Search for Periodic Time Variations of the Solar

We report a search for time variations of the solar ^{8}B neutrino flux using 5804 live days of Super-Kamiokande data collected between May 31, 1996, and May 30, 2018. Super-Kamiokande measured the precise time of each solar neutrino interaction over 22 calendar years to search for solar neutrino flux modulations with unprecedented precision. Periodic modulations are searched for in a dataset comprising five-day interval solar neutrino flux measurements with a maximum likelihood method. We also applied the Lomb-Scargle method to this dataset to compare it with previous reports. The only significant modulation found is due to the elliptic orbit of the Earth around the Sun. The observed modulation is consistent with astronomical data: we measured an eccentricity of (1.53±0.35)%, and a perihelion shift of (-1.5±13.5) days.

Infection of Diplostomum spp. in invasive round gobies in the St Lawrence River, Canada.

The round goby (Neogobius melanostomus) is a successful invader of the Great Lakes-St Lawrence River basin that harbours a number of local parasites. The most common are metacercariae of the genus Diplostomum. Species of Diplostomum are morphologically difficult to distinguish but can be separated using molecular techniques. While a few species have been sequenced from invasive round gobies in this study system, their relative abundance has not been documented. The purpose of this study was to determine the species composition of Diplostomum spp. and their relative abundance in round gobies in the St Lawrence River by sequencing the barcode region of cytochrome c oxidase I. In 2007-2011, Diplostomum huronense (=Diplostomum sp. 1) was the most common, followed in order by Diplostomum indistinctum (=Diplostomum sp. 4) and Diplostomum indistinctum sensu Galazzo, Dayanandan, Marcogliese & McLaughlin (2002). In 2012, the most common species infecting the round goby in the St Lawrence River was D. huronense, followed by D. indistinctum and Diplostomum gavium (=Diplostomum sp. 3). The invasion of the round goby in the St Lawrence River was followed by a decline of Diplostomum spp. in native fishes to low levels, leading to the previously published hypothesis that the presence of the round goby has led to a dilution effect. Herein, it is suggested that despite the low infection levels in the round goby, infections still may lead to spillback, helping to maintain Diplostomum spp. in native fishes, albeit at low levels.

Prospective enzymes for omega-3 PUFA biosynthesis found in endoparasitic classes within the phylum Platyhelminthes.

The free-living infectious stages of macroparasites, specifically, the cercariae of trematodes (flatworms), are likely to be significant (albeit underappreciated) vectors of nutritionally important polyunsaturated fatty acids (PUFA) to consumers within aquatic food webs, and other macroparasites could serve similar roles. In the context of de novo omega-3 (n-3) PUFA biosynthesis, it was thought that most animals lack the fatty acid (FA) desaturase enzymes that convert stearic acid (18:0) into ɑ-linolenic acid (ALA; 18:3n-3), the main FA precursor for n-3 long-chain PUFA. Recently, novel sequences of these enzymes were recovered from 80 species from six invertebrate phyla, with experimental confirmation of gene function in five phyla. Given this wide distribution, and the unusual attributes of flatworm genomes, we conducted an additional search for genes for de novo n-3 PUFA in the phylum Platyhelminthes. Searches with experimentally confirmed sequences from Rotifera recovered nine relevant FA desaturase sequences from eight species in four genera in the two exclusively endoparasite classes (Trematoda and Cestoda). These results could indicate adaptations of these particular parasite species, or may reflect the uneven taxonomic coverage of sequence databases. Although additional genomic data and, particularly, experimental study of gene functionality are important future validation steps, our results indicate endoparasitic platyhelminths may have enzymes for de novo n-3 PUFA biosynthesis, thereby contributing to global PUFA production, but also representing a potential target for clinical antihelmintic applications.

Cardiorespiratory fitness and accelerometer-determined physical activity following one year of free-living high-intensity interval training and moderate-intensity continuous training: a randomized trial.

BACKGROUND: Free-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT). METHODS: Ninety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models. RESULTS: CRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018). CONCLUSION: Despite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.

First Measurement of the Total Neutron Cross Section on Argon between 100 and 800 MeV.

We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.

Metacercariae of Heterodiplostomum lanceolatum (Trematoda: Proterodiplostomidae) found in Leptodactylus podicipinus (Anura: Leptodactylidae) from Brazil: a morphological, molecular and ecological study.

