The effect of erector spinae plane block on respiratory and analgesic outcomes in multiple rib fractures: a retrospective cohort study.

Regional anaesthesia is often helpful in improving respiratory function and analgesia following multiple rib fractures. The erector spinae plane block has become the technique of choice in our institution due to its relative simplicity and purported safety. The aim of this retrospective cohort study was to determine its effectiveness in improving respiratory and analgesic outcomes. We reviewed electronic medical records of patients with traumatic rib fractures admitted to a level-one trauma centre between January 2016 and July 2017, who also received erector spinae plane blocks. We analysed the following outcomes before and up to 72 h after erector spinae plane blockade: incentive spirometry volume; maximum numerical rating scale static pain scores; and 12-h opioid consumption. Pre- and post-block data were compared. We included 79 patients, 77% of whom received continuous erector spinae plane block for a mean (SD) of 3.7 (1.9) days. The majority (85%) had other associated injuries. Incentive spirometry volumes improved from 784 (694) to 1375 (667) ml (p < 0.01) during the first 24 h following erector spinae plane blockade. Pain scores were reduced from 7.7 (2.5) to 4.7 (3.2) in the first three hours (p < 0.01). Reductions in opioid consumption were observed but did not achieve statistical significance. These improvements were largely sustained for up to 72 h. Mean arterial blood pressure remained unchanged from baseline. In conclusion, erector spinae plane blocks were associated with improved inspiratory capacity and analgesic outcomes following rib fracture, without haemodynamic instability. We propose that it should be considered to be a viable alternative to other regional analgesic techniques when these are not feasible.

Search for Neutrinoless Double-ß Decay in

The Majorana Collaboration is operating an array of high purity Ge detectors to search for neutrinoless double-ß decay in ^{76}Ge. The Majorana Demonstrator comprises 44.1 kg of Ge detectors (29.7 kg enriched in ^{76}Ge) split between two modules contained in a low background shield at the Sanford Underground Research Facility in Lead, South Dakota. Here we present results from data taken during construction, commissioning, and the start of full operations. We achieve unprecedented energy resolution of 2.5 keV FWHM at Q_{ßß} and a very low background with no observed candidate events in 9.95 kg yr of enriched Ge exposure, resulting in a lower limit on the half-life of 1.9×10^{25} yr (90% C.L.). This result constrains the effective Majorana neutrino mass to below 240-520 meV, depending on the matrix elements used. In our experimental configuration with the lowest background, the background is 4.0_{-2.5}^{+3.1} counts/(FWHM t yr).

The Types of Click Beetles Described by Otto Schwarz from Mexico, Guatemala and Panama (Coleoptera: Elateridae).

The type specimens of Elateridae described by Otto Schwarz from Mesoamerica are redescribed, reassessed and lectotypes designated. Acanthathous championi (Schwarz), Smiliceroides quadrilineatus (Schwarz), Anoplischiopsis divisus Schwarz, Anoplischius dorsalis Schwarz, Atractosomus nigerrimus Schwarz, and Anchastomorphus minutus Schwarz are retained in their current status. Monocrepidius restinctus Schwarz is reduced to synonymy under Monocrepidius rugicollis Champion. Aeolus mediofasciatus Schwarz is transferred to Monocrepidius Eschscholtz. Tomicephalus bilineatus Schwarz is transferred to Anchastus LeConte, renamed Anchastus lapsus Fuller, and reduced to synonymy under Anchastus seminiger Champion. Crepidius blepharipes Schwarz is restricted to the lectotype and retained in its current status; the other syntypes are unidentified species of Dipropus Germar. Anchastus championi Schwarz is reduced to synonymy under Anchastus tenuistriatus Champion; one syntype is an unidentified species of Dipropus Germar. New country records are documented for A. dorsalis, A. nigerrimus and A. minutus (Guatemala), and A. tenuistriatus (United States).

