Results of a Search for Sub-GeV Dark Matter Using 2013 LUX Data.

The scattering of dark matter (DM) particles with sub-GeV masses off nuclei is difficult to detect using liquid xenon-based DM search instruments because the energy transfer during nuclear recoils is smaller than the typical detector threshold. However, the tree-level DM-nucleus scattering diagram can be accompanied by simultaneous emission of a bremsstrahlung photon or a so-called "Migdal" electron. These provide an electron recoil component to the experimental signature at higher energies than the corresponding nuclear recoil. The presence of this signature allows liquid xenon detectors to use both the scintillation and the ionization signals in the analysis where the nuclear recoil signal would not be otherwise visible. We report constraints on spin-independent DM-nucleon scattering for DM particles with masses of 0.4-5 GeV/c^{2} using 1.4×10^{4} kg day of search exposure from the 2013 data from the Large Underground Xenon (LUX) experiment for four different classes of mediators. This analysis extends the reach of liquid xenon-based DM search instruments to lower DM masses than has been achieved previously.

Limits on Spin-Dependent WIMP-Nucleon Cross Section Obtained from the Complete LUX Exposure.

We present experimental constraints on the spin-dependent WIMP-nucleon elastic cross sections from the total 129.5 kg yr exposure acquired by the Large Underground Xenon experiment (LUX), operating at the Sanford Underground Research Facility in Lead, South Dakota (USA). A profile likelihood ratio analysis allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=1.6×10^{-41} cm^{2} (σ_{p}=5×10^{-40} cm^{2}) at 35 GeV c^{-2}, almost a sixfold improvement over the previous LUX spin-dependent results. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

First Searches for Axions and Axionlike Particles with the LUX Experiment.

The first searches for axions and axionlike particles with the Large Underground Xenon experiment are presented. Under the assumption of an axioelectric interaction in xenon, the coupling constant between axions and electrons g_{Ae} is tested using data collected in 2013 with an exposure totaling 95 live days ×118 kg. A double-sided, profile likelihood ratio statistic test excludes g_{Ae} larger than 3.5×10^{-12} (90% C.L.) for solar axions. Assuming the Dine-Fischler-Srednicki-Zhitnitsky theoretical description, the upper limit in coupling corresponds to an upper limit on axion mass of 0.12 eV/c^{2}, while for the Kim-Shifman-Vainshtein-Zhakharov description masses above 36.6 eV/c^{2} are excluded. For galactic axionlike particles, values of g_{Ae} larger than 4.2×10^{-13} are excluded for particle masses in the range 1-16 keV/c^{2}. These are the most stringent constraints to date for these interactions.

Results from a Search for Dark Matter in the Complete LUX Exposure.

We report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4} kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50 GeV c^{-2}, WIMP-nucleon spin-independent cross sections above 2.2×10^{-46} cm^{2} are excluded at the 90% confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1×10^{-46} cm^{2} at 50 GeV c^{-2}.

Nutritional status of Vietnamese outpatients with chronic obstructive pulmonary disease.

BACKGROUND: Nutritional screening and assessment is not currently part of routine clinical practice in Vietnam. Therefore, the present study aimed to investigate the utility of the commonly used methods for identifying malnutrition in outpatients with chronic obstructive pulmonary disease (COPD). METHODS: A cross-sectional pilot study and a larger retrospective study were carried out in outpatients with COPD who were attending a respiratory clinic in Ho Chi Minh City, Vietnam. Routine clinical data were collected [body mass index (BMI), forced expiratory volume in 1 s (FEV1 )]. Nutritional screening and assessment were performed using the Malnutrition Screening Tool (MST) and Subjective Global Assessment (SGA) as the gold standard to diagnose malnutrition. RESULTS: In total, 393 outpatients had documented BMI and 29 were prospectively assessed using SGA: males, n = 25; females, n = 4; mean (SD) age 69.7 (9.6) years; mean (SD) BMI 21.0 (3.4) kg m-2 ; mean (SD) FEV1 percentage predicted 57.0% (19.7%). Malnutrition risk was identified in 20.7% (n = 6) of patients using the MST (38% sensitivity; 94% specificity). However, 45% (n = 13) were diagnosed as malnourished using the SGA (31% mild/moderate; 14% severe). All malnourished patients not identified by the MST had evidence of muscle wasting. BMI had a strong negative correlation with muscle wasting as assessed using the SGA (r = -0.857, n = 28; P < 0.001) and all malnourished patients had a BMI <21 kg m-2 (range 14.6-20.8 kg m-2 , nourished range 20.0-27.6 kg m-2 ). CONCLUSIONS: Malnutrition is common in Vietnamese outpatients with COPD. A BMI threshold of <21 kg m-2 appears to represent a useful and pragmatic cut-off point for identifying outpatients requiring comprehensive nutritional assessment and support.

