracking Application
Future distributed sensor fusion applications will require efficient methods of information management such as Cloud computing. Using a server-based cloud-enabled software architecture would increase performance over hardware con- straints (e.g., power, memory, and processors). In this paper, we propose a comprehensive framework for information fusion demonstrated for Cloud Robotics, which possesses user favorable features such as good scalability and elasticity. Robots are con- nected together to form a networked robotic system that is able to accomplish more computationally intensive tasks. Supported by the emerging Cloud computing technology, cloud-enabled robotic systems (CERS) provide even more powerful capabilities to users, yet keeping the simplicity of a set of distributed robots. Through an experimental study, we evaluate the memory, speed, and processors needed for a video tracking application.

domain: design


Pioneering gay site Badpuppy celebrates a decade of decadence.
AVN – AVNONLINE PROFILE 200512 – 10 Years in the Doghouse: Pioneering gay site Badpuppy celebrates a decade of decadence.
This past summer, enduringly popular gay site Badpuppy.com achieved an industry milestone: The pioneering site turned 10 years old. (With all the sites that have come and gone in that time, that’s at least 35 in webmaster years!)
Formed in 1995, the site – which has become a mainstay for thrill-seeking Web surfers wagging their tails for the hottest in gay content – had its official birthday on May 17 and spent an entire weekend celebrating with a slew of events at Orlando’s infamous Parliament House.
“Badpuppy turning 10 was a very wonderful feeling,” says Badpuppy president Bill Pinyon. “This is the longest I have ever been on the same job. I cannot imagine a world without Badpuppy, my partner Steve, and our entire staff. Some of them have given me as much as nine years of their lives, and most have been there more than six years. We owe a lot to them.”
Pinyon, a computer science specialist who was working as a network administrator at the Kennedy Space Center in Cape Canaveral when his boss asked him to participate in a project built around a new technology called the Internet, already had been using single-line dial-up BBS software and jumped at the chance to get involved with an international network that connected people from all over the world.
Taking the knowledge he learned on the job, Pinyon started his own site on the side, a resource site for gays and lesbians living in Florida. When someone suggested offering adult content on the site, Pinyon initially balked at the idea. “I thought if anyone found out I was doing anything related to pornography that they would not want to do business with me,” Pinyon says. But, after thinking it over a little bit more, Pinyon relented and posted a set of 30 pictures, then watched as people began clamoring to get a look at them. “Within one hour there were 35 people trying to get to the pictures one at a time,” he recalls.
Demand was so high for the adult content that several servers crashed in those early days, and Pinyon realized he had something big on his hands. In fact, the site (soon renamed Badpuppy) grew to such large proportions that Pinyon realized he needed to hire a staff of employees to support him. Along with his partner, vice president Steven Wojcik, Pinyon turned Badpuppy into such a successful enterprise that both men were forced to choose between their day jobs and their supposed “side project.” They chose Badpuppy. “Steven and I both quit our jobs the same day, and we have never looked back,” Pinyon says.
Today, Pinyon boasts, the site has grown exponentially to include the use of 34 servers running a multitude of different applications to support the Badpuppy system and the more than 600 sites it hosts. Although originally tagged as a “twink” site, Badpuppy now hosts pics and content of men of a wide range of types. According to Pinyon’s administrative assistant (and advertising guru) Lisa “Bulldog” Turner, “We quickly expanded, realizing that expansion in the market would broaden our horizons and therefore our member base.”
Faithful “puppy lovers” already know that frequenting the site is a perfect way to give any dog a “bone.” For the uninitiated, however, Badpuppy offers a plethora of content from not only its own extensive library of content (the last time they did the math in 2003, Turner reports, Badpuppy offered more than 500,000 pages of content), but a membership to the site will grant users access to more than 100 additional sites (such as GayJerking.com, DreamStuds.com, and MattSterling.com) as well.