Zonal differences in meniscus matrix turnover and cytokine response.

OBJECTIVE: To determine the mechanisms of meniscal degeneration and whether this varied zonally and from articular cartilage. DESIGN: Normal ovine menisci were dissected into inner and outer zones and along with cartilage cultured ±IL-1α and TNFα. Glycosaminoglycan (GAG) and collagen release, and gene expression were quantified. Aggrecan proteolysis was analysed by Western blotting with neoepitope-specific antibodies. Matrix metalloproteinase (MMP)2, MMP9 and MMP13 activity was evaluated by gelatin zymography or fluorogenic assay. RESULTS: Inner meniscus was more cartilaginous containing more GAG and expressing more ACAN and COL2A1 than outer zones. Higher expression of VCAN and ADAMTS4 in medial outer and both zones of the lateral meniscus reflected their embryologic origin from cells outside the cartilage anlagen. All meniscal regions released a greater % GAG in response to cytokines; only outer zones had cytokine-stimulated collagenolysis. Cytokine-induced aggrecanolysis was primarily due to increased ADAMTS cleavage in cartilage and inner menisci but MMPs in the outer menisci. Outer menisci always released more active MMP2 than other tissues and more active MMP13 in basal and TNF-stimulated cultures. Expression of ACAN, COL1A1 and COL2A1 was decreased by both cytokines in all tissues, while VCAN was increased by IL-1α in cartilage and inner menisci. Metalloproteinase expression was differentially regulated by IL-1α and TNFα: ADAMTS4, MMP1, MMP3 were upregulated more by IL-1α in inner zones whereas ADAMTS5, MMP13 and MMP9 were more upregulated by TNFα in outer zones. CONCLUSIONS: Meniscal degeneration mechanisms are zonally-dependent, and may contribute to the enzymatic burden in the joint.

Prevalence of high-risk sexual behaviour in Jamaican adults and its relationship to sociodemographic and religious factors: findings from the Jamaica Health and Lifestyle Survey 2007-2008.

OBJECTIVE: To estimate the prevalence of high-risk sexual behaviours among Jamaican adults and evaluate associations with sociodemographic and religious factors. METHODS: We performed a cross-sectional study, using a nationally representative sample of Jamaicans, 15-74 years old. Participants completed an interviewer-administered questionnaire including questions on sexual activity, sociodemographic factors and religious practice. Having two or more sexual partners in the past year, non-use of condoms among persons with multiple partners and a history of previous sexually transmitted infection (STI) were the high-risk characteristics considered in the analysis. We obtained crude and category specific prevalence estimates for high-risk behaviour and estimated odds ratios for association with sociodemographic and religious factors. RESULTS: Data from 2833 participants who reported on sexually activity were analysed. Approximately 25% (95% CI 22, 27) of Jamaican adults had two or more sexual partners in the past year while 15% (95% CI 13, 17) had a past history of an STI. Approximately 6% (95% CI 5, 7) of persons with multiple partners did not use condoms during sexual intercourse. Overall, 32% (95% CI 30, 35) had any one of the three high-risk characteristics (male, 48%; female, 17%, p < 0.001). Being married, active religious practice and weekly attendance at religious meetings were associated with lower odds of high-risk sexual behaviour while being in a visiting relationship was associated with higher odds of high-risk behaviour CONCLUSION: A third of Jamaicans reported sexual practices that increase their risk of HIV infection. High-risk sexual behaviour was more common among men. Being married and weekly attendance at religious services were associated with lower odds of high-risk behaviour

Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis.