Improved Limits on Scattering of Weakly Interacting Massive Particles from Reanalysis of 2013 LUX Data.

We present constraints on weakly interacting massive particles (WIMP)-nucleus scattering from the 2013 data of the Large Underground Xenon dark matter experiment, including 1.4×10^{4} kg day of search exposure. This new analysis incorporates several advances: single-photon calibration at the scintillation wavelength, improved event-reconstruction algorithms, a revised background model including events originating on the detector walls in an enlarged fiducial volume, and new calibrations from decays of an injected tritium ß source and from kinematically constrained nuclear recoils down to 1.1 keV. Sensitivity, especially to low-mass WIMPs, is enhanced compared to our previous results which modeled the signal only above a 3 keV minimum energy. Under standard dark matter halo assumptions and in the mass range above 4 GeV c^{-2}, these new results give the most stringent direct limits on the spin-independent WIMP-nucleon cross section. The 90% C.L. upper limit has a minimum of 0.6 zb at 33 GeV c^{-2} WIMP mass.

Results on the Spin-Dependent Scattering of Weakly Interacting Massive Particles on Nucleons from the Run 3 Data of the LUX Experiment.

We present experimental constraints on the spin-dependent WIMP (weakly interacting massive particle)-nucleon elastic cross sections from LUX data acquired in 2013. LUX is a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota), which is designed to observe the recoil signature of galactic WIMPs scattering from xenon nuclei. A profile likelihood ratio analysis of 1.4×10^{4} kg day of fiducial exposure allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=9.4×10^{-41} cm^{2} (σ_{p}=2.9×10^{-39} cm^{2}) at 33 GeV/c^{2}. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

Analysis of the Candida albicans Phosphoproteome.

Candida albicans is an important human fungal pathogen in both immunocompetent and immunocompromised individuals. C. albicans regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm formation, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that protein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in C. albicans regulation, we performed a deep analysis of the phosphoproteome in C. albicans. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896 proteins. The ratios of serine, threonine, and tyrosine phosphosites were 80.01%, 18.11%, and 1.81%, respectively. The majority of proteins (2,111) contained at least two detected phosphorylation sites. Consistent with findings in other fungi, cytoskeletal proteins were among the most highly phosphorylated proteins, and there were differences in Gene Ontology (GO) terms for proteins with serine and threonine versus tyrosine phosphorylation sites. This large-scale analysis identified phosphosites in protein components of Mediator, an important transcriptional coregulatory protein complex. A targeted analysis of the phosphosites in Mediator complex proteins confirmed the large-scale studies, and further in vitro assays identified a subset of these phosphorylations that were catalyzed by Cdk8 (Ssn3), a kinase within the Mediator complex. These data represent the deepest single analysis of a fungal phosphoproteome and lay the groundwork for future analyses of the C. albicans phosphoproteome and specific phosphoproteins.

Are Irish therapists at heightened risk for low back pain?

BACKGROUND: Within the international literature, no studies have been identified that compare prevalence rates of low back pain (LBP) in chartered physiotherapists, physical and athletic therapists and those in the national working population, making it unclear whether such therapists are an occupational group at high risk of developing LBP. AIMS: To establish the prevalence of LBP among therapists (both employed and self-employed) in Ireland, to compare the employment status-, gender- and age-specific LBP prevalence rates between therapists and the national working population and to estimate the adjusted odds of developing LBP among therapists relative to the national working population. METHODS: An analysis of data from the Health In Hand Intensive Tasks and Safety (HITS) study and the third national Survey on Lifestyle, Attitudes and Nutrition (SLÁN). The HITS study was a cross-sectional study investigating work-related musculoskeletal disorders in practising therapists. The SLÁN 2007 was a face-to-face interview study of adults. RESULTS: LBP prevalence in therapists was 49% with no significant difference by employment status. Therapists had a much higher prevalence compared with the national working population across all demographic strata, with therapists nearly five times more likely to suffer from LBP than the national working population after careful adjustment for differences in sociodemographic factors. CONCLUSIONS: Therapists in Ireland are an occupational group at high risk of developing LBP, warranting further research into their physical and psychosocial work-related risk factors.

Pacemaker-lead-associated thrombosis in dogs: a multicenter retrospective study.