The trematodes from South American reptiles are poorly known, with only one life cycle completely characterized. We used molecular and morphological methods to characterize diplostomoid metacercariae found in 29 of 86 pointedbelly frogs, Leptodactylus podicipinus (Cope, 1862) collected in a marsh pond in Selvíria, in the central-west region of Brazil. The metacercariae were identified as Heterodiplostomum lanceolatum Dubois, 1936 (Proterodiplostomidae), a rarely reported species that matures in snakes. In phylogenetic analysis of partial sequences from 28S rDNA, H. lanceolatum fell within a polytomy with the proterodiplostomid Crocodilicola pseudostoma (molecular divergence of 4.1%) and other members of the superfamily Diplostomoidea. Our collections provide insights into the ecology of this parasite, in that infected frogs were smaller than uninfected frogs, and metacercariae were more numerous in the abdominal cavity and hindlimb muscles than in abdominal muscles, which suggests directions for future research on the transmission and pathology of this proterodiplostomid.

Baloxavir marboxil: a novel cap-dependent endonuclease (CEN) inhibitor for the treatment of acute uncomplicated influenza.

Baloxavir marboxil is a newly approved antiviral agent with activity against influenza via a novel mechanism of action of inhibition of cap-dependent endonuclease (CEN). The novel agent was approved in October of 2018 in the United States for the treatment of acute uncomplicated influenza A and B in patients aged 12 years or older. Baloxavir is given as a single weight-based dose of 40 mg orally once for patients weighing less than 80 kg and 80 mg orally once for those weighing 80 kg or more within 48 hours of symptom onset. In comparison with current therapy, baloxavir is as effective in decreasing time to symptom alleviation as the drug of choice, oseltamivir, and significantly reduces viral load 1 day after treatment compared with placebo and oseltamivir. In safety analyses baloxavir was well tolerated with only mild adverse events reported (nausea, headache, diarrhea, bronchitis, nasopharyngitis), thus providing a safe and reliable alternative option to current therapy for acute uncomplicated influenza. Further studies are being conducted to evaluate the use of baloxavir in additional patient populations including pediatric patients less than 12 years of age and patients who are at high risk of complications related to influenza.

Letermovir for prophylaxis of cytomegalovirus in allogeneic hematopoietic stem cell recipients.

Letermovir is a new antiviral agent with activity against human cytomegalovirus (CMV). Letermovir works as an inhibitor of the CMV DNA terminase complex which further inhibits viral DNA processing and packaging. Letermovir is available both orally and intravenously in 480-mg and 240-mg dosage forms, and is approved for use in the prophylaxis of CMV infection and disease in CMV-seropositive recipients of allogeneic hematopoietic stem cell transplant (HSCT) over the age of 18. The recommended dose is 480 mg p.o./i.v. once daily initiated between day 0 through day 28 post-allogeneic HSCT and continued through day 100 post-transplantation; the dose should be reduced to 240 mg daily if coadministered with cyclosporine. Letermovir is metabolized primarily by hepatic OATP1B1/3 and is not recommended for patients with severe hepatic impairment (Child-Pugh class C). Renal dosage adjustments are not warranted until a creatinine clearance (CrCl) of less than 10 mL/min; however, serum creatinine should be monitored when administered to patients with a CrCl of less than 50 mL/min. Cross-resistance with other useful antiviral agents in the treatment of CMV has not been observed. Additionally, letermovir is active against DNA polymerase inhibitor-resistant viral strains. Letermovir has shown promising clinical efficacy and is generally well tolerated, thus providing a favorable new option in the prophylaxis of CMV infection and disease.

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

Risk stratification, treatment selection, and transplant eligibility in multiple myeloma: a qualitative study of the perspectives and self-reported practices of oncologists.

