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To date, in many countries the only legally valid method for evaporative cooling system (ECS) monitoring is the culture method. However, a duration of up to 14â¯days and a risk of underestimation of Legionella concentrations are seen as limitations of cultivation methods. Rapid cultivation-independent methods are an important step towards a more practicable monitoring of ECS to quickly control interventions if elevated concentrations of Legionella are found. Two commercial kits for quantitative polymerase chain reaction (qPCR) and viability-qPCR (v-qPCR) were studied, comprising sample filtration and DNA extraction. Cryopreserved Legionella pneumophila were established as calibration standard with intact (ILC) and total Legionella count (TLC) determined by flow cytometry before conducting spiking experiments in commercial mineral water and artificial process water. Final assessment was carried out using real ECS samples. Recovery and robustness ranged from 86 to 108â¯% for qPCR with a drop to 40-60â¯% for v-qPCR when compared to direct extraction, possibly attributable to cell damage during sample concentration. All methods including culture did perform well regarding linearity with R2â¯≥â¯0.95 for most trials. Detected concentrations in comparison to spiked Legionella counts differed with culture averaging 25⯱â¯7â¯% of spiked ILC and v-qPCR being closest to spiked concentrations with 65-144â¯%. In comparison, qPCR was several fold above spiked TLC concentrations. For real ECS samples Legionella spp. were detected in concentrations above 103 GU/100â¯mL by v-qPCR in 70-92â¯% of samples, depending on the kit used. Most of these samples were either culture-negative or not evaluable on agar plates. This study showed that a cryopreserved bacterial standard based examination is applicable and can be used for future v-qPCR verification. For assessment of differences in results between culture and v-qPCR/qPCR in ECS samples expert knowledge about the operating mode and used analytical methods is required. Guidelines addressing this issue could be a solution.
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Within the FLASH2020+ upgrade, the pump-probe laser capabilities of the extreme ultraviolet and soft x-ray free-electron laser (XFEL) FLASH in Hamburg will be extended. In particular, providing wavelength tunability, shorter pulse durations, and reduced arrival time jitter will increase the scientific opportunities and the time resolution for the XFEL-optical laser pump-probe experiments. We present here a novel concept for the pump-probe laser at FLASH that is based on the post-compression of picosecond pulses emitted from high-power Ytterbium:YAG slab amplifiers. Flexible reduction of the pulse duration is facilitated by spectral broadening in pressure-tunable multi-pass cells. As an application, we show the pumping of a commercial optical parametric amplifier with 150 fs post-compressed pulses. By means of an additional difference frequency generation stage, tunable spectral coverage from 1.3 to 16 µm is reached with multi-µJ, sub-150 fs pulses. Finally, a modular reconfiguration approach to the optical setups close to the free-electron laser instruments is implemented. This enables fast installation of the nonlinear frequency converters at the end stations for user operation and flexibility between different instruments in the two experimental halls.
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BACKGROUND AND PURPOSE: Conventional MR imaging scoring is a valuable tool for risk stratification and prognostication of outcomes, but manual scoring is time-consuming, operator-dependent, and requires high-level expertise. This study aimed to automate the regional measurements of an established brain MR imaging scoring system for preterm neonates scanned between 29 and 47 weeks' postmenstrual age. MATERIALS AND METHODS: This study used T2WI from the longitudinal Prediction of PREterm Motor Outcomes cohort study and the developing Human Connectome Project. Measures of biparietal width, interhemispheric distance, callosal thickness, transcerebellar diameter, lateral ventricular diameter, and deep gray matter area were extracted manually (Prediction of PREterm Motor Outcomes study only) and automatically. Scans with poor quality, failure of automated analysis, or severe pathology were excluded. Agreement, reliability, and associations between manual and automated measures were assessed and compared against statistics for manual measures. Associations between measures with postmenstrual age, gestational age at birth, and birth weight were examined (Pearson correlation) in both cohorts. RESULTS: A total of 652 MRIs (86%) were suitable for analysis. Automated measures showed good-to-excellent agreement and good reliability with manual measures, except for interhemispheric distance at early MR imaging (scanned between 29 and 35 weeks, postmenstrual age; in line with poor manual reliability) and callosal thickness measures. All measures were positively associated with postmenstrual age (r = 0.11-0.94; R2 = 0.01-0.89). Negative and positive associations were found with gestational age at birth (r = -0.26-0.71; R2 = 0.05-0.52) and birth weight (r = -0.25-0.75; R2 = 0.06-0.56). Automated measures were successfully extracted for 80%-99% of suitable scans. CONCLUSIONS: Measures of brain injury and impaired brain growth can be automatically extracted from neonatal MR imaging, which could assist with clinical reporting.