Purveyors of real-time sex will enjoy the live sex streams, while fans of more traditional stills will find a host of pics to keep them happy. “We offer a huge amount of diverse content,” Turner promises. “There’s something for everyone.” What’s more, the daily announcements of content updates are sure to keep randy Web surfers busy. Says Turner, “Let’s just say that there is so much content and updates that no one will ever be able to see it all.”
Allowing that today’s Web surfers are much choosier than they once were, Turner adds, “In order to retain today’s new members, one must give them countless reasons to come back time and time again. With Badpuppy, there is always something new at just about any given time. Not only does Badpuppy update itself around the clock, but the sites that are hosted as part of the network are updated often as well. Quality content is as important as quality traffic, and when that quality content can be delivered to the member in quantity, it will retain that member for months and years to come! Because Badpuppy provides itself a wide variety of content, there should be no reason for the Badpuppy member to go anywhere else.”
Though the site has gone through several design revamps and content obviously has grown since its inception, Pinyon has seen to keeping the tone fairly consistent over the years. “The overall premise for Badpuppy has remained the same,” he offers. “Provide the user with a quality experience, product, and customer service. [However], being that most of the staff at Badpuppy are very technically oriented, we strive to always make Badpuppy bigger, better, and faster than anything else on the market. I can safely say that there is not a day that has gone by in the last 10 years where we have not thought about ways to improve our site.”
In addition, Badpuppy’s customer service department is on call around the clock to assist webmasters with potential problems and questions. As Turner says, “We staff people [in] three shifts to assist with anything from simple access such as ‘I forgot my user ID’ to problems with the website itself. Our dedication to the customer, the webmasters, and our other business associates is truly unsurpassed in the industry.”
Turner acknowledges that the field is incredibly competitive, but says that she prefers not to think of other sites as competitors. “There are really only a couple of websites out there that I’m aware of that are truly mega sites,” she says. “And we work closely with them and are not just business associates, but think of them as friends as well.” As far as feeling the pressure to stay ahead of the pack, Turner says, “I would not call it pressure. We simply do what we do to the best of our ability and generally find ourselves in the forefront.”
All bragging excused, many webmasters admit to being influenced by Badpuppy’s formula for success. “Badpuppy was the first porn site I ever paid for when I went online,” says porn model/director-cum-webmaster Andy Dill, who founded and runs gay redhead fetish site RedHeadGuys.com. “I spent many hours with one hand on the mouse and one hand, well, somewhere else. I thought it had an amazing amount of content of some of the hottest guys in the world, and, as a webmaster today, I still do. The site converts great for me, and I’m even moving RedHeadGuys.com over there in the next week or so. Their team is amazing!”
Both Pinyon and Turner hint that bigger things are on the way for Badpuppy and its sister site, the more recently launched Video-on-Demand company Dog Gone Video. “Let’s just say that we are working with technology that will broaden the ability for our audience to view Badpuppy.com from anywhere they are in the world,” Pinyon says. “Our in-house mobile technology is new and state of the art. The day is coming very shortly where you can sit in the airport and watch Badpuppy, and if you see something you like, then when you get home [you can watch] the same movie in high definition on your home television.” Meanwhile, Turner is even more cryptic when she offers, “Without getting too terribly specific, we are going to be expanding in the technology area, which will benefit both Badpuppy and Dog Gone Video.”
Veiled though they are, those kinds of promises are what keep fans of the site coming back, and Pinyon, who now laughs when he recalls that there was a time when he thought such a venture was a bad idea, says he couldn’t be happier with Badpuppy’s success and longevity. “Every single day I remember where I came from and am thankful for everything that I have,” he enthuses. “It has taken a lot of work and patience, but if I had to do it over again, I would. Here’s to 10 more years!”
Ruff! Ruff! indeed. Let’s give these guys a loud round of our paws.


