Background While both the AAAAI/ACAAI and the EAACI/GA.sup.2LEN/EuroGuiDerm/APAAACI guidelines recommend starting cyclosporine for patients with chronic urticaria who have had an inadequate response ...to omalizumab, many clinicians are hesitant to initiate cyclosporine due to paucity of clinical data. The objective of this study was to report real-life clinical outcomes in adult patients with chronic urticaria who had an inadequate response to omalizumab and were switched from omalizumab to cyclosporine. Medical records of adult patients with chronic urticaria who had an inadequate response with omalizumab and were later treated with cyclosporine were reviewed retrospectively. Data pertaining to treatment method, clinical response, and adverse effects were recorded. Results/presentation of cases Five patients with omalizumab-refractory chronic urticaria, three of whom also had angioedema and one with an inducible urticaria, were treated with low doses of oral cyclosporine (1-3 mg/kg/d). Four of five patients in this case series had complete resolution of symptoms with oral cyclosporine, while continuing other standard therapies. Systemic side effects occurred in three patients which prompted drug discontinuation in two patients. Discussion Cyclosporine alone was effective in inducing urticaria control in adult patients with chronic urticaria who had an inadequate response to omalizumab, though the impact of cyclosporine was limited by reversible adverse effects. Adverse effects were associated with pre-existing medical conditions. As novel chronic urticaria therapies are being investigated, this experience highlights the importance of uncovering chronic urticaria subtypes which tend to respond to cyclosporine, while providing alternative treatments with better tolerability. Keywords: Chronic spontaneous urticaria, Refractory urticaria, Cyclosporine, Omalizumab
Adaptation to captivity in spawning programs can lead to unintentional consequences, such as domestication that results in reduced fitness in the wild. The timing of sexual maturation has been shown ...to be a trait under domestication selection in fish hatcheries, which affects a fish's access to mating opportunities and aligning their offspring's development with favorable environmental conditions. Earlier maturing fish may be favored in hatchery settings where managers provide artificially optimal growing conditions, but early maturation may reduce fitness in the wild if, for example, there is a mismatch between timing of reproduction and availability of resources that support recruitment. We investigated patterns of maturation timing in a delta smelt (Hypomesus transpacificus) conservation hatchery by quantifying changes to the median age at maturity since the captive spawning program was initiated in 2008. Over the span of a decade, we observed a small, but significant increase in age at maturity among broodstock by 2.2 weeks. This trait had low heritability and was largely controlled by phenotypic plasticity that was dependent on the time of year fish were born. Fish that were born later in the year matured faster, potentially a carryover from selection favoring synchronous spawning in the wild. However, higher DI (domestication index) fish showed a loss of plasticity, we argue, as a result of hatchery practices that breed individuals past peak periods of female ripeness. Our findings suggest that the hatchery setting has relaxed selection pressures for fish to mature quickly at the end of the year and, consequently, has led to a loss of plasticity in age at maturity. Hatchery fish that are re‐introduced in the wild may not be able to align maturation with population peaks if their maturation rates are too slow with reduced plasticity, potentially resulting in lower fitness.
Urbanization is decreasing wildlife habitat and connectivity worldwide, including for apex predators, such as the puma (Puma concolor). Puma populations along California's central and southern ...coastal habitats have experienced rapid fragmentation from development, leading to calls for demographic and genetic management. To address urgent conservation genomic concerns, we used double‐digest restriction‐site associated DNA (ddRAD) sequencing to analyze 16,285 genome‐wide single‐nucleotide polymorphisms (SNPs) from 401 pumas sampled broadly across the state. Our analyses indicated support for 4–10 geographically nested, broad‐ to fine‐scale genetic clusters. At the broadest scale, the four genetic clusters had high genetic diversity and exhibited low linkage disequilibrium, indicating that pumas have retained genomic diversity statewide. However, multiple lines of evidence indicated substructure, including 10 finer‐scale genetic clusters, some of which exhibited fixed alleles and linkage disequilibrium. Fragmented populations along the Southern Coast and Central Coast had particularly low genetic diversity and strong linkage disequilibrium, indicating genetic drift and close inbreeding. Our results demonstrate that genetically at risk populations are typically nested within a broader‐scale group of interconnected populations that collectively retain high genetic diversity and heterogenous fixations. Thus, extant variation at the broader scale has potential to restore diversity to local populations if management actions can enhance vital gene flow and recombine locally sequestered genetic diversity. These state‐ and genome‐wide results are critically important for science‐based conservation and management practices. Our nested population genomic analysis highlights the information that can be gained from population genomic studies aiming to provide guidance for the conservation of fragmented populations.