OBJECTIVES: To investigate the regulation of sclerostin (SOST) in osteoarthritis (OA) and its potential effects on articular cartilage degradation. METHODS: SOST and other Wnt-ß-catenin components were immuno-localised in osteochondral sections of surgically-induced OA in knees of sheep and mice, and human OA samples obtained at arthroplasty. Regulation of SOST mRNA and protein expression by ovine chondrocytes in response to interleukin-1α (IL-1α) or tumour necrosis factor-α (TNFα) was examined in explant cultures. The effect of 25 or 250 ng/ml recombinant SOST alone or in combination with IL-1α, on ovine articular cartilage explant aggrecan degradation, and chondrocyte gene expression of Wnt-ß-catenin pathway proteins, metalloproteinases and their inhibitors, and cartilage matrix proteins was quantified. RESULTS: Contrary to being an osteocyte-specific protein, SOST was expressed by articular chondrocytes, and mRNA levels were upregulated in vitro by IL-1α but not TNFα. Chondrocyte SOST staining was significantly increased only in the focal area of cartilage damage in surgically-induced OA in sheep and mice, as well as end-stage human OA. In contrast, osteocyte SOST was focally decreased in the subchondral bone in sheep OA in association with bone sclerosis. SOST was biologically active in chondrocytes, inhibiting Wnt-ß-catenin signalling and catabolic metalloproteinase [matrix metalloproteinases (MMP) and distintegrin and metalloproteinase with thrombospndin repeats (ADAMTS)] expression, but also decreasing mRNA levels of aggrecan, collagen II and tissue inhibitors of metalloproteinaes (TIMPs). Despite this mixed effect, SOST dose-dependently inhibited IL-1α-stimulated cartilage aggrecanolysis in vitro. CONCLUSIONS: These results implicate SOST in regulating the OA disease processes, but suggest opposing effects by promoting disease-associated subchondral bone sclerosis while inhibiting degradation of cartilage.

Smoking and pathogenesis of psoriasis: a review of oxidative, inflammatory and genetic mechanisms.

Recent studies suggest that cigarette smoking may trigger the development of psoriasis through oxidative, inflammatory and genetic mechanisms. Smoking initiates formation of free radicals that stimulate cell signalling pathways active in psoriasis including mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK-STAT). Smoking damages the skin by increasing formation of reactive oxygen species and decreasing the gene expression of antioxidants. Nicotine also stimulates innate immune cells integral to the pathogenesis of psoriasis including dendritic cells, macrophages and keratinocytes. These cells release cytokines that activate T lymphocytes and perpetuate a cycle of chronic inflammation. Smoking also enhances expression of genes known to confer an increased risk of psoriasis, including HLA-Cw6, HLA-DQA1*0201 and CYP1A1. Improved understanding of the possible link between smoking and psoriasis pathogenesis may provide further insight into mechanisms underlying smoking, psoriasis and risk of subsequent cardiovascular disease.

Chronic disease in the Caribbean: strategies to respond to the public health challenge in the region. What can we learn from Jamaica's experience?

With the advent of the epidemiological transition, chronic non-communicable diseases (CNCDs) have emerged as the leading cause of death globally. In this paper we present an overview of the burden of CNCDs in the Caribbean region and use Jamaica as a case-study to review the impact of policy initiatives and interventions implemented in response to the CNCD epidemic. The findings show that while Jamaica has implemented several policy initiatives aimed at stemming the tide of the CNCD epidemic, a comparison of data from two national health and lifestyle surveys conducted in Jamaica in 2000/01 and 2007/08 revealed that there was an increase in the prevalence of intermediate CNCD risk factors such as hypertension and obesity. We therefore present recommended strategies which we believe will enhance the current CNCD response and thus reduce, or at least stem, the current epidemic of CNCDs.

A multi-technique approach to understanding delithiation damage in LiCoO2 thin films.

