Oedema of the metatarsal heads II-IV and forefoot pain as an unusual manifestation of Lyme disease: a case report

We report the case of a healthy 36 year old man who suffered from foot pain lasting for weeks, without having a specific medical history relating to it. The clinical evaluation was interpreted as a transfer metatarsalgia caused by a splayfoot. The radiographs revealed no pathology except the splayfoot deformity. Due to persistent pain and swelling of the entire forefoot, after two weeks of conventional treatment, magnet resonance images (MRI) and a blood sample were taken. The laboratory investigation showed raised levels of white blood cell count and C-reactive protein. The MRI showed up oedema in the metatarsal heads II-IV, as well as soft tissue swelling of the forefoot without any signs of decomposition

Assessment of long-range correlation in animal behaviour time series: the temporal pattern of locomotor activity of Japanese quail (Coturnix coturnix) and mosquito larva (Culex quinquefasciatus)

The aim of this study was to evaluate the performance of a classical method of fractal analysis, Detrended Fluctuation Analysis (DFA), in the analysis of the dynamics of animal behavior time series. In order to correctly use DFA to assess the presence of long-range correlation, previous authors using statistical model systems have stated that different aspects should be taken into account such as: 1) the establishment by hypothesis testing of the absence of short term correlation, 2) an accurate estimation of a straight line in the log-log plot of the fluctuation function, 3) the elimination of artificial crossovers in the fluctuation function, and 4) the length of the time series. Taking into consideration these factors, herein we evaluated the presence of long-range correlation in the temporal pattern of locomotor activity of Japanese quail ({\sl Coturnix coturnix}) and mosquito larva ({\sl Culex quinquefasciatus}). In our study, modeling the data with the general ARFIMA model, we rejected the hypothesis of short range correlations (d=0) in all cases. We also observed that DFA was able to distinguish between the artificial crossover observed in the temporal pattern of locomotion of Japanese quail, and the crossovers in the correlation behavior observed in mosquito larvae locomotion. Although the test duration can slightly influence the parameter estimation, no qualitative differences were observed between different test durations

Spectrum and Inoculum Size Effect of a Rapid Antigen Detection Test for Group A Streptococcus in Children with Pharyngitis

BACKGROUND: The stability of the accuracy of a diagnostic test is critical to whether clinicians can rely on its result. We aimed to assess whether the performance of a rapid antigen detection test (RADT) for group A streptococcus (GAS) is affected by the clinical spectrum and/or bacterial inoculum size. METHODS: Throat swabs were collected from 785 children with pharyngitis in an office-based, prospective, multicenter study (2009-2010). We analysed the effect of clinical spectrum (i.e., the McIsaac score and its components) and inoculum size (light or heavy GAS growth) on the accuracy (sensitivity, specificity, likelihood ratios and predictive values) of a RADT, with laboratory throat culture as the reference test. We also evaluated the accuracy of a McIsaac-score-based decision rule. RESULTS: GAS prevalence was 36% (95CI: 33%-40%). The inoculum was heavy for 85% of cases (81%-89%). We found a significant spectrum effect on sensitivity, specificity, likelihood ratios and positive predictive value (p<0.05) but not negative predictive value, which was stable at about 92%. RADT sensitivity was greater for children with heavy than light inoculum (95% vs. 40%, p<0.001). After stratification by inoculum size, the spectrum effect on RADT sensitivity was significant only in patients with light inoculum, on univariate and multivariate analysis. The McIsaac-score-based decision rule had 99% (97%-100%) sensitivity and 52% (48%-57%) specificity. CONCLUSIONS: Variations in RADT sensitivity only occur in patients with light inocula. Because the spectrum effect does not affect the negative predictive value of the test, clinicians who want to rule out GAS can rely on negative RADT results regardless of clinical features if they accept that about 10% of children with negative RADT results will have a positive throat culture. However, such a policy is more acceptable in populations with very low incidence of complications of GAS infection

Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich Ataxia

Copyright © 2014 Anjomani Virmouni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background - Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC) transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats), YG8R (90 and 190 GAA repeats) and YG22R (190 GAA repeats). Methodology/Principal Findings - We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH) analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R. Conclusions/Significance - Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.European Union, Ataxia UK and FARA