INTRODUCTION: Pacemaker implantation is the treatment of choice for clinically relevant bradyarrhythmias. Pacemaker-lead-associated thrombosis (PLAT) occurs in 23.0-45.0% of people with permanent transvenous pacemakers. Serious thromboembolic complications are reported in 0.6-3.5%. The incidence of PLAT in dogs is unknown. ANIMALS, MATERIALS AND METHODS: multicenter retrospective study of seven centers with 606 client-owned dogs undergoing permanent pacemaker implantation between 2012 and 2019. 260 dogs with a transvenous pacemaker with echocardiographic follow-up, 268 dogs with a transvenous pacemaker without echocardiographic follow-up and 78 dogs with an epicardial pacemaker. RESULTS: 10.4% (27/260) of dogs with transvenous pacemakers and echocardiographic follow-up had PLAT identified. The median time to diagnosis was 175 days (6-1853 days). Pacemaker-lead-associated thrombosis was an incidental finding in 15/27 (55.6%) dogs. Of dogs with a urine protein:creatinine ratio measured at pacemaker implantation, dogs with PLAT were more likely to have proteinuria at pacemaker implantation vs. dogs without PLAT (6/6 (100.0%) vs. 21/52 (40.4%), P=0.007). Urine protein:creatinine ratio was measured in 12/27 (44.4%) dogs at PLAT diagnosis, with proteinuria identified in 10/12 (83.3%) dogs. Anti-thrombotic drugs were used following the identification of PLAT in 22/27 (81.5%) dogs. The thrombus resolved in 9/15 (60.0%) dogs in which follow-up echocardiography was performed. Dogs with PLAT had shorter survival times from implantation compared to those without PLAT (677 days [9-1988 days] vs. 1105 days [1-2661 days], P=0.003). CONCLUSIONS: Pacemaker-lead-associated thrombosis is identified in 10.4% (27/260) of dogs following transvenous pacing, is associated with proteinuria, can cause significant morbidity, and is associated with reduced survival times.

Prevalence of streptococci and increased polymicrobial diversity associated with cystic fibrosis patient stability.

Diverse microbial communities chronically colonize the lungs of cystic fibrosis patients. Pyrosequencing of amplicons for hypervariable regions in the 16S rRNA gene generated taxonomic profiles of bacterial communities for sputum genomic DNA samples from 22 patients during a state of clinical stability (outpatients) and 13 patients during acute exacerbation (inpatients). We employed quantitative PCR (qPCR) to confirm the detection of Pseudomonas aeruginosa and Streptococcus by the pyrosequencing data and human oral microbe identification microarray (HOMIM) analysis to determine the species of the streptococci identified by pyrosequencing. We show that outpatient sputum samples have significantly higher bacterial diversity than inpatients, but maintenance treatment with tobramycin did not impact overall diversity. Contrary to the current dogma in the field that Pseudomonas aeruginosa is the dominant organism in the majority of cystic fibrosis patients, Pseudomonas constituted the predominant genera in only half the patient samples analyzed and reported here. The increased fractional representation of Streptococcus in the outpatient cohort relative to the inpatient cohort was the strongest predictor of clinically stable lung disease. The most prevalent streptococci included species typically associated with the oral cavity (Streptococcus salivarius and Streptococcus parasanguis) and the Streptococcus milleri group species. These species of Streptococcus may play an important role in increasing the diversity of the cystic fibrosis lung environment and promoting patient stability.

Transvenous correction of patent ductus arteriosus in two toy-breed dogs with the Amplatzer™ Vascular Plug 4.

Two Pomeranian dogs referred for interventional correction of a left-to-right shunting patent ductus arteriosus (PDA) had inadequate femoral arterial access for any occlusion device other than micro coils. The decision was made to attempt correction of the PDA using the Amplatzer™ Vascular Plug 4 (AVP4) from a femoral venous approach. An AVP4 was successfully deployed in each dog with complete occlusion noted within 5 min. Complete occlusion was persistent at 24 h after the procedure, while both dogs were subclinical, had no residual ductal flow, and complete or near complete reverse cardiac remodeling at subsequent visits. This report demonstrates the feasibility of PDA occlusion with the AVP4 from the femoral venous approach in small dogs where femoral arterial access is inadequate for other occlusion devices.

On the surface or down below: Field observations reveal a high degree of surface activity in a burrowing crayfish, the Little Brown Mudbug (Lacunicambarus thomai).