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Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Humanos , Lactente , Recém-Nascido , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: Testing for active SARS-CoV-2 infection is a fundamental tool in the public health measures taken to control the COVID-19 pandemic. Because of the overwhelming use of SARS-CoV-2 reverse transcription (RT)-PCR tests worldwide, the availability of test kits has become a major bottleneck and the need to increase testing throughput is rising. We aim to overcome these challenges by pooling samples together, and performing RNA extraction and RT-PCR in pools. METHODS: We tested the efficiency and sensitivity of pooling strategies for RNA extraction and RT-PCR detection of SARS-CoV-2. We tested 184 samples both individually and in pools to estimate the effects of pooling. We further implemented Dorfman pooling with a pool size of eight samples in large-scale clinical tests. RESULTS: We demonstrated pooling strategies that increase testing throughput while maintaining high sensitivity. A comparison of 184 samples tested individually and in pools of eight samples showed that test results were not significantly affected. Implementing the eight-sample Dorfman pooling to test 26 576 samples from asymptomatic individuals, we identified 31 (0.12%) SARS-CoV-2 positive samples, achieving a 7.3-fold increase in throughput. DISCUSSION: Pooling approaches for SARS-CoV-2 testing allow a drastic increase in throughput while maintaining clinical sensitivity. We report the successful large-scale pooled screening of asymptomatic populations.
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Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/epidemiologia , Testes Diagnósticos de Rotina , Humanos , Pandemias , Pneumonia Viral/epidemiologia , RNA Viral/genética , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Sensibilidade e Especificidade , Manejo de EspécimesRESUMO
BACKGROUND: Aim of the present study is the evaluation of ultrasound as a physical method for virus inactivation in human plasma products prior to transfusion. Our study is focused on achieving a high level of virus inactivation simultaneously leaving blood products unaltered, measured by the level of degradation of coagulation factors, especially in third world countries where virus contamination of blood products poses a major problem. Virus inactivation plays an important role, especially in the light of newly discovered or unknown viruses, which cannot be safely excluded via prior testing. METHODS: Taking into account the necessary protection of the relevant coagulation activity for plasma, the basis for a sterile virus inactivation under shielding gas insufflation was developed for future practical use. Influence of frequency and power density in the range of soft and hard cavitation on the inactivation of transfusion-relevant model viruses for Hepatitis-(BVDV = bovine diarrhea virus), for Herpes-(SFV = Semliki Forest virus, PRV = pseudorabies virus) and Parvovirus B19 (PPV = porcine parvovirus) were examined. Coagulation activity was examined via standard time parameters to minimize reduction of functionality of coagulation proteins. A fragmentation of coagulation proteins via ultrasound was ruled out via gel electrophoresis. The resulting virus titer was examined using end point titration. RESULTS: Through CO2 shielding gas insufflation-to avoid radical emergence effects-the coagulation activity was less affected and the time window for virus inactivation substantially widened. In case of the non-lipidated model virus (AdV-luc = luciferase expressing adenoviral vector), the complete destruction of the virus capsid through hard cavitation was proven via scanning electron microscopy (SEM). This can be traced back to microjets and shockwaves occurring in hard cavitation. The degree of inactivation seems to depend on size and compactness of the type of viruses. Using our pre-tested and subsequently chosen process parameters with the exception of the small PPV, all model viruses were successfully inactivated and reduced by up to log 3 factor. For a broad clinical usage, protection of the coagulation activities may require further optimization. CONCLUSIONS: Building upon the information gained, an optimum inactivation can be reached via raising of power density up to 1200 W and simultaneous lowering of frequency down to 27 kHz. In addition, the combination of the two physical methods UV treatment and ultrasound may yield optimum results without the need of substance removal after the procedure.
