Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered Micafungin Pharmacokinetics in Intensive Care Unit Patients

ABSTRACT Micafungin is considered an important agent for the treatment of invasive fungal infections in the intensive care unit (ICU). Little is known on the pharmacokinetics of micafungin. We investigated micafungin pharmacokinetics (PK) in ICU patients and set out to explore the parameters that influence micafungin plasma concentrations. ICU patients receiving 100 mg of intravenous micafungin once daily for suspected or proven fungal infection or as prophylaxis were eligible. Daily trough concentrations and PK curves (days 3 and 7) were collected. Pharmacokinetic analysis was performed using a standard two-stage approach. Twenty patients from the ICUs of four hospitals were evaluated. On day 3 (n = 20), the median (interquartile range [IQR]) area under the concentration-time curve from 0 to 24 h (AUC0–24) was 78.6 (65.3 to 94.1) mg · h/liter, the maximum concentration of drug in serum (Cmax) was 7.2 (5.4 to 9.2) mg/liter, the concentration 24 h after dosing (C24) was 1.55 (1.4 to 3.1) mg/liter, the volume of distribution (V) was 25.6 (21.3 to 29.1) liters, the clearance (CL) was 1.3 (1.1 to 1.5) liters/h, and the elimination half-life (t1/2) was 13.7 (12.2 to 15.5) h. The pharmacokinetic parameters on day 7 (n = 12) were not significantly different from those on day 3. Daily trough concentrations (day 3 to the end of therapy) showed moderate interindividual (57.9%) and limited intraindividual variability (12.9%). No covariates of the influence on micafungin exposure were identified. Micafungin was considered safe and well tolerated. We performed the first PK study with very intensive sampling on multiple occasions in ICU patients, which aided in resolving micafungin PK. Strikingly, micafungin exposure in our cohort of ICU patients was lower than that in healthy volunteers but not significantly different from that of other reference populations. The clinical consequence of these findings must be investigated in a pharmacokinetic-pharmacodynamic (PK-PD) study incorporating outcome in a larger cohort. (This study is registered at ClinicalTrials.gov under registration no. NCT01783379.)
Output-sensitive Evaluation of Prioritized Skyline Queries

Skylines assume that all attributes are equally important, as each dimension can always be traded off for another. Prioritized skylines (p-skylines) take into account non-compensatory preferences, where some dimensions are deemed more important than others, and trade-offs are constrained by the relative importance of the attributes involved. In this paper we show that querying using non-compensatory preferences is computationally efficient. We focus on preferences that are representable with p-expressions, and develop an efficient in-memory divide-and-conquer algorithm for answering p-skyline queries. Our algorithm is output-sensitive; this is very desirable in the context of preference queries, since the output is expected to be, on average, only a small fraction of the input. We prove that our method is well behaved in both the worst- and the average-case scenarios. Additionally, we develop a general framework for benchmarking p-skyline algorithms, showing how to sample prioritized preference relations uniformly, and how to highlight the effect of data correlation on performance. We conclude our study with extensive experimental results.
Clinical characteristics and predisposing factors in acute drug-induced akathisia.

BACKGROUND As subtypes of drug-induced akathisia have become accepted and attempts have been made at establishing diagnostic criteria, a prospective study of the clinical features and predisposing factors of acute akathisia is a significant deficiency in the literature. METHODS One hundred consecutive inpatients with non-organic psychotic disorders, not receiving neuroleptics or other drugs and free of akathisia and related disorders at admission, were assessed for psychiatric status and movement disorders at baseline and daily for 2 weeks, with detailed examinations on days 7 and 14. Multiple operational criteria for akathisia were used. The following risk factors were examined: age, sex, current neuroleptic dose, rate of increment of dose, drug type, duration of illness, past use of neuroleptics, extrapyramidal side effects score, Zung Depression Scale score, Spielberger State Anxiety Inventory score, psychosis score, and smoking. RESULTS Using a global rating, mild akathisia developed in 41% and moderate-to-severe akathisia in 21%. The symptoms that best discriminated akathisia from non-akathisia were shifting weight from foot to foot or walking on the spot, inability to keep legs still, feelings of inner restlessness, and shifting of body position in the chair. The subjective and objective symptoms loaded on separate factors. Akathisia ratings had low correlations with the anxiety and Zung scores. Receiver operating characteristic analysis suggested a cutoff score of 4 on our 10-item Akathisia Scale as optimal for the diagnosis of akathisia, with a stricter criterion of scores of 2 or more on both the subjective and objective items being more suitable for research diagnosis. The most significant predisposing factors were the extrapyramidal side effects score and current neuroleptic dose and its rate of increment, with lesser contributions from serum iron status and medication type. Predictability was, however, modest. CONCLUSION Acute akathisia is a common syndrome with well-defined clinical features. Its occurrence can be predicted with only modest accuracy.
Lesions in deep gray nuclei after severe traumatic brain injury predict neurologic outcome

