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From the TNG50 cosmological simulation we build a sample of 191 well-resolved barred galaxies with stellar mass |$\mbox{$\log (M_{\star }/\mathrm{M}_{\odot })$}\gt 10$| at z  = 0. We search for box/peanut bulges (BPs) in this sample, finding them in 55 per cent of cases. We compute |$\mbox{$f_{\rm BP}$}$|⁠ , the BP probability for barred galaxies as a function of M ⋆, and find that this rises to a plateau, as found in observations of nearby galaxies. The transition mass where |$\mbox{$f_{\rm BP}$}$| reaches half the plateau value is |$\mbox{$\log (M_{\star }/\mathrm{M}_{\odot })$}= 10.13\pm 0.07$|⁠ , consistent with the observational value within measurement errors. We show that this transition in |$\mbox{$f_{\rm BP}$}$| can be attributed to the youth of the bars at low M ⋆, which is a consequence of downsizing. Young bars, being generally shorter and weaker, have not yet had time to form BPs. At high mass, while we find a plateau, the value is at |$\sim 60~{{\ \rm per\ cent}}$| whereas observations saturate at 100 per cent. We attribute this difference to excessive heating in TNG50 due to merger activity and numerical resolution effects. BPs in TNG50 tend to occur in galaxies with more quiescent merger histories. As a result, the main driver of whether a bar hosts a BP in TNG50 is not the galaxy mass, but how long and strong the bar is. Separating the BP sample into those that have visibly buckled and those that have not, we find that fully half of BP galaxies show clear signs of buckling, despite the excessive heating and limited vertical resolution of TNG50. [ABSTRACT FROM AUTHOR]

We present an analysis of major-axis surface-brightness profiles of bars in a volume-limited sample of 182 barred spiral galaxies, using Spitzer 3.6  |$\mu$| m images. Unlike most previous studies, we use the entire bar profile, and we classify profiles into four categories. These are 'Peak+Shoulders' (P+Sh) – updating the classic 'flat bar' profile – and three subtypes of the classic 'exponential' profile: (true) Exponential, 'Two-Slope' (shallow inner slope + steeper outer slope), and 'Flat-Top' (constant inner region, steep outer slope). P+Sh profiles are preferentially found in galaxies with high stellar masses, early Hubble types, red colours, and low gas fractions; the most significant factor is stellar mass, and previous correlations with Hubble type can be explained by the tendency of higher-mass galaxies to have earlier Hubble types. The most common type of non-P+Sh profile is Exponential, followed by Flat-Top profiles; all non-P+Sh profiles appear to have similar distributions of stellar mass, Hubble type, colour, and gas fraction. We also morphologically classify the bars of an inclined subsample into those with and without boxy/peanut-shaped (B/P) bulges; as previously reported, the presence of a B/P bulge is very strong function of stellar mass. Essentially all bars with B/P bulges have P+Sh profiles; we associate the profile shoulders with the outer, vertically thin part of the bar. We find a small number of P+Sh profiles in bars without clear B/P bulges, which may indicate that P+Sh formation precedes the formation of B/P bulges. [ABSTRACT FROM AUTHOR]

The short-lived buckling instability is responsible for the formation of at least some box/peanut (B/P) shaped bulges, which are observed in most massive, z  = 0, barred galaxies. Nevertheless, it has also been suggested that B/P bulges form via the slow trapping of stars on to vertically extended resonant orbits. The key difference between these two scenarios is that when the bar buckles, symmetry about the mid-plane is broken for a period of time. We use a suite of simulations (with and without gas) to show that when the buckling is sufficiently strong, a residual mid-plane asymmetry persists for several Gyrs after the end of the buckling phase, and is visible in simulation images. On the other hand, images of B/P bulges formed through resonant trapping and/or weak buckling remain symmetric about the mid-plane. We develop two related diagnostics to identify and quantify mid-plane asymmetry in simulation images of galaxies that are within 3° of edge-on orientation, allowing us to test whether the presence of a B/P-shaped bulge can be explained by a past buckling event. We apply our diagnostics to two nearly edge-on galaxies with B/P bulges from the Spitzer Survey of Stellar Structure in Galaxies, finding no mid-plane asymmetry, implying these galaxies formed their bulges either by resonant trapping or by buckling more than ∼5 Gyr ago. We conclude that the formation of B/P bulges through strong buckling may be a rare event in the past ∼5 Gyr. [ABSTRACT FROM AUTHOR]

The major-axis density profiles of bars are known to be either exponential or 'flat'. We develop an automated non-parametric algorithm to detect flat profiles and apply it to a suite of simulations (with and without gas). We demonstrate that flat profiles are a manifestation of a bar's secular growth, producing a 'shoulder' region (an overdensity above an exponential) in its outskirts. Shoulders are not present when bars form, but develop as the bar grows. If the bar does not grow, shoulders do not form. Shoulders are often accompanied by box/peanut bulges, but develop separately from them and are independent tracers of a bar's growth. They can be observed at a wide range of viewing orientations with only their slope varying significantly with inclination. We present evidence that shoulders are produced by looped x1 orbits. Since the growth rate of the bar moderately correlates with the growth rate of the shoulder strength, these orbits are probably recently trapped. Shoulders therefore are evidence of bar growth. The properties of the shoulders do not, however, establish the age of a bar, because secondary buckling or strong spirals may destroy shoulders, and also because shoulders do not form if the bar does not grow much. In particular, our results show that an exponential profile is not necessarily an indication of a young bar. [ABSTRACT FROM AUTHOR]

