Chikungunya fever is an arthropod-borne infection caused by Chikungunya virus (CHIKV). Even though clinical features of Chikungunya fever in the Mexican population have been described before, there ...is no detailed information. The aim of this study was to perform a full description of the clinical features in confirmed Chikungunya-infected patients and describe the molecular epidemiology of CHIKV. We evaluated febrile patients who sought medical assistance in Tapachula, Chiapas, Mexico, from June through July 2015. Infection was confirmed with molecular and serological methods. Viruses were isolated and the
gene was sequenced. Phylogeny reconstruction was inferred using maximum-likelihood and maximum clade credibility approaches. We studied 52 patients with confirmed CHIKV infection. They were more likely to have wrist, metacarpophalangeal, and knee arthralgia. Two combinations of clinical features were obtained to differentiate between Chikungunya fever and acute undifferentiated febrile illness. We obtained 10 CHIKV
sequences that grouped with the Asian lineage. Seven strains diverged from the formerly reported. Patients infected with the divergent CHIKV strains showed a broader spectrum of clinical manifestations. We defined the complete clinical features of Chikungunya fever in patients from Southeastern Mexico. Our results demonstrate co-circulation of different CHIKV strains in the state of Chiapas.
Background: Docetaxel is a widely accepted second-line treatment in advanced non-small-cell lung cancer (NSCLC) with a risk of myelotoxicity. This study evaluated the efficacy and toxicity profile of ...two docetaxel regimens in NSCLC patients who had failed first-line non-docetaxel-based chemotherapy. Patients and methods: A total of 259 patients from 33 Spanish centers were randomized to receive either docetaxel 75 mg/m2 administered every 3 weeks (3W arm) or docetaxel 36 mg/m2 given weekly (1W arm) for 6 weeks followed by 2 weeks of rest. The primary end point was 1-year survival; secondary end points were median survival, time to progression, response and toxicity. Results: One-year survival was 27% in the 3W and 22% in the 1W arm. Median time to progression was also similar in the two arms. Median survival was 6.6 months in the 3W arm versus 5.4 months in the 1W arm (P = 0.075). Response rates were 9.3% in the 3W arm and 4.8% in the 1W arm. More patients in the 1W arm experienced mucositis 1W, nine patients (7.2%); 3W, two patients (1.6%); P = 0.032, while febrile neutropenia was significantly higher in the 3W arm 3W, 10 patients (7.8%); 1W, one patient (0.8%); P = 0.010. Conclusions: Both weekly and 3-weekly docetaxel were effective and well-tolerated, with different toxicity profiles. In general, there was no indication to recommend the weekly schedule. However, the significant lower rate of febrile neutropenia observed in the weekly schedule makes it a good alternative for patients at risk of severe neutropenia.
The new Sysmex UF‐1000i analyzer – which incorporates bacteria morphology distinction – allows to automatically screen samples to be cultured at microbiology laboratories. We have evaluated the ...feasibility and accuracy of Sysmex UF‐1000i to screen urinary tract infections (UTIs). A total amount of 2468 urine samples from six Spanish hospitals were analysed. Demographic and clinical data such as age, gender, source and sample type, preserving conditions, cytometer parameters (bacteria, leucocytes and bacteria morphology) as well as urine culture results (gold standard) were recorded. After applying data mining techniques, the variables of age, bacteria count and rod morphology were defined as predictive variables of UTIs. By using the UF‐1000i in combination with a predictive algorithm of three decision rules, we could identify 94·9 and 47·4% positive and negative urine samples, respectively, with a negative predictive value of 97 and only 1·17% diagnostic error. This error was reduced down to 0·4% when contaminated samples were excluded. Our results show that flow cytometry parameters together with age, by means of a predictive algorithm model, can be used to screen UTIs. Its implementation would avoid culturing 38% of urine samples, and therefore, would reduce time to diagnosis with a discrete false negative ratio.
Significance and Impact of the Study
Fluorescent flow cytometry performance has recently spread for urine screening. However, controversy about cytometer results can be drawn from medical literature. This study shows the diagnosis accuracy of Sysmex UF‐1000i analyzer by means of a group of decision rules encompassing both demographic variables (age) and cytometer parameters (bacteria, leucocytes and bacteria morphology). After applying the predictive algorithm, the UF‐1000i could optimally identify 95% urinary tract infections with high negative predictive value and low diagnostic error. Implementation of UF‐1000i would avoid culturing almost 38% of urine samples, thus reducing time to diagnosis, unnecessary antibiotic treatments and consequently improving cost‐effectiveness.
Significance and Impact of the Study: Fluorescent flow cytometry performance has recently spread for urine screening. However, controversy about cytometer results can be drawn from medical literature. This study shows the diagnosis accuracy of Sysmex UF‐1000i analyzer by means of a group of decision rules encompassing both demographic variables (age) and cytometer parameters (bacteria, leucocytes and bacteria morphology). After applying the predictive algorithm, the UF‐1000i could optimally identify 95% urinary tract infections with high negative predictive value and low diagnostic error. Implementation of UF‐1000i would avoid culturing almost 38% of urine samples, thus reducing time to diagnosis, unnecessary antibiotic treatments and consequently improving cost‐effectiveness.