Purpose This study evaluates the correlation between injuries to deep gray matter nuclei, as quantitated by lesions in these nuclei on MR T2 Fast Spin Echo (T2 FSE) images, with 6-month neurological outcome after severe traumatic brain injury (TBI). Materials and methods Ninety-five patients (80 males, mean age = 36.7y) with severe TBI were prospectively enrolled. All patients underwent a MR scan within the 45 days after the trauma that included a T2 FSE acquisition. A 3D deformable atlas of the deep gray matter was registered to this sequence; deep gray matter lesions (DGML) were evaluated using a semi-quantitative classification scheme. The 6-month outcome was dichotomized into unfavorable (death, vegetative or minimally conscious state) or favorable (minimal or no neurologic deficit) outcome. Results Sixty-six percent of the patients (63/95) had both satisfactory registration of the 3D atlas on T2 FSE and available clinical follow-up. Patients without DGML had an 89% chance (P = 0.0016) of favorable outcome while those with bilateral DGML had an 80% risk of unfavorable outcome (P = 0.00008). Multivariate analysis based on DGML accurately classified patients with unfavorable neurological outcome in 90.5% of the cases. Conclusion Lesions in deep gray matter nuclei may predict long-term outcome after severe TBI with high sensitivity and specificity.
Mutations in the major DNA-binding protein gene of herpes simplex virus type 1 result in increased levels of viral gene expression

We have examined the effect of temperature-sensitive mutations in the herpes simplex virus 1 DNA-binding protein gene on viral gene expression. We have found that at the nonpermissive temperature, the synthesis of certain immediate early, early, and late viral polypeptides was greater in cells infected with the temperature-sensitive mutants than in cells infected with the wild-type virus. This effect was independent of the requirement for this viral protein for viral DNA replication. The altered rate of synthesis of viral proteins was due to a thermolabile gene product. Cells infected with these mutants at the permissive temperature and then shifted to the nonpermissive temperature exhibited enhanced levels of viral gene expression. The addition of actinomycin D at the time of the temperature shift prevented the alteration in viral protein synthesis. Therefore, continuing transcription is required for this change in gene expression. Northern blot analysis of cytoplasmic RNA showed that the steady-state level of specific viral transcripts expressed from parental virus genomes was greater in cells infected by these mutants at the nonpermissive temperature. These results indicate that the major DNA-binding protein of herpes simplex virus type 1 acts as a negative regulator of viral gene expression by affecting the abundance of cytoplasmic viral mRNAs.
State space models for partially observed biological and agricultural data

x CHAPTER 1. A MATRIX EXPRESSION FOR PARTIALLY OBSERVED OR MISCLASSIFIED STATE SPACE DATA . 1 CHAPTER 2. DYNAMICS OF POPULATION GROWTH IN COLLETOTRICHUM ACUTATUM . 6 2.
Interleukin‐4 influences the production of microfilariae in a mouse model of Brugia infection