Switching of magnetic domains reveals evidence for spatially inhomogeneous superconductivity

The interplay of magnetic and charge fluctuations can lead to quantum phases with exceptional electronic properties. A case in point is magnetically-driven superconductivity, where magnetic correlations fundamentally affect the underlying symmetry and generate new physical properties. The superconducting wave-function in most known magnetic superconductors does not break translational symmetry. However, it has been predicted that modulated triplet p-wave superconductivity occurs in singlet d-wave superconductors with spin-density wave (SDW) order. Here we report evidence for the presence of a spatially inhomogeneous p-wave Cooper pair-density wave (PDW) in CeCoIn5. We show that the SDW domains can be switched completely by a tiny change of the magnetic field direction, which is naturally explained by the presence of triplet superconductivity. Further, the Q-phase emerges in a common magneto-superconducting quantum critical point. The Q-phase of CeCoIn5 thus represents an example where spatially modulated superconductivity is associated with SDW order

Post-streptococcal reactive arthritis in children: a distinct entity from acute rheumatic fever

There is a debate whether post-streptococcal reactive arthritis (PSRA) is a separate entity or a condition on the spectrum of acute rheumatic fever (ARF). We believe that PSRA is a distinct entity and in this paper we review the substantial differences between PSRA and ARF. We show how the demographic, clinical, genetic and treatment characteristics of PSRA differ from ARF. We review diagnostic criteria and regression formulas that attempt to classify patients with PSRA as opposed to ARF. The important implication of these findings may relate to the issue of prophylactic antibiotics after PSRA. However, future trials will be necessary to conclusively answer that question

Design and formative evaluation of a virtual voice-based coach for problem-solving treatment: Observational study

BACKGROUND: Artificial intelligence has provided new opportunities for human interactions with technology for the practice of medicine. Among the recent artificial intelligence innovations, personal voice assistants have been broadly adopted. This highlights their potential for health care-related applications such as behavioral counseling to promote healthy lifestyle habits and emotional well-being. However, the use of voice-based applications for behavioral therapy has not been previously evaluated. OBJECTIVE: This study aimed to conduct a formative user evaluation of Lumen, a virtual voice-based coach developed as an Alexa skill that delivers evidence-based, problem-solving treatment for patients with mild to moderate depression and/or anxiety. METHODS: A total of 26 participants completed 2 therapy sessions-an introductory (session 1) and a problem-solving (session 2)-with Lumen. Following each session with Lumen, participants completed user experience, task-related workload, and work alliance surveys. They also participated in semistructured interviews addressing the benefits, challenges and barriers to Lumen use, and design recommendations. We evaluated the differences in user experience, task load, and work alliance between sessions using 2-tailed paired t tests. Interview transcripts were coded using an inductive thematic analysis to characterize the participants\u27 perspectives regarding Lumen use. RESULTS: Participants found Lumen to provide high pragmatic usability and favorable user experience, with marginal task load during interactions for both Lumen sessions. However, participants experienced a higher temporal workload during the problem-solving session, suggesting a feeling of being rushed during their communicative interactions. On the basis of the qualitative analysis, the following themes were identified: Lumen\u27s on-demand accessibility and the delivery of a complex problem-solving treatment task with a simplistic structure for achieving therapy goals; themes related to Lumen improvements included streamlining and improved personalization of conversations, slower pacing of conversations, and providing additional context during therapy sessions. CONCLUSIONS: On the basis of an in-depth formative evaluation, we found that Lumen supported the ability to conduct cognitively plausible interactions for the delivery of behavioral therapy. Several design suggestions identified from the study including reducing temporal and cognitive load during conversational interactions, developing more natural conversations, and expanding privacy and security features were incorporated in the revised version of Lumen. Although further research is needed, the promising findings from this study highlight the potential for using Lumen to deliver personalized and accessible mental health care, filling a gap in traditional mental health services