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Plasma/virologia , Sonicação , Inativação de Vírus , Vírus/patogenicidade , Animais , Humanos , Suínos , VirosesRESUMO
A 5-year-old patient treated for acute lymphoblastic leukaemia (ALL) developed proven pulmonary invasive fungal disease (IFD) due to Actinomucor elegans. While completing ALL treatment according to AIEOP ALL protocol 2009 for further 15 months, antifungal treatment with liposomal amphotericin B and intermittent additional posaconazole was continued until immune reconstitution 7 months after the end of ALL treatment. Repeated imaging guided treatment decisions. Twenty-six and 19 months after the end of ALL treatment and antifungal treatment, respectively, the patient is still in the first complete remission and shows no signs of active invasive fungal disease (IFD).
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Anfotericina B/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Pneumopatias Fúngicas/tratamento farmacológico , Mucormicose/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antifúngicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Asparaginase/administração & dosagem , Pré-Escolar , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Humanos , Pneumopatias Fúngicas/microbiologia , Masculino , Mercaptopurina/administração & dosagem , Metotrexato/administração & dosagem , Mucorales/isolamento & purificação , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologia , Prednisona/administração & dosagem , Indução de Remissão , Triazóis/uso terapêutico , Vincristina/administração & dosagemRESUMO
When using superconducting (SC) magnets in a gantry for proton therapy, the gantry will benefit from some reduction in size and a large reduction in weight. In this contribution we show an important additional advantage of SC magnets in proton therapy treatments. We present the design of a gantry with a SC bending section and achromatic beam optics with a very large beam momentum acceptance of [Formula: see text]15% (corresponding to about [Formula: see text]30% in the energy domain). Due to the related very large energy acceptance, approximately 70% of the treatments can be performed without changing the magnetic field for synchronization with energy modulation. In our design this is combined with a 2D lateral scanning system and a fast degrader mounted in the gantry, so that this gantry will be able to perform pencil beam scanning with very rapid energy variations at the patient, allowing a significant reduction of the irradiation time. We describe the iterative process we have applied to design the magnets and the beam transport, for which we have used different codes. COSY Infinity and OPAL have been used to design the beam transport optics and to track the particles in the magnetic fields, which are produced by the magnets designed in Opera. With beam optics calculations we have derived an optimal achromatic beam transport with the large momentum acceptance of the proton pencil beam and we show the agreement with particle tracking calculations in the 3D magnetic field map. A new cyclotron based facility with this gantry will have a significantly smaller footprint, since one can refrain from the standard degrader and energy selection system behind the cyclotron. In the treatments, this gantry will enable a very fast proton beam delivery sequence, which may be of advantage for treatments in moving tissue.