We report on the delithiation of LiCoO2 thin films using oxalic acid (C2H2O4) with the goal of understanding the structural degradation of an insertion oxide associated with Li chemical extraction. Using a multi-technique approach that includes synchrotron radiation X-ray diffraction, scanning electron microscopy, micro Raman spectroscopy, photoelectron spectroscopy and conductive atomic force microscopy we reveal the balance between selective Li extraction and structural damage. We identify three different delithiation regimes, related to surface processes, bulk delithiation and damage generation. We find that only a fraction of the grains is affected by the delithiation process, which may create local inhomogeneities. However, the bulk delithiation regime is effective to delithiate the LCO film. All experimental evidence collected indicates that the delithiation process in this regime mimics the behavior of LCO upon electrochemical delithiation. We discard the formation of Co oxalate during the chemical extraction process. In conclusion, the chemical route to Li extraction provides additional opportunities to investigate delithiation while avoiding the complications associated with electrolyte breakdown and simplifying in-situ measurements.

Background characterization of an ultra-low background liquid scintillation counter.

The Ultra-Low Background Liquid Scintillation Counter developed by Pacific Northwest National Laboratory will expand the application of liquid scintillation counting by enabling lower detection limits and smaller sample volumes. By reducing the overall count rate of the background environment approximately 2 orders of magnitude below that of commercially available systems, backgrounds on the order of tens of counts per day over an energy range of ~3-3600keV can be realized. Initial test results of the ULB LSC show promising results for ultra-low background detection with liquid scintillation counting.

Clinical significance of the ABCB1 and ABCG2 gene expression levels in acute lymphoblastic leukemia.

OBJECTIVES: Acute lymphoblastic leukemia (ALL) is a clonal disease that accounts for 20% of acute leukemias in adults. A high percentage of adult patients (ranging from 70 to 80%) reach complete remission; however, the 5-year survival rate is only 20-40%. One of the main obstacles to treatment success is the drug resistance of leukemic cells. Therefore, our research group analyzed the ABCB1 and ABCG2 gene expression levels in 61 patients diagnosed with ALL and assessed whether the levels affected the clinical parameters and 40-month survival rate. METHODS: The ABCB1 and ABCG2 gene expression levels were analyzed using real-time polymerase chain reaction in 61 patients diagnosed with ALL and 99 healthy donors as controls. The association between ABCB1 and ABCG2 gene expression levels and clinical variables was determined using the Chi-square test and Fisher's exact test. Overall survival (OS) was determined using the Kaplan-Meier method. RESULTS: The results showed high ABCB1 and ABCG2 gene levels, which were 4.5 and 2.3 times the levels of healthy donors, respectively. A total of 52% of the study patients expressed high ABCB1 levels and were significantly associated with the high-risk patient group and a decreased 40-month survival rate of 78%. Only 49% of the patients expressed high ABCG2 gene levels. No association was found between the clinical parameters and the ABCG2 gene expression levels. CONCLUSIONS: Early detection of ABCB1 gene expression levels could be important for the diagnosis and monitoring of ALL patients.

Development of a low-level 39Ar calibration standard - Analysis by absolute gas counting measurements augmented with simulation.

This paper describes the generation of 39Ar, via reactor irradiation of potassium carbonate, followed by quantitative analysis (length-compensated proportional counting) to yield two calibration standards that are respectively 50 and 3 times atmospheric background levels. Measurements were performed in Pacific Northwest National Laboratory's shallow underground counting laboratory studying the effect of gas density on beta-transport; these results are compared with simulation. The total expanded uncertainty of the specific activity for the ~50× 39Ar in P10 standard is 3.6% (k=2).

Recent Bremsstrahlung-based assays of 210Pb in lead and comments on current availability of low-background lead in North America.

Low-background lead for radiation measurement shielding is often assayed for 210Pb to ensure acceptable backgrounds. Samples of lead assayed with a germanium spectrometer calibrated for bremsstrahlung-based assay of 210Pb provide a view into the 210Pb content of commercial lead in the U.S. (other than stockpiled Doe Run lead). Results suggest that the loss of lead smelting in the U.S. has eliminated the traditional supply of "low background" lead (~30Bqkg-1), and indicate current commercial supplies contain roughly an order of magnitude higher 210Pb levels.

