Discovery of Claytonia lanceolata var. peirsonii in the San Bernardino Mountains Perpetuates a History of Taxonomic Uncertainty

Claytonia lanceolata is a widespread perennial herb that typically blooms in areas where snow persists, occurring along mountain corridors from Canada to southern California. Numerous varieties have been described for this species, but most are not recognized under current taxonomic treatments. The discovery of new populations of C. lanceolata in southern California is reported, and the taxonomic uncertainties associated with the C. lanceolata species complex and the southern California var. peirsonii are discussed. Subtle characters for distinguishing the southern populations of C. lanceolata may be obscured during the process of making herbarium specimens. We clarify some of the distinguishing morphological features and associated ecology of C. lanceolata var. peirsonii. Based on detailed field observations in southern California, information is collated for populations across the entire known range of the variety. Recommendations are made regarding opportunities for further investigation, and information pertinent to the conservation of C. lanceolata var. peirsonii in California is updated

C1 inhibitor deficiency: 2014 United Kingdom consensus document

C1 inhibitor deficiency is a rare disorder manifesting with recurrent attacks of disabling and potentially life-threatening angioedema. Here we present an updated 2014 United Kingdom consensus document for the management of C1 inhibitor-deficient patients, representing a joint venture between the United Kingdom Primary Immunodeficiency Network and Hereditary Angioedema UK. To develop the consensus, we assembled a multi-disciplinary steering group of clinicians, nurses and a patient representative. This steering group first met in 2012, developing a total of 48 recommendations across 11 themes. The statements were distributed to relevant clinicians and a representative group of patients to be scored for agreement on a Likert scale. All 48 statements achieved a high degree of consensus, indicating strong alignment of opinion. The recommendations have evolved significantly since the 2005 document, with particularly notable developments including an improved evidence base to guide dosing and indications for acute treatment, greater emphasis on home therapy for acute attacks and a strong focus on service organisation. This article is protected by copyright. All rights reserved

Bioimpedance spectroscopy for swelling evaluation following total knee arthroplasty: a validation study

BACKGROUND: The evaluation of swelling is important for the outcome of total knee arthroplasty (TKA) surgery. The circumference or volume measurements are applicable at the bedside of the patient but are altered by muscular atrophy and the post-surgical dressing. Bioimpedance spectroscopy might overcome these limitations; however, it should be validated. This study aimed to explore the validity, the reliability and the responsiveness of bioimpedance spectroscopy for measuring swelling after TKA. METHODS: The degree of swelling in 25 patients undergoing TKA surgery was measured using bioimpedance spectroscopy (BIS R0), knee circumference and limb volume. The measurements were performed on D-1 (day before surgery), D + 2 (2 days after surgery) and D + 8 (8 days after surgery). The BIS R0 measurements were repeated twice, alternating between two evaluators. The percentage of the difference between the limbs was calculated for BIS R0, circumference and volume. The intra- and inter-observer intraclass correlation coefficients (ICCs), limits of agreement (LOA), effect size (Cohen's d), correlations between the methods and diagnostic sensitivity were calculated. RESULTS: BIS R0, circumference and volume detected swelling < 3.5% at D-1. The swelling at D2 and D8 was greater with BIS R0 [mean (SD) 29.9% (±9.8) and 38.27 (±7.8)] than with volume [14.7 (±9.5) and 14.9 (±8.2)] and circumference [11.1 (±5.7) and 11.7 (±4.1)]. The BIS R0 intra- and inter-evaluator ICCs ranged from 0.89 to 0.99, whereas the LOA were < 5.2%. The BIS R0 correlation was 0.73 with volume and 0.75 with circumference. The BIS R0 Cohen's d was 3.32 for the D-1-D2 evolution. The diagnostic sensitivity was 83% D2 and 96% at D8. CONCLUSION: Bioimpedance is a valid method for the evaluation of swelling following TKA. BIS R0 also demonstrated excellent intra- and inter-evaluator reliability. The diagnostic sensitivity and responsiveness is superior to that of concurrent methods. BIS R0 is an efficient method for post-surgical follow up at the bedside of the patient. The measurement of BIS R0 is a straightforward, valid, reliable and responsive method for lower limb swelling following TKA surgery that could be used in clinics and research. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00627770

Secondary antibody deficiency: a complication of anti-CD20 therapy for neuroinflammation

B-cell depleting anti-CD20 monoclonal antibody therapies are being increasingly used as long-term maintenance therapy for neuroinflammatory disease compared to many non-neurological diseases where they are used as remission-inducing agents. While hypogammaglobulinaemia is known to occur in over half of patients treated with medium to long-term B-cell-depleting therapy (in our cohort IgG 38, IgM 56 and IgA 18%), the risk of infections it poses seems to be under-recognised. Here, we report five cases of serious infections associated with hypogammaglobulinaemia occurring in patients receiving rituximab for neuromyelitis optica spectrum disorders. Sixty-four per cent of the whole cohort of patients studied had hypogammaglobulinemia. We discuss the implications of these cases to the wider use of anti-CD20 therapy in neuroinflammatory disease

Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies

A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2-67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0.022/patient-year, P /= 8 g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non-serious AEs occurred at a rate of 0.101 event/infusion. The incidence of local related AEs was 0.069 event/infusion (0.036 event/infusion, when excluding a 13-year-old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0.032 event/infusion. Most related AEs were mild, none were severe. For 64.6% of patients and in 94.8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0.95 (range = 0.3-4.1) h using mainly one to two administration sites [median = 2 sites (range = 1-5)]. Almost all infusions (99.8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well-tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment

Context-dependent costs and benefits of tuberculosis resistance traits in a wild mammalian host

Disease acts as a powerful driver of evolution in natural host populations, yet individuals in a population often vary in their susceptibility to infection. Energetic trade-offs between immune and reproductive investment lead to the evolution of distinct life history strategies, driven by the relative fitness costs and benefits of resisting infection. However, examples quantifying the cost of resistance outside of the laboratory are rare. Here, we observe two distinct forms of resistance to bovine tuberculosis (bTB), an important zoonotic pathogen, in a free-ranging African buffalo (Syncerus caffer) population. We characterize these phenotypes as “infection resistance,” in which hosts delay or prevent infection, and “proliferation resistance,” in which the host limits the spread of lesions caused by the pathogen after infection has occurred. We found weak evidence that infection resistance to bTB may be heritable in this buffalo population (h2 = 0.10) and comes at the cost of reduced body condition and marginally reduced survival once infected, but also associates with an overall higher reproductive rate. Infection-resistant animals thus appear to follow a “fast” pace-of-life syndrome, in that they reproduce more quickly but die upon infection. In contrast, proliferation resistance had no apparent costs and was associated with measures of positive host health—such as having a higher body condition and reproductive rate. This study quantifies striking phenotypic variation in pathogen resistance and provides evidence for a link between life history variation and a disease resistance trait in a wild mammalian host population

Reducing Alaska Native paediatric oral health disparities: a systematic review of oral health interventions and a case study on multilevel strategies to reduce sugar-sweetened beverage intake

Background. Tooth decay is the most common paediatric disease and there is a serious paediatric tooth decay epidemic in Alaska Native communities. When untreated, tooth decay can lead to pain, infection, systemic health problems, hospitalisations and in rare cases death, as well as school absenteeism, poor grades and low quality-of-life. The extent to which population-based oral health interventions have been conducted in Alaska Native paediatric populations is unknown. Objective. To conduct a systematic review of oral health interventions aimed at Alaska Native children below age 18 and to present a case study and conceptual model on multilevel intervention strategies aimed at reducing sugar-sweetened beverage (SSB) intake among Alaska Native children. Design. Based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement, the terms “Alaska Native”, “children” and “oral health” were used to search Medline, Embase, Web of Science, GoogleScholar and health foundation websites (1970–2012) for relevant clinical trials and evaluation studies. Results. Eighty-five studies were found in Medline, Embase and Web of Science databases and there were 663 hits in GoogleScholar. A total of 9 publications were included in the qualitative review. These publications describe 3 interventions that focused on: reducing paediatric tooth decay by educating families and communities; providing dental chemotherapeutics to pregnant women; and training mid-level dental care providers. While these approaches have the potential to improve the oral health of Alaska Native children, there are unique challenges regarding intervention acceptability, reach and sustainability. A case study and conceptual model are presented on multilevel strategies to reduce SSB intake among Alaska Native children. Conclusions. Few oral health interventions have been tested within Alaska Native communities. Community-centred multilevel interventions are promising approaches to improve the oral and systemic health of Alaska Native children. Future investigators should evaluate the feasibility of implementing multilevel interventions and policies within Alaska Native communities as a way to reduce children's health disparities

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

Tibial tunnel placement in posterior cruciate ligament reconstruction: a systematic review

Purpose: Reconstruction of the posterior cruciate ligament (PCL) yields less satisfying results than anterior cruciate ligament reconstruction with respect to laxity control. Accurate tibial tunnel placement is crucial for successful PCL reconstruction using arthroscopic tibial tunnel techniques. A discrepancy between anatomical studies of the tibial PCL insertion site and surgical recommendations for tibial tunnel placement remains. The objective of this study was to identify the optimal placement of the tibial tunnel in PCL reconstruction based on clinical studies. Methods: In a systematic review of the literature, MEDLINE, EMBASE, Cochrane Review, and Cochrane Central Register of Controlled Trials were screened for articles about PCL reconstruction from January 1990 to September 2011. Clinical trials comparing at least two PCL reconstruction techniques were extracted and independently analysed by each author. Only studies comparing different tibial tunnel placements in the retrospinal area were included. Results: This systematic review found no comparative clinical trial for tibial tunnel placement in PCL reconstruction. Several anatomical, radiological, and biomechanical studies have described the tibial insertion sites of the native PCL and have led to recommendations for placement of the tibial tunnel outlet in the retrospinal area. However, surgical recommendations and the results of morphological studies are often contradictory. Conclusions: Reliable anatomical landmarks for tunnel placement are lacking. Future randomized controlled trials could compare precisely defined tibial tunnel placements in PCL reconstruction, which would require an established mapping of the retrospinal area of the tibial plateau with defined anatomical and radiological landmarks. Level of evidence: III