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The Ministry of Public Health (MoPH) on Saturday reported 13 new positive cases of coronavirus out of 840 samples tested in the last 24 hours.
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The ministry said no deaths from coronavirus were recorded and 90 recoveries from COVID-19 in the last 24 hours.
The cumulative number of total cases is now 55,031 the number of total reported deaths is 2,400 and the total number of recoveries is 47,609.
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The new cases were reported in Kabul, Kandahar, Balkh, Paktia, Nimroz, Wardak, Helmand and Paktika provinces.


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Apple Inc. (NASDAQ:AAPL)’s tablet share in China fell significantly during the second quarter, according to the latest data from IDC. Bloomberg News reports that Apple’s iPad made up 28 percent of tablet shipments in China during the quarter. That’s down from 49 percent in the same quarter a year ago, IDC researcher Dickie Chang told Bloomberg today via email.
Samsung, others steal from Apple
IDC reported that Samsung Electronics Co., Ltd. (LON:BC94) (KRX:005930) saw its tablet share surge during the second quarter, rising to 11 percent. Samsung’s tablet shipments climbed more than fourfold to 571,000 units shipped to China during the second quarter. Apple only increased its tablet shipments in the region by 28 percent.
Baupost's investment process involves "never-ending" gleaning of facts to help support investment ideas Seth Klarman writes in his end-of-year letter to investors. In the letter, a copy of which ValueWalk has been able to review, the value investor describes the Baupost Group's process to identify ideas and answer the most critical questions about its potential Read More
Half of all tablet shipments in China came from producers which had 1 percent or less of the nation’s tablet market share apiece. That’s a significant increase from 36 percent in the same quarter of last year.
Chinese companies are Apple’s biggest threat
The biggest problem Apple Inc. (NASDAQ:AAPL) seems to be facing is competition from less expensive Android tablets. Chinese companies like Lenovo Group Ltd. (PINK:LNVGY) (HKG:0992), Ramos and Teclast are taking advantage of the high price of Apple’s tablets and offering products that cost far less. This same trend slashed the company’s smartphone market share almost in half.
According to IDC, Apple Inc. (NASDAQ:AAPL)’s biggest challenge is from these small Chinese companies, especially those making tablets using the free open source Android operating system made by Google Inc (NASDAQ:GOOG). The company said the majority of Apple’s lost market share when to these companies.
Apple also struggling in smartphones
IDC also reports that Chinese vendors are taking advantage of the fact that Apple hasn’t released a new iPhone or iPad since last year. The company saw its iPhone shipments to China drop to 5 percent during the second quarter, compared to 9 percent in the same quarter a year ago. That’s the lowest market share for Apple since the fourth quarter of 2010, according to Canalys.

domain: finance


We are very pleased to see the government turn down the Northern Gateway Pipeline. It comes at a cost: Kinder Morgan’s Trans Mountain Expansion and Line 3. There is still more work to be done.
Please see the new Press Release from the Council of the Haida Nation on Trudeau’s announcement. According to CHN President Peter Lantin:
“There has to be a better government-to-government consultation process to deal with these projects before they get rolling,” said Lantin. “Avoiding this type of confrontation through frank dialogue will result in more common ground. Protecting the coast and the waters surrounding Haida Gwaii is paramount for our Nation. But within this framework there is room to develop practical solutions and resolve issues nation-to-nation and to do that we have to talk.”
On Friday July 3rd, Haida Gwaii came together on Masset inlet to show their support for a Tanker-Free ocean, and rode the tide from Gaauu (Old Massett) to Masset harbour. Part of Pull Together’s “Week to End Enbridge,” the ‘Ride the Tide’ event shaped up in true Haida Gwaii style with Christian and Candace’s Haida Canoe alongside paddle boarders and kayakers from across the islands. There was a crush of people, naaniis (grandmothers), youth and spectators all along the shore following the action and cheering on the paddlers.
A huge thank you/haw’aa to Christian White and Candace Weir for bringing the canoe out. As well to Guy Kimola for documenting the event so well, and Jim Hart and his crew for coming out to show their support. Haw’aa to Harmony and Old Massett Youth Centre for providing rides. A big haw’aa/thank you to all who came out to paddle and take show that Haida Gwaii stands unified in protection of our waters!
Please read the latest letter from the CHN presenting the affirmation by Haida Hereditary Chiefs, Band Councils and citizens stating the continuing role of the Council of the Haida Nation in representing all Haidas, and their continuing opposition to the Enbridge Northern Gateway Project.
Please read this open letter from the Council to the Haida Nation regarding the efforts companies like Enbridge are making to buy people off from First Nations communities in order to push their pipeline through.
Kaalts’ida Kah, Laughing Crow Productions is proud to announce the release of their newest Animation, a music video for recording artist Kinnie Star called Save Our Waters. Prime Minister Harper sets out on the maiden voyage of the supertanker Bitumen Valdez and is met by opposition out on the waters in the form of a floatilla of canoes, fishing boats and killerwhales!