Objective: The objective of this experiment was to investigate the effects of fat-soluble vitamin injection on plasma and tissue vitamin status in nursery pigs. Methods: A total of 16 pigs (initial body weight: 7.15±1.1 kg) were allotted to 2 treatments at d 7 post-weaning. Pigs were fed a corn-soybean meal-based basal diet with no supplemental vitamin A and i.m. injected with 300,000 IU of retinyl palmitate, 900 IU of d-a-tocopherol and 30,000 IU of vitamin D3 with control pigs having no vitamin injection. Blood (d 0, 3, 7, and 14 post-injection) and tissue samples (liver, brain, heart, lung, and muscle; d 7 and 14 post-injection) were collected from pigs. Retinyl palmitate, retinol, and a-tocopherol concentrations were analyzed in plasma and tissues, while plasma was assayed for 25-hydroxycholecalciferol (25-OHD3). Results: Plasma retinol and 25-OHD3 concentrations increased by the vitamin injection from d 3 to 14 post-injection (p<0.05) whereas plasma retinyl palmitate was detected only in the vitamin treatment at d 3 and 7 post-injection (115.51 and 4.97 µg/mL, respectively). Liver retinol, retinyl palmitate, and retinol+retinyl palmitate concentrations increased by retinyl palmitate injection at d 7 and 14 post-injection (p<0.05) whereas those were not detected in the other tissues. The d-a-tocopherol injection increased a-tocopherol concentrations in plasma at d 3 and 7 post-injection (p<0.05) and in liver, heart (p<0.10), and muscle (p<0.05) at d 7 post-injection. Conclusion: Fat-soluble vitamin injection increased plasma status of a-tocopherol, retinol, retinyl palmitate and 25-OHD3. As plasma levels decreased post-injection, vitamin A level in liver and vitamin E level in muscle, heart and liver increased. The a-tocopherol found in plasma after injection was distributed to various tissues but retinyl palmitate only to the liver. [ABSTRACT FROM AUTHOR]

A national undergraduate curriculum for General Practice might address current concerns regarding intellectual challenge and recruitment through articulating disciplinary knowledge and providing teaching guidance. However, there is ambivalence regarding this idea and the reasons appear incompletely understood. Aims: To better understand ambivalence towards a GP curriculum and to assess the acceptability of a new approach to national curriculum design. Methods: Questionnaire informed by Kotter's model of change, distributed to Heads of Teaching (HOTs) at each UK medical school, regarding the acceptability of both conventional and new approaches to the design of national curriculum guidelines. Qualitative and quantitative data collection with grounded theory-informed analysis of qualitative data. Results: Support for a conventional, detailed curriculum of clinical conditions is weak but there is strong support for a curriculum outlining general disciplinary principles. Identification with general practice as an independent academic discipline is important in predicting support or otherwise for any type of national curriculum. Conclusion: The identity of GP as an independent academic discipline emerges as a key issue. Further research on designing and implementing curricula that use principles rather than detailed outcomes is needed. [ABSTRACT FROM AUTHOR]

Background: Selenium or alpha‐tocopherol deficiency can cause neuromuscular disease. Beta‐carotene has limited documentation in horses. Objective: To evaluate the effect of owner practices on plasma beta‐carotene concentration and risk of selenium and alpha‐tocopherol deficiencies. Animals Three‐hundred and forty‐nine adult (≥1 year), university and privately owned horses and mules. Methods: Cross‐sectional study. Whole blood selenium, plasma alpha‐tocopherol, and plasma beta‐carotene concentrations were measured once. Estimates of daily selenium and vitamin E intake, pasture access, and exercise load were determined by owner questionnaire. Data were analyzed using t tests, Mann‐Whitney tests, parametric or nonparametric analysis of variance (ANOVA), Kruskal‐Wallis test, Spearman's correlation and contingency tables (P <.05). Results: Nearly 88% of the horses received supplemental selenium; 71.3% received ≥1 mg/d. Low blood selenium concentration (<80 ng/mL) was identified in 3.3% of horses, and 13.6% had marginal concentrations (80‐159 ng/mL). Non‐supplemented horses were much more likely to have low blood selenium (odds ratio [OR], 20.2; 95% confidence interval [CI], 9.26‐42.7; P <.001). Supplemental vitamin E was provided to 87.3% of horses; 57.7% received ≥500 IU/d. Deficient (<1.5 μg/mL) and marginal (1.5‐2.0 μg/mL) plasma (alpha‐tocopherol) occurred in 15.4% and 19.9% of horses, respectively. Pasture access (>6 h/d) and daily provision of ≥500 IU of vitamin E was associated (P <.001) with higher plasma alpha‐tocopherol concentrations. Plasma beta‐carotene concentration was higher in horses with pasture access (0.26 ± 0.43 versus 0.12 ± 0.13 μg/mL, P =.003). Conclusions and Clinical Importance: Suboptimal blood selenium and plasma alpha‐tocopherol concentrations occurred in 16.7% and 35.5% of horses, respectively, despite most owners providing supplementation. Inadequate pasture access was associated with alpha‐tocopherol deficiency, and reliance on selenium‐containing salt blocks was associated with selenium deficiency. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The type III secretion system (T3SS) of P. aeruginosa mediates many of the adverse effects of infection with this pathogen, including increased lung permeability in a Toll-like receptor 4/RhoA/PAI-1 (plasminogen activator inhibitor-1)-dependent manner. a-Tocopherol has antiinflammatory properties that may make it a useful adjunct in treatment of this moribund infection. We measured transendothelial and transepithelial resistance, RhoA and PAI-1 activation, stress fiber formation, P. aeruginosa T3SS exoenzyme (ExoY) intoxication into host cells, and survival in a murine model of pneumonia in the presence of P. aeruginosa and pretreatment with a-tocopherol. We found that a-tocopherol alleviated P. aeruginosa-mediated alveolar endothelial and epithelial paracellular permeability by inhibiting RhoA, in part, via PAI-1 activation, and increased survival in a mouse model of P. aeruginosa pneumonia. Furthermore, we found that a-tocopherol decreased the activation of RhoA and PAI-1 by blocking the injection of T3SS exoenzymes into alveolar epithelial cells. P. aeruginosa is becoming increasingly antibiotic resistant. We provide evidence that a-tocopherol could be a useful therapeutic agent for individuals who are susceptible to infection with P. aeruginosa, such as those who are immunocompromised or critically ill. [ABSTRACT FROM AUTHOR]