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Terapia com Prótons/instrumentação , Supercondutividade , Ciclotrons , Humanos , Óptica e Fotônica , Terapia com Prótons/métodos , Dosagem RadioterapêuticaRESUMO
There is a growing interest in the combined use of Stereotactic Body Radiation Therapy (SBRT) with Flattening Filter Free (FFF) due to the high local control rates and reduced treatment times, compared to conventionally fractionated treatments. It has been suggested that they may also provide a better radiation protection to radiotherapy patients as a consequence of the expected decrease in peripheral doses. This work aims to determine this reduction in unattended out-of-field regions, where no CT information is available but an important percentage of second primary cancers occur. For that purpose, ten different cases suitable for SBRT were chosen. Thus, 142 different treatment plans including SBRT, as well as 3D-CRT, IMRT and VMAT (with standard fractionation) in low and high energies for Varian (FF and FFF), Siemens and Elekta machines were created. Then, photon and neutron peripheral dose in 14 organs were assessed and compared using two analytical models. For the prostate case, uncomplicated and cancer free control probability estimation was also carried out. As a general behavior, SBRT plans led to the lowest peripheral doses followed by 3D-CRT, VMAT and IMRT, in this order. Unflattened beams proved to be the most effective in reducing peripheral doses, especially for 10 MV. The obtained results suggest that FFF beams for SBRT with 10 MV represent the best compromise between dose delivery efficiency and peripheral dose reduction.
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Filtração/instrumentação , Segunda Neoplasia Primária/epidemiologia , Neoplasias/cirurgia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Filtração/métodos , Humanos , Incidência , Neoplasias/classificação , Neoplasias/patologia , Segunda Neoplasia Primária/diagnóstico , Órgãos em Risco/efeitos da radiação , Prognóstico , Dosagem Radioterapêutica , Espanha/epidemiologiaRESUMO
BACKGROUND: Previous studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC). METHODS: fMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group × stimulation condition × stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis. RESULTS: AN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity. CONCLUSION: Increased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN.
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Anorexia Nervosa/fisiopatologia , Córtex Cerebral/fisiopatologia , Alimentos , Neuroimagem Funcional/métodos , Reconhecimento Visual de Modelos/fisiologia , Recompensa , Estimulação Subliminar , Adolescente , Adulto , Anorexia Nervosa/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Adulto JovemRESUMO
The unintentional poisoning with aconite in a 32-year-old healthy woman led to life-threatening neurological and cardiovascular effects with cardiac arrest and need for resuscitation. The combined administration of magnesium and amiodarone was able to stabilize heart rhythm and circulation. Organ damage was not recognized in the follow-up.
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Aconitum , Parada Cardíaca , Intoxicação , Aconitum/química , Aconitum/intoxicação , Adulto , Amiodarona/uso terapêutico , Feminino , Parada Cardíaca/induzido quimicamente , Humanos , Intoxicação/etiologia , Intoxicação/terapia , Bloqueadores dos Canais de Potássio/uso terapêutico , RessuscitaçãoRESUMO
Chronic immune thrombocytopenia (cITP) is often associated with an underlying predisposition towards autoimmunity, recognition of which is relevant to guide treatment. International recommendations on diagnostic steps and therapeutic measures of cITP in childhood exist. However, due to the low prevalence (1-2/100,000) and a variation of availability of immunological and hematological tests and treatments across pediatric units, we postulated that these guidelines are not uniformly adhered to and that immune dysregulation syndromes remained undiscovered. To delineate the current management of children and adolescents with cITP in Austria, we performed a nationwide cross-sectional study. Between 2011 and 2014, 81 children with cITP were seen at seven centers (median age 8.75 years; range 1-17; female:male ratio 47:34) at 641 visits during 180 patient years after diagnosis of cITP (>12 months ITP duration). Additional diagnoses were noted, most frequently immune or autoimmune disorders, hematologic diseases, or infections (in 37.3%, including Evans syndrome, autoimmune lymphoproliferative syndrome, systemic lupus erythematosus, and Fanconi anemia), or other symptoms like bi- or pancytopenia (n=9), lymphoproliferation or granulomatous inflammation (n = 3). Both decision to treat as well as choice of treatment varied: smaller centers tended to observe more frequently, larger centers applied a pattern of treatment modalities that appeared to depend less on bleeding tendency than on center policy. More than 50% of therapeutic interventions occurred in bleedings scores ≤2 (of 5), suggesting a strong psychosocial intention to treat. Platelet increment upon 479 therapeutic interventions of eight types was evaluated, with multiple treatment approaches being pursued sequentially in refractory patients. These data confirm the hypothesis of heterogeneous diagnostic and therapeutic management of cITP in Austrian children and corroborate the need for (1) a precise panel of parameters to exclude underlying disorders and (2) for biomarkers to predict treatment response.