Large Process Models: Business Process Management in the Age of Generative AI

The continued success of Large Language Models (LLMs) and other generative artificial intelligence approaches highlights the advantages that large information corpora can have over rigidly defined symbolic models, but also serves as a proof-point of the challenges that purely statistics-based approaches have in terms of safety and trustworthiness. As a framework for contextualizing the potential, as well as the limitations of LLMs and other foundation model-based technologies, we propose the concept of a Large Process Model (LPM) that combines the correlation power of LLMs with the analytical precision and reliability of knowledge-based systems and automated reasoning approaches. LPMs are envisioned to directly utilize the wealth of process management experience that experts have accumulated, as well as process performance data of organizations with diverse characteristics, e.g., regarding size, region, or industry. In this vision, the proposed LPM would allow organizations to receive context-specific (tailored) process and other business models, analytical deep-dives, and improvement recommendations. As such, they would allow to substantially decrease the time and effort required for business transformation, while also allowing for deeper, more impactful, and more actionable insights than previously possible. We argue that implementing an LPM is feasible, but also highlight limitations and research challenges that need to be solved to implement particular aspects of the LPM vision

Fractal superconductivity near localization threshold

We develop a semi-quantitative theory of electron pairing and resulting superconductivity in bulk "poor conductors" in which Fermi energy $E_F$ is located in the region of localized states not so far from the Anderson mobility edge $E_c$. We review the existing theories and experimental data and argue that a large class of disordered films is described by this model. Our theoretical analysis is based on the analytical treatment of pairing correlations, described in the basis of the exact single-particle eigenstates of the 3D Anderson model, which we combine with numerical data on eigenfunction correlations. Fractal nature of critical wavefunction's correlations is shown to be crucial for the physics of these systems. We identify three distinct phases: 'critical' superconductive state formed at $E_F=E_c$, superconducting state with a strong pseudogap, realized due to pairing of weakly localized electrons and insulating state realized at $E_F$ still deeper inside localized band. The 'critical' superconducting phase is characterized by the enhancement of the transition temperature with respect to BCS result, by the inhomogeneous spatial distribution of superconductive order parameter and local density of states. The major new feature of the pseudo-gaped state is the presence of two independent energy scales: superconducting gap $\Delta$, that is due to many-body correlations and a new "pseudogap" energy scale $\Delta_P$ which characterizes typical binding energy of localized electron pairs and leads to the insulating behavior of the resistivity as a function of temperature above superconductive $T_c$. Two gap nature of the "pseudo-gaped superconductor" is shown to lead to a number of unusual physical properties.Comment: 110 pages, 39 figures. The revised version corrects a number of typos, adds references and discussion of recent result

Detection and quantification of fluconazole within Candida glabrata biofilms

Candida infections are often associated with biofilms and consequent high resistance to most common drugs (e.g. azoles). These resistance mechanisms are not only associated with the biofilm yeast physiology, but also with the presence of a diffusional barrier imposed by the biofilm matrix; however, the real biochemical role of the biofilm components remains very unclear. So, in order to further clarify this issue, we intend to determine, for the first time, fluconazole in biofilms within both supernatants and matrices. Candida biofilms were formed in the presence of fluconazole, and it was recovered from both supernatant and matrix cell-free fractions. Then, high-pressure liquid chromatography was used to identify and quantify the amount of drug that was present in the two fractions. Moreover, this study also showed that the presence of fluconazole in both fractions indicated that the drug administrated did not completely reach the cells, so this phenomena can easily be associated with lower biofilm susceptibility, since the drug administered did not completely reach the cells.This work was supported by the Programa Operacional, Fatores de competitividade-COMPETE and by national funds through FCT-Fundacao para a Ciencia e a Tecnologia on the scope of the projects FCT PTDC/SAU-MIC/119069/2010, RECI/EBB-EBI/0179/2012, PEst-OE/EQB/LA0023/2013 and Celia F. Rodrigue's SFRH/BD/93078/2013 PhD grant. The authors thank the Project "BioHealth-Biotechnology and Bioengineering approaches to improve health quality,'' Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON. 2-O Novo Norte), QREN, FEDER. We also would like to acknowledge Pfizer (R), S.A., for the kindly donation of fluconazole