Patients with multiple myeloma (MM) inevitably relapse on initial treatment regimens, and novel combination therapies are needed. Ibrutinib is a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, an enzyme implicated in growth and survival of MM cells. Preclinical data suggest supra-additivity or synergy between ibrutinib and proteasome inhibitors (PIs) against MM. This phase 1/2b study evaluated the efficacy and safety of ibrutinib plus the PI carfilzomib and dexamethasone in patients with relapsed/refractory MM (RRMM). In this final analysis, we report results in patients who received the recommended phase 2 dose (RP2D; ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone), which was determined in phase 1. The primary efficacy endpoint was overall response rate (ORR). Fifty-nine patients with RRMM received the RP2D (18 in phase 1 and 41 in phase 2b). These patients had received a median of three prior lines of therapy; 69% were refractory to bortezomib, and 90% were refractory to their last treatment. ORR in the RP2D population was 71% (stringent complete response and complete response: 3% each). Median duration of clinical benefit and median duration of response were both 6.5 months. Median progression-free survival (PFS) was 7.4 months, and median overall survival (OS) was 35.9 months. High-risk patients had comparable ORR and median PFS (67% and 7.7 months, respectively) to non-high-risk patients, whose ORR was 73% and median PFS was 6.9 months, whereas median OS in high-risk patients was 13.9 months and not reached in non-high-risk patients. The most common grade ≥3 hematologic treatment-emergent adverse events (TEAEs) were anemia and thrombocytopenia (17% each); the most common grade ≥3 non-hematologic TEAE was hypertension (19%). In patients with RRMM treated with multiple previous lines of therapy, ibrutinib plus carfilzomib demonstrated anticancer activity within the expected efficacy range. No new safety signals were identified and the combination was well-tolerated. [ABSTRACT FROM AUTHOR]

CPX-351 is a dual-drug liposomal encapsulation of cytarabine/daunorubicin. In a phase 3 study (ClinicalTrials.gov Identifier: NCT01696084), patients aged 60–75 years with newly diagnosed, high-risk/secondary AML received 1–2 induction cycles with CPX-351 or 7 + 3 chemotherapy; those achieving complete remission (including with incomplete platelet or neutrophil recovery) could receive up to 2 consolidation cycles with CPX-351 or 5 + 2 chemotherapy, respectively. In this exploratory analysis of the subgroup of patients who received consolidation, median overall survival was prolonged among patients receiving CPX-351 induction/consolidation versus 7 + 3/5 + 2 (25.43 vs. 8.53 months; HR = 0.44 [95% CI: 0.25–0.77]). The safety profile of CPX-351 consolidation was consistent with that of the overall study. Outpatient administration of CPX-351 consolidation occurred in 51%–61% of patients and did not diminish overall survival. These findings suggest consolidation with CPX-351 in this patient population contributed to the prolonged overall survival versus 7 + 3/5 + 2, building upon findings from the overall study population, and provide evidence that, with careful monitoring, some patients can successfully receive CPX-351 as outpatients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of cardiorespiratory fitness with all-cause mortality, and cardiovascular disease (CVD), respiratory disease, chronic obstructive pulmonary disease (COPD) and cancer mortality and incidence.Design: Prospective population-based study.Setting: UK Biobank.Participants: Of the 5 02 628 (5.5% response rate) participants recruited by UK Biobank, we included 73 259 (14.6%) participants with available data in this analysis. Of these, 1374 participants died and 4210 developed circulatory diseases, 1293 respiratory diseases and 4281 cancer, over a median of 5.0 years (IQR 4.3-5.7) follow-up.Main Outcome Measures: All-cause mortality and circulatory disease, respiratory disease, COPD and cancer (such as colorectal, lung, breast and prostate) mortality/incidence. Fitness was estimated using a submaximal cycle ergometer test.Results: The HR for all-cause mortality for each metabolic equivalent of task (MET) higher fitness was 0.96 (95% CI 0.93 to 0.98). Similar results were observed for incident circulatory disease (HR 0.96 [0.95 to 0.97]), respiratory disease (HR 0.96 [0.94 to 0.98]), COPD (HR 0.90 [0.86 to 0.95) and colorectal cancer (HR 0.96 [0.92 to 1.00]). Nonlinear analysis revealed that a high level of fitness (>10METs) was associated with a greater incidence of atrial fibrillation (HR 1.24 [1.07 to 1.44]) and prostate cancer (HR 1.16 [1.02 to 1.32]) compared with average fitness. All results were adjusted for sociodemographic, lifestyle and dietary factors, body composition, and morbidity at baseline and excluded events in the first 2 years of follow-up.Conclusions: Higher cardiorespiratory fitness was associated with lower risk of premature mortality and incidence of CVD, respiratory disease and colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: Daunorubicin can induce left ventricular dysfunction and QT interval prolongation. This study assessed the effects of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, on cardiac repolarization.Methods: Twenty-six adults with acute leukemia were treated with CPX-351 for 1-2 induction cycles and ≤ 4 consolidation cycles. The primary endpoint was mean change in QTcF from baseline.Results: Mean QTcF changes were < 10 ms at all time points. No clinically meaningful effects on heart rate, QRS interval, PR interval, or QTcB were observed. Estimated mean half-lives for total cytarabine and daunorubicin were > 30 h. Thirteen (50%) patients achieved remission. The most common adverse events were febrile neutropenia, fatigue, and nausea.Conclusions: The cytarabine and daunorubicin in CPX-351 liposomes were metabolized and excreted similarly to conventional formulation; however, plasma pharmacokinetics were altered. CPX-351 did not prolong the QT interval, suggesting that CPX-351 may induce less cardiotoxicity than previously reported for conventional daunorubicin.Trial Registration: Clinicaltrials.gov identifier: NCT02238925. [ABSTRACT FROM AUTHOR]