Recent crimes and emergencies
- Faulty part diverted Rutgers softball team to Avoca airport
- Wayne County corrections officer charged for selling pills
- Frein jury selection nears end
- Trio take cash, cigarettes during Wayne Co. burglary
- Judge dismisses case challenging DRBC fracking moratorium
- Wilkes-Barre man allegedly beat pregnant woman
- NEPA's Most Wanted 3/26/2017
Recent Scranton News
- Scranton downtown snow melting 10 blocks away
- Scranton roundtable talk explores future of health insurance
- Aquarium, reptile attraction planned for Marketplace at Steamtown
- Scranton schools to receive energy upgrade; board changes calendar
- Community Events Listings, March 28, 2017
- School Notes 3/27/2017
- Montage ski resort says goodbye to winter
Police nab man wanted in Florida
SCRANTON - A city man is awaiting extradition to Florida on grand theft charges after Scranton police ran his name through a criminal information check on Sunday afternoon following a tip that he was wanted.
Benjamin A. Sironel, 24, of 1143 W. Elm St., was taken into custody in the 700 block of South Main Avenue on Sunday, according to a criminal complaint. He has been wanted out of Sarasota County, Fla., since July 30.
He is in Lackawanna County Prison in lieu of $50,000 bail.


text:
Dealing with a bird’s poo might be unsettling as a pet owner, but sadly, it’s something you have to cope with. The only way to successfully manage it is by potty training your bird. Although potty training a bird seems difficult and unattainable, I am about to show you how you can do it effortlessly.
Birds are social animals and can learn behaviours like other higher animals. The caveat there is that you need to learn what their natural behaviour is before you can alter it to your desire; this is the same basis on which you can potty train a pet bird.
Steps to potty train your pet bird
- change in posture, restlessness, or as subtle as a change in how they look.
- Pay attention to the frequency of your pet’s poo. Babies can potty every 20 minutes while an adult can vary from 30 minutes to about 8 hours. The frequency of dropping is highly individual.
- Pick a potty place and take your bird there once you’ve mastered the time and frequency of pooping. You can use the bird’s cage, old newspaper, or a garbage can. If you are using paper, you won’t need to move the bird, rather, place the paper under the bird when it is potty time.
- Repeat the process for every potty time and praise with kind words.
Training duration varies with birds. It can be as short as 72 hours and can take up to months. If you can do your part of observing your bird’s potty behaviour and schedule combined with positive reinforcement, potty training will be a walk in the park.

domain: pet


|Home page World|
Russian representatives have registered 18 violations of the Syrian ceasefire regime over the past 24 hours, the Russian Defense Ministry said Sunday.
Axar.az reports citing to Sputnik Russian representatives in the Russian-Turkish commission on the Syrian truce have registered a total of 18 violations of the ceasefire regime in Syria over the past 24 hours, while Turkey informed about 15 cases, the Russian Defense Ministry said Sunday.
"Within last 24 hours, the Russian party of the Russia-Turkey Commission on violations of the Joint Agreement has registered 18 ceasefire violations in the provinces of Damascus (10), Latakia (3), Hama (2). The Turkish party has registered 15 cases of ceasefire violations in the provinces of Damascus (2), Daraa (3), Hama (7), Homs (3),” the ministry's center for Syrian reconciliation said in a daily bulletin.
The Syrian civil war has been raging for six years, with government forces fighting against both Syrian opposition groups who strive to overthrow President Bashar Assad, and numerous extremist and terrorist groups such as Daesh and Jabhat Fatah al Sham, both of which are outlawed in Russia.
Russia and Turkey are the guarantors of a nationwide Syrian ceasefire regime that came into force on December 30, 2016 and has been holding up in general, despite continued reports of violations. The UN Security Council passed a resolution in December 2016 supporting the effort.
2017.05.07 / 13:19


