bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninferiority Clinical Trials: The Good, the Bad, and the Ugly
Authors: Lesaffre Emmanuel
Published: June 2018

For decades, the superiority trial has been the most popular design to assess the efficacy of newly developed drugs in a randomized controlled clinical trial. In a superiority trial, the aim is to show that the new (experimental) treatment is better than the standard treatment or placebo. However, it becomes increasingly difficult to improve the efficacy upon that of existing drugs. For this reason, noninferiority designs have been suggested. In a noninferiority study, one aims to show that the experimental treatment does not lower the efficacy of the standard treatment too much, but this loss of efficacy should be compensated by other better properties. In this article, the design, aims, and properties of the superiority and the noninferiority trial are contrasted and illustrated on recently published studies to treat patients with advanced hepatocellular carcinoma. The author discusses the reasons why noninferiority studies are becoming popular, but also why the results of noninferiority studies may be difficult to interpret and can be easily misused. Since only a few noninferiority studies in hepatocellular cancer have been organized, also examples from other therapeutic areas were taken. Finally, it is indicated how to appreciate the qualities of published noninferiority studies.
Elektrophoretische Untersuchungen der verschiedenen Gerinnungsfaktoren des Blutes
Authors: Gouttas A , Tsevrenis H , Priovolos J , Fessas Ph , Rombos K , Mandalaki T
Published: June 2018

Wir haben elektrophoretische Untersuchungen der Gerinnungsfaktoren mit der Methode der Papierelektrophorese durchgeführt. Dabei konnten wir feststellen, daß die Wanderungsorte dieser Faktoren auf dem elektrophoretischen Streifen folgende sind:

1. Das Prothrombin wandert zum α-Globulin und bleibt zwischen diesem und dem Albumin liegen.

2. der Faktor V (Proaccelerin), der Faktor VII (Prokonvertin), der Anti-Hämophilie-Faktor A und der Antihämophilie-Faktor B sind zwischen β- und γ-Globulin näher am ß-Globulin zu finden.

3. Der fehlende Faktor bei zwei hämophilieähnlichen Fällen, welche weder zur Form A noch zur Form A gehören, und bei denen wahrscheinlich der P. T. F.-D- oder ein anderer auch temperaturempfindlicher Faktor fehlt (da eine Hämophilie C ebenfalls mit Wahrscheinlichkeit auszuschließen ist), besteht aus zwei Fraktionen, wie die elektrophoretischen Untersuchungen ergaben. Die eine nimmt bei der Elektrophorese eine Stelle zwischen β- und γ-Globulin und die andere zwischen β- und α-Globulin ein.
A Case of Unusual Obstetric Coagulopathy
Authors: Zilliacus Harry
Published: June 2018

A case of unusual obstetric coagulopathy is described. A woman near term of a normal pregnancy contracted severe damage to muscles and other tissues. The infant, placenta and uterine function remained unimpaired.

Subsequently to the trauma the patient developed transitoric myoglobinuria and three days later after an otherwise normal delivery a severe hemorrhage occured, which was caused by hypofibrinogenemia. A possible fibrinogenolytic part in this condition is discussed.

A lower nephron nephrosis syndrome developed, which was similar to the syndrome in abruptio placentae. It is considered that the hypofibrinogenemia in this case developed on the basis of a defibrination and dissemination of fibrin in the sense of Schneider.
Content of Tissue Activator of Plasminogen in Monkey Tissues
Authors: Roberts H. R , Astrup Tage
Published: June 2018

The content of the tissue activator of plasminogen in various organs from monkey is generally lower than in the corresponding human organs and approaches the concentration in the organs of other animals.
Studien über den lipoiden Aktivator der Blutgerinnung
Authors: Hecht E
Published: June 2018

1. Neben anderen angewandten Methoden wird eine ausführliche Beschreibung unserer Technik des Thrombokinasebildungstestes gegeben.

2. Die lipoiden Aktivatoren aus Aceton-getrocknetem Gehirn von Mensch, Rind, Pferd, Schwein, Kaninchen und Taube wurden vergleichend untersucht.

3. Die lipoiden Aktivatoren zeigen ein identisches Verhalten

a) bezüglich ihres Einflusses auf die Gerinnung sowohl von Hühnerplasma als auch von menschlichem Plasma,

b) bezüglich des negativen Ausfalls der Eiweißreaktionen,

c) hinsichtlich der RF-Werte der papierchromatographisch erhaltenen vier Ninhydrin-positiven Reaktionen und

d) bezüglich ihrer gleichwertigen Leistung, die Blutplättchen im Rahmen des Thrombokinasebildungstestes zu ersetzen.

Die aus Hirnsubstanz erhältlichen lipoiden Aktivatoren scheinen demnach identisch zu sein.

4. Die Aktivitätskurven der aus den gleichen Aceton-getrockneten Hirnsubstanzen stammenden Thrombokinasen mit Hühner- und menschlichem Plasma als Gerinnungssubstrat weichen von den Aktivitätskurven der entsprechenden lipoiden Aktivatoren in spezifischer Weise ab.

