Miracle-dz/UniFAR-FTUs huggingface dataset:
Urinary tract infections in multiple sclerosis: under-diagnosed and under-treated? A clinical audit at a large University Hospital.

Multiple sclerosis (MS) is a chronic demyelinating immune-mediated disease of the central nervous system. Infections have been implicated in different aspects of the disease such as induction of relapses and possibly, progression. Bladder dysfunction and associated urinary tract colonization (UTC) and infections (UTIs) are common in MS patients. UTIs can exacerbate neurological symptoms in MS, whilst high-dose steroid treatment of acute neurological worsening with concurrent untreated UTC may lead to unmasking of infection. This clinical audit was designed to investigate whether our institution is adhering to the National Institute for Health Care and Excellence (NICE) Clinical Guideline 148 for the management of patients with lower urinary tract symptoms due to neurogenic bladder dysfunction. We identified 21 patients with abnormal urine dipsticks out of 118 patients presenting at Nottingham University Hospitals for clinical review or for assessment of a relapse. Patients were asked about catheter status and the presence of any lower urinary tract symptoms. In all cases of relapse assessment, current practice at our institution had been to delay treatment with methylprednisolone (MP), pending the results of microbiology culture and sensitivity testing. If the patient was confirmed to have an infection, treatment with MP was delayed further awaiting completion of a course of antibiotics. We suggest that corticosteroid treatment need not be delayed but rather administered simultaneously with antibiotic treatment for the UTI, provided that the patient has no systemic symptoms of infection (e.g. fever, rigors, raised CRP). Patients must be educated and cautioned to contact their doctor in the event that systemic symptoms do develop during treatment.
Compartmentalization of signaling by vesicular trafficking: a shared building design for the immune synapse and the primary cilium

Accumulating evidence underscores the immune synapse (IS) of naive T cells as a site of intense vesicular trafficking. At variance with helper and cytolytic effectors, which use the IS as a secretory platform to deliver cytokines and/or lytic granules to their cellular targets, this process is exploited by naive T cells as a means to regulate the assembly and maintenance of the IS, on which productive signaling and cell activation crucially depend. We have recently identified a role of the intraflagellar transport (IFT) system, which is responsible for the assembly of the primary cilium, in the non‐ciliated T‐cell, where it controls IS assembly by promoting polarized T‐cell receptor recycling. This unexpected finding not only provides new insight into the mechanisms of IS assembly but also strongly supports the notion that the IS and the primary cilium, which are both characterized by a specialized membrane domain highly enriched in receptors and signaling mediators, share architectural similarities and are homologous structures. Here, we review our current understanding of vesicular trafficking in the regulation of the assembly and maintenance of the naive T‐cell IS and the primary cilium, with a focus on the IFT system.
Particulate Matter Physicochemistry and Toxicology: In Search of Causality—A Critical Perspective

Results from epidemiology studies have shown statistical associations between ambient air particulate matter (PM) concentrations and mortality/morbidity, particularly among susceptible subpopulations. Although the epidemiology of ambient air PM is compelling, there remains considerable uncertainty in PM risk assessment, particularly with regard to identification of PM properties and mechanisms that are responsible for its observed adverse health effects. In addition, the biological mechanisms by which specific PM properties mediate their adverse health effects are currently not known. In vivo and in vitro toxicological studies have examined particles derived from a number of sources such as ambient air, combustion, and natural sources, as well as laboratory-derived surrogate particles, in order to identify the characteristics of particles that are responsible for their adverse health effects. These studies have identified a number of potential causal biogenic, physical, and chemical properties of PM. A number of PM physical and chemical properties have been found to elicit biological responses in animal models of disease, which has enhanced their plausibility as being properties responsible for PM-associated health effects. In vitro mechanistic studies have shown that PM derived from a variety of sources mediate their adverse biological effects by inducing an oxidative stress, which may alter intracellular signal transduction pathways that regulate a number of biological responses such as cell growth, stress response, apoptosis, and inflammation. The challenge of future PM toxicology research will be to demonstrate “biological plausibility and coherence” for potential causal PM properties.
The use of brief interventions adapted from motivational interviewing across behavioral domains: a systematic review.