Introduction: There has been a surge in robotic surgery research publications over the past 20 years. However, to date, there has been no characterization of urology's contribution to the robotic field, and there is a lack of bibliometric literature to guide future investigation. We conducted this bibliometric analysis to characterize the distributions and characteristics of robotic surgery research in the urologic field, with subanalysis of the top 100 articles. Materials and Methods: The Web of Science Core Collection of the ISI Web of Science was searched and analyzed to determine distributions and characteristics of robotic urologic surgery research. The top 100 articles were categorized by urologic subfield and organ of pathology, with a level of evidence rating system applied (adapted from the Centre of Evidence-Based Medicine). Results: The total number of articles retrieved was 1294 from 1999 to 2018. The number of articles published in the last decade has increased by 845.75%, with 153 articles published in the preceding decade. The United States leads countries in publication with 699 (54.02%) articles across the field, and 71 within the top 100 articles. The Journal of Endourology published most articles (n = 292, 22.57%) within the field, while European Urology published most (n = 36) within the top 100 articles. Top 100 articles where generally associated with cancer (n = 76), with prostate cancer dominating literature (n = 38). The most common level of evidence for top 100 articles was that of a level 3 study (n = 31). Conclusions: This analysis of research activity has the potential to guide future robotic surgery research trends in the field of urology. There has been an explosion in robotic surgery urologic research activity over the last decade, with level 3 evidence dominating the top 100 articles of the field. [ABSTRACT FROM AUTHOR]

Background: "Ankle sprain" is a common injury, and >20% of patients may develop chronic instability for which surgery is indicated. The modified Broström-Gould (MBG) procedure remains the gold standard; however, there are a number of relative contraindications to this procedure, and the longer-term outcomes after the MBG have been questioned. An alternative procedure is augmentation of a primary repair with a ligament augmentation reconstruction system (LARS). Purpose: To conduct a randomized controlled trial testing the null-hypothesis that there is no difference in patient scored outcomes and activity levels, between patients undergoing a MBG procedure compared with those undergoing a primary repair with LARS augmentation, for lateral ligament instability of the ankle. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients who satisfied the inclusion criteria were invited to take part in the study. Patients were randomly allocated to undergo the LARS or MBG procedure. Both groups followed similar postoperative rehabilitation. Patients completed the Foot and Ankle Outcome Score (FAOS) before surgery and then at 1, 2, and 5 years after surgery. Tegner activity scores were recorded at 5years. The scores in the 2 groups were compared via statistical analysis (P < .05). Results: Of the 50 patients satisfying the inclusion criteria, 47 agreed to take part in the study. Twenty-two were randomized to the LARS group and 25 to the MBG group. At 5 years, follow-up data were complete for 20 patients in the LARS group and 21 in the MBG. There were 2 failures in the MBG group and 0 in the LARS group. The LARS group had significantly better improvement in total FAOS at 1 year (mean ± SD, 92.4 ± 2.5 vs 78.2 ± 3.4, P = .005), 2 years (94.0 ± 3.0 vs 78.0 ± 5.2, P = .003), and 5 years (93.7 ± 6.0 vs 75.1 ± 5.5, P = .002) after surgery. The 5-year Tegner activity scores were higher in the LARS group (8.25 ± 1.1 vs 7.2 ± 0.9, P = .03). Conclusion: Among physically active patients with chronic lateral ligament instability, primary repair combined with LARS results in better total FAOS at 5-year follow-up and higher Tegner activity scores as compared with the MBG procedure. Registration: ACTRN12618000906257 (Australia New Zealand Clinical Trial Registry). [ABSTRACT FROM AUTHOR]

Objective: Two experiments were conducted to evaluate vitamin D3 administration to nursery pigs by injection or in drinking water on serum 25-hydroxycholecalciferol (25-OHD3) concentrations. Methods: At weaning, 51 pigs (27 and 24 pigs in experiments 1 and 2, respectively) were allotted to vitamin D3 treatments. Treatments in experiment 1 were: i) control (CON), no vitamin administration beyond that in the diet, ii) intramuscular (IM) injection of 40,000 IU of vitamin D3 at weaning, and iii) water administration, 5,493 IU of vitamin D3/L drinking water for 14 d postweaning. Treatments in experiment 2 were: i) control (CON), no vitamin administration, and ii) water administration, 92 IU of d-α-tocopherol and 5,493 IU of vitamin D3/L drinking water for 28 d postweaning. The lightest 2 pigs within each pen were IM injected with an additional 1,000 IU of d-α-tocopherol, 100,000 IU of retinyl palmitate, and 100,000 IU of vitamin D3. Results: In both experiments, serum 25-OHD3 was changed after vitamin D3 administration (p<0.05). In experiment 1, injection and water groups had greater values than CON group through d 35 and 21 post-administration, respectively (p<0.05). In experiment 2, serum values peaked at d 3 post-administration in the injection groups regardless of water treatments (p<0.05) whereas CON and water-only groups had peaks at d 14 and 28 post-administration, respectively (p<0.05). Even though the injection groups had greater serum 25-OHD3 concentrations than the noninjection groups through d 7 post-administration regardless of water treatments (p<0.05), the water-only group had greater values than the injection-only group from d 21 post-administration onward (p<0.05). Conclusion: Serum 25-OHD3 concentrations in pigs increased either by vitamin D3 injection or drinking water administration. Although a single vitamin D3 injection enhanced serum 25-OHD3 concentrations greater than water administration in the initial period post-administration, a continuous supply of vitamin D3 via drinking water could maintain higher serum values than the single injection. [ABSTRACT FROM AUTHOR]