BACKGROUND: Since the early 2000s, treatment options for multiple myeloma have rapidly expanded, adding significant complexity to the management of this disease. To our knowledge, no systematic qualitative research on clinical decision-making in multiple myeloma has been published. We sought to characterize how physicians view and implement guidelines and incorporate novel approaches into patient care. METHODS: We designed a semi-structured qualitative interview guide informed by literature review and an expert advisory panel. We conducted 60-minute interviews with a diverse sample of oncology physicians in the southeast United States. We used a constant comparative method to code and analyze interview transcripts. The research team and advisory panel discussed and validated emergent themes. RESULTS: Participants were 13 oncologists representing 5 academic and 4 community practices. Academic physicians reported using formal risk-stratification schemas; community physicians typically did not. Physicians also described differences in eligibility criteria for transplantation; community physicians emphasized distance, social support, and psychosocial capacity in making decisions about transplantation referral; the academic physicians reported using more specific clinical criteria. All physicians reported using a maintenance strategy both for post-transplant and for transplant-ineligible patients; however, determining the timing of maintenance therapy initiation and the response were reported as challenging, as was recognition or definition of relapse, especially in terms of when treatment re-initiation is indicated. CONCLUSIONS: Practices reported by both academic and community physicians suggest opportunities for interventions to improve patient care and outcomes through optimal multiple myeloma management and therapy selection. Community physicians in particular might benefit from targeted education interventions about risk stratification, transplant eligibility, and novel therapies.

Completion of the life cycle of Tylodelphys mashonense (Sudarikov, 1971) (Digenea: Diplostomidae) with DNA barcodes and rDNA sequences.

The life cycle of Tylodelphys mashonense (Digenea: Diplostomidae), whose metacercariae occur in the cranial cavity of the widely cultivated catfish Clarias gariepinus, was resolved by the application of molecular markers. Both COI barcodes and ITS sequences obtained from diplostomid-like cercariae infecting Bulinus spp. from Mindu Dam, Morogoro, matched those acquired from metacercariae from the catfish C. gariepinus, and those from adult T. mashonense from the grey heron Ardea cinerea and the white egret Egretta alba. The success in linking the life cycle stages of T. mashonense using molecular tools highlights the usefulness of this approach in resolving the complex life cycles of digeneans in the absence of experimental establishment.

A diagnostic evaluation of real-time PCR, fluorescent antibody and microscopic agglutination tests in cases of equine leptospiral abortion.

REASONS FOR PERFORMING STUDY: A comprehensive evaluation of the real-time PCR assay for leptospirosis in comparison with other diagnostic assays on a large-scale basis is fundamental in validating the assay and determining the causes of equine abortions. OBJECTIVES: To compare and evaluate the diagnostic value of real-time PCR assay for leptospirosis with traditional methods in equine leptospiral abortions. STUDY DESIGN: Cross-sectional observational study. METHODS: A Leptospira spp. fluorescent antibody test (FAT), microscopic agglutination test (MAT) and real-time PCR (targeting the LipL32 gene) were compared and evaluated in equine fetal necropsy specimens (placenta, kidney, liver and heart blood) and maternal serum (when available) in 339 equine fetuses. RESULTS: From a total of 339 equine fetuses necropsied, 21 cases (6.19%) were diagnosed as leptospiral abortion. The majority of leptospiral abortions occurred in January (8 cases) and February (5 cases). Real-time PCR detected 21 of 21 cases, whereas MAT and FAT detected 19 and 18 (including 2 suspicious cases) cases, respectively. Comparing tissues, placenta yielded somewhat similar cycle of threshold values by real-time PCR compared with kidney, whereas kidney was the best specimen for the diagnosis of leptospirosis by the FAT test. In all MAT positive cases, the predominant titre in fetal heart blood was to serovar Pomona (ranging 1:100 to 1:204,800) with little or no cross-reaction to serovar Grippotyphosa. CONCLUSIONS: The results indicate that real-time PCR is an effective method for the diagnosis of leptospiral abortion in horses. However, MAT should continue to be used in clinical cases for serovar determination.

Morphometric and molecular analyses of Tylodelphys sp. metacercariae (Digenea: Diplostomidae) from the vitreous humour of four fish species from Lake Naivasha, Kenya.