5. An Hand orientierender Versuche, welche die Eiweißfreiheit der Hirnthrombokinasen suggerieren, wird erwogen, die unter 4. genannten Beobachtungen u. a. den Unterschieden in der lipoiden Zusammensetzung der Präparate zuzuschreiben.
Über das Vorkommen eines Antiheparinfaktors in Thrombozyten und Geweben)
Authors: Deutsch E , Wawersich E , Franke G
Published: June 2018

Die als Thrombozytenfaktor 4 bezeichnete Antiheparin-Aktivität der Thrombozyten kann auf chemischem Wege von den anderen bekannten Thrombozytenfaktoren abgetrennt werden. Diese Aktivität ist bei — 25° lange stabil, ist hitzelabil, wird durch Ansäuern auf pH 5,0 gefällt und bleibt bei 50% iger Sättigung mit Ammonsulfat in Lösung. Sie ist nicht dialysabel. Es besteht die Möglichkeit, daß die Aktivität einem Eiweißkörper zukommt oder an einen solchen adsorbiert ist.
The blood coagulation mechanisms in thrombocytopenic blood
Authors: Johnson Shirley A. , Caldwell M. June , Monto Raymond W.
Published: June 2018

Thrombocytopenic serum supports a short prothrombin consumption time, however, the same serum contains as little prothrombin as normal serum. The prothrombin consumption test of thrombocytopenic serum can be prolonged by adsorption on BaCO3 or reduced again by the addition of the sodium citrate eluate. The antihemophilic activity of thrombocytopenic blood disappears when the blood clots as in normal blood and autoprothrombin I is present in much smaller amounts than in normal serum. The authors suggest that a new factor, a possible derivative of prothrombin, is responsible for the short prothrombin consumption value in thrombocytopenic blood.
Hämorrhagische Diathese mit Störung mehrerer Teilvorgänge der Blutstillung
Authors: Brockhaus Johannes
Published: June 2018

Es wird eine schwere hämorrhagische Diathese bei einem 4jährigen Jungen beschrieben, die sporadisch aufgetreten ist und schon über 2 Jahre verfolgt wird. Dabei ist die Blutungszeit immer extrem verlängert und ein Gefäßschaden sowie ein Mangel an AHG nachweisbar. Die Krankheit entspricht in Symptomen und Befunden der im Schrifttum als Haemophilia vascularis oder Angiohämophilie bezeichneten Krankheit, welche nach unseren Vorstellungen eine Sonderform der Thrombopathia v. Willebrand-Jürgens sein kann. Sie kommt wie diese als dominant erbliches Leiden vor und tritt auch sporadisch auf. Pathogenetisch lassen sich dabei heute weder die dauernd erhöhte Blutdurchlässigkeit der Gefäße, die zu der erhöhten Blutungsneigung führt, noch die Unberechenbarkeit der Schübe schwer stillbarer Blutungen durch die gerinnungsphysiologische Analyse allein befriedigend erklären. Abschließend werden neuere noch hypothetische Vorstellungen über den Einfluß von Gerinnungsdefekten auf die pathologische Gefäßdurchlässigkeit wiedergegeben und für die Krankheit erwogen.
Haemoglobinaemia and Haemoglobinuria Following the Administration of Neodymium 3-Sulpho-Isonicotinate (Thrombodym)
Authors: Rizza C. R , Shepherd D. M , Walker W
Published: June 2018

Nine of thirteen patients receiving daily intravenous injections of 375 mg. 3-sulpho-isonicotinate for four to eight days developed haemoglobinaemia, accompanied in one case by haemoglobinuria and methaemalbuminaemia. In addition to haemoglobinaemia, a rise in blood cholesterol was observed in rabbits given larger doses.
Endoscopic Ultrasound for the Hepatologist: A Comprehensive Review
Authors: Rimbaş Mihai , Di Maurizio Luca , Rizzatti Gianenrico , Gasbarrini Antonio , Costamagna Guido , Larghi Alberto
Published: June 2018

In the last few years, the diagnostic and therapeutic utilization of endoscopic ultrasound (EUS) for a variety of liver conditions has exponentially grown. We performed a thorough search for all available studies on the performance of diagnostic and therapeutic EUS in the field of hepatology. This article reviews the indication of EUS in the evaluation and treatment of portal hypertension, portal vein pressure measurement, focal liver lesions, and parenchymal liver diseases, and presents all the clinical evidences available so far in this regard. All the review data suggest that EUS is becoming an increasingly important tool in the armamentarium of the hepatologists for the management of certain liver-related conditions. Implementation in the education of the hepatologists of means to become more familiar with both diagnostic and therapeutic capabilities of EUS is warranted.
Bacterial Infections in Acute-on-Chronic Liver Failure
Authors: Yang Lingling , Wu Tianzhou , Li Jiang , Li Jun
Published: June 2018

Acute-on-chronic liver failure (ACLF) is a newly recognized clinical syndrome characterized by preexisting chronic liver disease or cirrhosis with organ failure and high 28-day mortality (50–90%). Bacterial infections (BIs) play pivotal roles in the development and progression of ACLF either as a main precipitating event or a specific complication. The main organisms isolated as triggering ACLF are Gram-positive bacteria, followed by Gram-negative bacteria. Spontaneous bacterial peritonitis, pneumonia, urinary tract infections, and skin infections are prevalent infections that trigger and complicate ACLF. Despite appropriate antibiotic treatment, BIs account for poor ACLF outcomes and lead to a worse clinical course and higher intensive care unit admission and short-term mortality. Early diagnosis and novel nonantibiotic methods are highly important for managing BIs. Thus, this review focuses on the epidemiology, prognosis, and diagnosis of and management strategies for BIs in ACLF patients as well as the relationship between BIs and ACLF.
Unterschiedliche Wachstumsverläufe von Kindern mit Übergewicht im Vergleich zu normalgewichtigen Kindern
Authors: Vogel T. , Kempf E. , Stanik J. , Körner A.
Published: June 2018

Kontext: Körpergröße und Wachstum sind wichtige Parameter der kindlichen Entwicklung, die durch Genetik und Umwelt beeinflusst werden. Ein Umwelteinfluss ist die Ernährung. Bei steigernder, kindlicher Adipositas-Prävalenz kommt der Untersuchung des Zusammenhangs zwischen Wachstum und Übergewicht daher besondere Bedeutung zu.