Invisibility stickers could trick tough-to-fool infrared cameras.
A proposed device would create a veil of heated, ionized air to bend shock waves around people, vehicles or other objects.
The laser system is designed to protect military forces and key infrastructure.
Broadcast will go out live to ships, aircraft carriers and submarines.
The US Central Command's Twitter and YouTube accounts were compromised.
The U.S.'s newest military drone could someday transport troops or wounded soldiers.
A directed-energy gun is now authorized for use in Persian Gulf.
Similar to playing a video game, service members can train on digital versions of real world equipment or on virtual landscapes.
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text:
from Birmingham Mail
15th December 2009
The family of a man who died in police custody wept tears of joy as they claimed that an inquest had given them “truth and justice”. The jury at the hearing found that Michael Powell died from positional asphyxia caused by lying on his front in the back of a police van.
The jury also recorded that Mr Powell, aged 38, became more vulnerable to death for one or more possible reasons. They included being hit by a moving police car, being sprayed with CS gas, being struck by a baton or being restrained on the ground while suffering a psychosis and extreme exertion.
It took the ten-man jury three days to reach an eight-to-two majority verdict. They could not agree on whether the police restraint was “reasonable in the circumstances”.
The father-of-three died on September 7, 2003, at the age of 38.
He was restrained by several officers after smashing windows at his mother’s home in Wilton Street, Lozells, and attacking a police car. He was conscious at the time he was bundled into a police van and taken to the cells at Thornhill Road police station, but on arrival he had no pulse, had saliva foaming from his mouth and his body was limp. He was taken to the A&E department at City Hospital where he was pronounced dead.


text:
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Weapons maker Chemring’s shares plunged after a fatal explosion at one of its factories forced it to shut down operations ahead of a crucial sales period.
The blast at its countermeasures facility near Salisbury in Wiltshire on Friday killed one worker and left another badly injured in hospital.
Chemring, which also makes grenades, mine detectors and fighter jet ejector seats, said it was too early to say precisely how big the financial impact would be.
But it warned annual underlying profits were likely to come in between £10m and £20m lower than previously expected, "with a corresponding impact on the group's operating cash flow and net debt".
Sanjay Jha, an analyst at Panmure Gordon, said...
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The pilots of an Indonesian passenger jet were arguing about the plane's speed moments before it crashed last month, a senior investigator has said.
The blaze took two hours to put out and gutted the jet
Tatang Kurniadi told Australian television that the co-pilot wanted to turn around instead of landing.
The two pilots, who both survived, were flying together for the first time.
The Garuda Airlines Boeing 737-400 crashed as it landed at Yogyakarta airport on 7 March, killing 21 of the 140 people on board.
Survivors and witnesses said the plane came in to land at a high speed before it overshot the runway into a rice field and burst into flames.
Passengers and crew scrambled for safety through emergency exits as fire raced through the cabin, leaving the wreckage a gutted shell.
The voice and flight data recorders are being analysed in Australia.
"There was also some argumentation between the co-pilot and the pilot and captain relating with the speed and flaps," Mr Kurniadi told the Nine Network.
He said the wing flaps, which help slow the plane down for landing, did not jam and it appeared it would have been possible to circle around for another attempt at landing.
The retrieved black boxes were immediately flown to Australia
He said he did not know why the pilot chose to continue with the landing.
"I worry that this accident came from the absent-mindedness of the cockpit," he said.
He said the pilot was very experienced with more than 15,000 flying hours. The co-pilot was a "young pilot with just about 2,000 flying hours".
The cockpit voice recorder was badly burnt in the crash but investigators said last month that they had been able to recover the last 30 minutes of the crew's conversation.
Mr Kurniadi said he expected the investigation to be completed in a month.


text:
Some doctors, like people in other professions, simply need to
be encouraged to retire. Last year, the board threatened to take
the license of an Encinitas physician, who is in his early 80s. The
doctor never had any disciplinary actions or lawsuits against him
during his 51 years of practice but there had been a patient
complaint. The doctor surrendered his license and gave up his
practice in December 2000.
"In a number of these cases, the doctor has had a distinguished
career for many years and you don't want it to end in a sad note so
the board pressures them to retire without embarrassing them,"
Norcross said. "I've never seen an 85-year-old pilot at the helm of
a flight and with the tremendous responsibility for human life and
safety, I think it's important to test for skills at regular
But most doctors, Norcross says, just need refresher courses in
basic skills, including the keeping of records. Like most other
sciences, medicine relies on observations to reach conclusions.
Doctors are required to keep notes of the information that leads to
a diagnosis and treatment -- notes that become invaluable when
explaining or defending the course of treatment.
Otherwise, the diagnosis -- and subsequent treatment -- are
suspect, Norcross said.
When mistakes are make
And sometimes, the doctors are just screwing up.
For example, in an accusation filed by the state attorney
general against a Del Mar cardiologist, the state cited eight
patients whose heart surgery or follow-up care allegedly was done
incorrectly, including one who died and a second who was left with
severe, irreversible brain damage. In several instances, the
surgeon refused to return to the hospital after a patient
experienced post-operative problems -- an absolute no-no for
"We have designated physicians in the specialties who work with
the specialists once we've completed the basic evaluations,"
Norcross said. "We've never had someone from a specialty where we
couldn't find a physician to supervise.
"They actually come back to the medical school and work side by
side with their peers," he added.
In the Canadian medical system, Norcross says, doctors are
evaluated periodically for their skills. The result is that about 2
percent are weeded out, either through retraining or losing their
"If the public thought about it, they would want it," he said.
"But doctors would fight it if it seemed too onerous, too expensive
or if it took them out of their practices."
Instead,Norcross said, the United States has a system where
doctors are supervised primarily by medical malpractice lawyers and
where skills are evaluated by methods used in trial court.
"Everyone gets their experts and they go at it," he said.
"People are paid to argue about who is right and what we can prove,
and patient care gets lost in the process."
"So if doctors don't get in trouble, no one worries about their
skills, and once they do get in trouble, the results are
devastating for everyone," Norcross added.
Contact staff writer Marty Graham at (760) 740-3517 or


