Miracle-dz/UniFAR-FTUs huggingface dataset:
Approximate discrete time analysis of the hybrid token-CDMA MAC system

In this paper a hybrid Token-CDMA based medium access control (MAC) protocol is considered. The MAC scheme is analytically modeled as a multiserver multiqueue (MSMQ) system in the case of a gated service discipline. We present an approximated discrete time analysis for the queue inside the system where the analysis is concerned with the general case in which the system accommodates several traffic classes. Each queue in the system is assumed to incorporate the input model, the vacation model and the buffer model. The packet arrival process is assumed to be a Poisson distribution, with the same rate for the queues in each traffic class, and data rate quality of service (c) is incorporated to regulate the input. Packet service time is modeled with independent, identically distributed random variables with geometric distributions. Moments of the packet delay are derived using the probability generating function approach.
Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease.

AIM To clarify whether nonalcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular disease. METHODS We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program. NAFLD was diagnosed by abdominal ultrasonography. The metabolic syndrome (MS) was defined according to the modified National Cholesterol Education Program (NCEP) ATP III criteria. Five years after the baseline evaluations, the incidence of cardiovascular disease was assessed by a self-administered questionnaire. RESULTS Among 1221 participants available for outcome analyses, the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline (5 coronary heart disease, 6 ischemic stroke, and 1 cerebral hemorrhage) than 990 subjects without NAFLD (3 coronary heart disease, 6 ischemic stroke, and 1 cerebral hemorrhage). Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors (odds ratio 4.12, 95% CI, 1.58 to 10.75, P = 0.004). MS was also independently associated with cardiovascular events. But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease. CONCLUSION Although both of them were predictors of cardiovascular disease, NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model. NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.
Ca2+ permeability of nicotinic acetylcholine receptors in rat hippocampal CA1 interneurones

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely expressed in the brain where they are involved in a variety of physiological processes, including cognition and development. The nAChRs are ligand‐gated cationic channels, and different subtypes are known to be differentially permeable to Ca2+; the α7‐containing nAChRs are generally considered to be the most permeable. Ca2+ can activate and regulate a variety of signal transduction cascades, and the influx of Ca2+ through these receptors may have implications for synaptic plasticity. To determine the Ca2+ permeability of the nAChRs in rat hippocampal interneurones in the slice, which contain diverse subtypes of α7‐ and non‐α7‐containing nAChRs, we combined patch‐clamp electrophysiology recordings with conventional fura‐2 fluorescence imaging techniques. We estimated the relative Ca2+ permeability of the channels by determining the ratio of the increase in [Ca2+]i level (Δ[Ca2+]i) in the soma to the integrated transmembrane current (charge, Q) induced by the activation of the nAChRs, and compared this ratio to the highly Ca2+ permeable NMDA subtype of glutamate receptor channel. In all cells tested, the Δ[Ca2+]i/Q ratio was significantly larger (i.e. more than twice as big) for responses activated by NMDA than for α7‐containing nAChRs in interneurones; the activation of the non‐α7 nAChRs did not produce any significant increase in [Ca2+]i. Interestingly, the Ca2+ permeability of native α7 nAChRs in PC12 cells was significantly larger than in hippocampal interneurones, and not significantly different from NMDA receptors. Therefore, the α7‐containing nAChRs in rat hippocampal interneurones are significantly less permeable to Ca2+ than not only NMDA receptors but also α7 nAChRs in PC12 cells.
Glycemic control and selected pregnancy outcomes in type 1 diabetes women on continuous subcutaneous insulin infusion and multiple daily injections: the significance of pregnancy planning.

BACKGROUND Two regimens are used to achieve excellent glycemic control during pregnancy in type 1 diabetes mellitus (T1DM): continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI). We assessed their efficacy and safety and the effect of pregnancy planning. METHODS We examined 269 pregnant T1DM women: 157 treated with MDI (MDI group), 42 with CSII (CSII group), and 70 who switched from MDI to CSII in the first trimester (MDI/CSII group). There were 116 women who planned pregnancy: 58 in the MDI group, 38 in the CSII group, and 20 in the MDI/CSII group. The estimated differences in glycemic control and maternal and fetal outcomes were adjusted for baseline characteristics. RESULTS Mean glycated A1c (HbA1c) in the first trimester in the whole group was 6.9%, and the women differed depending on whether they planned pregnancy or not (P < 0.0001). A multiple regression model showed an average difference of about 0.9% in favor of pregnancy planning, with no interaction between the planning and treatments. In the second trimester, HbA1c decreased to a mean value of 5.8%, with improvement of HbA1c across all treatments: by 1.5% in not-planning and 0.9% in planning women. Despite greater improvement, not-planning women still had a higher HbA1c (by 0.3%, P = 0.05). In the third trimester, there was no further significant changes; nevertheless, women who planned pregnancy still had a lower HbA1c (by 0.5%, P = 0.02). There were 14 malformations, stillbirths, and perinatal infant deaths in the not-planning versus five in the planning group (P = 0.07). Patients in the CSII group had a 2 kg greater weight gain compared to the MDI group (15.0 kg vs. 13.0 kg; P = 0.005). CONCLUSIONS In pregnancy with T1DM, both MDI and CSII can provide excellent glycemic control. Pregnancy planning has a beneficial effect on glycemic control, independent from the therapy model. CSII seems to predispose to a larger weight gain in mothers.
Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy.