Background: The binding of CXCR4 with its ligand (stromal-derived factor-1) maintains hematopoietic stem/ progenitor cells (HSPCs) in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT) promotes hematopoiesis by inducing HSC proliferation. Methods: We conducted a phase I/II trial of plerixafor on hematopoietic cell recovery following myeloablative allogeneic HSCT. Patients with hematologic malignancies receiving myeloablative conditioning were enrolled. Plerixafor 240 μg/kg was administered subcutaneously every other day beginning day +2 until day +21 or until neutrophil recovery. The primary efficacy endpoints of the study were time to absolute neutrophil count >500/μl and platelet count >20,000/μl. The cumulative incidence of neutrophil and platelet engraftment of the study cohort was compared to that of a cohort of 95 allogeneic peripheral blood stem cell transplant recipients treated during the same period of time and who received similar conditioning and graft-versus-host disease prophylaxis. Results: Thirty patients received plerixafor following peripheral blood stem cell (n = 28) (PBSC) or bone marrow (n = 2) transplantation. Adverse events attributable to plerixafor were mild and indistinguishable from effects of conditioning. The kinetics of neutrophil and platelet engraftment, as demonstrated by cumulative incidence, from the 28 study subjects receiving PBSC showed faster neutrophil (p = 0.04) and platelet recovery >20 K (p = 0.04) compared to the controls. Conclusions: Our study demonstrated that plerixafor can be given safely following myeloablative HSCT. It provides proof of principle that blocking CXCR4 after HSCT enhances hematopoietic recovery. Larger, confirmatory studies in other settings are warranted. [ABSTRACT FROM AUTHOR]

Treatment and cure of salivary gland neoplasms requires surgical intervention in most cases. For parotid neoplasms, the most common surgical procedure performed is the superficial parotidectomy with facial nerve preservation. Postoperative radiation therapy is indicated in high-grade salivary gland malignancies and malignancies with increased risk of locoregional recurrence. Primary radiation, including neutron beam techniques, may play a role in certain histologic types or nonoperative candidates. Chemotherapy has yet to result in improvements in survival or quality of life in the treatment of salivary gland malignancy. Advances in radiation therapy techniques, including intensity-modulated radiation therapy, provide opportunities for reduced morbidity. [ABSTRACT FROM AUTHOR]

Background: Krill oil is a rich source of the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which may alter immune function after exercise. The aim of the study was to determine the effects of krill oil supplementation on post exercise immune function and performance. Methods: Nineteen males and 18 females (age: 25.8 ± 5.3 years; mean ± S.D.) were randomly assigned to 2 g/day of krill oil (n = 18) or placebo (n = 19) supplementation for 6 weeks. A maximal incremental exercise test and cycling time trial (time to complete set amount of work) were performed pre-supplementation with the time trial repeated post-supplementation. Blood samples collected pre- and post- supplementation at rest, and immediately, 1 and 3h post-exercise. Plasma IL-6 and thiobarbituric acid reactive substances (TBARS) concentrations and, erythrocyte fatty acid composition were measured. Natural killer (NK) cell cytotoxic activity and peripheral blood mononuclear cell (PBMC) IL-2, IL-4, IL-10, IL-17 and IFNγ production were also measured. Results: No effects of gender were noted for any variable. PBMC IL-2 and NK cell cytotoxic activity were greater (P < 0.05) 3h post exercise in the krill oil compared to the control group. Plasma IL-6 and TBARS, PBMC IL-4, IL-10, IL-17 and IFNγ production, along with performance and physiological measures during exercise, were not different between groups. Conclusion: Six weeks of krill oil supplementation can increase PBMC IL-2 production and NK cell cytotoxic activity 3h post-exercise in both healthy young males and females. Krill oil does not modify exercise performance. [ABSTRACT FROM AUTHOR]

Single-agent dacetuzumab has demonstrated antitumor activity in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Preclinical data demonstrated improved dacetuzumab antitumor activity in combination with rituximab, ± chemotherapy. We designed a phase 2b, double-blind, placebo-controlled trial to compare rituximab, ifosfamide, carboplatin and etoposide (R-ICE) + dacetuzumab with R-ICE + placebo in patients with DLBCL who relapsed after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) (ClinicalTrials.gov #NCT00529503). The primary endpoint was complete response (CR); additional endpoints included failure-free survival and overall survival (OS). Overall, 151 patients were randomized (75 dacetuzumab, 76 placebo). No notable differences between arms in demographics or subsequent treatment parameters were observed. Cytopenias, cough and infection were more frequent with dacetuzumab. Futility analysis failed to demonstrate higher CR rates with dacetuzumab (36% dacetuzumab, 42% placebo); consequently, enrollment was stopped. Unplannedpost hocanalysis showed that patients who underwent subsequent autologous stem cell transplant experienced improvement in OS (hazard ratio = 0.195,p= 0.004), which may be explained by potential immunomodulatory effects of dacetuzumab on antigen-presenting cells. [ABSTRACT FROM PUBLISHER]

This phase 2 study ( N = 116) evaluated single-agent vosaroxin, a first-in-class anticancer quinolone derivative, in patients ≥60 years of age with previously untreated unfavourable prognosis acute myeloid leukaemia. Dose regimen optimization was explored in sequential cohorts ( A: 72 mg/m2 d 1, 8, 15; B: 72 mg/m2 d 1, 8; C: 72 mg/m2 or 90 mg/m2 d 1, 4). The primary endpoint was combined complete remission rate (complete remission [ CR] plus CR with incomplete platelet recovery [ CRp]). Common (>20%) grade ≥3 adverse events were thrombocytopenia, febrile neutropenia, anaemia, neutropenia, sepsis, pneumonia, stomatitis and hypokalaemia. Overall CR and CR/ CRp rates were 29% and 32%; median overall survival ( OS) was 7·0 months; 1-year OS was 34%. Schedule C (72 mg/m2) had the most favourable safety and efficacy profile, with faster haematological recovery (median 27 d) and lowest incidence of aggregate sepsis (24%) and 30-d (7%) and 60-d (17%) all-cause mortality; at this dose and schedule, CR and CR/ CRp rates were 31% and 35%, median OS was 7·7 months and 1-year OS was 38%. Overall, vosaroxin resulted in low early mortality and an encouraging response rate; vosaroxin 72 mg/m2 d 1, 4 is recommended for further study in this population. Registered at : # NCT00607997. [ABSTRACT FROM AUTHOR]

