Tailoring the flow of soft glasses by soft additives

We examine the vitrification and melting of asymmetric star polymers mixtures by combining rheological measurements with mode coupling theory. We identify two types of glassy states, a {\it single} glass, in which the small component is fluid in the glassy matrix of the big one and a {\it double} glass, in which both components are vitrified. Addition of small star polymers leads to melting of {\it both} glasses and the melting curve has a non-monotonic dependence on the star-star size ratio. The phenomenon opens new ways for externally steering the rheological behavior of soft matter systems.Comment: 4 pages, 4 figures, accepted in Phys. Rev. Let

Polydisperse star polymer solutions

We analyze the effect of polydispersity in the arm number on the effective interactions, structural correlations and the phase behavior of star polymers in a good solvent. The effective interaction potential between two star polymers with different arm numbers is derived using scaling theory. The resulting expression is tested against monomer-resolved molecular dynamics simulations. We find that the theoretical pair potential is in agreement with the simulation data in a much wider polydispersity range than other proposed potentials. We then use this pair potential as an input in a many-body theory to investigate polydispersity effects on the structural correlations and the phase diagram of dense star polymer solutions. In particular we find that a polydispersity of 10%, which is typical in experimental samples, does not significantly alter previous findings for the phase diagram of monodisperse solutions.Comment: 14 pages, 7 figure

Self-diffusion in binary blends of cyclic and linear polymers

A lattice model is used to estimate the self-diffusivity of entangled cyclic and linear polymers in blends of varying compositions. To interpret simulation results, we suggest a minimal model based on the physical idea that constraints imposed on a cyclic polymer by infiltrating linear chains have to be released, before it can diffuse beyond a radius of gyration. Both, the simulation, and recently reported experimental data on entangled DNA solutions support the simple model over a wide range of blend compositions, concentrations, and molecular weights.Comment: 10 pages, 2 figure

High-affinity recombinant phage antibodies to the pan-carcinoma marker epithelial glycoprotein-2 for tumour targeting.

The tumour-associated antigen epithelial glycoprotein-2 (EGP-2) is a promising target for detection and treatment of a variety of human carcinomas. Antibodies to this antigen have been successfully used in patients for imaging of small-cell lung cancer and for adjuvant treatment of minimal residual disease of colon cancer. We describe here the isolation and complete characterization of high-affinity single-chain variable fragments (scFv) to the EGP-2 antigen. First, the binding kinetics of four murine whole antibodies directed to EGP-2 (17-1A, 323/A3, MOC-31 and MOC-161) were determined using surface plasmon resonance (SPR). The MOC-31 antibody has the lowest apparent off-rate, followed by MOC-161 and 323/A3. The V-genes of the two MOC hybridomas were cloned as scFv in a phage display vector and antigen-binding phage were selected by panning on recombinant antigen. The scFvs compete with the original hybridoma antibodies for binding to antigen and specifically bind to human carcinomas in immunohistochemistry. MOC-31 scFv has an off-rate which is better than those of the bivalent 17-1A and 323/A3 whole antibodies, providing it with an essential characteristic for tumour retention in vivo. The availability of these high-affinity anti-EGP-2 antibody fragments and of their encoding V-genes creates a variety of possibilities for their future use as tumour-targeting vehicles

CD98hc facilitates B cell proliferation and adaptive humoral immunity.

The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

The effectiveness of surgical correction of uterine prolapse: cervical amputation with uterosacral ligament plication (modified Manchester) versus vaginal hysterectomy with high uterosacral ligament plication