Design: Analyse anthropmetrischer Daten und IGF-1-Serumspiegel von 7968 Probanden mit 24 561 Messungen zwischen 3–20 Jahren aus verschiedenen Kohorten der Universität Leipzig

Ergebnisse: Übergewichtige Kinder sind bis zur Pubertät größer als schlanke Kinder. Diese Wachstumsunterschiede sind mit einer leicht erhöhten Geburtslänge und präpubertär erhöhten IGF-1-Serumspiegel-SDS assoziiert. Auch die Wachstumsgeschwindigkeit scheint eine Rolle zu spielen: Übergewichtige Kinder haben präpubertär eine höhere Wachstumsgeschwindigkeit als schlanke Kinder. Jedoch ist der pubertätstypische Wachstumsschub trotz normaler IGF-1-Serumspiegel vermindert ausgeprägt. So können die schlanken Kinder die Körpergrößenunterschiede wieder ausgleichen, die sich mit Abschluss der Pubertät nivellieren.
Digitale Brusttomosynthese (DBT) – ein großer Schritt in der Mammografie
Authors: Hondl-Adametz Michaela
Published: June 2018

Die digitale Brusttomosynthese ist ein modernes Verfahren in der bildgebenden Diagnostik zur Früherkennung von Brustkrebs. Die Anhebung der diagnostischen Befundgenauigkeit beruht vor allem auf der Verringerung der Überlagerungseffekte. Immer mehr Hersteller bieten Mammografieanlagen mit Tomosynthesemöglichkeit an. Die Geräte unterscheiden sich in einigen technischen Parametern, in der Bildqualität, dem Handling der Einstelltechnik und der Untersuchungszeit.
Plasma ion implantation enabled bio-functionalization of PEEK improves osteoblastic activity
Authors: Wakelin Edgar A. , Yeo Giselle C. , McKenzie David R. , Bilek Marcela M. M. , Weiss Anthony S.
Published: June 2018

Slow appositional growth of bone in vivo is a major problem associated with polyether ether ketone (PEEK) based orthopaedic implants. Early stage promotion of osteoblast activity, particularly bone nodule formation, would help to improve contact between PEEK implantable materials and the surrounding bone tissue. To improve interactions with bone cells, we explored here the use of plasma immersion ion implantation (PIII) treatment of PEEK to covalently immobilize biomolecules to the surface. In this study, a single step process was used to covalently immobilize tropoelastin on the surface of PIII modified PEEK through reactions with radicals generated by the treatment. Improved bioactivity was observed using the human osteoblast-like cell line, SAOS-2. Cells on surfaces that were PIII-treated or tropoelastin-coated exhibited improved attachment, spreading, proliferation, and bone nodule formation compared to cells on untreated samples. Surfaces that were both PIII-treated and tropoelastin-coated triggered the most favorable osteoblast-like responses. Surface treatment or tropoelastin coating did not alter alkaline phosphatase gene expression and activity of bound cells but did influence the expression of other bone markers including osteocalcin, osteonectin, and collagen I. We conclude that the surface modification of PEEK improves osteoblast interactions, particularly with respect to bone apposition, and enhances the orthopedic utility of PEEK.
Investigation of high-voltage pulse trigger generator based on photo-conductive semiconductor switch
Authors: Chu Xu , Liu Jin-Liang , Wang Lang-Ning , Qiu Yong-Feng
Published: June 2018

The trigger to generate high-voltage pulse is one of the most important parts in a pulsed-power system, especially for the conduction characteristics of the main switch. However, traditional triggers usually have the drawbacks of large structure and worse long-term working stability, which goes against the demands of pulsed-power system miniaturization and stability. In the paper, a pulse trigger using photo-conductive semiconductor switch was developed, which is of small size, stable performance and steep leading edge of the output pulse rise. It is found that the output trigger pulse rise time is 14 ns, and the jitter of 20 shots is 330 ps. Applying the designed pulsed trigger in a field distortion switch and a triggered vacuum switch, experiments show that the switches could be triggered stably with reduced jitter.
A method to eliminate the influence of incident light variations in spectral analysis
Authors: Luo Yongshun , Li Gang , Fu Zhigang , Guan Yang , Zhang Shengzhao , Lin Ling
Published: June 2018

The intensity of the light source and consistency of the spectrum are the most important factors influencing the accuracy in quantitative spectrometric analysis. An efficient “measuring in layer” method was proposed in this paper to limit the influence of inconsistencies in the intensity and spectrum of the light source. In order to verify the effectiveness of this method, a light source with a variable intensity and spectrum was designed according to Planck’s law and Wien’s displacement law. Intra-lipid samples with 12 different concentrations were prepared and divided into modeling sets and prediction sets according to different incident lights and solution concentrations. The spectra of each sample were measured with five different light intensities. The experimental results showed that the proposed method was effective in eliminating the influence caused by incident light changes and was more effective than normalized processing.
Extensive range contraction predicted under climate warming for a gliding mammal in north-eastern Australia
Authors: Handayani Fathimah , Goldingay Ross L. , McHugh Darren , Leslie Nicole
Published: June 2018