Sub‐cutaneous infection of interleukin (IL)‐4−/– mice on the BALB/c background with third stage larva (L3) of Brugia pahangi revealed an altered cytokine profile consistent with the absence of the Th2 promoting cytokine IL‐4. Splenocytes from IL‐4−/– mice secreted significantly more antigen (Ag)‐specific IL‐2 and interferon‐γ and significantly less Ag‐specific IL‐5, compared to those from L3‐infected wild‐type mice. However, levels of Ag‐specific IL‐13 were similar between groups. Despite the alteration in immune responses, there was no significant difference in recovery of developing worms from the peritoneal cavity of the two strains of mice at any time postinfection. However, at later time points of infection, the IL‐4−/– mice contained large numbers of microfilariae (Mf) in the peritoneal cavity while the wild‐type mice contained comparatively few Mf. The differences in Mf levels appear to relate to differences in worm fecundity in the two strains of mice, with adult female worms from the wild‐type mice containing few developing Mf. Moreover, implantation of sexually mature adult female worms into the peritoneal cavity of both strains of mice resulted in equal levels of Mf, confirming that the primary role of IL‐4 is to limit fecundity during the maturation phase of infection.
Reduced design time by load distribution with CAD framework methodology information

This paper is focused on reducing the design time in a CAD framework environment by the optimal use of resources. A user-transparent load distribution system (Framework based LOad Distribution System-FLODIS) is presented that enables a distributed execution of design tools over a heterogeneous network of workstations. The basic idea of the proposed algorithm is to allocate tools to workstations by using estimations about the required resources. These values can be obtained by user-defined tool characteristics, recorded previous tool executions and by methodology information provided by the framework. Compared with standard distribution approaches that use less information about the activities, experimental data show a significant average reduction (40-50%) of the tool execution time.
Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice

Abstract Objective To reassess the prevalence of aspirin induced asthma and other issues related to the syndrome. Data sources Biosis, SciSearch (1990 to March 2002), Embase (1974 to March 2002), Medline (1966 to March 2002), Toxline, Derwent Drug File (1964 to March 2002), Conference Papers Index and Inside Conferences, Int'l Pharmaceutical Abstracts, Pharma-Online (1978 to March 2002). Selection criteria Study type, patient population, and outcome measures. Review was restricted to respiratory responses to analgesics available without prescription. Results The prevalence of aspirin induced asthma was highest when determined by oral provocation testing (adults 21%, 95% confidence interval 14% to 29%; children 5%, 0% to 14%) than by verbal history (adults 3%, 2% to 4%; children 2%, 1% to 3%). Cross sensitivity to doses of over the counter non-steroidal anti-inflammatory drugs was present in most patients with aspirin induced asthma: ibuprofen, 98%; naproxen, 100%; and diclofenac, 93%. The incidence of cross sensitivity to paracetamol among such patients was only 7%. Conclusions Aspirin induced asthma in adults is more prevalent than previously suggested. When there is a clinical necessity to use aspirin or a non-steroidal anti-inflammatory drug and there is uncertainty about safety, oral provocation testing should be performed.
Emergence of Preferred Structures in a Simple Model of Protein Folding

Protein structures in nature often exhibit a high degree of regularity (for example, secondary structure and tertiary symmetries) that is absent from random compact conformations. With the use of a simple lattice model of protein folding, it was demonstrated that structural regularities are related to high “designability” and evolutionary stability. The designability of each compact structure is measured by the number of sequences that can design the structure—that is, sequences that possess the structure as their nondegenerate ground state. Compact structures differ markedly in terms of their designability; highly designable structures emerge with a number of associated sequences much larger than the average. These highly designable structures possess “proteinlike” secondary structure and even tertiary symmetries. In addition, they are thermodynamically more stable than other structures. These results suggest that protein structures are selected in nature because they are readily designed and stable against mutations, and that such a selection simultaneously leads to thermodynamic stability.
Scenario-based performance analysis of routing protocols for mobile ad-hoc networks

