Summary
Porcine pleuropneumonia, caused by the bacterial porcine respiratory tract pathogen Actinobacillus pleuropneumoniae, leads to high economic losses in affected swine herds in most countries of ...the world. Pigs affected by peracute and acute disease suffer from severe respiratory distress with high lethality. The agent was first described in 1957 and, since then, knowledge about the pathogen itself, and its interactions with the host, has increased continuously. This is, in part, due to the fact that experimental infections can be studied in the natural host. However, the fact that most commercial pigs are colonized by this pathogen has hampered the applicability of knowledge gained under experimental conditions. In addition, several factors are involved in development of disease, and these have often been studied individually. In a DISCONTOOLS initiative, members from science, industry and clinics exchanged their expertise and empirical observations and identified the major gaps in knowledge. This review sums up published results and expert opinions, within the fields of pathogenesis, epidemiology, transmission, immune response to infection, as well as the main means of prevention, detection and control. The gaps that still remain to be filled are highlighted, and present as well as future challenges in the control of this disease are addressed.
Patients with advanced systemic mastocytosis (SM) (e.g. aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN) and mast cell leukemia (MCL)) have limited treatment options and ...exhibit reduced survival. Midostaurin is an oral multikinase inhibitor that inhibits D816V-mutated KIT, a primary driver of SM pathogenesis. We conducted a phase II trial of midostaurin 100 mg twice daily, administered as 28-day cycles, in 26 patients (ASM, n=3; SM-AHN, n= 17; MCL, n=6) with at least one sign of organ damage. During the first 12 cycles, the overall response rate was 69% (major/partial response: 50/19%) with clinical benefit in all advanced SM variants. With ongoing therapy, 2 patients achieved a complete remission of their SM. Midostaurin produced a ⩾50% reduction in bone marrow mast cell burden and serum tryptase level in 68% and 46% of patients, respectively. Median overall survival for the entire cohort was 40 months, and 18.5 months for MCL patients. Low-grade gastrointestinal side effects were common and manageable with antiemetics. The most frequent grade 3/4 nonhematologic and hematologic toxicities were asymptomatic hyperlipasemia (15%) and anemia (12%). With median follow-up of 10 years, no unexpected toxicities emerged. These data establish the durable activity and tolerability of midostaurin in advanced SM.
Dropwise condensation of water vapor from a naturally cooling, hot water reservoir onto a hydrophobic polymer film and a silanized glass slide was studied by direct observation and simulations. The ...observed drop growth kinetics suggests that smallest drops grow principally by the diffusion of water adsorbed on the substrate to the drop perimeter, while drops larger than about 50 μm in diameter grow principally by direct deposition from the vapor onto the drop surface. Drop coalescence plays a critical role in determining the drop-size distribution and stimulates the nucleation of new, small drops on the substrates. Simulations of drop growth incorporating these growth mechanisms provide a good description of the observed drop-size distribution. Because of the large role played by coalescence, details of individual drop growth make little difference to the final drop-size distribution. The rate of condensation per unit substrate area is especially high for the smallest drops and may help account for the high heat transfer rates associated with dropwise condensation relative to filmwise condensation in heat exchange applications.
Previous studies provide evidence for an association between modifications of the gut microbiota in early life and the development of food allergies. We studied the faecal microbiota composition (16S ...rRNA gene amplicon sequencing) and faecal microbiome functionality (metaproteomics) in a cohort of 40 infants diagnosed with cow's milk allergy (CMA) when entering the study. Some of the infants showed outgrowth of CMA after 12 months, while others did not. Faecal microbiota composition of infants was analysed directly after CMA diagnosis (baseline) as well as 6 and 12 months after entering the study. The aim was to gain insight on gut microbiome parameters in relation to outgrowth of CMA. The results of this study show that microbiome differences related to outgrowth of CMA can be mainly identified at the taxonomic level of the 16S rRNA gene, and to a lesser extent at the protein-based microbial taxonomy and functional protein level. At the 16S rRNA gene level outgrowth of CMA is characterized by lower relative abundance of Lachnospiraceae at baseline and lower Bacteroidaceae at visit 12 months.