We used MaxEnt to model the current distribution of the yellow-bellied glider (Petaurus australis) and to predict the likely shift in the species’ future distribution under climate-warming scenarios in the Wet Tropics (WT) Bioregion in north Queensland and in the South-eastern Queensland (SEQld) Bioregion, which encompasses south-eastern Queensland and north-eastern New South Wales. Bioclimatic layers were used to generate models from 57 independent records in the WT and 428 records in SEQld. The modelled distribution of core habitat under current climate showed a good fit to the data, encompassing 91% and 88% of the records in each area, respectively. Modelling of future warming scenarios suggests that large contractions in distribution could occur in both bioregions. In the WT, 98% of core habitat is predicted to be lost under low warming (1°C increase) and 100% under high warming (2−3°C increase) by 2070. In SEQld, 80% of core habitat is predicted to be lost under low warming and 90% under high warming by 2070. These results suggest that this species is highly vulnerable to climate warming and highlight the importance of focusing conservation efforts at the bioregional scale. There is also a need to identify potential thermal refuges and ensure habitat connectivity.
Genetic analysis of three remnant populations of the rufous hare-wallaby (Lagorchestes hirsutus) in arid Australia
Authors: Eldridge Mark D. B. , Neaves Linda E. , Spencer Peter B. S.
Published: June 2018

The rufous hare-wallaby (Lagorchestes hirsutus) is now extinct in the wild on mainland Australia, but survives in captivity. However, endemic populations persist on Bernier and Dorre Islands, Western Australia. This study aimed to compare the genetic diversity and differentiation amongst three remaining rufous hare-wallaby populations using mitochondrial DNA (mtDNA) (cytochrome b, control region) sequence data and nuclear (microsatellite) markers. Levels of microsatellite diversity were low in both island populations but high in the captive mainland population. Levels of mtDNA diversity were low in all three populations. The mainland and island populations of L. hirsutus were found to be significantly differentiated for both microsatellite and mtDNA data, but the two island populations were significantly differentiated only for the microsatellite data. This pattern of differentiation is not consistent with the recognition of two separate island subspecies, but we recommend that the mainland and island populations be regarded as separate subspecies. The low diversity of the island populations and differentiation between island and mainland populations presents both challenges and opportunities for future management.
Dietary threonine supplementation improves hepatic lipid metabolism of Pekin ducks
Authors: Jiang Y. , Liao X. D. , Xie M. , Tang J. , Qiao S. Y. , Wen Z. G. , Hou S. S.
Published: June 2018

The present study was conducted to evaluate the regulatory role of threonine (Thr) on hepatic lipid metabolism by determining the effects of dietary Thr concentration on lipid deposition and on genes related to lipid expression in the liver of Pekin duck. In total, 240 1-day-old ducklings were randomly allocated according to the average bodyweight to one of five dietary treatments with six replicate cages of eight birds per cage for each treatment. Birds were fed diets with 0.52%, 0.59%, 0.66%, 0.73% and 0.80% Thr (as-fed basis) from 1 to 21 days of age respectively. The results showed that dietary Thr supplementation increased average daily gain (P < 0.0001), average daily feed intake (P < 0.0001) and abdominal fat percentage (P < 0.04), while it decreased feed to gain ratio (P < 0.0001), the hepatic contents of total lipid (P < 0.003) and triglycerides (P < 0.003) of Pekin ducks. However, dietary Thr supplementation had no influence (P > 0.05) on the concentration of hepatic cholesterol, and plasma amino acids and biochemical parameters of Pekin ducks. Moreover, Thr-unsupplemented control diet upregulated (P < 0.05) hepatic gene expression related to lipid uptake (fatty acid-binding protein, apolipoprotein A4, lipoprotein lipase), fatty acid synthesis (sterol regulatory element-binding protein 1c, malic enzyme), fatty acid β-oxidation (peroxisome proliferator-activated receptor α, fatty acyl– coenzyme A (CoA) oxidase), ketogenesis (hydroxymethylglutaryl–CoA synthase 1, and acetyl–CoA synthetase1), responsive genes to amino acid deficiency (general control non-derepressible 2 (GCN2), GCN1, eukaryotic initiation factor 2α, impact RWD domain protein (IMPACT)), and triglyceride transport (apolipoprotein B) of Pekin ducks. In addition, dietary Thr deficiency had no effect on the expression of stearoyl CoA desaturase, fatty acid synthase, and ATP–citrate lyase in the liver of Pekin ducks. It is suggested that dietary Thr supplementation improved hepatic lipid metabolism of Pekin ducks by regulating lipid synthesis, transport and oxidation.
Identification of drought-inducible regulatory factors in Lablab purpureus by a comparative genomic approach
Authors: Wang Biao , Zhao Mingzhe , Yao Luming , Joao V Maldonado dos Santos , Babu Valliyodan , Wu Tianlong , Nguyen Henry T.
Published: June 2018

Physiological indices of two lines of hyacinth bean (Lablab purpureus (L.) Sweet), MEIDOU 2012 and NANHUI 23, were compared during a progressive course of water-withholding treatments. MEIDOU 2012 was shown to be a superior drought-tolerant genotype. A suppressive subtractive hybridisation library was then constructed by using drought-stressed MEIDOU 2012 roots and sequenced to screen for transcripts with differential abundance variations. In total, 2792 unigenes were assembled from 4064 drought-induced expressed sequence tags. Comparative analysis with other legume genomic sequences, including soybean (Glycine max (L.) Merr.), common bean (Phaseolus vulgaris L.) and lucerne (Medicago sativa L.), was performed, from which 338 unigenes associated with root growth and drought response were identified. Among these unigenes, 27 transcription factors were deduced by functional-domain prediction. The transcription levels of a GRAS and a WRKY transcription factor were confirmed to be responding sensitively to water stresses. Additionally, protein–protein interaction (PPI) networks were predicted for all drought-induced root-related unigenes with different stringency levels. A mitogen-activated protein kinase (MAPK4) and an EF-hand calcium-binding protein (CML24) module were pinpointed to be putative ‘master’ signalling hubs in these PPI networks. Detailed examination of these genomic resources would further reveal key regulators of Lablab drought tolerance.
Arthur James McComb 1936–2017
Authors: McComb Jen
Published: June 2018