AIMS To examine the effectiveness of brief behavioral interventions adapting the principles and techniques of Motivational Interviewing (MI) to four behavioral domains: substance abuse, smoking, HIV risk and diet/exercise. DESIGN We conducted a systematic review of 29 randomized trials of MI interventions. Data on methodological quality were extracted and tabulated. Between-group behavior change effect sizes and confidence intervals were calculated for each study. FINDINGS Due to varying intervention time lengths, targeted problem behaviors, settings and interventionists' backgrounds and skill levels, outcomes were not combined meta-analytically. Sixty per cent of the 29 studies yielded at least one significant behavior change effect size. No significant association between length of follow-up time and magnitude of effect sizes was found across studies. There was substantial evidence that MI is an effective substance abuse intervention method when used by clinicians who are non-specialists in substance abuse treatment, particularly when enhancing entry to and engagement in more intensive substance abuse treatment treatment-as-usual. Data were inadequate to judge the effect of MI in the other domains. Client attribute-treatment interactions were understudied and the sparse and inconsistent findings revealed little about the mechanism by which MI works or for whom it works best. CONCLUSION To determine more effectively how well MI works in domains other than substance abuse and for whom it works best in all domains, researchers should study MI with risk behaviors other than substance abuse, while examining both interactions and the theoretical components of MI.
MRI Profile of the Perihematomal Region in Acute Intracerebral Hemorrhage

Background and Purpose— The pathophysiology of the presumed perihematomal edema immediately surrounding an acute intracerebral hemorrhage is poorly understood, and its composition may influence clinical outcome. Method— Twenty-three patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were prospectively enrolled and studied with MRI. Perfusion-weighted imaging, diffusion-weighted imaging, and fluid-attenuated inversion recovery sequences were coregistered. TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient values in the presumed perihematomal edema regions of interest were compared with contralateral mirror and remote ipsilateral hemispheric regions of interest. Results— Compared with mirror and ipsilateral hemispheric regions of interest, TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient were consistently increased in the presumed perihematomal edema. Two thirds of the patients also exhibited patchy regions of restricted diffusion in the presumed perihematomal edema. Conclusion— The MRI profile of the presumed perihematomal edema in acute intracerebral hemorrhage exhibits delayed perfusion and increased diffusivity mixed with areas of reduced diffusion.
Measure DP Adverbials : Measure Phrase Modification in VP

This paper seeks to establish that measure phrases in the extended AP and PP—such as six feet tall and twenty minutes before midnight—have a direct counterpart in the verbal domain. These verbal measure phrases, exemplified in English in e.g. He slept several hours, constitute a natural class distinct from other DP adverbials and characterized by obligatorily narrow scope, low structural position, an Aktionsart-related presupposition, and quantificationally weak interpretations. This constellation of characteristics is shown to follow naturally from the view that these expressions mirror core syntactic and semantic properties of AP and PP measure phrases. In particular, it will be argued here that these expressions have a syntax that places them in the specifier of a functional projection, just as has long been assumed for AP/PP measure phrases and as has been proposed in a different and independent line of research for adverbials more generally; and that they have a semantics in which they are interpreted as arguments of the head of this licensing projection, and therefore scopally and distributionally constrained and implicated in the aspectual semantics of the clause. Aktionsart information which cannot plausibly come from the DP itself is thereby attributed instead to a verbal feature responsible for licensing the adverbial. Independent evidence for this approach is adduced from true adverbs and parallels with proposals made in the analysis of accusative adverbials in Slavic and in Finnish.
Weak magnetism and non-Fermi liquids near heavy-fermion critical points

This paper is concerned with the weak-moment magnetism in heavy-fermion materials and its relation to the non-Fermi liquid physics observed near the transition to the Fermi liquid. We explore the hypothesis that the primary fluctuations responsible for the non-Fermi liquid physics are those associated with the destruction of the large Fermi surface of the Fermi liquid. Magnetism is suggested to be a low-energy instability of the resulting small Fermi surface state. A concrete realization of this picture is provided by a fractionalized Fermi liquid state which has a small Fermi surface of conduction electrons, but also has other exotic excitations with interactions described by a gauge theory in its deconfined phase. Of particular interest is a three-dimensional fractionalized Fermi liquid with a spinon Fermi surface and a U(1) gauge structure. A direct second-order transition from this state to the conventional Fermi liquid is possible and involves a jump in the electron Fermi surface volume. The critical point displays non-Fermi liquid behavior. A magnetic phase may develop from a spin density wave instability of the spinon Fermi surface. This exotic magnetic metal may have a weak ordered moment although the local moments do not participate in the Fermi surface. Experimental signatures of this phase and implications for heavy-fermion systems are discussed.
Hepatitis B viral DNA is methylated in liver tissues