Ofatumumab is a fully human anti-CD20 monoclonal antibody with enhanced antibody dependent and complement dependent cytotoxicity. Lenalidomide induces T cell and natural killer (NK) cell activation and in vitro enhances clearance of chronic lymphocytic leukemia (CLL) cells by monoclonal antibodies. We performed a multi-center, phase 2 trial of sequential treatment with ofatumumab and lenalidomide in patients with advanced, relapsed and refractory (R/R) CLL, consisting of ofatumumab 2000 mg intravenously on day 1 and lenalidomide 10 mg on days 8-28, for up to six cycles. Twenty-one subjects were included with median age of 63 years and two prior lines of therapy. The overall response rate was 47.6% and 23.8% had stable disease. Median overall survival was 21.5 months. Neutropenia and thrombocytopenia were the most frequent adverse events. Tumor flare reaction occurred in 43% of subjects. Intracycle sequential ofatumumab plus lenalidomide is active in high-risk R/R CLL and well tolerated except for frequent cytopenias. [ABSTRACT FROM AUTHOR]

Background More than 20% of patients develop chronic instability following appropriate management of an 'ankle sprain'. There is little research comparing surgical techniques. 'Anatomical' procedures, such as the modified Brostrom- Gould ( MBG), are generally preferred. However, not all patients are suitable for this procedure. Augmentation of a primary repair using a synthetic ligament, such as the ligament augmentation reconstruction system ( LARS), is another 'anatomic' option. Our objective was to compare the clinical outcome following the MBG with that following the LARS technique using a prospective randomized clinical trial. Methods Patients who satisfied the study criteria were randomly allocated to undergo the LARS procedure or the MBG procedure. All patients followed a similar rehabilitation programme. Patients completed the foot and ankle outcome score ( FAOS) before surgery, and then at 1 year and 2 years following surgery. Statistical analysis was used to compare the groups ( P < 0.05). Results Forty-one patients took part in the study, 21 were randomized to the LARS group and 20 to the MBG group. The LARS group had a significantly better improvement in the total FAOS at both 1 year (25.5 standard error ( SE) 3.8 versus 16.0 SE 3.3) and 2 years (27.1 SE 4.5 versus 15.8 SE 4.9) post-surgery. Conclusion Primary repair combined with LARS results in better patient-scored clinical outcome, at 2 years post-surgery, than the MBG procedure. Although longer follow-up is required, the LARS procedure may be considered as an alternative, especially in those patients for whom the MBG is relatively contra-indicated. [ABSTRACT FROM AUTHOR]

Background Compared with growth factor ( G) alone, the combination of G with plerixafor ( G + P) increases peripheral blood CD34+ count ( PB- CD34+) and improves CD34+ collection yield ( yCD34+) in multiple myeloma and lymphoma patients undergoing autologous hematopoietic progenitor cell ( AHPC) mobilization. It is unknown whether the improved yCD34+ with G + P results entirely from expansion of PB- CD34+ or also from increased intraapheresis CD34+ recruitment and collection efficiency. Study Design and Methods We retrospectively studied 192 patients who underwent AHPC mobilization and collection with G (n = 73) or G + P (n = 119) to compare the adjusted relative efficiency ( aRE), the proportion of the circulating CD34+ pool that is captured for each blood volume processed. Additionally, in a prospective cohort of nine patients mobilizing with G and 11 with G + P, PB- CD34+ after leukapheresis allowed calculation of the recruitment coefficient ( RC), proportion of the initial CD34+ pool recruited from the marrow into peripheral blood for each blood volume processed. Results There was no difference in aRE between G and G + P (0.50 vs. 0.46; p = 0.37) and no substantial decline in aRE with higher blood volumes processed in either group. RC was also not different between G and G + P (median, 0.39 and 0.38, respectively; p = 0.7). Prediction of yCD34+ was determined essentially by PB- CD34+ and not affected independently by plerixafor. Conclusion Kinetics of intraapheresis CD34+ recruitment and collection is proportional to PB-CD34+ but not influenced further by plerixafor. [ABSTRACT FROM AUTHOR]

It is well established that regular exercise can reduce the risk of cardiovascular disease, although the most time-efficient exercise protocol to confer benefits has yet to be established. The aim of the current study was to determine the effects of short-duration sprint interval exercise on postprandial triacylglycerol. Fifteen healthy male participants completed two 2 day trials. On day 1, participants rested (control) or carried out twenty 6 s sprints, interspersed with 24 s recovery (sprint interval exercise – 14 min for total exercise session). On day 2, participants consumed a high-fat meal for breakfast with blood samples collected at baseline, 2 h and 4 h. Gas exchange was also measured at these time points. On day 2 of control and sprint interval exercise trials, there were no differences (P <0.05) between trials in plasma glucose, triacylglycerol, insulin or respiratory exchange ratio (RER). The area under the curve for plasma triacylglycerol was 7.67 ± 2.37 mmol · l–1.4 h–1in the control trial and 7.26 ± 2.49 mmol · l–1.4 h–1in the sprint interval exercise trial. Although the sprint exercise protocol employed had no significant effect on postprandial triacylglycerol, there was a clear variability in responses that warrants further investigation. [ABSTRACT FROM AUTHOR]

On 14 August 2003, three 345-kV transmission circuits in northeastern Ohio contacted overgrown trees during a 40-min time span, starting a chain of events that culminated in the collapse of the electrical grid across the eastern Great Lakes region, the northeastern United States, and parts of eastern Canada. In the aftermath of the disturbance, large portions of the Eastern Interconnection were blacked out, and several electrical islands were present. System operators faced a formidable task: to reassemble the grid and restore power to tens of millions of customers. The challenges that had to be overcome varied significantly from one state or province to another. New York, New England, Ontario, Michigan, and Ohio each had unique problems that operators had to address. [ABSTRACT FROM PUBLISHER]