Infectious diseases play an important role in wildlife population dynamics by altering individual fitness, but detecting disease-driven natural selection in free-ranging populations is difficult due ...to complex disease-host relationships. Chronic wasting disease (CWD) is a fatal infectious prion disease in cervids for which mutations in a single gene have been mechanistically linked to disease outcomes, providing a rare opportunity to study disease-driven selection in wildlife. In Wyoming, USA, CWD has gradually spread across mule deer (
) populations, producing natural variation in disease history to evaluate selection pressure. We used spatial variation and a novel temporal comparison to investigate the relationship between CWD and a mutation at codon 225 of the mule deer prion protein gene that slows disease progression. We found that individuals with the 'slow' 225F allele were less likely to test positive for CWD, and the 225F allele was more common in herds exposed to CWD longer. We also found that in the past 2 decades, the 225F allele frequency increased more in herds with higher CWD prevalence. This study expanded on previous research by analysing spatio-temporal patterns of individual and herd-based disease data to present multiple lines of evidence for disease-driven selection in free-ranging wildlife.
A full-size prototype of a Micromegas precision tracking chamber for the upgrade of the ATLAS detector at the LHC Collider has been built between October 2015 and April 2016. This paper describes in ...detail the procedures followed in the construction of the components of the chamber in various INFN laboratories and the final assembly in the Laboratori Nazionali di Frascati (LNF). In addition, the results of the chamber exposure to a particle beam at SPS/H8 at CERN in June 2016 are presented. The performances obtained in the construction and the results of the test beam are compared with the requirements set in order to sustain the high radiation levels expected during the data-taking of the LHC in the next years.
A comparison of BGO and BSO crystals used in the dual-readout mode Akchurin, N.; Bedeschi, F.; Cardini, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
06/2011, Volume:
640, Issue:
1
Journal Article
Peer reviewed
We report on a systematic study of the properties of two high-
Z scintillating crystals, bismuth germanate (BGO) and bismuth silicate (BSO), in view of the possible application of such crystals in ...dual-readout calorimeters. Whereas the light attenuation characteristics of both crystals are about the same, BSO offers a considerably higher Cherenkov light yield, and with a given UV filter the separation between the Cherenkov and scintillation signals is substantially better in this crystal.
The tracking detector of the KLOE experiment Adinolfi, M; Ambrosino, F; Andryakov, A ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2002, Volume:
488, Issue:
1
Journal Article
Peer reviewed
The design and construction of the large Drift Chamber for the KLOE experiment at the Frascati φ-factory, DAΦNE, are described. The relevant aspects of the various elements of the detector are ...reviewed together with a description of the track reconstruction program and of the calibration procedures. The performance of the detector based on measurements with cosmic rays and with e
+e
− colliding beams during DAΦNE commissioning is presented.
Detection of electron showers in dual-readout crystal calorimeters Akchurin, N.; Bedeschi, F.; Cardini, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
09/2012, Volume:
686
Journal Article
Peer reviewed
Some high-Z scintillating crystals offer the possibility to distinguish the contributions from the scintillation and Čherenkov mechanisms to the generated signals. Among these crystals are BGO and ...PbWO4. We have tested matrices of these crystals as electromagnetic calorimeters and studied the properties of the Čherenkov and scintillation components of the signals generated by high-energy electrons showering in these detectors.
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