Summary. The mechanisms that regulate hepatitis B virus (HBV) replication within the liver are poorly understood. Given that methylation of CpG islands regulates gene expression in human tissues, we sought to identify CpG islands in HBV‐DNA and to determine if they are methylated in human tissues. In silico analysis demonstrated three CpG islands in HBV genotype A sequences, two of which were of particular interest because of their proximity to the HBV surface gene start codon (island 1) and to the enhancer 1/X gene promoter region (island 2). Human sera with intact virions that were largely unmethylated were used to transfect HepG2 cells and HBV‐DNA became partially methylated at both islands 1 and 2 by day 6 following exposure of HepG2 to virus. Examination of three additional human sera and 10 liver tissues showed no methylation in sera but tissues showed methylation of island 1 in six of 10 cases and of island 2 in five of 10 cases. The cell line Hep3B, with integrated HBV, showed complete methylation of island 1 but no methylation of island 2. In conclusion, HBV‐DNA can be methylated in human tissues and methylation may play an important role in regulation of HBV gene expression.
Experimental validation of a proposed single-phase five-level active rectifier operating with model predictive current control

This paper presents a model predictive current control applied to a proposed single-phase five-level active rectifier (FLAR). This current control strategy uses the discrete-time nature of the active rectifier to define its state in each sampling interval. Although the switching frequency is not constant, this current control strategy allows to follow the reference with low total harmonic distortion (THDF). The implementation of the active rectifier that was used to obtain the experimental results is described in detail along the paper, presenting the circuit topology, the principle of operation, the power theory, and the current control strategy. The experimental results confirm the robustness and good performance (with low current THDF and controlled output voltage) of the proposed single-phase FLAR operating with model predictive current control.
Clinical Neuropsychology Within Adolescent and Young-Adult Psychiatry: Conceptualizing Theory and Practice

Historically, clinical neuropsychology has made significant contributions to the understanding of brain–behavior relationships, particularly in neurological conditions. During the past several decades, neuropsychology has also become established as an important discipline in psychiatric settings. Cognition is increasingly recognized as being core to psychiatric illnesses and predictive of functional outcomes, augmenting theories regarding symptomatology and illness progression. Adult-type psychiatric disorders (including schizophrenia and other psychotic, mood, anxiety, eating, substance-related, and personality disorders) typically emerge during adolescence or young adulthood, a critical neurodevelopmental period. Clinical neuropsychological assessment in adolescent psychiatric patients is particularly valuable in informing clinical formulation and intervention and can be therapeutic across a number of levels. This article articulates the theoretical considerations and practical challenges and applications of clinical neuropsychology within adolescent and young-adult psychiatry. The importance of considering the neurodevelopmental context and its relationship to current theoretical models underpinning clinical practice are discussed.
Seismic triggering by rectified diffusion in geothermal systems

Widespread seismicity was triggered by the June 28, 1992, Landers California, earthquake at a rate which was maximum immediately after passage of the exciting seismic waves. Rectified diffusion of vapor from hydrothermal liquids and magma into bubbles oscillating in an earthquake can increase the local pore pressure to seismically significant levels within the duration of the earthquake. In a hydrothermal system modeled as a two-component H_2O-CO_2 fluid in porous rock the pressure initially increases linearly with time. The rate of pressure buildup depends sensitively on the mean bubble radius and is large for small bubbles. The diffusion-induced pressure is relaxed by percolation and resorption of vapor into the liquid solution. The induced seismicity itself also relieves stress. Values of parameters used in the present calculations give results consistent with observations of triggered seismicity at Long Valley caldera after the Landers earthquake. For one representative condition, at 250°C and 5.6 km depth, oscillating strain acting on 10-μm-diameter bubbles increases pore pressure at the rate of 151 Pa/s resulting in a pressure increase of 12 kPa in the 80-s duration of the Landers earthquake. The elevated pressure induced by a single 26-m-diameter cloud of bubbles in saturated rock relaxes by percolation through soil of 0.2-mdarcy permeability in 53.6 hours. Observations of earthquake swarms at other locations suggest that self-induced buildup of pore pressure by rectified diffusion can provide a positive feedback mechanism for amplifying seismicity.
Pathfinding: A design methodology for fast exploration and optimisation of 3D-stacked integrated circuits