Neutral particle detection in high-background environments is greatly aided by the ability to easily load 6Li into liquid scintillators. We describe a readily available and inexpensive liquid ...scintillation cocktail stably loaded with a Li mass fraction up to 1%. Compositions that give thermodynamically stable microemulsions (reverse-micellar systems) were explored, using a Compton spectrum quenching technique to distinguish these from unstable emulsions. Scintillation light yield and transmittance were characterized. Pulse shape discrimination (PSD) was measured using a 252Cf source, showing that electron-like and proton-like recoil events are well-resolved even for Li loading up to 1%, providing a means of background suppression in neutron/neutrino detectors. While samples in this work were prepared with natLi (7.59% 6Li), the neutron capture peak was clearly visible in the PSD spectrum; this implies that while extremely high capture efficiency could be achieved with 6Li-enriched material, a very inexpensive neutron-sensitive detector can be prepared with natLi.
Actinobacillus pleuropneumoniae is a Gram-negative bacterium belonging to the Pasteurellaceae family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing ...important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of A. pleuropneumoniae, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by A. pleuropneumoniae serotype 1. Well-characterized mutants were used: an O-antigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-N-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of pgaA, cpxR, and cpxA mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of A. pleuropneumoniae to form a biofilm, and this is associated with the reduced expression and production of PGA.
The disappearance of reactor
ν
¯
e
observed by the Daya Bay experiment is examined in the framework of a model in which the neutrino is described by a wave packet with a relative intrinsic momentum ...dispersion
σ
rel
. Three pairs of nuclear reactors and eight antineutrino detectors, each with good energy resolution, distributed among three experimental halls, supply a high-statistics sample of
ν
¯
e
acquired at nine different baselines. This provides a unique platform to test the effects which arise from the wave packet treatment of neutrino oscillation. The modified survival probability formula was used to fit Daya Bay data, providing the first experimental limits:
2.38
×
10
-
17
<
σ
rel
<
0.23
. Treating the dimensions of the reactor cores and detectors as constraints, the limits are improved:
10
-
14
≲
σ
rel
<
0.23
, and an upper limit of
σ
rel
<
0.20
(which corresponds to
σ
x
≳
10
-
11
cm
) is obtained. All limits correspond to a 95% C.L. Furthermore, the effect due to the wave packet nature of neutrino oscillation is found to be insignificant for reactor antineutrinos detected by the Daya Bay experiment thus ensuring an unbiased measurement of the oscillation parameters
sin
2
2
θ
13
and
Δ
m
32
2
within the plane wave model.
Tolerance development is an important clinical outcome for infants with cow’s milk allergy.
This multicenter, prospective, randomized, double-blind, controlled clinical study (NTR3725) evaluated ...tolerance development to cow’s milk (CM) and safety of an amino acid–based formula (AAF) including synbiotics (AAF-S) comprising prebiotic oligosaccharides (oligofructose, inulin) and probiotic Bifidobacterium breve M-16V in infants with confirmed IgE-mediated CM allergy.
Subjects aged ≤13 months with IgE-mediated CM allergy were randomized to receive AAF-S (n = 80) or AAF (n = 89) for 12 months. Stratification was based on CM skin prick test wheal size and study site. After 12 and 24 months, CM tolerance was evaluated by double-blind, placebo-controlled food challenge. A logistic regression model used the all-subjects randomized data set.
At baseline, mean ± SD age was 9.36 ± 2.53 months. At 12 and 24 months, respectively, 49% and 62% of subjects were CM tolerant (AAF-S 45% and 64%; AAF 52% and 59%), and not differ significantly between groups. During the 12-month intervention, the number of subjects reporting at least 1 adverse event did not significantly differ between groups; however, fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P = .036).
After 12 and 24 months, CM tolerance was not different between groups and was in line with natural outgrowth. Results suggest that during the intervention, fewer subjects receiving AAF-S required hospitalization due to infections.
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