Effectiveness of daily versus non‐daily granulocyte colony‐stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice
We ...conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony‐stimulating factors (G‐CSF) and chemotherapy. We investigated the effectiveness of daily vs. non‐daily G‐CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G‐CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G‐CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G‐CSF received it for ≥7 days. In the multivariate models, daily G‐CSF was associated with higher risk of grade 3‐4 neutropenia (G3‐4N) vs. pegfilgrastim odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004–2.97. Relative to SP, PP protected against G3‐4N (OR for SP vs. PP: 6.0, 95%CI: 3.2–11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1–8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7–5.4) and higher response rate (OR: 2.1, 95%CI: 1.2–3.7). Data suggest that pegfilgrastim, compared with a daily G‐CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice.
Recently, an acute restriction of imiglucerase has occurred as a result of viral contamination and manufacturing problems. A position statement from the European Working Group for Gaucher Disease and ...European Gaucher Alliance established a set of key recommendations for identifying and monitoring at-risk patients. In Spain, a profile of the shortage situation was obtained through follow-up of patients with Gaucher disease (GD) and compliance with the therapy recommendations. Here we describe a group of patients, with modified doses of imiglucerase, during the shortage. Fifty adult GD1 patients (25 males/25 females), previously on ERT, were analysed before and after the 6-month shortage. The mean age was 45.3
±
15.3
years (range: 18–84). The mean Severity Score Index at diagnosis was 8.7
±
3.8 (range: 3–19); 20% of patients were splenectomized; and 78% had bone disease. During the shortage, 23 patients (46%) discontinued therapy; as complications in this group only one patient suffered a bone crisis and another anaemia (Hb <
10.0
g/dL). The mean reduction of haemoglobin level (−2.7%) and platelet counts (−5.4%) were non-significant. Chitotriosidase (CT) activity was increased 135% (
p
<
0.03) and CCL18/PARC 8.2% (
p
<
0.08) in this group. Imiglucerase was reduced by 50% in 17 patients (34%) in this group, seven patients (41.0%) suffered bone pain, three of them true bone crisis and four (23.5%) required support therapy. The mean reduction of haemoglobin (−2.8%) and platelet counts (−10.7%), CT activity was increased 48.2% (
p
<
0.03) and no changes were observed in CCL18/PARC concentration. In both groups no significant changes in visceral size were observed. In 3 patients (6%), imiglucerase was reduced 75% and 7 patients (14%) needed to switch to another ERT (4 patients) or miglustat (3 patients) due to a restart of symptomatic disease. In Spain the 6 first months shortage of imiglucerase have produced a 20% incidence of bone pain, one case of anaemia, and a significant increase in CT activity. Fourteen percent of patients had to switch to another therapy. No significant changes in blood counts, visceral volumes and CCL18/PARC concentration were observed.
Photoinduced phase transitions in correlated materials promise diverse applications from ultrafast switches to optoelectronics. Resolving those transitions and possible metastable phases temporally ...are key enablers for these applications, but challenge existing experimental approaches. Extreme nonlinear optics can help probe phase changes, as higher-order nonlinearities have higher sensitivity and temporal resolution to band structure and lattice deformations. Here the ultrafast transition from the semiconducting to the metallic phases in polycrystalline thin-film NbO_{2} is investigated by time-resolved harmonic spectroscopy. The emission strength of all harmonic orders shows a steplike suppression when the excitation fluence exceeds a threshold (∼11-12 mJ/cm^{2}), below the fluence required for the thermal transition-a signature of the nonthermal emergence of a metallic phase within 100±20 fs. This observation is backed by full ab initio simulations as well as a 1D chain model of high-harmonic generation from both phases. Our results demonstrate femtosecond harmonic probing of phase transitions and nonthermal dynamics in solids.
A high speed, low power and programmable readout front-end system is presented for silicon detectors to be used in nuclear physics applications. The architecture consists of a folded cascode charge ...sensitive amplifier, a pole-zero cancellation circuit to eliminate undershoots and a shaper circuit with Gm-C topology. All building blocks include a regulated cascode technique based gain enhancement. Experimental results show that the whole front-end system can be programmed for peaking times of 100ns, 200ns and 400ns maintaining the amplitude of the output voltage. Programmability is achieved by switching different resistors for all poles and zeros. The system has been designed in a 130nm CMOS technology and powered from a 1.2V supply. The output pulse has peak amplitude of 200mV for an input energy of 5MeV from the detector. A power consumption low noise tradeoff will be considered.
Pulse shape analysis techniques for the identification of heavy ions produced in nuclear reactions have been recently proposed as an alternative to energy loss and time of flight methods. However ...this technique requires a large amount of memory for storing the shapes of charge and current signals. We have implemented a hardware solution for fast on-line processing of the signals producing the relevant information needed for particle identification. Since the pulse shape analysis can be formulated in terms of a pattern recognition problem, a neural network has been implemented in a FPGA device. The design concept has been tested using 12,13C ions produced in heavy ion reactions. The actual latency of the system is about 20μs when using a clock frequency of 50MHz.
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