Physicians' human papillomavirus vaccine recommendations in the context of permissive guidelines for male patients: a national study

BACKGROUND: Little is known about physicians' human papillomavirus (HPV) vaccine recommendations for males while the Advisory Committee on Immunization Practices' (ACIP) permissive guidelines for male vaccination were in effect. The purpose of this study was to examine and explore factors associated with U.S. physicians' HPV vaccine recommendations to early (ages 11-12), middle (13-17), and late adolescent/young adult (18-26) males. METHODS: Nationally representative samples of family physicians and pediatricians were selected in 2011 (n = 1,219). Physicians reported the frequency with which they recommended HPV vaccine to male patients ["always" (>75% of the time) vs. other] for each age group. Statistically significant predictors of vaccine recommendation were identified using multivariable logistic regression. RESULTS: The prevalence of physicians reporting they "always" recommended HPV vaccination for males was 10.8% for ages 11 to 12, 12.9% for ages 13 to 17, and 13.2% for ages 18 to 26. Pediatrician specialty and self-reported early adoption of new vaccines were significantly associated with recommendation for all patient age groups. In addition, physician race and patient payment method were associated with physician recommendations to patients ages 11 to 12, and patient race was associated with recommendations to ages 13 to 17 and 18 to 26. CONCLUSIONS: Less than 15% of physicians surveyed reported "always" recommending HPV vaccine to male patients following national guidelines for permissive vaccination. Vaccine financing may have affected physicians' vaccine recommendations. IMPACT: If these recommendation practices continue following the ACIP's routine recommendation for males in October 2011, then interventions designed to increase recommendations should target family physicians and possibly use early adopters to encourage support of HPV vaccination guidelines

Addition of T2-Guided Optical Tomography Improves Noncontrast Breast Magnetic Resonance Imaging Diagnosis.

BACKGROUND: While dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is recognized as the most sensitive examination for breast cancer detection, it has a substantial false positive rate and gadolinium (Gd) contrast agents are not universally well tolerated. As a result, alternatives to diagnosing breast cancer based on endogenous contrast are of growing interest. In this study, endogenous near-infrared spectral tomography (NIRST) guided by T2 MRI was evaluated to explore whether the combined imaging modality, which does not require contrast injection or involve ionizing radiation, can achieve acceptable diagnostic performance. METHODS: Twenty-four subjects-16 with pathologically confirmed malignancy and 8 with benign abnormalities-were simultaneously imaged with MRI and NIRST prior to definitive pathological diagnosis. MRIs were evaluated independently by three breast radiologists blinded to the pathological results. Optical image reconstructions were constrained by grayscale values in the T2 MRI. MRI and NIRST images were used, alone and in combination, to estimate the diagnostic performance of the data. Outcomes were compared to DCE results. RESULTS: Sensitivity, specificity, accuracy, and area under the curve (AUC) of noncontrast MRI when combined with T2-guided NIRST were 94%, 100%, 96%, and 0.95, respectively, whereas these values were 94%, 63%, 88%, and 0.81 for DCE MRI alone, and 88%, 88%, 88%, and 0.94 when DCE-guided NIRST was added. CONCLUSION: In this study, the overall accuracy of imaging diagnosis improved to 96% when T2-guided NIRST was added to noncontrast MRI alone, relative to 88% for DCE MRI, suggesting that similar or better diagnostic accuracy can be achieved without requiring a contrast agent

Inhibition of Soluble Epoxide Hydrolase Limits Mitochondrial Damage and Preserves Function Following Ischemic Injury

Aims: Myocardial ischemia can result in marked mitochondrial damage leading to cardiac dysfunction, as such identifying novel mechanisms to limit mitochondrial injury is important. This study investigated the hypothesis that inhibiting soluble epoxide hydrolase (sEH), responsible for converting epoxyeicosatrienoic acids to dihydroxyeicosatrienoic acids protects mitochondrial from injury caused by myocardial infarction. Methods: sEH null and WT littermate mice were subjected to surgical occlusion of the left anterior descending (LAD) artery or sham operation. A parallel group of WT mice received an sEH inhibitor, trans-4-[4-(3-adamantan-1-y1-ureido)-cyclohexyloxy]-benzoic acid (tAUCB; 10 mg/L) or vehicle in the drinking water 4 days prior and 7 days post-MI. Cardiac function was assessed by echocardiography prior- and 7-days post-surgery. Heart tissues were dissected into infarct, peri-, and non-infarct regions to assess ultrastructure by electron microscopy. Complexes I, II, IV, citrate synthase, PI3K activities, and mitochondrial respiration were assessed in non-infarct regions. Isolated working hearts were used to measure the rates of glucose and palmitate oxidation. Results: Echocardiography revealed that tAUCB treatment or sEH deficiency significantly improved systolic and diastolic function post-MI compared to controls. Reduced infarct expansion and less adverse cardiac remodeling were observed in tAUCB-treated and sEH null groups. EM data demonstrated mitochondrial ultrastructure damage occurred in infarct and peri-infarct regions but not in non-infarct regions. Inhibition of sEH resulted in significant improvements in mitochondrial respiration, ATP content, mitochondrial enzymatic activities and restored insulin sensitivity and PI3K activity. Conclusion: Inhibition or genetic deletion of sEH protects against long-term ischemia by preserving cardiac function and maintaining mitochondrial efficiency