Phase Transformations in the High-Tc Superconducting Compounds, Ba2RCu3O7-δ (R = Nd, Sm, Gd, Y, Ho, and Er).

The phase transformation between the orthorhombic and tetragonal structures of six high-T c superconductors, Ba2RCu3O7- δ , where R = Nd, Sm, Gd, Y, Ho, and Er, and δ = 0 to 1, has been investigated using techniques of x-ray diffraction, differential thermal analysis/thermogravimetric analysis (DTA/TGA) and electron diffraction. The transformation from the oxygen-rich orthorhombic phase to the oxygen-deficient tetragonal phase involves two orthorhombic phases. A superlattice cell caused by oxygen ordering, with a' = 2a, was observed for materials with smaller ionic radius (Y, Ho, and Er). For the larger lanthanide samples (Nd, Sm, and Gd), the a' = 2a type superlattice cell was not observed. The structural phase transition temperatures, oxygen stoichiometry and characteristics of the T c plateaus appear to correlate with the ionic radius, which varies based on the number of f electrons. Lanthanide elements with a smaller ionic radius stabilize the orthorhombic phase to higher temperatures and lower oxygen content. Also, the superconducting temperature is less sensitive to the oxygen content for materials with smaller ionic radius. The trend of dependence of the phase transformation temperature on ionic radius across the lanthanide series can be explained using a quasi-chemical approximation (QCA) whereby the strain effect plays an important role on the order-disorder transition due to the effect of oxygen content on the CuO chain sites.

A simple fluorescent biosensor for theophylline based on its RNA aptamer.

Theophylline is a potent bronchodilator with a narrow therapeutic index. A simple fluorescent biosensor that detects clinically relevant theophylline concentrations has been developed using the well-characterized theophylline binding RNA aptamer. Hybridization of the RNA aptamer to a fluorescently labeled DNA strand (FL-DNA) yields a fluorescent RNA:DNA hybrid that is sensitive to theophylline. The biosensor retains the remarkable selectivity of the RNA aptamer for theophylline over caffeine and is sensitive to 0-2 muM theophylline, well below the clinically relevant concentration (5-20 mg/L or approximately 10-50 muM). Adding a dabcyl quenching dye to the 3'-terminus of the fluorescently labeled DNA strand yielded a dual-labeled DNA strand (FL-DNA-Q) and increased the dynamic range of this simple biosensor from 1.5-fold to 4-fold.

The orthodontic condition of children in England, Wales and Northern Ireland 2013.

Background The 2013 Children's Dental Health Survey is the fifth in a series of national surveys.Aims This paper reports the orthodontic condition of 12- and 15-year-olds and how they and their parents feel about the appearance of their teeth.Methodology A representative sample of children (5y, 8y, 12y, 15y) in England, Wales and Northern Ireland were invited to participate in dental examinations. A modified Index of Orthodontic Treatment Need (IOTN) was used as a measure of orthodontic treatment need for 12- and 15-year-olds. Children and parents were invited to complete a questionnaire about oral health behaviour and attitudes.Results Nine percent of 12-year-olds and 18% of 15-year-olds were undergoing orthodontic treatment at the time of the survey. Forty-four percent of 12-year-olds and 29% of 15-year-olds expressed a desire for straighter teeth, however over half of this group would not qualify for NHS treatment. Unmet treatment need was higher in children eligible for free school meals (P <0.05 at 15y).Conclusions Provision of and demand for orthodontic treatment is increasing, with a significant proportion of children who desire orthodontic care not eligible to receive it. Children from deprived backgrounds have greater unmet orthodontic treatment need.

pMINERVA: A donor-acceptor system for the in vivo recombineering of scFv into IgG molecules.