Across the Anglo-American world, a pervasive sense of wariness and concern about strangers continues to haunt influential discourses and practices that regulate and shape youth citizenship. In particular, (1) media-centred accounts of ‘stranger danger’, (2) dominant citizenship discourses taught in schools and (3) government policies regulating young people's civic lives, remain significant in shaping how strangers are made meaningful for youth. Through these discourses and practices, the stranger increasingly comes to be a fetish figure, a body and symbolic form whose very figurability is rendered a problem in the first instance. These developments are problematic, in large part because strangers are a necessary and enabling feature of modern democracies. Accordingly, in this paper, I examine the three aforementioned fields of discourse and practice as they have operated broadly over the past decade in Canada, Britain and the United States. I show how strangers are made difficult and dangerous others for youth and make clear how these constructions regulate and threaten a vibrant public world. I conclude by hinting at how stranger hospitality might be taken up differently in schools (and other public fora) as part of nurturing our collective democratic futures. [ABSTRACT FROM PUBLISHER]

Therapies for AML have remained mostly unchanged since the introduction of anthracyline- and cytarabine-based regimens in the 1970s. Though some changes have been made in the dosing of anthracylines, in the choice of consolidation regimens versus allogeneic stem cell transplant, and in supportive care, clinical outcomes remain poor for most patients. As we continue to strive for better treatment options to improve upon outcomes, different agents, both chemotherapeutic and targeted therapies, are being studied. Here we discuss new chemotherapeutic agents that show promise in recent clinical trials and attempt to answer the question if there are any new effective cytotoxic chemotherapy agents out there. [ABSTRACT FROM AUTHOR]

We utilized a cohort with a high frequency of young patients to explore the correlation between fluorescence in situ hybridization (FISH) detected chromosomal abnormalities (CA) and age in multiple myeloma (MM). One hundred and nineteen patients with MM were included in the analysis. The median age was 60 years, 51% of patients were female and 56% were Caucasian. Translocations involving the IGH gene on chromosome 14 were more likely to be detected in older (≥60 years) patients (32.8% vs. 15.5%, p =0.03), particularly because of a higher frequency of t(4;14) (14.8% vs. 3.4%, p =0.05). Myeloma cells from older patients were also three times more likely to have multiple CA. The presence of high-risk CA influenced survival in patients <60 but not in patients ≥60. Among standard-risk patients, survival was significantly superior for patients <60. No effect of age on survival was detected for high-risk patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+ cells but adds cost to the mobilization. We hypothesized that replacing weight-based FIL with flat-dose pegfilgrastim (PEG) in a validated cost-based mobilization algorithm for patient-adapted use of plerixafor would add convenience without increased cost. STUDY DESIGN AND METHODS: A single-center retrospective analysis compared two consecutive cohorts undergoing FIL or PEG mobilization before autologous hematopoietic stem cell transplantation for multiple myeloma or lymphoma. FIL dose was 10 µg/kg/day continuing until completion of collection and a 12-mg flat dose of PEG. Peripheral blood CD34+ cells (PB-CD34+) enumeration was performed on the fourth day after initiation of growth factor. Subjects surpassing a certain target-specific threshold of PB-CD34+ started apheresis immediately while subjects with lower PB-CD34+ received plerixafor with apheresis starting on the fifth day. RESULTS: Overall 68 of 74 in the FIL group and 52 of 57 patients in the PEG group met the mobilization target. Only one patient in each cohort required remobilization. Median PB-CD34+ on Day 4 was significantly higher in patients in the PEG group (18.1 × 106 vs. 28.7 × 106 cells/L, p = 0.01). Consequently, patients in the PEG group were less likely to require administration of plerixafor (67.5% vs. 45.6%, p = 0.01). Cohorts had near identical mean number of apheresis sessions and comparable CD34+ yield. The estimated cost associated with growth factor was higher in patients in the PEG group, but it was counterbalanced by lower cost associated with use of plerixafor. CONCLUSION: Single administration of 12 mg of PEG is associated with better CD34+ mobilization than FIL allowing for effective, convenient mobilization with less frequent use of plerixafor. [ABSTRACT FROM AUTHOR]

BACKGROUND: The dose of CD34+ cells/kg in the mobilized peripheral blood product is the main determinant of neutrophil and platelet (PLT) engraftment after autologous hematopoietic stem cell transplantation (AHSCT). Whether the method of mobilization, namely, granulocyte-colony-stimulating factor (G-CSF) alone (G), G-CSF plus plerixafor (G+P), or cyclophosphamide + G/granulocyte-macrophage (GM)-CSF (Cy+G/GM), independently affects number of colony-forming unit (CFU)-GM, engraftment, and hematopoietic graft function is unknown. STUDY DESIGN AND METHODS: We used a database of AHSCT patients with multiple myeloma or lymphoma to identify three groups with different mobilization strategies receiving transplantation with similar CD34+ cell doses. Groups were compared in terms of CFU-GM, ratio of CFU-GM/CD34+, engraftment of neutrophils and PLTs, and hematopoietic graft function on Day +100. RESULTS: Ninety-six patients were included in the analysis, 26 G, 32 G+P, and 38 Cy+G/GM, with median cell doses of 4.21 × 106, 4.11 × 106, and 4.67 × 106 CD34+/kg, respectively (p = 0.433). There was no significant difference in number of CFU-GM between the three groups; however, the ratio of CFU-GM/CD34+ was significantly lower for G+P (p = 0.008). Median time for neutrophil engraftment was 13 days in G+P and 12 days in G and Cy+G/GM (p = 0.028), while PLT engraftment happened at a median of 14.5 days in G+P versus 12 days in G and 11 days in Cy+G/GM (p = 0.012). There was no difference in hematopoietic graft function at Day +100. CONCLUSION: Plerixafor-based mobilization is associated with slightly reduced number of CFU-GM and minimal delay in engraftment that is independent of CD34+ cell dose. Hematopoietic graft function on Day 100 is not affected by mobilization strategy. [ABSTRACT FROM AUTHOR]