Professor Arthur McComb conducted pioneer research on the occurrence and mode of action of the plant growth hormones gibberellins for fifteen years. He then applied his experimental skills and physiological knowledge to develop a whole ecosystem approach to the study of aquatic systems. He was passionate in wanting to improve the state of environmental management, based on rational, logical and well-founded biological principles. He and his team focused primarily on the mechanisms controlling plant growth and productivity in aquatic environments, and especially the effects of nutrient enrichment and its consequences, eutrophication. He became a leader in nutrient analysis of water systems, with innovations in how to determine nutrient pathways into waterways and strategies for fixing these issues. This important research has informed the long-term management of several important aquatic systems in Western Australia: the Blackwood River Estuary, the Peel Harvey Estuary, and the protection of seagrasses in Shark Bay, the Swan River and Cockburn Sound. Arthur McComb had a seminal influence on a generation of researchers. Thirty-nine students completed their higher degrees under his supervision and they are spread internationally and throughout Australia in universities, state government departments and consulting firms, confirming his influence on driving our understanding and management of marine, estuarine and freshwater systems.
Vegetation responses to fire history and soil properties in grazed semi-arid tropical savanna
Authors: Lebbink Gabrielle , Fensham Rod , Cowley Robyn
Published: June 2018

A long-term (1993–2016) fire experiment in the grazed semi-arid savanna of the Northern Territory was used to investigate the relative impacts of soil properties and fire history on vegetation composition and diversity in grassland and woodland habitats. Subtle variation in soil texture influenced vegetation composition and abundance independently of fire variables and was generally a more important control on floristic patterns. Total species richness, lifeform richness and the abundance and presence of many individual plant species declined with increasing clay content. Linear mixed effect models with combined habitat data, showed total richness and richness of annual and perennial forbs, annual grasses and legumes increased with more frequent fire. Perennial grass abundance and richness was not influenced by fire. Total and lifeform mean richness did not vary between two and four yearly or early and late burnt treatments. Richness and abundance was generally significantly higher on burnt blocks than unburnt blocks regardless of fire season or interval. These results suggest greater diversity after burning is a result of an increase in ephemeral species. However, the overall influence of fire on floristic patterns is relatively moderate and fire regimes may therefore be manipulated for other management imperatives, such as fauna conservation, carbon sequestration and pastoral productivity without substantial impacts on botanical values in semi-arid tropical savannas.
Kinematic analysis of the shot‐put: A method of assessing the mechanical work of the hand action force
Authors: Landolsi Mounir , Labiadh Lazhar , Zarrouk Fayçal , Maaref Khaled , Ghannouchi Slaheddine , Tabka Zouhair , Lacouture Patrick
Published: June 2018

The aims of this study were to (1) propose a method for evaluating shot‐putters mechanical power, (2) investigate the relationship between mechanical work of hand action force (WHAF), peak power output (PPO) of different limbs and shot‐put performance and (3) show which of these two parameters (WHAF, PPO) were the most appropriate to characterize the explosive abilities of the shot‐putter. Twelve junior right‐handed shot‐putters, practised glide technique shot‐put throwers (personal best = 13.57 ± 1.72 m), participated in this study. Arm and leg force‐velocity tests were performed to measure PPO. Kinematic analysis was conducted during a shot‐putting event in regular conditions to quantify the WHAF at the release moment and shot‐put performance. Significant correlations were found between absolute arm and leg PPO with upper and lower muscle volumes (r = .67; p = .03; r = .76; p = .01; r = .74, p = .01; r = .65, p = .04). Positive relationships were recorded between absolute arm and leg PPO and shot‐put performance (r = .67, p = .02; r = .81, p = .004, respectively). Shot‐put performance was also closely related to the WHAF (r = .93, p = .0001) and release velocity parameter (r = .86, p = .001). The present results confirm that force‐velocity test and WHAF constitute useful tools for assessing mechanical power in throwing. The WHAF could be considered as more suitable than force‐velocity test.
AA9int: SNP interaction pattern search using non-hierarchical additive model set
Authors: Lin Hui-Yi , Huang Po-Yu , Chen Dung-Tsa , Tung Heng-Yuan , Sellers Thomas A , Pow-Sang Julio M , Eeles Rosalind , Easton Doug , Kote-Jarai Zsofia , Amin Al Olama Ali , Benlloch Sara , Muir Kenneth , Giles Graham G , Wiklund Fredrik , Gronberg Henrik , Haiman Christopher A , Schleutker Johanna , Nordestgaard Børge G , Travis Ruth C , Hamdy Freddie , Neal David E , Pashayan Nora , Khaw Kay-Tee , Stanford Janet L , Blot William J , Thibodeau Stephen N , Maier Christiane , Kibel Adam S , Cybulski Cezary , Cannon-Albright Lisa , Brenner Hermann , Kaneva Radka , Batra Jyotsna , Teixeira Manuel R , Pandha Hardev , Lu Yong-Jie ,   The PRACTICAL Consortium, Park Jong Y
Published: June 2018

Motivation

The use of single nucleotide polymorphism (SNP) interactions to predict complex diseases is getting more attention during the past decade, but related statistical methods are still immature. We previously proposed the SNP Interaction Pattern Identifier (SIPI) approach to evaluate 45 SNP interaction patterns/patterns. SIPI is statistically powerful but suffers from a large computation burden. For large-scale studies, it is necessary to use a powerful and computation-efficient method. The objective of this study is to develop an evidence-based mini-version of SIPI as the screening tool or solitary use and to evaluate the impact of inheritance mode and model structure on detecting SNP–SNP interactions.