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Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Áustria , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Feminino , Humanos , Lactente , MasculinoRESUMO
This work presents an on-chip isothermal nucleic acid amplification test (iNAAT) for the multiplex amplification and detection of viral and bacterial DNA by a flow-based chemiluminescence microarray. In a principle study, on-chip recombinase polymerase amplification (RPA) on defined spots of a DNA microarray was used to spatially separate the amplification reaction of DNA from two viruses (Human adenovirus 41, Phi X 174) and the bacterium Enterococcus faecalis, which are relevant for water hygiene. By establishing the developed assay on the microarray analysis platform MCR 3, the automation of isothermal multiplex-amplification (39 °C, 40 min) and subsequent detection by chemiluminescence imaging was realized. Within 48 min, the microbes could be identified by the spot position on the microarray while the generated chemiluminescence signal correlated with the amount of applied microbe DNA. The limit of detection (LOD) determined for HAdV 41, Phi X 174, and E. faecalis was 35 GU/µL, 1 GU/µL, and 5 × 10(3) GU/µL (genomic units), which is comparable to the sensitivity reported for qPCR analysis, respectively. Moreover the simultaneous amplification and detection of DNA from all three microbes was possible. The presented assay shows that complex enzymatic reactions like an isothermal amplification can be performed in an easy-to-use experimental setup. Furthermore, iNAATs can be potent candidates for multipathogen detection in clinical, food, or environmental samples in routine or field monitoring approaches.
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Adenovírus Humanos/isolamento & purificação , Bacteriófago phi X 174/isolamento & purificação , Enterococcus faecalis/isolamento & purificação , Medições Luminescentes/instrumentação , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Análise de Sequência com Séries de Oligonucleotídeos/instrumentação , TemperaturaRESUMO
Waveform-stabilized laser pulses have revolutionized the exploration of the electronic structure and dynamics of matter by serving as the technological basis for frequency-comb and attosecond spectroscopy. Their primary sources, mode-locked titanium-doped sapphire lasers and erbium/ytterbium-doped fibre lasers, deliver pulses with several nanojoules energy, which is insufficient for many important applications. Here we present the waveform-stabilized light source that is scalable to microjoule energy levels at the full (megahertz) repetition rate of the laser oscillator. A diode-pumped Kerr-lens-mode-locked Yb:YAG thin-disk laser combined with extracavity pulse compression yields waveform-stabilized few-cycle pulses (7.7 fs, 2.2 cycles) with a pulse energy of 0.15 µJ and an average power of 6 W. The demonstrated concept is scalable to pulse energies of several microjoules and near-gigawatt peak powers. The generation of attosecond pulses at the full repetition rate of the oscillator comes into reach. The presented system could serve as a primary source for frequency combs in the mid infrared and vacuum UV with unprecedented high power levels.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Lectina de Ligação a Manose/deficiência , Polimorfismo de Nucleotídeo Único , Doença Aguda , Adolescente , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Taxa de SobrevidaRESUMO
AIM: Clinical differentiation of psoriatic arthritis (PsA) and rheumatoid arthritis (rA) based on the pattern of joint involvement can be difficult; the frequent form of PsA with polyarthritis of the peripheral joints may sometime resemble rA. We investigated a metabolic joint asymmetry score (MJAS), reflecting the overall asymmetric joint involvement on conventional bone scintigraphy, for differentiating PsA from rA in patients presenting with peripheral polyarthritis. PATIENTS, METHODS: 106 patients (n = 61, PsA; n = 45, rA) with peripheral polyarthritis (≥ 5 joints) as well as 26 control subjects with no history of chronic joint disorders were analyzed. The intensity of articular 99mTc-MDP uptake in 40 peripheral joint pairs was scored regarding the bilateral difference of each joint based on