•We have built and tested an Optically Pumped Magnetometer based on non-linear magnetooptical rotation.•We present a new approach to OPM- based MEG using a modular NOPM sensor.•Our sensor is ...resilient to non-zero and non-uniform magnetic field environments and crosstalk free.•We demonstrate the operation of the NOPM sensor by measuring auditory response and calculating time-frequency representation of power.
Optically Pumped Magnetometers (OPMs) have been hailed as the future of human magnetoencephalography, as they enable a level of flexibility and adaptability that cannot be obtained with systems based on superconductors. While OPM sensors are already commercially available, there is plenty of room for further improvements and customization. In this work, we detected auditory evoked brain fields using an OPM based on the nonlinear magneto-optical rotation (NMOR) technique. Our sensor head, containing only optical and non-magnetizable elements, is connected to an external module including all the electronic components, placed outside the magnetically shielded room. The use of the NMOR allowed us to detect the brain signals in non-zero magnetic field environments. In particular, we were able to detect auditory evoked fields in a background field of 70 nT. We benchmarked our sensor with conventional SQUID sensors, showing comparable performance. We further demonstrated that our sensor can be employed to detect modulations of brain oscillations in the alpha band. Our results are a promising stepping-stone towards the realization of resilient OPM-based magnetoencephalography systems that do not require active compensation.
•We present a model to optimise the sensing volume of OPM sensors for MEG applications in realistic conditions•We show how the optimal cell dimensions and number of sensors in the array depend on the ...environmental and brain noise•We find the optimal sensing dimensions both for SERF and NMOR OPM in a single sensor arrangement and in ∼70 sensor arrays•Our model can be used as a toolkit for optimising OPM-MEG systems in a wide range of experimental conditions
Magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has been hailed as the future of electrophysiological recordings from the human brain. In this work, we investigate how the dimensions of the sensing volume (the vapour cell) affect the performance of both a single OPM-MEG sensor and a multi-sensor OPM-MEG system. We consider a realistic noise model that accounts for background brain activity and residual noise. By using source reconstruction metrics such as localization accuracy and time-course reconstruction accuracy, we demonstrate that the best overall sensitivity and reconstruction accuracy are achieved with cells that are significantly longer and wider that those of the majority of current commercial OPM sensors. Our work provides useful tools to optimise the cell dimensions of OPM sensors in a wide range of environments.
Cancer biomarkers offer unique prospects for the development of cancer diagnostics and therapy. One of such biomarkers, protein survivin (Sur), exhibits strong antiapoptotic and ...proliferation-enhancing properties and is heavily expressed in multiple cancers. Thus, it can be utilized to provide new modalities for modulating the cell-growth rate, essential for effective cancer treatment. Herein, we have focused on the development of a new survivin-based cancer detection platform for colorectal cancer cells SW480 using a turn-on fluorescence oligonucleotide molecular beacon (MB) probe, encoded to recognize Sur messenger RNA (mRNA). Contrary to the expectations, we have found that both the complementary target oligonucleotide strands as well as the single- and double-mismatch targets, instead of exhibiting the anticipated simple random conformations, preferentially formed secondary structure motifs by folding into small-loop hairpin structures. Such a conformation may interfere with, or even undermine, the biorecognition process. To gain better understanding of the interactions involved, we have replaced the classical Tyagi–Kramer model of interactions between a straight target oligonucleotide strand and a hairpin MB with a new model to account for the hairpin–hairpin interactions as the biorecognition principle. A detailed mechanism of these interactions has been proposed. Furthermore, in experimental work, we have demonstrated an efficient transfection of malignant SW480 cells with SurMB probes containing a fluorophore Joe (SurMB-Joe) using liposomal nanocarriers. The green emission from SurMB-Joe in transfected cancer cells, due to the hybridization of the SurMB-Joe loop with Sur mRNA hairpin target, corroborates Sur overexpression. On the other hand, healthy human-colon epithelial cells CCD 841 CoN show only negligible expression of survivin mRNA. These experiments provide the proof-of-concept for distinguishing between the cancer and normal cells by the proposed hairpin–hairpin interaction method. The single nucleotide polymorphism sensitivity and a low detection limit of 26 nM (S/N = 3σ) for complementary targets have been achieved.
A solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated ...nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activated MnO2. The second step proceeds via an exclusive deacylative pathway, to give a series of 1,4-diarylpyrazoles functionalized with a fluorinated (CF3) or non-fluorinated (Ph, COOEt, Ac) substituent at C(3) of the heterocyclic ring. In contrast, MnO2-mediated oxidation of a model isomeric 4-acylpyrazoline proceeded with low chemoselectivity, leading to fully substituted pyrazole as a major product formed via dehydrogenative aromatization. The presented approach extends the scope of the known methods carried out in organic solvents and enables the preparation of polyfunctionalized pyrazoles, which are of general interest in medicine and material sciences.
New drugs, including immune checkpoint inhibitors and targeted therapy, have changed the prognosis in a subset of patients with advanced lung cancer, and are now actively investigated in a number of ...trials with neoadjuvant and adjuvant regimens. However, no phase III randomized studies were published yet. The current narrative review proves that targeted therapies are safe in neoadjuvant approach. Unsurprisingly, administration of therapy is related to an acceptable toxicity profile. Severe adverse events' rate that rarely compromises outcomes of patients with advanced lung cancer is not that commonly accepted in early lung cancer as it may lead to missing the chance of curative surgery. Among those complications, the most important factors that may limit the use of targeted therapies are severe respiratory adverse events precluding the resection occurring after treatment with some anaplastic lymphoma kinase and rarely after epidermal growth factor receptor tyrosine kinase inhibitors. At this point, in the presented literature assessing the feasibility of neoadjuvant therapies with anaplastic lymphoma kinase and epidermal growth factor receptor tyrosine kinase inhibitors, we did not find any unexpected intraoperative events that would be of special interest to a thoracic surgeon. Moreover, the postoperative course was associated with typical rate of complications.
Celem artykułu jest analiza przestrzennego zróżnicowania bezrobocia we włoskich regionach. W pracy ujęte są opisowe analizy przeciętnego PKB per capita i przeciętnych stóp bezrobocia oraz analiza ...skupień. Badania przeprowadzono w oparciu o dane z Urzędu Statystycznego Włoch (Istituto Centrale di Statistica ISTAT) i ze względu na dostępność odpowiednich danych obejmuje lata 1998-2015. Ponadto w artykule wykorzystano prosty model teoretyczny dotyczący kształtowania się przyrostu stóp bezrobocia, w którym to owe przyrosty w kolejnych latach oraz regionach zależą od stóp wzrostu PKB per capita oraz stóp procentowych z roku poprzedniego. Do oszacowania parametrów modelu zastosowano klasyczną metodę najmniejszych kwadratów z wykorzystaniem procedury fixed effect. Wyniki analizy dotyczącej przestrzennego zróżnicowania bezrobocia we włoskich regionach pokazują, że bezrobocie we Włoszech odznacza się dużym przestrzennym zróżnicowaniem. Regiony Południowych Włoch odznaczają się dużo większym bezrobociem, niż regiony należące do Północnych czy Środkowych Włoch. Skład grup kwartylowych dotyczących PKB na mieszkańca oraz stopy bezrobocia w analizowanym okresie charakteryzują się stabilnością, zauważyć można również, że regiony z południa Włoch zawsze tworzą pierwszą lub drugą grupę kwartylową. Ponadto badania pokazują, że przyrosty stóp bezrobocia we włoskich regionach wynikają ze stopy wzrostu PKB per capita oraz stopy bezrobocia, a przyrost ten jest objaśniany przez stopę wzrostu PKB oraz stopy bezrobocia z okresu poprzedniego w około 70 procentach.
We experimentally realize a method to produce nonequilibrium Bose-Einstein condensates with condensed fraction exceeding those of equilibrium samples with the same parameters. To do this, we immerse ...an ultracold Bose gas of 87 Rb in a cloud of 39 K with substantially higher temperatures, providing a controlled source of dissipation. By combining the action of the dissipative environment with evaporative cooling, we are able to progressively distil the nonequilibrium Bose-Einstein condensate from the thermal cloud. We show that by increasing the strength of the dissipation it is even possible to produce condensates above the critical temperature. We finally demonstrate that our out-of-equilibrium samples are long lived and do not reach equilibrium in a time that is accessible for our experiment. Due to its high degree of control, our distillation process is a promising tool for the engineering of open quantum systems.
