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The idiopathic hypereosinophilic syndrome (HES) comprises a heterogenous group of disorders characterized by marked blood eosinophilia with eosinophilia-associated organ damage. Eight patients with a median age at diagnosis of 42 years (range 19-67) received imatinib mesylate (IM) for FIP1L1-PDGFRα-negative HES resistant to previous conventional treatment. Median number of prior therapies was 3 (range 2-4). Median time from diagnosis to IM initiation was 112 months (range 2-293). Four patients were treated daily with 100 mg IM, whereas the remaining four patients were treated daily with 400 mg IM. Four male patients (50%) achieved complete haematologic response (CHR) after median of 7 days (range 3-150) using 100 mg daily IM (n = 2) and 400 mg (n = 2). Median duration of IM treatment for IM responders was 18 months (range 2-88). No adverse events were reported throughout the treatment duration. Two patients maintained CHR while on 100 mg weekly IM. Four patients (2 men and 2 women) failed IM treatment. Median duration of IM for non-responding patients was 3 weeks (range 3-12). Non-responding HES patients were significantly older and had lower percentage of blood eosinophilia when compared with IM responders. Our results suggest that IM, even at lower than conventional doses, may induce and maintain long-term remission for FIP1L1-PDGFRα-negative HES. [ABSTRACT FROM AUTHOR]

Our goal is to state and prove the almost sure central limit theorem for maxima (Mn) of X1, X2, ..., Xn, n ∈ ℕ, where (Xi) forms a stochastic process of identically distributed r.v.’s of the continuous type, such that, for any fixed n, the family of r.v.’s (X1, ...,Xn) has the Archimedean copula CΨ.

The territoriality of young, wild-type European rabbits, Oryctolagus cuniculus was studied in the laboratory. The experimental procedure was to introduce a strange animal into the pen (‘home’) of another rabbit and to record the occurrence of the following forms of behaviour: approach, sniffing, following and chasing; aggression. Altogether 290 rabbits of the following age classes were used—16 to 30, 31 to 60, 61 to 90, 91 to 120 days old, and adult females and males. The young rabbits were members of 62 separate litters. Thirty tests were carried out for each of 21 age-class combinations giving a total of 630 separate tests each lasting 10 minutes. The data collected were subjected to statistically analysis using a multivariate parametric approach to paired comparisons. The multiple discriminant analysis was used. The results indicated the preparedness of even the youngest rabbits to defend their own territory and the inhibiting effect of strange territory on all rabbits, except the 61–90-day-old subjects referred to as adolescents. The adolescents displayed aggression to younger as well as older rabbits. Within their own age group even a few days seniority of the introduced individual leveled the intensity of aggression of contestants. This behavioural characteristic was not present in the oldest age class (91–121 days old). The results are discussed in relation to information on the behaviour of free-living rabbits. The innate nature of territoriality of the species is emphasized. [ABSTRACT FROM AUTHOR]

Examines the population dynamics and habitat preferences of the dusky rat, Rattus colletti, in the seasonal wetlands of the South Alligator River in Australia. Details on the flexible life history strategy and movement patterns of R. colletti; Influence of the harsh wet-dry seasonality on abundance, reproduction and movement patterns; Analysis of variance between vegetation types and years.

Examines the impact of water buffalo on the monsoon forest ecosystem in Kakadu National Park. Calculation of the sum of the distances to important features of human activity; Features of human activity; Examination of monsoon forest sites by simple linear regression.

Discusses the survey on the hypothetical correlations between temporal and spatial patterning in Landsat data and temporal and spatial heterogeneity, required by persistent small populations of animals vulnerable to extinction. Association of vulnerable animals with gradual gradients in multi-temporal texture transforms of Landsat imagery; Analysis of the link between potential pest species and sites without fauna with textureless areas and with abrupt boundaries.

This article focuses on a study related to the joint use of habitat by red kangaroos and shorthorn cattle in arid central Australia. The distribution of cattle and red kangaroos among the major communities of a 170 square km paddock in central Australia was determined from 108 and 82 air surveys respectively over a four and a half year period. The utilization of particular habitats by two or more species of grazing herbivores may result in competition between the two species for the available forage resource.