Background: A number of accepted criteria, including pathological tumor, node, metastasis system stage, lymph node metastasis, and tumor differentiation, predict survival in patients undergoing surgery for gastroesophageal cancer. We examined the interrelationships between standard clinicopathological factors, systemic and local inflammatory responses, tumor proliferative activity, and survival. Methods: The interrelationships between the systemic inflammatory response (Glasgow prognostic score, mGPS), standard clinicopathological factors, local inflammatory response (Klintrup criteria, macrophage infiltration), and tumor proliferative activity (Ki-67) were examined by immunohistochemistry in 100 patients (44 esophageal [19 squamous, 25 adenocarcinoma], 19 junctional, and 37 gastric cancers) selected for potentially curative resection. Results: The minimum follow-up was 59 months. On multivariate survival analysis, lymph node ratio (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.11-2.40, P < 0.05), tumor differentiation (HR 2.63, 95% CI 1.45-4.77, P = 0.001), mGPS (HR 3.91, 95% CI 1.96-8.11, P < 0.001), Klintrup score (HR 3.47, 95% CI 1.14-10.55, P < 0.05), and Ki-67 (HR 0.67, 95% CI 0.47-0.96, P < 0.05) were independently associated with cancer-specific survival. A higher lymph node ratio was associated with poor tumor differentiation ( P < 0.05), low-grade Klintrup criteria ( P < 0.005), and low tumor proliferative activity ( P < 0.05). Conclusion: Tumor proliferation rate and local and systemic inflammatory responses are important predictors of survival, albeit in a heterogeneous cohort of patients including esophageal, junctional, and gastric cancers. These scores may be combined with accepted tumor-based factors to improve prediction of outcome. [ABSTRACT FROM AUTHOR]

Background and Methods: We report the case of a young woman with delayed cerebral infarction and intracranial hypertension following subarachnoid hemorrhage requiring hemicraniectomy, who underwent multimodality neuromonitoring of the contralateral hemisphere before and after craniectomy. Results: Intracranial hypertension was preceded by signs of ischemia and impaired brain metabolism diagnosed through cerebral microdialysis and PbtO2 monitoring, as well as a decrease in cerebral perfusion pressure (CPP) to <40 mmHg despite increasing vasopressor requirements. We describe how a comprehensive multimodality neuromonitoring approach was utilized to inform the decision to perform an early decompressive hemicraniectomy. Post-operatively, CPP and intracranial pressure (ICP) normalized, and the patient was weaned off all pressors within hours. The modified Rankin score at 3 and 12 months was 5. Conclusions: Delayed rescue hemicraniectomy can be life-saving after poor grade SAH. The role of multimodality brain monitoring for determining the optimal timing of hemicraniectomy deserves further study. [ABSTRACT FROM AUTHOR]

Background: Endoscopic mucosal resection (EMR) of early gastric and esophageal tumors is effective and avoids the morbidity and mortality of surgery. We report the long-term results of a consecutive series of 93 endoscopic resections, during a 7-year period, in a U.K. population. Methods: Eighty-eight patients with 93 lesions were included. EMR was performed for 64 and 29 malignant and benign lesions, respectively. Patients with malignant disease were subgrouped into 'high risk' or 'low risk' for recurrence. Results: Of the 35 lesions in the low-risk group, local control was achieved in 31; 29 after 1 EMR session. Two had residual invasive carcinoma, one had treatment ceased due to pancreatic cancer, and one patient did not attend follow-up. Of the 29 lesions in the high-risk group, local control was achieved in 15; 13 after 1 EMR session. Median follow-up was 53 months. Cancer specific survival for the 45 invasive cancers (T1m and T1sm) was 93%; three patients died from their disease. Conclusions: This study has shown for the first time in a U.K. population that EMR is effective in controlling disease in patients with local high grade dysplasia (HGD) and early invasive carcinoma, with no mortality and low morbidity. [ABSTRACT FROM AUTHOR]

Introduction: Efficacy of a continuous high-dose intravenous infusion of esomeprazole, followed by an oral regimen after successful endoscopic therapy for peptic ulcer bleeding (PUB) was established in the PUB study (ClinicalTrials. gov identifier: NCT00251979). Mortality rates and detailed safety and tolerability results from this study are reported here. Methods: This was a double-blind, randomized study in patients ≥18 years with overt signs of upper gastrointestinal bleeding, following endoscopic diagnosis of a single gastric or duodenal ulcer (≥5 mm) with stigmata indicating current/ recent bleeding (Forrest class Ia, Ib, IIa, or IIb). Postendoscopic hemostasis, patients received intravenous esomeprazole (80 mg/30 minutes, then 8 mg/hour for 71.5 hours) or placebo. Postinfusion, all patients received open-label oral esomeprazole 40 mg once daily for 27 days. Mortality rates were analyzed using Fisher's exact test; other safety variables were analyzed descriptively. Results: A total of 767 patients were randomized; 764 comprised the safety analysis set (375 patients received esomeprazole, 389 placebo). Baseline characteristics were similar across the two treatment groups. Three deaths from the esomeprazole treatment group and eight from the placebo group occurred during the trial (0.8% versus 2.1%; P=0.22). From these 11 all-cause deaths, one (esomeprazole group; rebleeding from duodenal ulcer) occurred during the 72-hour intravenous treatment phase. Adverse event (AE) frequency was similar for the two groups over the intravenous treatment phase (esomeprazole, 39.2%; placebo, 41.9%), with gastrointestinal disorders being most commonly reported (12.3% and 19.8%, respectively). Serious AEs were mostly related to bleeding events. Infusion-site reactions (mild, transient) were reported in 4.3% of esomeprazole-treated patients versus 0.5% of placebo patients. These did not lead to treatment discontinuation. Conclusion: Esomeprazole, given as a continuous high-dose intravenous infusion followed by an oral regimen after successful endoscopic therapy for PUB, was well tolerated, with no apparent safety concerns from either the high-dose intravenous treatment or oral phases. [ABSTRACT FROM AUTHOR]