a scale of 0-2 (no significant, moderate, and marked asymmetry, respectively). The patient's MJAS was defined as the sum of uptake difference scores of all joint pairs. The association of MJAS with the underlying condition (Psoriasis criteria, Revised Criteria of the ACR) was examined. RESULTS: 5280 peripheral joint pairs were investigated. There was no significant difference in the total number of involved joints in PsA 15.0 ± 8.2 versus rA 17.5 ± 8.8 patients (p = 0.132), but significantly less involvement in the control group (6.7 ± 5.0, p < 0.001). MJAS was markedly higher in PsA (17.0 ± 9.6) than in rA (4.8 ± 3.9, p < 0.001), and correlated with the total number of involved joints in PsA (r = 0.516, p < 0.001), but not in rA (r = 0.078, p = 0.380). The MJAS disparity between PsA and rA persisted after exclusion of the DIP joints (14.4 ± 7.7 vs. 4.4 ± 3.3; p<0.001). CONCLUSIONS: The new reproducible semi-quantification method for the asymmetry of metabolic joint involvement permits differentiation of psoriatic from rheumatoid peripheral arthritis with MJAS being markedly higher in patients with PsA as compared to rA patients. The score may offer an effective complementary tool for characterizing patients with peripheral polyarthritis.
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Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/metabolismo , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/metabolismo , Interpretação de Imagem Assistida por Computador/métodos , Medronato de Tecnécio Tc 99m/farmacocinética , Adulto , Idoso , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Simulação por Computador , Diagnóstico Diferencial , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , SoftwareRESUMO
Compression of 250-fs, 1-µJ pulses from a KLM Yb:YAG thin-disk oscillator down to 9.1 fs is demonstrated. A kagomé-PCF with a 36-µm core-diameter is used with a pressure gradient from 0 to 40 bar of krypton. Compression to 22 fs is achieved by 1200 fs2 group-delay-dispersion provided by chirped mirrors. By coupling the output into a second kagomé-PCF with a pressure gradient from 0 to 25 bar of argon, octave spanning spectral broadening via the soliton-effect is observed at 18-W average output power. Self-compression to 9.1 fs is measured, with compressibility to 5 fs predicted. Also observed is strong emission in the visible via dispersive wave generation, amounting to 4% of the total output power.
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INTRODUCTION: Complement immunodeficiencies (excluding hereditary angioedema and mannose binding lectin deficiency) are rare. Published literature consists largely of case reports and small series. We collated data from 18 cities across Europe to provide an overview of primarily homozygous, rather than partial genotypes and their impact and management. METHODS: Patients were recruited through the ESID registry. Clinical and laboratory information was collected onto standardized forms and analyzed using SPSS software. RESULTS: Seventy-seven patients aged 1 to 68 years were identified. 44 % presented in their first decade of life. 29 % had C2 deficiency, defects in 11 other complement factors were found. 50 (65 %) had serious invasive infections. 61 % of Neisseria meningitidis infections occurred in patients with terminal pathway defects, while 74 % of Streptococcus pneumoniae infections occurred in patients with classical pathway defects (p < 0.001). Physicians in the UK were more likely to prescribe antibiotic prophylaxis than colleagues on the Continent for patients with classical pathway defects. After diagnosis, 16 % of patients suffered serious bacterial infections. Age of the patient and use of prophylactic antibiotics were not associated with subsequent infection risk. Inflammatory/autoimmune diseases were not seen in patients with terminal pathway, but in one third of patients classical and alternative pathway defects. CONCLUSION: The clinical phenotypes of specific complement immunodeficiencies vary considerably both in terms of the predominant bacterial pathogen, and the risk and type of auto-inflammatory disease. Appreciation of these phenotypic differences should help both immunologists and other specialists in their diagnosis and management of these rare and complex patients.