text:
Memory Unleashing Blueprint
Hey, did you know that your brain has storage capacity of 2.5 petabytes, which is enough to run for HD quality videos for 300 years.
I know it sounds crazy because we are so used to hearing about memory recall problems, and while that is important , I’ m going to share three secrets with you today that are going to revolutionize the way you can train your memory to keep 3x times more data in your brain and can recall it whenever you want it.
I am Chakradhar Dixit, and I am a Memory Coach who has helped more than 1000 people to get their 10x memory power.
So, what is secret of getting 3x Memory power
It’s just 3 secrets
It’s to change your eating habits, do some mental exercise and try using memory tricks or training to recall all your valuable information.
So, I’m going to share with you three secrets about increasing your memory recall power and how you can become unforgettable.
And I know what you’re probably thinking if is it going to be that easy why you have not heard it before?
But again, I’m going to show you a great way you can use these three secrets and get amazing results.
So, the first secret is to include Avocado, Blueberries, Broccoli, Plant oil, Eggs, Green Leafy Vegetables, Salmon Fish, Turmeric (Curcumin), Walnuts, Dark chocolates and enough water.
The big idea here is these brain foods will keep your brain forever young and will give all the nutrients it needs to function at the optimum level.
This is important because our brain has scientifically proven plasticity that is it can be improved at any stage if we care for it and given the essential nutrients.
The second secret is mental exercise i.e. using your non dominant hand for brushing your teeth, hand-writing your scripts, playing chess and sudoku and reading books daily.
The main thing to understand here is that mental exercises are not that difficult as the physical exercises but gives multifold results in building your smarter and brighter brains.
This means by doing mental exercises you build your brain muscles to give you better ideas and helps in better functioning of your brain. Researches have proved that mental challenging games even keep you away from Alzheimer’s’ to certain extent.
The third secret is memory training or memory tricks for recalling complex information in shortest possible time. The three widely used memory tricks are association technique, memory palace and story method.
The main thing to understand here is these memory techniques are known to us from our course books but we never use it in our daily lives. To tell you an example we learn our ABCD by means of pictures i.e. A for Apple, B for Bat but we do not associate our complex information to any thing which we already know and hence we are not able to recall it when we need it.
This is the key because memory training is your answer for all the questions and issues related to your memory recall such why I forgot certain piece of information or things or the person’s name whom I met earlier today? Why I am not keep the information in my mind which I have read last week or how to speak confidently in public speaking event without using cheat sheets?
Now, I know what you’re thinking.
It can not be that simple or how I can be so confident about this and if it is so simple why so many people are afraid of public speaking and even so afraid that they will prefer dying that to deliver a speech on stage?
Well the tricky thing is that we all are so busy in finding solutions to our problems in complex and most tedious manner that we never realize that we are the owner of the fastest super computer and it needs a very little care and practice to run it on optimal level and get maximum benefits out of it.
So, I’ve created this Memory Unleashing Blueprint by using this you can become unforgettable in no time.
It’s so effective that I have unlocked my potential of being an author, a podcaster and even a memory coach within 6 months of time and my students are getting amazed by their memory power as it shows results in as early as within a week of taking this course.
And so, what this is going to do is it will make you remember all the names of people you meet, learn any foreign language, use your brain’s full potential and inculcate the habits which will bring the best version of yours hidden inside you. You can do whatever you have dreamt of for yourself.