This study is a comparison of three routing protocols proposed for wireless mobile ad-hoc networks. The protocols are: Destination Sequenced Distance Vector (DSDV), Ad-hoc On demand Distance Vector (AODV) and Dynamic Source Routing (DSR). Extensive simulations are made on a scenario where nodes moves randomly. Results are presented as a function of a novel mobility metric designed to reflect the relative speeds of the nodes in a scenario. Furthermore, three realistic scenarios are introduced to test the protocols in more specialized contexts. In most simulations the reactive protocols (AODV and DSR) performed significantly better than DSDV. At moderate traffic load DSR performed better than AODV for all tested mobility values, while AODV performed better than DSR at higher traffic loads. The latter is caused by the source routes in DSR data packets, which increase the load on the network. routers and hosts, thus a node may forward packets between other nodes as well as run user applications. Mobile ad-hoc networks have been the focus of many recent research and development efforts. Ad-hoc packet radio networks have so far mainly concerned military applications, where a decentralized network configuration is an operative advantage or even a necessity. Networks using ad-hoc configuration concepts can be used in many military applications, ranging from interconnected wireless access points to networks of wireless devices carried by individuals, e.g., digital maps, sensors attached to the body, voice communication, etc. Combinations of wide range and short range ad-hoc networks seek to provide robust, global coverage, even during adverse operating conditions.
Dehydration of football referees during a match

Objectives: To study hydration status in referees (main) and assistant referees (linesmen) during official football matches. Methods: Twelve male football referees were evaluated; all were volunteers. Before and after each match, the referee and one of the assistants were weighed without clothes and a blood sample was taken. Total water loss was determined for each subject from the change in body weight. The main haematological variables were analysed in the blood samples. Total plasma protein concentration and osmolarity were also determined. Variation in plasma volume was determined from changes in packed cell volume and a combination of changes in packed cell volume and haemoglobin concentrations. Results: During a match, total body water loss was 1.60 (0.13) litres, equivalent to 2.05 (0.18)% of body weight. Body weight was reduced by 1.55 (0.12)%, showing that water ingestion during the interval replaces only 24.4% of the body fluids lost during the match. The assistants lost 0.79 (0.19) litre of water, equivalent to 1.05 (0.25)% of body weight. The referees showed a significant decrease in plasma volume of 4.99 (1.33)%. The assistants showed a non-significant increase in plasma volume. The reduction in plasma volume observed in the referees correlated significantly with total body water loss (r = 0.9623). From these data, it is possible to predict that a dehydration of 1% reflects a reduction in plasma volume of nearly 2.5%. Conclusions: Referees are moderately dehydrated after a football match (2%), whereas assistants show a non-significant dehydration of 1% of their body weight.
Assessing Creativity

In exploring the question of whether a computer program is behaving creatively, it is important to be explicit, and if possible formal, about the criteria that are being applied in making judgements of creativity. We propose a formal (and rather simplified) outline of the relevant attributes of a potentially creative program. Based on this, we posit a number of formal criteria that could be applied to rate the extent to which the program has behaved creatively. A guiding principle is that the question of what computational mechanisms might lead to creative behaviour is open and empirical, and hence we should clearly distinguish between judgements about creative achievements and theoretical proposals about potentially creative mechanisms. The intention is to focus, clarify and make more concrete the debate about creative programs.
A learned feature descriptor for object recognition in RGB-D data

In this work we address the problem of feature extraction for object recognition in the context of cameras providing RGB and depth information (RGB-D data). We consider this problem in a bag of features like setting and propose a new, learned, local feature descriptor for RGB-D images, the convolutional k-means descriptor. The descriptor is based on recent results from the machine learning community. It automatically learns feature responses in the neighborhood of detected interest points and is able to combine all available information, such as color and depth into one, concise representation. To demonstrate the strength of this approach we show its applicability to different recognition problems. We evaluate the quality of the descriptor on the RGB-D Object Dataset where it is competitive with previously published results and propose an embedding into an image processing pipeline for object recognition and pose estimation.
Is the ABCD Score Useful for Risk Stratification of Patients With Acute Transient Ischemic Attack?