Even in the relatively well-characterized faunas of the developed world, it is difficult to discriminate species of metacercariae in the Diplostomidae using morphology, infection site or host use. The taxonomy, diversity and ecology of diplostomids infecting freshwater fishes in the African continent are particularly poorly known, but recent morphometric and genetic studies have revealed four species of diplostomids in the eyes and brains of siluriform fishes. In the present study, diplostomid metacercariae were collected from the eyes of 288 fish comprising two species within the Cyprinidae (Cyprinus carpio, n = 145, and Barbus paludinosus, n = 67), two Cichlidae (Oreochromis leucostictus, n = 56, and Tilapia zillii, n = 18) and one Centrarchidae (Micropterus salmoides, n = 2) caught in Lake Naivasha, Kenya. Morphometric (14 characters and 8 indices in 111 specimens) and molecular (sequences from the barcode region of the cytochrome c oxidase 1 gene in 11 specimens) data were used to discriminate species. All fish species except B. paludinosus were infected with Tylodelphys metacercariae that were initially separated into two types differing mainly in body length. However, this morphological distinction received only intermediate support in quantitative morphological analysis and molecular data indicated that both morphotypes were conspecific. All the specimens therefore are inferred to belong to a single unidentified species of Tylodelphys, which is not conspecific with any other diplostomid for which comparable molecular data are available, including four diplostomid species known from siluriform fish in Nigeria and Tanzania.

Estimating diet in individual pumpkinseed sunfish Lepomis gibbosus using stomach contents, stable isotopes and parasites.

The diets of 99 pumpkinseed sunfish Lepomis gibbosus from a pair of small, adjacent lakes in Ontario, Canada, were estimated from their stomach contents, trophically transmitted parasites and stable isotopes of carbon and nitrogen in fish tissue. The three methods provided virtually unrelated information. There was no significant correlation in the importance of any prey item across all three methods. Fish with similar diets according to one method of estimating diet showed no tendency to be similar according to other methods. Although there was limited variation in fish size and the spatial scale of the study was small, both fish size and spatial origin showed comparatively strong associations with diet data obtained with all three methods. These results suggest that a multidisciplinary approach that accounts for fish size and spatial origins is necessary to accurately characterize diets of individual fish.

Persistent fatigue in young athletes: measuring the clinical course and identifying variables affecting clinical recovery.

The objective of this paper is to measure the clinical course (months) in young athletes with persistent fatigue and to identify any covariates affecting the duration of recovery. This was a prospective longitudinal study of 68 athletes; 87% were elite (42 males, 26 females), aged 20.5±3.74 years (SD), who presented with the symptom of persistent fatigue. The collective duration to full clinical recovery was estimated using Kaplan-Meier product-limit curves, and covariates associated with prolonging recovery were identified from Cox proportional hazard models. The median recovery was 5 months (range 1-60 months). The range of presenting symptom duration was 0.5-36 months. The covariates identified were an increased duration of presenting symptoms [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.02-1.12; P=0.005] and the response of serum cortisol concentration to a standard exercise challenge (HR, 1.92; 95% CI, 1.09-3.38; P=0.03). Delay in recovery was not associated with categories of fatigue that included medical, training-related diagnoses, or other causes. In conclusion, the fatigued athlete represents a significant clinical problem with a median recovery of 5 months, whose collective clinical course to recovery can be estimated by Kaplan-Meier curves and appears to be a continuum.

Identification of bidirectional promoters in the human KIR genes.

Although the class I MHC receptors expressed by human and mouse natural killer (NK) cells have distinct molecular origins, they are functional analogues that are expressed in a variegated pattern. The murine Ly49 class I receptors contain bidirectional promoters that have been proposed to control the probabilistic expression of these genes. Whether similar elements are present in the human killer Ig-like receptor (KIR) genes is a fundamental question. A detailed analysis of the 2 kb intergenic region separating the KIR2DL4 gene and the adjacent KIR3DL1 gene revealed that additional promoter elements exist in the human KIR genes. Remarkably, the previously characterized KIR3DL1 proximal promoter possesses bidirectional promoter activity that maps to an 88 bp DNA fragment containing CREB, AML, Sp1 and Ets transcription factor binding sites. Individual KIR genes and alleles possess bidirectional promoters with distinct properties. Analysis of KIR(+)and KIR(-) NK cells and NK precursors indicates that reverse transcripts from the bidirectional promoter are found in cells that lack KIR protein expression, but are not present in mature KIR-expressing NK cells, suggesting that reverse transcription from the proximal promoter blocks gene activation in immature NK and precursor cells.