Phage display is the most widely used method for selecting binding molecules from recombinant antibody libraries. However, validation of the phage antibodies often requires early production of the cognate full-length immunoglobulin G (IgG). The conversion of phage library outputs to a full immunoglobulin via standard subcloning is time-consuming and limits the number of clones that can be evaluated. We have developed a novel system to convert scFvs from a phage display vector directly into IgGs without any in vitro subcloning steps. This new vector system, named pMINERVA, makes clever use of site-specific bacteriophage integrases that are expressed in Escherichia coli and intron splicing that occurs within mammalian cells. Using this system, a phage display vector contains both bacterial and mammalian regulatory regions that support antibody expression in E. coli and mammalian cells. A single-chain variable fragment (scFv) antibody is expressed on the surface of bacteriophage M13 as a genetic fusion to the gpIII coat protein. The scFv is converted to an IgG that can be expressed in mammalian cells by transducing a second E. coli strain. In that strain, the phiC31 recombinase fuses the heavy chain constant domain from an acceptor plasmid to the heavy chain variable domain and introduces controlling elements upstream of the light chain variable domain. Splicing in mammalian cells removes a synthetic intron containing the M13 gpIII gene to produce the fusion of the light chain variable domain to the constant domain. We show that phage displaying a scFv and recombinant IgGs generated using this system are expressed at wild-type levels and retain normal function. Use of the pMINERVA completely eliminates the labor-intensive subcloning and DNA sequence confirmation steps currently needed to convert a scFv into a functional IgG Ab.

Development of a low-level (37)Ar calibration standard.

Argon-37 is an environmental signature of an underground nuclear explosion. Producing and quantifying low-level (37)Ar standards is an important step in the development of sensitive field measurement instruments. This paper describes progress at Pacific Northwest National Laboratory in developing a process to generate and quantify low-level (37)Ar standards, which can be used to calibrate sensitive field systems at activities consistent with soil background levels. This paper presents a discussion of the measurement analysis, along with assumptions and uncertainty estimates.

The Jamaican Diabetes Survey. A protocol for the Caribbean.

OBJECTIVE: This study was designed to investigate the point prevalence of diabetes in Jamaica. RESEARCH DESIGN AND METHODS: A two-stage stratified random sampling design was used, and individuals aged 15 years and over were interviewed. Nonresponse was documented and factored into the final analysis of the survey data. The overall response rate obtained was 57.9%. All subjects with fasting blood glucose (FBG) greater than 6.1 mmol/1 (110 mg/dl) were brought back for an abbreviated glucose tolerance test. The data was analyzed using Epi 5, an advanced statistical program designed specifically for use with epidemiological data. RESULTS: The 2,109 subjects who participated were the basis for estimates of diabetes and IGT prevalence. Among those with previously diagnosed diabetes, diet therapy alone, oral hypoglycemic agents plus diet therapy, insulin therapy, and lack of treatment were reported. CONCLUSIONS: By the World Health Organization (WHO) criteria, Jamaica has a point prevalence of diabetes of 17.9% in the 15-and-over age-group.

Insulin-like growth factor 1 is a direct HOXA9 target important for hematopoietic transformation.

HOX homeobox proteins are key oncogenic drivers in hematopoietic malignancies. Here we demonstrate that HOXA1, HOXA6 and predominantly HOXA9 are able to induce the production of insulin-like growth factor 1 (Igf1). In chromatin immunoprecipitations, HOXA9 bound directly to the putative promoter and a DNase-hypersensitive region in the first intron of the Igf1 gene. Transcription rates of the Igf1 gene paralleled HOXA9 activity. Primary cells transformed by HOXA9 expressed functional Igf1 receptors and activated the protein kinase Akt in response to Igf1 stimulation, suggesting the existence of an autocrine signaling loop. Genomic deletion of the Igf1 gene by Cre-mediated recombination increased sensitivity toward apoptosis after serum starvation. In addition, the leukemogenic potential of Igf1-negative, HOXA9-transformed cells was impaired, leading to a significant delay in disease development on transplantation into recipient animals.