Background and Purpose— A 6-point scoring system (ABCD) was described recently for stratifying risk after transient ischemic attack (TIA). This score incorporates age (A), blood pressure (B), clinical features (C), and duration (D) of TIA. A score <4 reportedly indicates minimal short-term stroke risk. We evaluated this scoring system in an independent population. Methods— This was a prospective study of TIA patients (diagnosed by a neurologist using the classic <24-hour definition) hospitalized <48 hours from symptom onset. The primary outcome assessment consisted of dichotomization of patients into 2 groups. The high-risk group included patients with stroke or death within 90 days, ≥50% stenosis in a relevant artery, or a cardioembolic source warranting anticoagulation. All others were classified as low risk. Findings on diffusion-weighted MRI (DWI) were also evaluated when performed and patients classified as DWI+ or DWI−. Results— Over 3 years, 117 patients were enrolled. Median time from symptom onset to enrollment was 25.2 hours (interquartile range 19.8 to 30.2). Overall, 26 patients (22%) were classified as high risk, including 2 strokes, 2 deaths, 15 with ≥50% stenosis, and 10 with cardioembolic source. The frequency of high-risk patients increased with ABCD score (0 to 1 13%; 2 8%; 3 17%; 4 27%; 5 26%; 6 30%; P for trend=0.11). ABCD scores in the 2 patients with stroke were 3 and 6. Of those who underwent MRI, 15 of 61 (25%) were DWI+, but this correlated poorly with ABCD score (0 to 1 17%; 2 10%; 3 36%; 4 24%; 5 13%; 6 60%; P for trend=0.24). Conclusions— Although the ABCD score has some predictive value, patients with a score <4 still have a substantial probability of having a high-risk cause of cerebral ischemia or radiographic evidence of acute infarction despite transient symptoms.
Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease

The efficacy of acetyl-L-carnitine (gamma-trimethyl-&bgr;-acetylbutyrobetaine (Alcar) in mild cognitive impairment (MCI) and mild (early) Alzheimer's disease (AD) was investigated with a meta-analysis of double-blind, placebo-controlled prospective, parallel group comparison studies of at least 3 months duration. The duration of the studies was 3, 6 or 12 months and the daily dose varied between studies from 1.5–3.0 g/day. An effect size was calculated to reflect the results of the variety of measures used in the studies grouped into the categories of clinical tests and psychometric tests. The effect sizes from the categories were integrated into an overall summary effect size. The effect size for the Clinical Global Impression of Change (CGI-CH) was calculated separately. Meta-analysis showed a significant advantage for Alcar compared to placebo for the integrated summary effect [ESall scales=0.201, 95% confidence interval (CI)=0.107–0.295] and CGI-CH (ESCGI-CH=0.32, 95% CI=0.18–0.47). The beneficial effects were seen on both the clinical scales and the psychometric tests. The advantage for Alcar was seen by the time of the first assessment at 3 months and increased over time. Alcar was well tolerated in all studies.
Outcome Measures for Individuals With Stroke: Process and Recommendations From the American Physical Therapy Association Neurology Section Task Force

Background and Purpose The use of standardized outcome measures (OMs) can support clinicians' development of appropriate care plans, guide educators in curricular decisions, and enhance the methodological quality and generalizability of clinical trials. The purposes of this case report are: (1) to describe a framework and process for assessing psychometrics and clinical utility of OMs used poststroke; (2) to describe a consensus process used to develop recommendations for stroke-related OMs in clinical practice, research, and professional (entry-level) physical therapist education; (3) to present examples demonstrating how the recommendations have been utilized to date; and (4) to make suggestions for future efforts. Case Description A task force of 7 physical therapists with diverse clinical and research expertise in stroke rehabilitation used a 3-stage, modified Delphi consensus process to develop recommendations on OM use. An evidence-based systematic review template and a 4-point rating scheme were used to make recommendations on OM use by care setting and patient acuity, for research, and for inclusion in professional education. Outcomes An initial list of 77 OMs was developed based on input from numerous professional sources. Screening measures and duplicate measures were eliminated. Fifty-six OMs received full review. Measures spanned the constructs of body structure/function (21), activity (28), and participation (14). Fourteen measures received a rating of “highly recommend. ” Discussion Use of highly recommended OMs may provide a common set of tools enabling comparisons across patients, interventions, settings, and studies. The use of a clearly defined, comprehensive assessment template may facilitate the pooling of data on OMs and contribute to best practice guidelines. Educational recommendations may inform curricular decisions.