Are the prevalence and treatment of asthma similar in elite athletes and the aged-matched non-athlete population?

The objective of this study was to determine the prevalence of asthma and use of asthma medications in elite athletes compared with an age-matched non-athlete population. Data were collected from the respiratory component of annual medical screening of 424 elite athletes from the Queensland Academy of Sport. Measures included the prevalence of current asthma and ever doctor-diagnosed asthma, and the prevalence of use of treatment for asthma including beta-agonists and inhaled corticosteroid medication. The prevalence of current asthma in athletes aged 18-29 years was 14% (95% CI, 9-19%), which did not differ significantly from the prevalence in the non-athlete control population (11%; 95% CI, 9-12%, P=0.3). Of athletes with current asthma, 27% were not taking any medications for asthma, and 25% were treated with short-acting beta-agonist medications alone and were not taking inhaled corticosteroids. These data indicate that the overall cumulative and period prevalence of asthma in Queensland athletes is similar to that in the general age-matched population. Athletes use beta-agonists with a frequency similar to the general population.

Slicing and spreading of heterochromatic silencing by RNA interference.

RNA interference (RNAi) can mediate gene silencing posttranscriptionally by target RNA cleavage, or transcriptionally by chromatin and DNA modification. Argonaute is an essential component of the RNAi machinery that displays endonucleolytic activity guided by bound small RNAs. This slicing activity has recently been shown to be required for gene silencing and spreading of histone modifications characteristic of heterochromatin in Schizosaccharomyces pombe. Argonaute proteins with catalytic and nucleic acid binding capacities are found to function in RNAi within both the plant and animal kingdoms. Here we review the requirement of slicing for silencing and spreading in S. pombe, plants, and humans.

Psychological predictors of injury among elite athletes.

OBJECTIVES: To establish injury rates among a population of elite athletes, to provide normative data for psychological variables hypothesised to be predictive of sport injuries, and to establish relations between measures of mood, perceived life stress, and injury characteristics as a precursor to introducing a psychological intervention to ameliorate the injury problem. METHODS: As part of annual screening procedures, athletes at the Queensland Academy of Sport report medical and psychological status. Data from 845 screenings (433 female and 412 male athletes) were reviewed. Population specific tables of normative data were established for the Brunel mood scale and the perceived stress scale. RESULTS: About 67% of athletes were injured each year, and about 18% were injured at the time of screening. Fifty percent of variance in stress scores could be predicted from mood scores, especially for vigour, depression, and tension. Mood and stress scores collectively had significant utility in predicting injury characteristics. Injury status (current, healed, no injury) was correctly classified with 39% accuracy, and back pain with 48% accuracy. Among a subset of 233 uninjured athletes (116 female and 117 male), five mood dimensions (anger, confusion, fatigue, tension, depression) were significantly related to orthopaedic incidents over the preceding 12 months, with each mood dimension explaining 6-7% of the variance. No sex differences in these relations were found. CONCLUSIONS: The findings support suggestions that psychological measures have utility in predicting athletic injury, although the relatively modest explained variance highlights the need to also include underlying physiological indicators of allostatic load, such as stress hormones, in predictive models.

Lepeophtheirus salmonis: characterization of prostaglandin E(2) in secretory products of the salmon louse by RP-HPLC and mass spectrometry.

Lepeophtheirus salmonis is an ectoparasitic copepod that causes serious disease outbreaks in both wild and farmed salmonids. As the relationship between L. salmonis and its hosts is not well understood, the current investigation was undertaken to investigate whether any immunomodulatory compounds could be identified from secretions of L. salmonis. By incubating live L. salmonis adults with the neurotransmitter dopamine in seawater, we were able to obtain secretions from the parasite. These were analyzed by RP-HPLC column, as well as LC-MS. L. salmonis secretions contained a compound with the same retention time and mass of PGE(2). The identity of this compound as PGE(2) was confirmed by MS-in source dissociation. The concentrations of PGE(2) in L. salmonis secretions ranged from 0.2 to 12.3 ng/individual and varied with incubation temperature and time kept off the host. Prostaglandin E(2) is a potent vasodilator and thought to aid in parasite evasion from host immune responses. This is the first reported evidence of prostaglandin production in parasitic copepod secretions and its implications for the host-parasite relationship are discussed.