BACKGROUND Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. METHODS Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. RESULTS The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. CONCLUSIONS Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors. CLINICAL TRIALS REGISTRATION NCT00031486.
Comparison of the ability of nicardipine, theophylline and zaprinast to restore cardiovascular haemodynamics following inhibition of nitric oxide synthesis

1 The use of pharmacological inhibitors of nitric oxide (NO) synthesis to treat patients with septic shock is limited by the observation that they cause a fall in cardiac output in some subjects. The aim of this work was to investigate this fall and to test whether it was reversible by subsequent administration of nicardipine, theophylline or the cyclic GMP‐selective phosphodiesterase inhibitor, zaprinast (M&B 22948). 2 In pentobarbitone‐anaesthetized pigs, haemodynamic indices were measured before and after intravenous administration of NG‐nitro‐l‐arginine methyl ester (l‐NAME) in a dose‐response protocol (0.2–20 mg kg−1; n = 6) and as a single bolus of 10 mg kg−1 either alone or followed by increasing doses of nicardipine, theophylline or zaprinast (n = 8 in each group). 3 l‐NAME caused a dose‐dependent rise in systemic vascular resistance and mean systemic arterial pressure and a dose‐dependent fall in cardiac output. A single bolus of l‐NAME (10 mg kg−1) produced these effects within 15 min. 4 Subsequent administration of nicardipine (0.05–0.2 mg kg−1) caused complete reversal of systemic vasoconstriction and hypertension and in doing so completely restored cardiac output. Theophylline (7.5–10 mg kg−1) partially reversed the rise in systemic vascular resistance and partially restored cardiac output but the effect was small compared to that of nicardipine. Zaprinast (1–5 mg kg−1) had no significant effect on any of these variables. 5 These results suggest that reduced cardiac output following inhibition of NO synthesis is an effect of increased afterload on the heart and is reversible by nicardipine and to a lesser extent by theophylline. These findings may have potential value for those using NO synthase inhibitors to treat patients with septic shock.
Together We Stand, Divided We Fall -- Analyzing Information Systems Acquisition as Service

Information systems (IS) acquisition is not a widely studied topic in the literature. In particular, although the role and participation of different stakeholders such as business people, IT people, and external vendors and consultants is acknowledged, little is known about how they cooperate in an IS acquisition project. In this paper, we will apply a value co-creation framework taken from service research as a lens to study an IS acquisition project in an organization. The case organization intends to acquire their new IS as a cloud service. This approach is novel to all stakeholders, so they have to intensively cooperate for example under tight time constraints. The analysis reveals that appropriate cooperative work adds value to all participants, creates a win-win situation, and that the original value co-creation framework needs to be tailored according to the context.
Dengue Virus-Reactive CD8+ T Cells Display Quantitative and Qualitative Differences in Their Response to Variant Epitopes of Heterologous Viral Serotypes1

Reactivation of serotype cross-reactive CD8+ memory T lymphocytes is thought to contribute to the immunopathogenesis of dengue disease during secondary infection by a heterologous serotype. Using cytokine flow cytometry, we have defined four novel HLA-A*02-restricted dengue viral epitopes recognized by up to 1.5% of circulating CD8+ T cells in four donors after primary vaccination. All four donors had the highest cytokine response to the epitope NS4b 2353. We also studied the effect of sequence differences in heterologous dengue serotypes on dengue-reactive CD8+ memory T cell cytokine and proliferative responses. The D3 variant of a different NS4b epitope 2423 and the D2 variant of the NS4a epitope 2148 induced the largest cytokine response, compared with their respective heterologous sequences in all donors regardless of the primary vaccination serotype. Stimulation with variant peptides also altered the relative frequencies of the various subsets of cells that expressed IFN-γ, TNF-α, MIP-1β, and combinations of these cytokines. These results indicate that the prior infection history of the individual as well as the serotypes of the primary and heterologous secondary viruses influence the nature of the secondary response. These differences in the effector functions of serotype cross-reactive memory T cells induced by heterologous variant epitopes, which are both quantitative and qualitative, may contribute to the clinical outcome of secondary dengue infection.
Therapeutic drug monitoring of anti-infective agents in critically ill patients