Results

We tested two candidate approaches: the ‘Five-Full’ and ‘AA9int’ method. The Five-Full approach is composed of the five full interaction models considering three inheritance modes (additive, dominant and recessive). The AA9int approach is composed of nine interaction models by considering non-hierarchical model structure and the additive mode. Our simulation results show that AA9int has similar statistical power compared to SIPI and is superior to the Five-Full approach, and the impact of the non-hierarchical model structure is greater than that of the inheritance mode in detecting SNP–SNP interactions. In summary, it is recommended that AA9int is a powerful tool to be used either alone or as the screening stage of a two-stage approach (AA9int+SIPI) for detecting SNP–SNP interactions in large-scale studies.

Availability and implementation

The ‘AA9int’ and ‘parAA9int’ functions (standard and parallel computing version) are added in the SIPI R package, which is freely available at https://linhuiyi.github.io/LinHY_Software/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Models of cytokine dynamics in the inflammatory response of viral zoonotic infectious diseases
Authors: Zhang Wenjing , Jang Sophia , Jonsson Colleen B , Allen Linda J S
Published: June 2018

Inflammatory responses to an infection from a zoonotic pathogen, such as avian influenza viruses, hantaviruses and some coronaviruses, are distinctly different in their natural reservoir versus human host. While not as well studied in the natural reservoirs, the pro-inflammatory response and viral replication appear controlled and show no obvious pathology. In contrast, infection in humans results in an initial high viral load marked by an aggressive pro-inflammatory response known as a cytokine storm. The key difference in the course of the infection between the reservoir and human host is the inflammatory response. In this investigation, we apply a simple two-component differential equation model for pro-inflammatory and anti-inflammatory responses and a detailed mathematical analysis to identify specific regions in parameter space for single stable endemic equilibrium, bistability or periodic solutions. The extensions of the deterministic model to two stochastic models account for variability in responses seen at the cell (local) or tissue (global) levels. Numerical solutions of the stochastic models exhibit outcomes that are typical of a chronic infection in the natural reservoir or a cytokine storm in human infection. In the chronic infection, occasional flare-ups between high and low responses occur when model parameters are in a region of bistability or periodic solutions. The cytokine storm with a vigorous pro-inflammatory response and less vigorous anti-inflammatory response occurs in the parameter region for a single stable endemic equilibrium with a strong pro-inflammatory response. The results of the model analyses and the simulations are interpreted in terms of the functional role of the cytokines and the inflammatory responses seen in infection of the natural reservoir or of the human host.
Learning predictive models of drug side-effect relationships from distributed representations of literature-derived semantic predications
Authors: Mower Justin , Subramanian Devika , Cohen Trevor
Published: June 2018

Objective

The aim of this work is to leverage relational information extracted from biomedical literature using a novel synthesis of unsupervised pretraining, representational composition, and supervised machine learning for drug safety monitoring.

Methods

Using ≈80 million concept-relationship-concept triples extracted from the literature using the SemRep Natural Language Processing system, distributed vector representations (embeddings) were generated for concepts as functions of their relationships utilizing two unsupervised representational approaches. Embeddings for drugs and side effects of interest from two widely used reference standards were then composed to generate embeddings of drug/side-effect pairs, which were used as input for supervised machine learning. This methodology was developed and evaluated using cross-validation strategies and compared to contemporary approaches. To qualitatively assess generalization, models trained on the Observational Medical Outcomes Partnership (OMOP) drug/side-effect reference set were evaluated against a list of ≈1100 drugs from an online database.

Results

The employed method improved performance over previous approaches. Cross-validation results advance the state of the art (AUC 0.96; F1 0.90 and AUC 0.95; F1 0.84 across the two sets), outperforming methods utilizing literature and/or spontaneous reporting system data. Examination of predictions for unseen drug/side-effect pairs indicates the ability of these methods to generalize, with over tenfold label support enrichment in the top 100 predictions versus the bottom 100 predictions.

Discussion and Conclusion

Our methods can assist the pharmacovigilance process using information from the biomedical literature. Unsupervised pretraining generates a rich relationship-based representational foundation for machine learning techniques to classify drugs in the context of a putative side effect, given known examples.
Monetary diet cost is positively associated with diet quality and obesity: an analysis of school-aged children in Southwest China
Authors: Zhang Xiao , Gong Yunhui , Jia Peng , Zhang Jieyi , Xue Hongmei , Quan Liming , Tian Guo , Xiong Jingyuan , Zhang Lishi , Wang Yu , Zhang Lin , Cheng Guo
Published: June 2018

Background

Little is known about the relationships between diet cost, dietary intake and obesity in Chinese populations. This study explored how diet cost was related to diet quality and obesity among school-aged children in Southwest China.

Methods

Data from a cross-sectional study was analysed. Diet cost was estimated based on dietary intake assessed with 24-h dietary recalls and retail food prices. Diet quality was measured using the Chinese Children Dietary Index. Body height, weight, waist circumference and skinfold thicknesses were measured, and their body mass index standard deviation score (BMISDS), waist-to-height ratio (WHtR), fat mass index (FMI) and fat-free mass index (FFMI) were calculated. Multivariate regression models were used to explore the relevance of diet cost to diet quality and obesity.