We study the thermodynamic properties of a spin-1 Bose gas across the Bose-Einstein condensation transition. We present the theoretical description of the thermodynamics of a trapped ideal spin-1 ...Bose gas and we describe the phases that can be obtained in this system as a function of the temperature and of the populations in the different spin components. We propose a simple way to realize a 'synthetic magnetization' that can be used to probe the entire phase diagram while keeping the real magnetization of the system fixed. We experimentally demonstrate the use of such method to explore different phases in a sample with zero total magnetization. Our work opens up new perspectives to study isothermal quenching dynamics through different magnetic phases in spinor condensates.
MTX is widely used to treat synovitis in PsA without supporting trial evidence. The aim of our study was to test the value of MTX in the first large randomized placebo-controlled trial (RCT) in PsA.
...A 6-month double-blind RCT compared MTX (15 mg/week) with placebo in active PsA. The primary outcome was PsA response criteria (PsARC). Other outcomes included ACR20, DAS-28 and their individual components. Missing data were imputed using multiple imputation methods. Treatments were compared using logistic regression analysis (adjusted for age, sex, disease duration and, where appropriate, individual baseline scores).
Four hundred and sixty-two patients were screened and 221 recruited. One hundred and nine patients received MTX and 112 received placebo. Forty-four patients were lost to follow-up (21 MTX, 23 placebo). Twenty-six patients discontinued treatment (14 MTX, 12 placebo). Comparing MTX with placebo in all randomized patients at 6 months showed no significant effect on PsARC odds ratio (OR) 1.77, 95% CI 0.97, 3.23, ACR20 (OR 2.00, 95% CI 0.65, 6.22) or DAS-28 (OR 1.70, 95% CI 0.90, 3.17). There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ and pain. The only benefits of MTX were reductions in patient and assessor global scores and skin scores at 6 months (P = 0.03, P < 0.001 and P = 0.02, respectively). There were no unexpected adverse events.
This trial of active PsA found no evidence for MTX improving synovitis and consequently raises questions about its classification as a disease-modifying drug in PsA. Trial registration. Current Controlled Trials, www.controlled-trials.com, ISRCTN:54376151.
ObjectivesTo evaluate the prevalence and identify demographic, economic and environmental local community determinants of chronic obstructive pulmonary disease (COPD) exacerbations in elderly in ...primary care using Big Data approach.DesignRetrospective observational case–control study based on Big Data from the National Health Found, Tax Office and National Statistics Center databases in 2016.SettingPrimary care clinics in the Lodz province in Poland.Participants472 314 patients aged 65 and older in primary care, including 17 240 patients with COPD and 1784 with exacerbations (including deaths).Outcome measuresExacerbations with demographic, economic and environmental local community determinants were retrieved. Conditional logistic regression for matched pairs was used to evaluate the local community determinants of COPD exacerbations among patients with COPD.ResultsThe overall prevalence of COPD in the population of elderly patients registered in primary healthcare clinic clinics in Lodz province in 2016 was 3.65%, 95% CI (3.60% to 3.70%) and the prevalence of exacerbations was 10.35%, 95% CI (9.89% to 10.80%). The high number of consultations in primary care clinics was associated with higher risk of COPD exacerbations (p=0.0687).High-income patients were less likely to have exacerbations than low-income patients (high vs low OR 0.601, 95% CI (0.385 to 0.939)). The specialisation of the primary care physician did not have an effect on exacerbations (OR 1.076, 95% CI (0.920 to 1.257)). Neither the forest cover per gmina (high vs low OR 0.897, 95% CI (0.605 to 1.331); medium vs low OR 0.925, 95% CI (0.648 to 1.322)), nor location of gmina (urban vs urban–rural OR 1.044; 95% CI (0.673 to 1.620)), (rural vs urban–rural OR 0.897, 95% CI (0.630 to 1.277)) appears to influence COPD exacerbations.ConclusionsBig Data statistical analysis facilitated the evaluation of the prevalence and determinants of COPD exacerbation in the elderly residents of Lodz province, Poland.Modification of identified local community determinants may potentially decrease the number of exacerbations in elderly patients with COPD.
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