Cylindrocladium quinqueseptatum is a pathogen on a wide range of hosts. It affects at least 20 species of eucalypts and is an important causal agent of leaf blight of Eucalyptus camaldulensis in central andsouthern Vietnam. Results from previous studies and observations of broadscale infection patterns in mainland South East Asia were used to derive simple rules (i.e. mean minimum temperature of coldest month16 deg. C and mean annual precipitation 1400 mm) to identify locations which are likely to have a high risk of C. quinqueseptatum leaf blight (CqLB). Climatic mapping programs, which include interpolated climatic data estimated for numerous locations, were used to map these high risk areas in Africa, Australia and Latin America as well as in South East Asia. The predicted high-risk areas included several regions where CqLB has already been reported and the maps generated suggested other areas which may be at risk under present climatic conditions given the presence of C. quinqueseptatum and susceptible hosts. Some simple climate change scenarios were also used to suggest areas in mainland South East Asia which may become vulnerable to CqLB over thenext 50 years. It is concluded that climatic mapping programs can assist the broadscale evaluation of risk of CqLB infections, although it is recognised that more detailed models and survey information are also needed. [ABSTRACT FROM AUTHOR]

Dothistroma needle blight is a serious foliar disease in Australian Pinus radiata plantations causing defoliation, decreased productivity and, in extreme cases, tree death. Conventional methods of monitoring forest health such as aerial survey and ground assessments are labor intensive, time consuming, and subjective. Remote sensing provides a synoptic view of the canopy and can indicate areas affected by damaging agents such as pests and pathogens. Hyperspectral airborne remote sensing imagery (CASI-2) was acquired over pine stands in southern New South Wales, Australia which had been ground assessed and ranked on an individual tree basis, according to the extent of Dothistroma needle blight. A series of spectral indices were tested using two different approaches for extracting crown-scale reflectance measurements and relating these to ground-based estimates of severity. Dothistroma needle blight is most severe in the lower crown and statistically significant relationships were found between crown reflectance values and ground estimates using a 'halo' approach (which ignored each tree crown's brightest central pixels). Independent accuracy assessment of the method indicated that the technique could successfully detect three levels of Dothistroma needle blight infection with an accuracy of over 70%. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10 -9 ) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46 , IKBKE , PARK2 , ULK4 , ATG5 , and CDKN2A associated with MM risk ( p = 4.47 × 10 -4 -5.79 × 10 -14 ). Mechanistically, we found that the ULK4 rs6599175 SNP correlated with circulating concentrations of vitamin D3 ( p = 4.0 × 10 -4 ), whereas the IKBKE rs17433804 SNP correlated with the number of transitional CD24 + CD38 + B cells ( p = 4.8 × 10 -4 ) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 ( p = 3.6 × 10 -4 ). We also found that the CD46 rs1142469 SNP correlated with numbers of CD19 + B cells, CD19 + CD3 - B cells, CD5 + IgD - cells, IgM - cells, IgD - IgM - cells, and CD4 - CD8 - PBMCs ( p = 4.9 × 10 -4 -8.6 × 10 -4 ) and circulating concentrations of interleukin (IL)-20 ( p = 0.00082). Finally, we observed that the CDKN2A rs2811710 SNP correlated with levels of CD4 + EMCD45RO + CD27 - cells ( p = 9.3 × 10 -4 ). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3 - , MCP-2 - , and IL20-dependent pathways.