Results

After adjustment for potential confounders, a positive association was observed between diet quality and energy-adjusted diet cost (β = 0.143, 95% confidence interval, CI: 0.014–0.285, Pfor-trend = 0.0006). Energy-adjusted diet cost also showed a positive association with FMI (β = 0.0354, 95% CI: 0.0001–0.0709, Pfor-trend = 0.01), BMISDS (β = 0.0200, 95% CI: 0.0006–0.0394, Pfor-trend = 0.002) and WHtR (β = 0.0010, 95% CI: 0.0003–0.0017, Pfor-trend = 0.02).

Conclusions

Energy-adjusted diet cost was independently and positively associated with diet quality and obesity among Chinese school-aged children.
Relationships among quarter milk leukocyte proportions and cow and quarter-level variables under different intramammary infection statuses
Authors: Paudyal Sushil , Pena Gustavo , Melendez Pedro , Roman-Muniz Ivette Noa , Pinedo Pablo J
Published: June 2018

The use of milk leukocyte differential (MLD) test has been proposed as a complement to somatic cell count (SCC) to assess the presence and the severity of intramammary infection. However, detailed information regarding the behavior of MLD under different physiological or pathological stages of the cow is nonexistent. The objective was to analyze the association between milk leukocyte proportions provided by a commercial automated MLD test and multiple cow and quarter-level variables. The study population consisted of 104 Holstein cows (32 primiparous and 72 multiparous) in one farm. Cows were categorized by days in milk as early (<50 DIM; n=29), middle (50–250 DIM; n=25), and late lactation (>250 DIM; n = 50). Milk from 416 quarters was collected and analyzed for lymphocytes (LYM), neutrophils (NEU), and macrophages (MAC) counts using an automated milk fluorescence microscopy system. Concurrently, a sterile composite milk sample was collected from each cow for pathogen identification through microbiological culture. Culture results were classified as no growth (NOG), gram-negative (GN), gram-positive (GP), or other (OTH). Milk leukocyte proportions varied depending on the level of total leukocyte counts (TLC; P < 0.001). Similarly, leukocyte ratios (NEU:LYM, NEU:MAC, and phagocyte:LYM) were different for multiple TLC categories (P < 0.05). There was no association between parity number and MLD; however, cows in early lactation had the greatest proportions of NEU and LYM. Leukocyte ratios varied depending on parity number and stage of lactation. Cows in the medium milk-yield category had the smallest proportions of NEU and LYM, and there was significant variation in leukocyte ratios, depending on the level of milk yield. In healthy quarters, MLD were not associated with quarter position; however, the NEU:MAC ratio was greater in rear quarters than in front quarters. In quarters with TLC >100,000, NEU% was greater in rear quarters than in front quarters (P = 0.03). For quarters with pathogen growth, TLC was greatest for GN followed by OTH and GP (P < 0.001). Milk LD depended on the isolated pathogen group, although the magnitudes of the differences were small. Although the changes in the proportions of leukocytes in milk were associated with categories of TLC, levels of milk yield, and mastitis-causing pathogen groups, the deviations were small in magnitude. Additional research is necessary to determine the potential applications for this methodology.
Heat-Shock Proteins MoSsb1, MoSsz1, and MoZuo1 Attenuate MoMkk1-Mediated Cell-Wall Integrity Signaling and Are Important for Growth and Pathogenicity of Magnaporthe oryzae
Authors: Yang Jie , Liu Muxing , Liu Xinyu , Yin Ziyi , Sun Yi , Zhang Haifeng , Zheng Xiaobo , Wang Ping , Zhang Zhengguang
Published: June 2018

The mitogen-activated protein kinase (MAPK) MoMkk1 governs the cell-wall integrity (CWI) pathway in rice blast fungus Magnaporthe oryzae. To understand the underlying mechanism, we have identified MoSsb1 as one of the MoMkk1-interacting proteins. MoSsb1 is a stress-seventy subfamily B (Ssb) protein homolog, sharing high amino acid sequence homology with the 70-kDa heat shock proteins (Hsp70s). Hsp70 are a family of conserved and ubiquitously expressed chaperones that regulate protein biogenesis by promoting protein folding, preventing protein aggregation, and controlling protein degradation. We found that MoSsb1 regulates the synthesis of nascent polypeptide chains and this regulation is achieved by being in complex with other members of Hsp70s MoSsz1 and 40-kDa Hsp40 MoZuo1. MoSsb1 is important for the growth, conidiation, and full virulence of the blast fungus and this role is also shared by MoSsz1 and MoZuo1. Importantly, MoSsb1, MoSsz1, and MoZuo1 are all involved in the regulation of the CWI MAPK pathway by modulating MoMkk1 biosynthesis. Our studies reveal novel insights into how MoSsb1, MoSsz1, and MoZuo1 affect CWI signaling that is involved in regulating growth, differentiation, and virulence of M. oryzae and highlight the conserved functional mechanisms of heat-shock proteins in pathogenic fungi.
Variation in Disease Severity Caused by Phytophthora cinnamomi, P. plurivora, and Pythium cryptoirregulare on Two Rhododendron Cultivars
Authors: Weiland Jerry E. , Scagel Carolyn F. , Grünwald Niklaus J. , Davis E. Anne , Beck Bryan R. , Fieland Val J.
Published: June 2018

