Peripartum hysterectomy incidence, risk factors and clinical characteristics in Ireland

Background: The incidence of peripartum hysterectomy (PH) shows fifty-fold variation worldwide (0.2–10.5/1000 deliveries) and risk factors include advancing maternal age and parity, previous caesarean section (CS) and abnormal placentation. Objectives: In this first national study of PH in Ireland, our objectives were threefold: to describe the national trend in PH incidence over 15 years since 1999; to assess risk of PH associated with morbidly adherent placenta (MAP), placenta praevia and postpartum haemorrhage (PPH) during 2005–2013; and to describe the causes, interventions and outcomes of PH cases during 2011–2013. Study design: For the 15-year time-trend analysis, PH cases and denominator data were extracted from Ireland’s Hospital In-Patient Enquiry database. Multivariate Poisson regression analysis assessed risk of PH associated with MAP, placenta praevia and PPH. In collaboration with the 20 Irish maternity units we carried out a three-year national clinical audit of severe maternity morbidity. PH was a notifiable morbidity and the audit included detailed review of MOH cases. Results: In 1999–2013 there were 298 PH cases, a rate of 0.32/1000 deliveries. During the period 2005–2013, the PH rate was 50 times higher in deliveries involving PPH, 100 times higher with placenta praevia and 1000 times higher with MAP. During the clinical audit (2011–2013) there were 65 PH cases, a rate of 0.33/1000 deliveries, increasing with advancing age and parity. The reporting of abnormal placentation, primarily the co-occurrence of placenta praevia and MAP, was linked with previous CS. Fifty-six of the 65 cases suffered MOH, most commonly associated with placenta praevia, MAP and uterine atony. Prophylactic and therapeutic uterotonic agents were appropriately used in the majority of cases. Conclusions: The incidence of PH in Ireland has been consistently low over 15 years, averaging one case every 3000 deliveries. The recognised risk factors of MAP, placenta praevia and PPH were independently associated with PH, with MAP being by far the strongest predictor. The vast majority of PH cases in our clinical audit were associated with MOH. Some deficiencies were noted in antenatal care, in certain elements of treatment and clinical governance protocols but adherence to guidelines was generally high

NC1 Domain of Type VII Collagen Binds to the β3 Chain of Laminin 5 Via a Unique Subdomain Within the Fibronectin-Like Repeats

Type VII collagen, the major component of anchoring fibrils, consists of a central collagenous triple-helical domain flanked by two noncollagenous, globular domains, NC1 and NC2. Approximately 50% of the molecular mass of the molecule is consumed by the NC1 domain. We previously demonstrated that NC1 binds to various extracellular matrix components including a complex of laminin 5 and laminin 6 (Chen et al. 1997a). In this study, we examined the interaction of NC1 with laminin 5 (a component of anchoring filaments). Both authentic and purified recombinant NC1 bound to human and rat laminin 5 as measured by enzyme-linked immunosorbant assay and by binding of 125I-radiolabeled NC1 to laminin 5-coated wells, but not to laminin 1 or albumin. NC1 bound predominantly to the β3 chain of laminin 5, but also to the γ2 chain when examined by a protein overlay assay. The binding of 125I-NC1 to laminin 5 was inhibited by a 50-fold excess of unlabeled NC1 or de-glycosylated NC1, as well as a polyclonal antibody to laminin 5 or a monoclonal antibody to the β3 chain. In contrast, the NC1–laminin 5 interaction was not affected by a monoclonal antibody to the α3 chain. Using NC1 deletion mutant recombinant proteins, a 285 AA (residues 760–1045) subdomain of NC1 was identified as the binding site for laminin 5. IgG from an epidermolysis bullosa acquisita serum containing autoantibodies to epitopes within NC1 that colocalized with the laminin 5 binding site inhibited the binding of NC1 to laminin 5. Thus, perturbation of the NC1–laminin 5 interaction may contribute to the pathogenesis of epidermolysis bullosa acquisita

Ultra-trace element characterization of the central Ottawa River basin using a rapid, flexible, and low-volume ICP-MS method

Ultra-trace (<1 ng g-1) rare earth elements and yttrium (REE+Y) and high field strength element (HFSE) geochemistry of freshwater can constrain element sources, aqueous processes in hydrologic catchments, and the signature of dissolved terrestrial fluxes to the oceans. This study details an adapted method capable of quantifying ≥38 elements (including all REE+Y, Nb, Ta, Zr, Hf, Mo, W, Th, U) with minimal sample preparation in natural water aliquots as low as ≤2 mL. The method precision and accuracy are demonstrated using measurement of the National Research Council – Conseil national de recherches Canada (NRC-CNRC) river water certified reference material (CRM) SLRS-6 sampled from the Ottawa River (OR). Data from SLRS CRM are compared to those of new, filtered (HREE-enriched REE+Y patterns, small natural positive Y and Gd anomalies, and negative Eu and Ce anomalies. These REE+Y features are coherent downstream in the OR apart from amplification of Eu and Ce anomalies during REE removal/dilution. The OR samples capture a downstream decrease in sparingly soluble HFSE (Th, Nb, Ta, Zr, Hf), presumably related to their colloid-particulate removal from the dissolved load, accompanied by crustal Zr/Hf (32.5 ± 5.1) and supercrustal Nb/Ta (25.1 ± 7.7) ratios. Subcrustal Th/U (0.17-0.96) and supercrustal Mo/W (12.0-74.5) ratios in all ORB waters indicate preferential release and aqueous solubility of U>Th and Mo>W, with the latter attributed primarily to preferential W adsorption on soil or upstream aquatic (oxy)(hydr)oxide surfaces

The impact of routine open nonsuction drainage on fluid accumulation after thyroid surgery: a prospective randomised clinical trial.