domain: psychology


Everything about Diana Airguns.
DIANA airguns history
DIANA celebrated its 100-year anniversary in 1990: the Company premises were built in Rastatt in 1890 by Jakob Mayer and Josef Gammelspacher. Their first air gun entered the market only two years later. The first patent was issued by the Imperial Patent Office on January 31, 1908. In the 1910s the early DIANA air rifles did not have any wooden front stocks, and the grips were bare metal. Factory facilities were completely dismantled in 1947. The reconstruction began in Rastatt in 1950. The year 1960 saw the DIANA Mod. 60, the only impact and percussion-free compressed air rifle marketed at the time.
DIANA: legendary air rifles and air pistols
For 125 years the label DIANA has been standing for constantly perfected innovation and tradition in the classical construction of air rifles. The results are high-quality industrially manufactured masterpieces. Uncompromising in quality and reliability with outstanding accuracy. These characteristics have been highly appreciated by over 10 million satisfied customers in more than 60 countries worldwide.
DIANA products: rifles, pistols, optics, pellets, accessories
In DIANA production line are included: break barrel rfles, fixed barrel rifles, pre-charged rifles and pistols. Moreover, DIANA offers a wide selection of accessories, optics, scope mounts, silhouette targets, pellets and gunbags, all of which can be found on DIANA website.
On all4shooters.com we publish articles of new products from DIANA.


RoadToMastery is an analysis of League of Legends' 350K+ champion mastery data entries, based on 60K+ NA Platinum+ players. Besides some general counters, the web app features two kinds of analysis on all champions: mastery progression and Tier 5 averages.
The numbers of mastery progression show the average improvement/regression when mastery of a given champion levels up from Tier 3 to Tier 4, or from Tier 4 to Tier 5. For example, Rengar has a 0.538 on average number of kills per game, which means that a player typically gains an extra 0.538 kills when reaching a higher tier on Rengar.
When players reach Tier 5 of a champion, we assume that they have deep enough understanding of it. So what kind of contributions does a Tier 5 champion x make on average? For any given champion, the average performance of all Tier 5 summoners is calculated, leading to a "profile" of a typical Tier 5 game stats of that champion. On the champion's page, you can see how the Tier 5 profile progresses from Tier 3 or 4 on the radar chart, or get some food for thought by comparing you own ranked stats on the same champion with the Tier 5 profile.
For each of all the stats above, RoadToMastery shows a ranking of all champions. From there, you can get a glimpse at the what kind of role a champion plays in the League. But of course, the rankings are subject to different interpretations, so feel free to weigh in!
From the API endpoints provided by Riot. Only Platinum+ player stats are included for the analysis since they in general already have a good grasp of the gameplay, and their champion stats should contain relatively less noise.
By doing a linear regression between the mastery tier and the metric we are interested in. For example, for progression of win rate on Gangplank, firstly a number pair of (mastery tier, Gangplank win rate) is obtained from all Gangplank summoners. Then we put all the mastery tier data on the a chart's x axis and all the win rate data on the y axis, and try to put a straight line on the chart to best fit both data. By this, we are essentially asking, what kind of win rate on Gangplank we can preidict if we know a summoner's mastery tier on him? Once we know that straight line, the slope of it, also the delta difference of win rate of two consecutive mastery tiers, is the progression metric we report.
Of course, whether using linear regression to model data with discrete levels like mastery tier is up to debate. Here I am using it as a preliminary method to pulse-check the data.
For each champion we trace the Tier 3-5 average stats on the radar graph, highlighting the difference among different mastery tiers. For instance, in this radar graph of Gangplank below, we can see that as a player climbs the ladder of mastery tiers, all stats of kills, deaths, assists, physical damage, gold, cs and turrets improve. The net result is the boost in win rate.
Note that the relative position on the radar graph is based on the percentage of the highest achieved value on the given metric among all champions.
The site itself is based on ASP.NET MVC 5 framework, and this is actually the first time I tried it. I'm also using this opportunity to experiment with bootstrap for easy layout styling and d3.js for svg charts. The site is published as an Azure web app.