Contourlet textual features: Improving the diagnosis of solitary pulmonary nodules in two dimensional ct images

Materials and Methods: A total of 6,299 CT images were acquired from 336 patients, with 1,454 benign pulmonary nodule images from 84 patients (50 male, 34 female) and 4,845 malignant from 252 patients (150 male, 102 female). Further to this, nineteen patient information categories, which included seven demographic parameters and twelve morphological features, were also collected. A contourlet was used to extract fourteen types of textural features. These were then used to establish three support vector machine models. One comprised a database constructed of nineteen collected patient information categories, another included contourlet textural features and the third one contained both sets of information. Ten-fold cross-validation was used to evaluate the diagnosis results for the three databases, with sensitivity, specificity, accuracy, the area under the curve (AUC), precision, Youden index, and F-measure were used as the assessment criteria. In addition, the synthetic minority over-sampling technique (SMOTE) was used to preprocess the unbalanced data.Results: Using a database containing textural features and patient information, sensitivity, specificity, accuracy, AUC, precision, Youden index, and F-measure were: 0.95, 0.71, 0.89, 0.89, 0.92, 0.66, and 0.93 respectively. These results were higher than results derived using the database without textural features (0.82, 0.47, 0.74, 0.67, 0.84, 0.29, and 0.83 respectively) as well as the database comprising only textural features (0.81, 0.64, 0.67, 0.72, 0.88, 0.44, and 0.85 respectively). Using the SMOTE as a pre-processing procedure, new balanced database generated, including observations of 5,816 benign ROIs and 5,815 malignant ROIs, and accuracy was 0.93.Objective: To determine the value of contourlet textural features obtained from solitary pulmonary nodules in two dimensional CT images used in diagnoses of lung cancer. Copyright:Conclusion: Our results indicate that the combined contourlet textural features of solitary pulmonary nodules in CT images with patient profile information could potentially improve the diagnosis of lung cancer

Positive Selection of a Pre-Expansion CAG Repeat of the Human SCA2 Gene

A region of approximately one megabase of human Chromosome 12 shows extensive linkage disequilibrium in Utah residents with ancestry from northern and western Europe. This strikingly large linkage disequilibrium block was analyzed with statistical and experimental methods to determine whether natural selection could be implicated in shaping the current genome structure. Extended Haplotype Homozygosity and Relative Extended Haplotype Homozygosity analyses on this region mapped a core region of the strongest conserved haplotype to the exon 1 of the Spinocerebellar ataxia type 2 gene (SCA2). Direct DNA sequencing of this region of the SCA2 gene revealed a significant association between a pre-expanded allele [(CAG)(8)CAA(CAG)(4)CAA(CAG)(8)] of CAG repeats within exon 1 and the selected haplotype of the SCA2 gene. A significantly negative Tajima's D value (−2.20, p < 0.01) on this site consistently suggested selection on the CAG repeat. This region was also investigated in the three other populations, none of which showed signs of selection. These results suggest that a recent positive selection of the pre-expansion SCA2 CAG repeat has occurred in Utah residents with European ancestry

Association of systemic lupus erythematosus associates with decreased immunosuppressive potential of the IgG glycome

Objective: Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA–DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case–control study to determine whether SLE is associated with altered IgG glycosylation. Methods: Using ultra-performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China). Results: Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N-acetylglucosamine (which affect antibody-dependent cell-mediated cytotoxicity). Conclusion: The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE

A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma

AZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma (MM) cells. This phase 2 study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory MM

A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma

A combination of cetuximab and sorafenib in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) were assessed for potential benefit