ABSTRACT Initial adequate anti-infective therapy is associated with significantly improved clinical outcomes for patients with severe infections. However, in critically ill patients, several pathophysiological and/or iatrogenic factors may affect the pharmacokinetics of anti-infective agents leading to suboptimal drug exposure, in particular during the early phase of therapy. Therapeutic drug monitoring (TDM) may assist to overcome this problem. We discuss the available evidence on the use of TDM in critically ill patient populations for a number of anti-infective agents, including aminoglycosides, β-lactams, glycopeptides, antifungals and antivirals. Also, we present the available evidence on the practices of anti-infective TDM and describe the potential utility of TDM to improve treatment outcome in critically ill patients with severe infections. For aminoglycosides, glycopeptides and voriconazole, beneficial effects of TDM have been established on both drug effectiveness and potential side effects. However, for other drugs, therapeutic ranges need to be further defined to optimize treatment prescription in this setting.
Distribution and degree of heterogeneity of the afimbrial-adhesin-encoding operon (afa) among uropathogenic Escherichia coli isolates

The afimbrial adhesin (AFA-I) from a pyelonephritic Escherichia coli isolate (KS52) is a mannose-resistant, P-independent, X-binding adhesin, expressed by the afa-1 operon. It is distinct from the E. coli X-binding adhesins with M and S specificity. A total of 138 E. coli isolates belonging to various serotypes, mostly from urinary tract infections, were screened for the presence of DNA sequences related to the afa operon and for the expression of an X-adhesin able to mediate mannose-resistant hemagglutination (MRHA) and adhesion to uroepithelial cells. Fifteen strains were shown to harbor DNA sequences related to the AFA-I-encoding operon, and 13 of them expressed an X-adhesin. Using as probes different DNA segments of the AFA-I-encoding operon in Southern experiments, we demonstrated that only three of these clinical isolates contained genetic determinants closely related to those identified in the original afa prototype strain (KS52): presence of the afaA, afaB, afaC, afaD, and afaE genes associated with the expression of a 16,000-dalton hemagglutinin-adhesin which strongly cross-reacted with AFA-I-specific antibodies. The other E. coli isolates harbored DNA sequences homologous to the afaA, afaB, afaC, and afaD genes, but lacked the sequence corresponding to the adhesin-producing gene afaE; Western blots allowed the detection of polypeptides (15,000, 15,500, or 16,000 daltons) in these strains which cross-reacted with variable intensity with antibodies raised against the denatured AFA-I protein, but did not cross-react with native AFA-I-specific antibodies. Following DNA cloning experiments from chromosomal DNA of two of those strains (A22 and A30), we demonstrated that although the AFA-related operon in A22 and A30 strains lacked the AFA-I adhesin-encoding gene, they synthesized a functional X-adhesin. Thus, strains A22 and A30 encode adhesins designated AFA-II and AFA-III, which were cloned on recombinant plasmids pILL72 and pILL61, respectively. Southern hybridization experiments and Western blot analyses of the 15 AFA-related strains demonstrate the heterogeneity of the genetic sequences encoding the structural adhesin and suggest the bases for the serological diversity of the AFA adhesins.
Effects of α and β recombinant FSH (Gonal-F, Puregon) and progesterone upon human endometrial cell proliferation in-vitro: a preliminary study

Endometrial proliferation or regeneration during menstrual cycle is regulated by sexual hormones. However, the effect of gonadotrophins on the endometrial cell growth remains obscure. Herein, we aimed to investigate the effects of r-FSH (Gonal-F, Puregon) and progesterone on the proliferation of human endometrial cells in-vitro. According as gonadotrophin concentrations, the follicular-phase endometrial cells were divided into six groups: (1) 0 (controls), (2) 1; (3) 10; (4) 100; (5) 1000; (6) 100,000 μIU/ml. The cell countings with microscopy and cell proliferation kit assay were used to assess the endometrial cell proliferations. In Gonal-F groups, the cell absorptions (%) after 24/48 h culture were: (1) 100/100; (2) 103.8/102.3; (3) 104.8/102.8; (4) 102.3/101.3; (5) 96.3/94.2; (6) 86.8/84.3. In Puregon groups, the cell absorptions were: (1) 100/100; (2) 102.8/101.9; (3) 103/102.3; (4) 103.9/103.5; (5) 102.9/102.4; (6) 103.7/103.2 (non-different). In progesterone groups, the cell absorptions were: (1) 100/100; (2) 99.1/101.9; (3) 83.5/80.4; (4) 80.7/82.4. Higher dosage of Gonal-F (100,000 μIU/ml) and progesterone (10, 100 μg/ml) appeared the significant inhibition upon endometrium. We conclude that lower dosages of Gonal-F, Puregon, and progesterone appear the non-significant influence upon endometrium. Higher dosage of Gonal-F (10,000 μIU/ml) and progesterone (10, 100 μg/ml), but not Puregon, might interfere with the endometrial proliferation during follicular phase.
Disturbing post‐operative symptoms are not reduced by prophylactic antiemetic treatment in patients at high risk of post‐operative nausea and vomiting