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Proteínas do Sistema Complemento/deficiência , Proteínas do Sistema Complemento/genética , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Ativação do Complemento/genética , Ativação do Complemento/imunologia , Proteínas do Sistema Complemento/imunologia , Consanguinidade , Bases de Dados Factuais , Gerenciamento Clínico , Europa (Continente)/epidemiologia , Feminino , Genótipo , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Patients with anorexia nervosa (AN) are characterized by a very low body weight but readily give up immediate rewards (food) for long-term goals (slim figure), which might indicate an unusual level of self-control. This everyday clinical observation may be quantifiable in the framework of the anticipation-discounting dilemma. METHOD: Using a cross-sectional design, this study compared the capacity to delay reward in 34 patients suffering from acute AN (acAN), 33 weight-recovered AN patients (recAN) and 54 healthy controls. We also used a longitudinal study to reassess 21 acAN patients after short-term weight restoration. A validated intertemporal choice task and a hyperbolic model were used to estimate temporal discounting rates. RESULTS: Confirming the validity of the task used, decreased delay discounting was associated with age and low self-reported impulsivity. However, no group differences in key measures of temporal discounting of monetary rewards were found. CONCLUSIONS: Increased cognitive control, which has been suggested as a key characteristic of AN, does not seem to extend the capacity to wait for delayed monetary rewards. Differences between our study and the only previous study reporting decreased delay discounting in adult AN patients may be explained by the different age range and chronicity of acute patients, but the fact that weight recovery was not associated with changes in discount rates suggests that discounting behavior is not a trait marker in AN. Future studies using paradigms with disorder-specific stimuli may help to clarify the role of delay discounting in AN.
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Anorexia Nervosa/fisiopatologia , Desvalorização pelo Atraso/fisiologia , Função Executiva/fisiologia , Adolescente , Adulto , Anorexia Nervosa/reabilitação , Peso Corporal , Criança , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Recompensa , Adulto JovemRESUMO
We demonstrate a simple scheme for dual frequency comb spectroscopy in which the second frequency comb is generated by propagating the primary pulse train through a dazzler. The two frequency combs are combined behind a Mach-Zehnder interferometer, and the optical spectrum is read out by an rf-spectrum analyzer. The method is applied to record the overtone absorption spectrum of C2H2 (acetylene) in the wavelength region around 1.03 µm. A spectrum with a resolution of 4 cm(-1) is obtained, which compares well with that from the HITRAN database. A simple method for improving the spectral resolution is demonstrated.
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Simultaneous detection of small and large molecules on microarray immunoassays is a challenge that limits some applications in multiplex analysis. This is the case for biosecurity, where fast, cheap and reliable simultaneous detection of proteotoxins and small toxins is needed. Two highly relevant proteotoxins, ricin (60 kDa) and bacterial toxin staphylococcal enterotoxin B (SEB, 30 kDa) and the small phycotoxin saxitoxin (STX, 0.3 kDa) are potential biological warfare agents and require an analytical tool for simultaneous detection. Proteotoxins are successfully detected by sandwich immunoassays, whereas competitive immunoassays are more suitable for small toxins (<1 kDa). Based on this need, this work provides a novel and efficient solution based on anti-idiotypic antibodies for small molecules to combine both assay principles on one microarray. The biotoxin measurements are performed on a flow-through chemiluminescence microarray platform MCR3 in 18 minutes. The chemiluminescence signal was amplified by using a poly-horseradish peroxidase complex (polyHRP), resulting in low detection limits: 2.9 ± 3.1 µg L(-1) for ricin, 0.1 ± 0.1 µg L(-1) for SEB and 2.3 ± 1.7 µg L(-1) for STX. The developed multiplex system for the three biotoxins is completely novel, relevant in the context of biosecurity and establishes the basis for research on anti-idiotypic antibodies for microarray immunoassays.