Item does not contain fulltextINTRODUCTION AND HYPOTHESIS: The objective of this study is to evaluate cervical amputation with uterosacral ligament plication (modified Manchester) and compare it to vaginal hysterectomy with high uterosacral ligament plication procedure with special regard to the middle compartment. METHODS: Consecutive women with pelvic organ prolapse who underwent either vaginal hysterectomy or a modified Manchester procedure were included. Assessments were made preoperatively and at 1-year follow-up, including physical examination with pelvic organ prolapse quantification standardised questionnaires (incontinence impact questionnaire, urogenital distress inventory, and defaecatory distress inventory). RESULTS: Between 2002 and 2007, 156 patients were included. Ninety-eight patients returned for a 1-year follow-up. In the modified Manchester group, we found no middle compartment recurrence versus two (4%) in the vaginal hysterectomy group. Anterior and posterior compartment prolapse recurrences (stage >or=2) were similar (approximately 50%). Considering operating time and blood loss, modified Manchester was more favourable. There was no difference in the pre- and postoperative subjective scores. The overall functional outcome was acceptable. CONCLUSIONS: We found an excellent performance of both procedures regarding middle compartment recurrences

Protocol for the value of urodynamics prior to stress incontinence surgery (VUSIS) study: a multicenter randomized controlled trial to assess the cost effectiveness of urodynamics in women with symptoms of stress urinary incontinence in whom surgical treatment is considered

BACKGROUND: Stress urinary incontinence (SUI) is a common problem. In the Netherlands, yearly 64.000 new patients, of whom 96% are women, consult their general practitioner because of urinary incontinence. Approximately 7500 urodynamic evaluations and approximately 5000 operations for SUI are performed every year. In all major national and international guidelines from both gynaecological and urological scientific societies, it is advised to perform urodynamics prior to invasive treatment for SUI, but neither its effectiveness nor its cost-effectiveness has been assessed in a randomized setting. The Value of Urodynamics prior to Stress Incontinence Surgery (VUSIS) study evaluates the positive and negative effects with regard to outcome, as well as the costs of urodynamics, in women with symptoms of SUI in whom surgical treatment is considered. METHODS/DESIGN: A multicentre diagnostic cohort study will be performed with an embedded randomized controlled trial among women presenting with symptoms of (predominant) SUI. Urinary incontinence has to be demonstrated on clinical examination and/or voiding diary. Physiotherapy must have failed and surgical treatment needs to be under consideration. Patients will be excluded in case of previous incontinence surgery, in case of pelvic organ prolapse more than 1 centimeter beyond the hymen and/or in case of residual bladder volume of more than 150 milliliter on ultrasound or catheterisation. Patients with discordant findings between the diagnosis based on urodynamic investigation and the diagnosis based on their history, clinical examination and/or micturition diary will be randomized to operative therapy or individually tailored therapy based on all available information. Patients will be followed for two years after treatment by their attending urologist or gynaecologist, in combination with the completion of questionnaires. Six hundred female patients will be recruited for registration from approximately twenty-seven hospitals in the Netherlands. We aspect that one hundred and two women with discordant findings will be randomized. The primary outcome of this study is clinical improvement of incontinence as measured with the validated Dutch version of the Urinary Distress Inventory (UDI). Secondary outcomes of this study include costs, cure of incontinence as measured by voiding diary parameters, complications related to the intervention, re-interventions, and generic quality of life changes. TRIAL REGISTRATION: Clinical Trials NCT0081474

Anterior colporrhaphy does not induce bladder outlet obstruction

We aimed to evaluate if anterior colporrhaphy causes incomplete voiding due to bladder outlet obstruction. Women scheduled for anterior colporrhaphy were asked to undergo multichannel urodynamic investigation before surgery and the first postoperative day. Bladder outlet obstruction was assessed using the Blaivas-Groutz voiding nomogram. Maximum flow rate, detrusor pressure and residual volume were compared between pre- and postoperative measurements and between women with and without an abnormal post-void residual volume (PVR; volume exceeding 150 ml). Seventeen women participated. One woman who was unobstructed before surgery was obstructed after surgery. Overall, detrusor pressure and maximum flow rate before and after surgery did not differ. After surgery, six women had an abnormal PVR, one was unable to void, four were mildly obstructed and one moderately obstructed. Urodynamic investigation the first day after anterior colporrhaphy did not show that anterior colporrhaphy induces bladder outlet obstruction. The explanation for postoperative urinary retention can therefore also lie in non-anatomical causes such as postoperative pain and psychological factor