Rhododendrons are an important crop in the ornamental nursery industry, but are prone to Phytophthora root rot. Phytophthora root rot is a continuing issue on rhododendrons despite decades of research. Several Phytophthora species are known to cause root rot, but most research has focused on P. cinnamomi, and comparative information on pathogenicity is limited for other commonly encountered oomycetes, including Phytophthora plurivora and Pythium cryptoirregulare. In this study, three isolates each of P. cinnamomi, P. plurivora, and Py. cryptoirregulare were used to inoculate rhododendron cultivars Cunningham’s White and Yaku Princess at two different inoculum levels. All three species caused disease, especially at the higher inoculum level. P. cinnamomi and P. plurivora were the most aggressive pathogens, causing severe root rot, whereas Py. cryptoirregulare was a weak pathogen that only caused mild disease. Within each pathogen species, isolate had no influence on disease. Both P. cinnamomi and P. plurivora caused more severe disease on Cunningham’s White than on Yaku Princess, suggesting that the relative resistance and susceptibility among rhododendron cultivars might be similar for both pathogens. Reisolation of P. cinnamomi and P. plurivora was also greater from plants exhibiting aboveground symptoms of wilting and plant death and belowground symptoms of root rot than from those without symptoms. Results show that both P. cinnamomi and P. plurivora, but not Py. cryptoirregulare, are important pathogens causing severe root rot in rhododendron. This study establishes the risks for disease resulting from low and high levels of inoculum for each pathogen. Further research is needed to evaluate longer term risks associated with low inoculum levels on rhododendron health and to explore whether differences among pathogen species affect disease control.
Resistance of Sclerotinia homoeocarpa Field Isolates to Succinate Dehydrogenase Inhibitor Fungicides
Authors: Popko James T. , Sang Hyunkyu , Lee Jaemin , Yamada Toshihiko , Hoshino Yoichiro , Jung Geunhwa
Published: June 2018

Sclerotinia homoeocarpa isolates were collected from golf courses in Japan and the United States (2016–2017). Japan isolates were collected during a monitoring study and the U.S. isolates were collected due to field failure. Five succinate dehydrogenase inhibitor (SDHI) active ingredients (boscalid, fluopyram, fluxapyroxad, isofetamid, and penthiopyrad) were examined using in vitro sensitivity assays to determine cross-resistance. Sequence analysis revealed a point mutation leading to an amino acid substitution (H267Y) and a silent mutation (CTT to CTC) at codon 181 in the SdhB subunit gene. Isolates with the B-H267Y (n = 10) mutation were resistant to boscalid and penthiopyrad and had increased sensitivity to fluopyram. SdhB silent mutation 181C>T isolates (n = 2) were resistant to boscalid, isofetamid, and penthiopyrad. Sequence analysis revealed 3 mutations leading to an amino acid substitution (G91R, n = 5; G150R, n = 1; G159W, n = 1) in the SdhC subunit gene. Isolates harboring the SdhC (G91R or G150R) mutations were resistant to boscalid, fluxapyroxad, isofetamid, and penthiopyrad. A genetic transformation system was used to generate mutants from a SDHI sensitive isolate to confirm the B-H267Y and C-G91R mutations were direct determinants of SDHI resistance and associated with in vitro sensitivity assay results.
Development of Molecular Methods to Detect Macrophomina phaseolina from Strawberry Plants and Soil
Authors: Burkhardt Alyssa , Ramon Marina L. , Smith Brett , Koike Steven T. , Martin Frank
Published: June 2018

Macrophomina phaseolina is a broad-host-range fungus that shows some degree of host preference on strawberry, and causes symptoms that include crown rot and root rot. Recently, this pathogen has affected strawberry production as fumigation practices have changed, leaving many growers in California and around the world in need of accurate, rapid diagnostic tools for M. phaseolina in soil and infected plants. This study uses next-generation sequencing and comparative genomics to identify a locus that is unique to isolates within a main genotype shared by a majority of isolates that infect strawberry. This locus was used to develop a quantitative single-tube nested TaqMan polymerase chain reaction assay which is able to quantify as little as 2 to 3 microsclerotia/g of soil with 100% genotype specificity. An isothermal assay using recombinase polymerase amplification was developed from the same locus and has been validated on over 200 infected strawberry plants with a diagnostic sensitivity of 93% and a diagnostic specificity of 99%. Together, this work demonstrates the value of using new approaches to identify loci for detection and provides valuable diagnostic tools that can be used to monitor soil and strawberry plant samples for M. phaseolina.
Interventions to Improve the Breaking of Bad or Difficult News by Physicians, Medical Students, and Interns/Residents: A Systematic Review and Meta-Analysis
Authors: Johnson Judith , Panagioti Maria
Published: June 2018

Purpose

To assess the effectiveness of news delivery interventions to improve observer-rated skills, physician confidence, and patient-reported depression/anxiety.

Method

MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Register of Controlled Trials databases were searched from inception to September 5, 2016 (updated February 2017). Eligible studies included randomized controlled trials (RCTs), non-RCTs, and controlled before–after studies of interventions to improve the communication of bad or difficult news by physicians, medical students, and residents/interns. The EPOC risk of bias tool was used to conduct a risk of bias assessment. Main and secondary meta-analyses examined the effectiveness of the identified interventions for improving observer-rated news delivery skills and improving physician confidence in delivering news and patient-reported depression/anxiety, respectively.

Results

Seventeen studies were included in the systematic review and meta-analysis, including 19 independent comparisons on 1,322 participants and 9 independent comparisons on 985 participants for the main and secondary (physician confidence) analyses (mean [SD] age = 35 [7] years; 46% male), respectively. Interventions were associated with large, significant improvements in observer-rated news delivery skills (19 comparisons: standardized mean difference [SMD] = 0.74; 95% CI = 0.47–1.01) and moderate, significant improvements in physician confidence (9 comparisons: SMD = 0.60; 95% CI = 0.26–0.95). One study reported intervention effects on patient-reported depression/anxiety. The risk of bias findings did not influence the significance of the results.

Conclusions

Interventions are effective for improving news delivery and physician confidence. Further research is needed to test the impact of interventions on patient outcomes and determine optimal components and length.