Introduction: United Kingdom pharmacy students need to efficiently navigate the British National Formulary (BNF), a standard medicines reference source. "Pharmacy Challenge" is a web-based prototype game based on the BNF. This research aimed to evaluate the game in terms of design, content, and impact on students' performance and confidence., Methods: Evaluation was comprised of three phases: implementation, perception, and impact. Game design and evaluation methods were modelled using adapted elements of the Relevance Embedding Translation Adaption Immersion and Naturalisation framework. Qualitative and quantitative questionnaires were utilised to assess students' perceptions of the game and its role in their education and to evaluate changes in confidence and performance after playing the game. Quizzes were developed to determine changes in performance., Results: The questionnaire evaluation (n = 152) found students' confidence increased significantly (p < .05) in speed of using, knowledge of BNF sections, extracting information, and knowing where to look for the answer. Most students (88%) felt they had learnt something new and 86% felt that it reinforced their learning. A significant (p < .05) increase in pre- and post- BNF quiz marks was observed., Conclusions: Statistically significant improvement in students' perceived confidence was noted. The study identified design elements such as the need for a simple interface to encourage engagement. The prototype has undergone a design transformation based on the feedback provided and is now released under the name "DOSE" with a bank of 300 questions, improved graphics, a leadership board, and medals., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/aim: To study the long-term clinical efficacy and tolerability of ibrutinib monotherapy in real-world relapsed and refractory chronic lymphocytic leukemia (RR-CLL) patients outside clinical trials., Patients and Methods: Clinical data of 171 RR-CLL patients treated with ibrutinib were collected within the observational study of the Polish Adult Leukemia Study Group., Results: Median patient age was 64 years. Patients were pretreated with 3 (1-10) median lines of therapy, while 42 (24.6%) had 17p deletion. The median observation time was 40 months (range=1-59 months), while median ibrutinib monotherapy reached 37.5 months (range=0.4-59.2 months). Response was noted in 132 (77.2%) patients. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 61.1% (95%CI=49.3-70.9%) and 56.8% (95%CI=45.6-66.6%), respectively. At the time of analysis 97 (56.7%) remained under ibrutinib monotherapy., Conclusion: Ibrutinib is clinically effective and tolerable as a monotherapy in real-world RR-CLL patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Radiofrequency electromagnetic fields (RF-EMF) are a basic requirement of modern wireless communication technology. Statutory thresholds of RF-EMF are established to limit relevant additional heat supply in human tissue. Nevertheless, to date, questions concerning nonthermal biological effects have yet to be fully addressed. New versions of microarrays (8 × 60K v2) provide a higher resolution of whole genome gene expression to display adaptive processes in cells after irradiation. In this ex vivo/ in vitro study, we irradiated peripheral blood cells from five donors with a continuous wave of 900 MHz RF-EMF for 0, 30, 60 and 90 min. Gene expression changes ( P ≤ 0.05 and ≥twofold differences above or below the room temperature control exposed samples) were evaluated with microarray analysis. The results were compared with data from room temperature + 2°C samples. Verification of microarray results was performed using bioinformatic analyses and qRT-PCR. We registered a lack of an EMF-specific gene expression response after applying the false discovery rate adjustment (FDR), using a high-stringency approach. Low-stringency analysis revealed 483 statistically significant deregulated transcripts in all RF-EMF groups relative to the room temperature exposed samples without an association with their corresponding room temperature + 2°C controls. Nevertheless, these transcripts must be regarded as statistical artefacts due to the absence of a targeted biological response, including enrichment and network analyses administered to microarray expressed gene subset profiles. Correspondingly, 14 most promising candidate transcripts examined by qRT-PCR displayed an absence of correlation with respect to the microarray results. In conclusion, these findings indicate that 900 MHz EMF exposure establishing an average specific absorption rate of 9.3 W/kg to whole blood cells is insufficient to induce nonthermal effects in gene expression during short-time exposure up to 90 min.

Cylindrocladium quinqueseptatum is a pathogen on a wide range of hosts. It affects at least 20 species of eucalypts and is an important causal agent of leaf blight of Eucalyptus camaldulensis in central and southern Vietnam. Results from previous studies and observations of broadscale infection patterns in mainland South East Asia were used to derive simple rules (i.e. mean minimum temperature of coldest month > or =16 degrees C and mean annual precipitation > or =1400 mm) to identify locations which are likely to have a high risk of C. quinqueseptatum leaf blight (CqLB). Climatic mapping programs, which include interpolated climatic data estimated for numerous locations, were used to map these high risk areas in Africa, Australia and Latin America as well as in South East Asia. The predicted high-risk areas included several regions where CqLB has already been reported and the maps generated suggested other areas which may be at risk under present climatic conditions given the presence of C. quinqueseptatum and susceptible hosts. Some simple climate change scenarios were also used to suggest areas in mainland South East Asia which may become vulnerable to CqLB over the next 50 years. It is concluded that climatic mapping programs can assist the broadscale evaluation of risk of CqLB infections, although it is recognised that more detailed models and survey information are also needed.

It is generally recognized that ovarian cancer tends to remain intraabdominal even in advanced cases and that dissemination is usually by invasion of adjacent viscera, diffuse intraperitoneal implantation, and metastatic involvement of aortic and pelvic lymph nodes. Primary ovarian lymphatic drainage occurs via the infundibulopelvic ligament to the paraaortic nodes. The presence of an ovarian tumor extending into adjacent pelvic viscera may allow direct lymphatic continuity with inguinal, external, and common iliac lymph nodes. In the absence of such extension it is traditionally believed that the drainage via the infundibulopelvics is so important that only with its blockage, presumably by tumor emboli, can retrograde drainage to pelvic and inguinal nodes occur. We report a case of a patient presenting with a large metastatic inguinal lymph node from a primary epithelial ovarian cancer without evidence of disseminated intraabdominal disease or gross evidence of pelvic or paraaortic lymph node involvement.