Background: Thyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours. Methods: We conducted a prospective randomised clinical trial on patients undergoing thyroid surgery. Patients were randomly assigned to a drain group (n = 49) or a no-drain group (n = 44) immediately prior to wound closure. Patients underwent a neck ultrasound on day 1 and day 2 postoperatively. After surgery, we evaluated visual analogue scale pain scores, postoperative analgesic requirements, self-reported scar satisfaction at 6 weeks and complications. Results: There was significantly less mean fluid accumulated in the drain group on both day 1, 16.4 versus 25.1 ml (P-value = 0.005), and day 2, 18.4 versus 25.7 ml (P-value = 0.026), following surgery. We found no significant differences between the groups with regard to length of stay, scar satisfaction, visual analogue scale pain score and analgesic requirements. There were four versus one wound infections in the drain versus no-drain groups. This finding was not statistically significant (P = 0.154). No life-threatening bleeds occurred in either group. Conclusions: Fluid accumulation after thyroid surgery was significantly lessened by drainage. However, this study did not show any clinical benefit associated with this finding in the non-emergent setting. Drains themselves showed a trend indicating that they may augment infection rates. The results of this study suggest that the frequency of acute life-threatening bleeds remains extremely low following abandoning drains. We advocate abandoning routine use of thyroid drains. Trial registration: ISRCTN94715414

Development and validation of risk models to predict outcomes following in-hospital cardiac arrest attended by a hospital-based resuscitation team

Aim The National Cardiac Arrest Audit (NCAA) is the UK national clinical audit for in-hospital cardiac arrest. To make fair comparisons among health care providers, clinical indicators require case mix adjustment using a validated risk model. The aim of this study was to develop and validate risk models to predict outcomes following in-hospital cardiac arrest attended by a hospital-based resuscitation team in UK hospitals. Methods Risk models for two outcomes—return of spontaneous circulation (ROSC) for greater than 20 min and survival to hospital discharge—were developed and validated using data for in-hospital cardiac arrests between April 2011 and March 2013. For each outcome, a full model was fitted and then simplified by testing for non-linearity, combining categories and stepwise reduction. Finally, interactions between predictors were considered. Models were assessed for discrimination, calibration and accuracy. Results 22,479 in-hospital cardiac arrests in 143 hospitals were included (14,688 development, 7791 validation). The final risk model for ROSC > 20 min included: age (non-linear), sex, prior length of stay in hospital, reason for attendance, location of arrest, presenting rhythm, and interactions between presenting rhythm and location of arrest. The model for hospital survival included the same predictors, excluding sex. Both models had acceptable performance across the range of measures, although discrimination for hospital mortality exceeded that for ROSC > 20 min (c index 0.81 versus 0.72). Conclusions Validated risk models for ROSC > 20 min and hospital survival following in-hospital cardiac arrest have been developed. These models will strengthen comparative reporting in NCAA and support local quality improvement

Targeted Nasal Vaccination Provides Antibody-Independent Protection Against Staphylococcus aureus

Despite showing promise in preclinical models, anti-Staphylococcus aureus vaccines have failed in clinical trials. To date, approaches have focused on neutralizing/opsonizing antibodies; however, vaccines exclusively inducing cellular immunity have not been studied to formally test whether a cellular-only response can protect against infection. We demonstrate that nasal vaccination with targeted nanoparticles loaded with Staphylococcus aureus antigen protects against acute systemic S. aureus infection in the absence of any antigen-specific antibodies. These findings can help inform future developments in staphylococcal vaccine development and studies into the requirements for protective immunity against S. aureu

Quasi-free π0\pi^0 Photoproduction from the Bound Nucleon

Differential cross-sections for quasi-free $\pi^0$ photoproduction from the proton and neutron bound in the deuteron have been measured for $E_\gamma= 200 - 400$ MeV at $\theta^{\rm lab}_\gamma = 136.2^\circ$ usind the Glasgow photon tagger at MAMI, the Mainz 48 cm $\varnothing$ $\times$ 64 cm NaI(Tl) photon detector and the G\"ottingen SENECA recoil detector. For the proton measurements made with both liquid deuterium and liquid hydrogen targets allow direct comparison of "free" $\pi^0$ photoproduction cross-sections as extracted from the bound proton data with experimental free cross sections which are found to be in reasonable agreement below 320 MeV. At higher energies the "free" cross sections extracted from quasifree data are significantly smaller than the experimental free cross sections and theoretical predictions based on multipole analysis. For the first time, "free" neutron cross sections have been extracted in the $\Delta$-region. They are also in agreement with the predictions from multipole analysis up to 320 MeV and significantly smaller at higher photon energies

Nanopore detection using supercharged polypeptide molecular carriers

The analysis at the single-molecule level of proteins and their interactions can provide critical information for understanding biological processes and diseases, particularly for proteins present in biological samples with low copy numbers. Nanopore sensing is an analytical technique that allows label-free detection of single proteins in solution and is ideally suited to applications, such as studying protein-protein interactions, biomarker screening, drug discovery, and even protein sequencing. However, given the current spatiotemporal limitations in protein nanopore sensing, challenges remain in controlling protein translocation through a nanopore and relating protein structures and functions with nanopore readouts. Here, we demonstrate that supercharged unstructured polypeptides (SUPs) can be genetically fused with proteins of interest and used as molecular carriers to facilitate nanopore detection of proteins. We show that cationic SUPs can substantially slow down the translocation of target proteins due to their electrostatic interactions with the nanopore surface. This approach enables the differentiation of individual proteins with different sizes and shapes via characteristic subpeaks in the nanopore current, thus facilitating a viable route to use polypeptide molecular carriers to control molecular transport and as a potential system to study protein-protein interactions at the single-molecule level