This paper introduces new design methodology and the corresponding EDA tool chain enabling fast design space exploration and high fidelity of results for emerging heterogeneous 3D-Stacked Integrated Circuits. The proposed framework allows designers to easily trade-off between different system level design choices (e.g. functional partitioning), physical design options (e.g. packaging strategies) and/or technology options (e.g. different technology nodes) and understand their impact on typical design parameters such as cost, performance and power. We demonstrate the proposed framework using existing MPSoC for video coding applications. The system is virtually prototyped as traditional 2D and then 3D design. For a 3D version we place the off-chip DRAM memory on the top of the processing die, and consider different packaging options. For different implementation scenarios we quantify typical design parameters showing the benefits of the 3D integration.
Quantile Regression Analysis of Microlending ’ s Poverty Impact

This paper aims to evaluate the impact of a microlending program on ameliorating measured poverty within its client population, with the aim of improving that impact. We analyze over 18,000 women micro-finance clients of the Negros Women for Tomorrow Foundation (NWTF), a database using the Progress out of Poverty (PPI) Scorecard as a measure of poverty. Analysis using both OLS and quantile multivariate regression models shows how observable borrower attributes affect the ability of clients to reduce their measured poverty. Loan size, duration, and the economic activity supported all have strongly identifiable effects. Moreover, estimates suggest which among the poor are receiving the greatest effective help by the program. Results offer specific advice to the NWTF and other micro-lenders: impact is greatest with fewer, larger loans in particular economic sectors (sari-sari, service and trade) but require patience as each additional year increases the client‟s average change in poverty score.
Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis

West Nile virus (WNV) has emerged as a significant cause of epidemic viral encephalitis and flaccid limb paralysis, yet the mechanism by which it enters the CNS remains uncertain. We used compartmentalized neuron cultures to demonstrate that WNV spreads in both retrograde and anterograde directions via axonal transport. Transneuronal spread of WNV required axonal release of viral particles and was blocked by addition of a therapeutic neutralizing antibody. To test the physiologic significance of axonal transport in vivo, we directly inoculated the sciatic nerve of hamsters with WNV. Intrasciatic infection resulted in paralysis of the hind limb ipsilateral but not contralateral to the injection site. Limb paralysis was blocked either by surgical transection of the sciatic nerve or treatment with the therapeutic neutralizing antibody. Collectively, these studies establish that WNV undergoes bidirectional spread in neurons and that axonal transport promotes viral entry into the CNS and acute limb paralysis. Moreover, antibody therapeutics directly inhibit transneuronal spread of WNV infection and prevent the development of paralysis in vivo.
Novel substituted heteroaromatic compounds as inhibitors of stearoyl-CoA desaturase

Stearoyl-CoA desaturase 1 (SCD1) has been implicated as a novel therapeutic target for the treatment of a variety of metabolic diseases, including diabetes, obesity, hepatic steatosis, atherosclerosis and cardiovascular disease. The application WO2009129625 from Merck Frosst Canada claims novel substituted heteroaromatic compounds as inhibitors of SCD and potential drugs for the pharmacological treatment of metabolic disorders, when used alone or in combination with other drugs. Based on in vitro activity of the patented compounds, these molecules may be considered as potential SCD inhibitors and could be of therapeutic value. However, further preclinical studies are needed to evaluate their curative potential and safety before clinical development.
Longitudinal melanonychia: a distinguishing feature of Bowen’s disease of the nail unit associated withhumanpapillomavirus type 56

Bowen's disease (BD) is uncommon in the nail unit and periungual areas. BD of the nail unit has multiple clinical presentations, which often makes diagnosis challenging. It can present as hyperkeratotic, papillomatous, or warty proliferations, erosions or scaling of the nail fold, or ulceration of the lateral nail groove, sometimes with granulation-like tissue underneath. Rarely, longitudinal melanonychia has also been reported as a presentation of BD of the nail unit.The majority of reported digital [. ]
Machiavellianism in Children in Dutch Elementary Schools and Sports Clubs: Prevalence and Stability According to Context, Sport Type, and Gender

The majority of research on children’s peer aggression has focused exclusively on the school context. Very few studies have investigated peer aggression in sports clubs. The prevalence and stability of peer aggression, prosocial behavior, and resource control strategies for children participating in three types of sports (martial arts, contact, and noncontact sports) were examined in two contexts: the sports club and the elementary school. We distinguished aggressive children with (i.e., Machiavellians) and without prosocial tendencies (i.e., coercive-aggressive children). Self-reports about experiences in the two contexts where gathered from 1,425 Dutch elementary school students (717 boys and 708 girls, fourth to sixth grade, mean age 11.25 years) who were participating in a sports club. We found roles for resource control strategies to be rather stable across contexts. The findings did not provide support for the “enhancement” assumption in these contexts with regard to martial arts participants.