Opposed to most crayfish species that inhabit permanent bodies of water, a unique burrowing lifestyle has evolved several times throughout the crayfish phylogeny. Burrowing crayfish are considered to be semi-terrestrial, as they burrow to the groundwater-creating complex burrows that occasionally reach 3 m in depth. Because burrowing crayfishes spend most of their lives within their burrow, we lack a basic understanding of the behavior and natural history of these species. However, recent work suggests that burrowing crayfishes may exhibit a higher level of surface activity than previously thought. In the current study, we conducted a behavioral study of the Little Brown Mudbug, Lacunicambarus thomai using video surveillance to determine their degree of surface activity and behavioral patterns. Throughout 664 hrs of footage, we observed a surprisingly high amount of activity at the surface of their burrows-both during the day and night. The percentage of time that individual crayfish was observed at the surface ranged from 21% to 69% per individual, with an average of 42.48% of the time spent at the surface across all crayfish. Additionally, we created an ethogram based on six observed behaviors and found that each behavior had a strong circadian effect. For example, we only observed a single observation of foraging on vegetation during the day, whereas 270 observations of this behavior were documented at night. Overall, our results suggest that burrowing crayfishes may exhibit higher levels of surface activity than previously thought. To increase our understanding of burrowing crayfish behaviors ecology, we encourage the continued use of video-recorded observations in the field and the laboratory.

Transarterial correction of patent ductus arteriosus in small dogs with the Amplatz™ Vascular Plug 4: A pilot study.

OBJECTIVES: Determine if the Amplatz™ Vascular Plug 4 (AVP4) can be used to occlude left-to-right shunting patent ductus arteriosus (PDA) in dogs with inadequate arterial vascular access for the Amplatz Canine Duct Occluder (ACDO). ANIMALS: Six adolescent dogs with PDA whose femoral artery was too small for insertion of a 4 Fr vascular access sheath. MATERIALS AND METHODS: Standard femoral arterial vascular access and a 4 Fr diagnostic catheter were used to deploy an appropriately sized AVP4 into the PDA of each dog. Successful occlusion was defined as no residual ductal flow and determined by color Doppler echocardiography and angiography. RESULTS: The AVP4 was successfully deployed, and complete occlusion of the PDA was achieved in all dogs. There were no complications encountered in any of the dogs. CONCLUSIONS: The AVP4 is a viable option for the correction of PDA in dogs with inadequate arterial vascular access for the ACDO and should be considered as one of the options available for PDA correction in this challenging animal population.

Homologue scanning mutagenesis reveals CD66 receptor residues required for neisserial Opa protein binding.

The immunoglobulin-like family of CD66 antigens, present on human neutrophils and epithelial cells, are used as receptors for adhesins expressed by the pathogenic Neisseriae. N. gonorrhoeae strain MS11 can express 11 isoforms of these adhesins, called opacity-related (Opa) proteins. Each MS11 Opa protein recognizes a distinct spectrum of CD66 receptors. CD66-Opa binding is mediated by the NH(2)-terminal domain of the receptor and occurs through protein-protein interactions. In this report, we have investigated the molecular basis for the binding between the CD66 and Opa protein families by mapping amino acids in CD66 receptors that determine Opa protein binding. We performed homologue scanning mutagenesis between CD66e, which binds multiple Opa variants, and CD66b, which binds none, and tested both loss-of-function by CD66e and gain-of-function by CD66b in solution assays and in assays involving full-length receptors expressed by epithelial cells. We found that three residues in the CD66e N-domain are required for maximal Opa protein receptor activity. Opa proteins that recognize the same spectrum of native CD66 molecules showed differential binding of receptors with submaximal activity, indicating that the binding characteristics of these Opa proteins are actually slightly different. These data provide a first step toward resolving the structural requirements for Opa-CD66 interaction.

Antibody-resistant mutants of Borrelia burgdorferi: in vitro selection and characterization.

We used polyclonal antisera and monoclonal antibodies (mAbs) to inhibit the growth of clonal populations of two strains of Borrelia burgdorferi, the Lyme disease agent, and thereby select for antibody-resistant mutants. mAbs were directed at the outer membrane proteins, OspA or OspB. Mutants resistant to the growth-inhibiting properties of the antibodies were present in the populations at frequencies ranging from 10(-5) to 10(-2). The several escape variants that were examined were of four classes. Class I mutants were resistant to all mAbs; they lacked OspA and OspB and the linear plasmid that encodes them. Two other proteins were expressed in larger amounts in class I mutants; mAbs to these proteins inhibited the mutant but not the wild-type cells. Class II mutants were resistant to some but not all mAbs; they had truncated OspA and/or OspB proteins. Class III mutants were resistant only to the selecting mAb; they had full-length Osp proteins that were not bound by the selecting antibody in Western blots. In two class III mutants resistant to different anti-OspA mAbs, missense mutations were demonstrated in the ospA genes. Class IV mutants were likewise resistant only to selecting antibody, but in this case the selecting antibody still bound in Western blots.

