Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Influence of Internode Length on Degradability of Lucerne Stems

Lignification of plant tissues restricts degradation of forages by ruminants. The undegradable lignified middle lamella/primary cell wall prevents rumen microbes from accessing undamaged adjacent plant cells. In contrast, walls of non-lignified tissues are completely degradable. Preliminary observations of how deeply rumen microbes could degrade different tissues within 20- to 30-mm long lucerne (Medicago sativa L.) stem pieces indicated a two-fold range in depth of degradation among stem samples. Studies were undertaken to determine if extent of cell wall degradation in lucerne was influenced by length of stem internodes

Induction of Thyroid Gene Expression and Radioiodine Uptake in Melanoma Cells: Novel Therapeutic Implications

Both the MAP kinase and PI3K/Akt pathways play an important role in the pathogenesis of melanoma. We conducted the present study to test the hypothesis that targeting the two pathways to potently induce cell inhibition accompanied with thyroid iodide-handling gene expression for adjunct radioiodine ablation could be a novel effective therapeutic strategy for melanoma. We used specific shRNA approaches and inhibitors to individually or dually suppress the MAP kinase and PI3K/Akt pathways and examined the effects on a variety of molecular and cellular responses of melanoma cells that harbored activating genetic alterations in the two pathways. Suppression of the MAP kinase and PI3K/Akt pathways showed potent anti-melanoma cell effects, including the inhibition of cell proliferation, transformation and invasion, induction of G0/G1 cell cycle arrest and, when the two pathways were dually suppressed, cell apoptosis. Remarkably, suppression of the two pathways, particularly simultaneous suppression of them, also induced expression of genes that are normally expressed in the thyroid gland, such as the genes for sodium/iodide symporter and thyroid-stimulating hormone receptor. Melanoma cells were consequently conferred the ability to take up radioiodide. We conclude that dually targeting the MAP kinase and PI3K/Akt pathways for potent cell inhibition coupled with induction of thyroid gene expression for adjunct radioiodine ablation therapy may prove to be a novel and effective therapeutic strategy for melanoma

Using redundancy to cope with failures in a delay tolerant network

We consider the problem of routing in a delay tolerant net-work (DTN) in the presence of path failures. Previous work on DTN routing has focused on using precisely known network dy-namics, which does not account for message losses due to link failures, buffer overruns, path selection errors, unscheduled de-lays, or other problems. We show how to split, replicate, and erasure code message fragments over multiple delivery paths to optimize the probability of successful message delivery. We provide a formulation of this problem and solve it for two cases: a 0/1 (Bernoulli) path delivery model where messages are ei-ther fully lost or delivered, and a Gaussian path delivery model where only a fraction of a message may be delivered. Ideas from the modern portfolio theory literature are borrowed to solve the underlying optimization problem. Our approach is directly relevant to solving similar problems that arise in replica place-ment in distributed file systems and virtual node placement in DHTs. In three different simulated DTN scenarios covering a wide range of applications, we show the effectiveness of our ap-proach in handling failures

Factors associated with excessive bleeding in cardiopulmonary bypass patients: a nested case-control study

<p>Abstract</p> <p>Introduction</p> <p>Excessive bleeding (EB) after cardiopulmonary bypass (CPB) may lead to increased mortality, morbidity, transfusion requirements and re-intervention. Less than 50% of patients undergoing re-intervention exhibit surgical sources of bleeding. We studied clinical and genetic factors associated with EB.</p> <p>Methods</p> <p>We performed a nested case-control study of 26 patients who did not receive antifibrinolytic prophylaxis. Variables were collected preoperatively, at intensive care unit (ICU) admission, at 4 and 24 hours post-CPB. EB was defined as 24-hour blood loss of >1 l post-CPB. Associations of EB with genetic, demographic, and clinical factors were analyzed, using SPSS-12.2 for statistical purposes.</p> <p>Results</p> <p>EB incidence was 50%, associated with body mass index (BMI)< 26.4 (25–28) Kg/m², (<it>P </it>= 0.03), lower preoperative levels of plasminogen activator inhibitor-1 (PAI-1) (<it>P </it>= 0.01), lower body temperature during CPB (<it>P </it>= 0.037) and at ICU admission (<it>P </it>= 0.029), and internal mammary artery graft (<it>P </it>= 0.03) in bypass surgery. We found a significant association between EB and 5G homozygotes for PAI-1, after adjusting for BMI (F = 6.07; <it>P </it>= 0.02) and temperature during CPB (F = 8.84; <it>P </it>= 0.007). EB patients showed higher consumption of complement, coagulation, fibrinolysis and hemoderivatives, with significantly lower leptin levels at all postoperative time points (<it>P </it>= 0.01, <it>P </it>< 0.01 and <it>P </it>< 0.01).</p> <p>Conclusion</p> <p>Excessive postoperative bleeding in CPB patients was associated with demographics, particularly less pronounced BMI, and surgical factors together with serine protease activation.</p

PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass

Background: Enhanced bleeding remains a serious problem after cardiac surgery, and fibrinolysis is often involved. We speculate that lower plasma concentrations of plasminogen activator inhibitor - 1 (PAI-1) preoperatively and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex postoperatively might predispose for enhanced fibrinolysis and increased postoperative bleeding.Methods: Totally 88 adult patients (mean age 66 ± 10 years) scheduled for cardiac surgery, were enrolled into a prospective study. Blood samples were collected pre-operatively, on admission to the recovery and at 6 and 24 hours postoperatively. Patients with a surgical bleeding that was diagnosed during reoperation were discarded from the study. The patients were allocated to two groups depending on the 24-hour postoperative chest tube drainage (CTD): Group I > 500ml, Group II ≤ 500ml. Associations between CTD, PAI-1, t-PA/PAI-1 complex and D-dimer were analyzed with SPSS.Results: Nine patients were excluded because of surgical bleeding. Of the 79 remaining patients, 38 were allocated to Group I and 41 to Group II. The CTD volumes correlated with the preoperative plasma levels of PAI-1 (r = - 0.3, P = 0.009). Plasma concentrations of preoperative PAI-1 and postoperative t-PA/PAI-1 complex differed significantly between the groups (P < 0.001 and P = 0.012, respectively). Group I displayed significantly lower plasma concentrations of fibrinogen and higher levels of D-dimer from immediately after the operation and throughout the first 24 hours postoperatively.Conclusions: Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with more postoperative bleeding after cardiac surgery.publishersversionPeer reviewe

The Developmental Significance of Adolescent Romantic Relationships: Parent and Peer Predictors of Engagement and Quality at Age 15

From a longitudinal sample (n = 957; 49.9% male; 77.3% White/non-Hispanic) of participants studied from infancy through age 15, adolescents’ depth of engagement in, and quality of romantic relationships were predicted from early and contemporaneous parent–child interactive quality and peer social competence. High quality maternal parenting and peer experiences prior to and during adolescence tended to be negatively associated with the depth of engagement in this domain for the full sample, yet positively associated with the quality of adolescents’ romantic relationships for the sub-set of individuals currently dating at age 15. Results reconcile contrasting views of the origins of romantic relationship engagement and quality and the positive versus negative developmental salience of romantic relationships in adolescence

Correction: Impact of autologous blood transfusion after bone marrow harvest on unrelated donor’s health and outcome: a CIBMTR analysis

Correction to "Impact of autologous blood transfusion after bone marrow harvest on unrelated donor’s health and outcome: a CIBMTR analysis

Impact of autologous blood transfusion after bone marrow harvest on unrelated donor’s health and outcome: a CIBMTR analysis

Pre-harvest autologous blood collection from bone marrow (BM) donors is performed to meet potential post-operative transfusion needs. This study examines the impact of autologous blood transfusion on BM donor’s health and safety. The study included first-time unrelated BM donors from the United States whose BM harvest was facilitated by the National Marrow Donor Program (NMDP) centers between 2006 and 2017. Examination of 7024 BM donors revealed that 60% received at least one unit of autologous blood. The donors who received autologous blood were older, had lower hemoglobin pre-harvest, underwent longer duration of anesthesia, and higher volume BM harvest. Only donors who underwent high-volume BM harvest, defined as a BM harvest volume &gt;27% of donor’s blood volume, benefited from autologous transfusion. After a high-volume BM harvest, autologous blood transfusion was shown to decrease grade 2 to 4 collection-associated toxicities within 48 h of BM donation (p = 0.010) and shorten the time to donor-reported “complete” recovery from donation-associated symptoms (p &lt; 0.001). Therefore, autologous transfusion could be avoided as support of marrow donation in the majority of unrelated BM donors and should be limited to cases where the planned BM harvest volume is expected to exceed 27% of donor’s blood volume