Overexpression of aldehyde dehydrogenase 1A1 reduces oxidation-induced toxicity in SH-SY5Y neuroblastoma cells.

Oxidative stress leading to lipid peroxidation is a problem in neurodegenerative diseases, because the brain is rich in polyunsaturated fatty acids and low in endogenous antioxidants. One of the most toxic byproducts of lipid peroxidation, 4-hydroxynonenal (HNE), is implicated in oxidative stress-induced damage in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). In this study, the human neuroblastoma cell line SH-SY5Y was used to test the protective effects of increasing the detoxification of HNE by overexpressing the HNE-detoxifying enzyme aldehyde dehydrogenase 1A1 (ALDH1). Overexpression of ALDH1 in the SH-SY5Y cells acts to reduce production of protein-HNE adducts and activation of caspase-3. Our data suggest that detoxification of HNE could be therapeutic in preventing some of the toxic disruptions of the brain's redox systems found in many neurodegenerative diseases.

Intravascular occlusion for the correction of extrahepatic portosystemic shunts in dogs.

BACKGROUND: Congential extrahepatic portosystemic shunts (EHPSS) are common in dogs. An effective minimally invasive technique for correction of EHPSS could result in reduced morbidity, reduced costs, and reduced hospitalization times. HYPOTHESIS: Use of an intravascular occlusion device can effectively and safely result in acute complete occlusion of EHPSS in dogs. ANIMALS: Seven dogs with naturally occurring EHPSS that presented to the Purdue University Veterinary Teaching Hospital. METHODS: Prospective, clinical trial. The 7 dogs were consecutively enrolled over a 2-year period. Results of serum biochemistry, total serum bile acids, fasting plasma ammonia, abdominal radiography, and ultrasonography suggested the diagnosis of portosystemic shunts in all dogs. Definitive diagnosis of EHPSS was achieved with cranial mesenteric arterial portography and acute occlusion was attempted by the deployment of the Amplatzer vascular plug (AVP). RESULTS: EHPSS were identified in all dogs consisting of 5 portocaval and 2 portoazygous variants; 1/7 dogs (14%) were intolerant to temporary complete occlusion of the EHPSS. Of the remaining 6 dogs, 5 (83%) had complete occlusion of the EHPSS by the AVP. There were no complications and resolution of abnormal clinical signs and laboratory values was achieved in 4/5 (80%) dogs with complete occlusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Intravascular correction of EHPSS by the AVP is a viable option to surgical correction while larger studies will be required to determine the clinical applicability of this procedure in the broader portosystemic shunt population.

Antithrombotic effect of enoxaparin in clinically healthy cats: a venous stasis model.

BACKGROUND: Systemic arterial thromboembolic events are a serious complication of cardiac disease in cats. OBJECTIVES: To determine if enoxaparin induces an antithrombotic effect in cats at a dosage of 1 mg/kg SC q12h and if this antithrombotic effect is predicted by anti-Xa activity. ANIMALS: Fourteen clinically healthy cats were divided into 3 groups: control (4 cats), treated and assessed at 4 hours (5 cats), and treated and assessed at 12 hours (5 cats). METHODS: A venous stasis model was used and the extent of thrombus formation estimated by measuring thrombus weight and accretion of 125I-fibrinogen. Plasma anti-Xa activity was measured in treated cats. RESULTS: There was a significant reduction in thrombus formation in the 4 h group compared with control (median weight, 0.000 versus 0.565mg/mm, P < .01; median % 125I-fibrinogen accretion, 0.0 versus 42.0%, P < .01). There was a reduction in thrombus formation in the 12 h group (median weight, 0.006 mg/mm, P = .09; median % 125I-fibrinogen accretion, 3.83%, P = .09) but this reduction was not significant. The median percent thrombus inhibition for treated cats was 100.0% at 4 hours and 91.4% at 12 hours. Plasma anti-Xa activity was not significantly correlated with thrombus formation. CONCLUSIONS AND CLINICAL IMPORTANCE: This pilot study demonstrates that enoxaparin, when administered at a dosage of 1 mg/kg SC q12h, produces an antithrombotic effect in a venous statsis model in clinically healthy cats. Furthermore, this study demonstrates that anti-Xa activity is a poor predictor of enoxaparin's antithrombotic effect.