Background: To give prophylactics or timely treatment for post‐operative nausea and vomiting (PONV) is the question. We compared the intensity and number of disturbing post‐operative symptoms (i.e. pain, PONV, headache, fatigue, etc.) after prophylactic antiemetic treatment in a group of patients with >30% risk for post‐operative vomiting.
1H-MRS alterations in the cerebellum of patients with familial hemiplegic migraine type 1

Background: About 20% of patients with familial hemiplegic migraine (FHM) develop progressive cerebellar signs. Genetic studies have established an association with mutations in the CACNA1A gene. However, the mechanisms underlying cerebellar involvement are largely unknown. Objective: To use proton MR spectroscopy (1H-MRS) to investigate metabolic alterations in the cerebellum as well as cortical regions known to be involved in the propagation of migraine aura. Methods: Fifteen CACNA1A mutation carriers from three FHM families and 17 healthy control subjects were studied. Eleven patients had clinical signs of cerebellar involvement. LCModel fits were used to estimate absolute concentrations of N-acetyl aspartate (NAA), myo-inositol (mI), glutamate (Glu), choline-containing compounds, total creatine, and lactate in the superior cerebellar vermis (SCV), parietal cortex, and occipital cortex. To control for atrophy effects, automated image segmentation was performed using SPM99. The brain parenchyma fraction (BPF) was determined for all three regions. Results: Compared with controls, the brain parenchyma fraction (BPF), NAA, and Glu were significantly reduced and mI was significantly elevated in the SCV of patients with FHM. In contrast, no metabolite alterations were found in supratentorial regions. BPF and NAA in the SCV significantly correlated with cerebellar scores, in particular, gait ataxia. Conclusions: The findings suggest that there is a regionally distinct neuronal impairment in the superior cerebellar vermis that exceeds macroscopic tissue loss. Correlations with clinical scores emphasize the functional relevance of localized atrophy (brain parenchyma fraction) and N-acetyl aspartate levels. These measures may be useful to monitor disease progression. The observed reduction in glutamate may in part reflect impaired glutamatergic neurotransmission.
Achilles tendon allograft reconstruction of the anterior cruciate ligament-deficient knee

Thirty-five patients had reconstruction of the anterior cruciate ligament with intraarticular fresh-frozen Achilles tendon allograft and extraarticular tibial band tenodesis. Patients were followed 2 to 4 years (mean, 2.5). Evaluation included clinical and functional exami nations, measurement of tibiofemoral displacement, and anteroposterior and lateral radiographs. Clinical results were considered satisfactory in 85% of the patients; 16 had arthroscopic examination after the allograft; allograft biopsies in 9 at this time showed cellular and vascular tissue without evidence of immune reaction. Clinical, arthroscopic, and biopsy results were favorable, but radiologic results were not. In most pa tients there was a significant size increase in femoral and tibial bone tunnels, as measured from radiographs. In the 6 most extreme cases, bone tunnels measured 20 mm or more in diameter, twice the initial size. Etiology and clinical significance of these bone tunnel changes remain unknown. Enlargement appears to oc cur early after operation; it stabilizes within 2 years. No statistical correlation was seen between tunnel enlarge ment and results of clinical and functional examinations; nevertheless, unexplained tunnel enlargement is cause for concern, and allograft replacement of the anterior cruciate ligament with fresh-frozen Achilles tendon al lograft should be considered a salvage procedure.
Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence.

RATIONALE During long-term lung infection in patients with cystic fibrosis (CF), Pseudomonas aeruginosa strains develop mutations leading to clonal expansion. This microevolution is believed to be correlated with a reduced virulence. OBJECTIVES We tested this hypothesis in models of lung infection, using mice with different genetic backgrounds. METHODS From infected airways of six patients with CF, 25 P. aeruginosa clones were isolated during a period of up to 16.3 years and genotypically and phenotypically characterized. Virulence of the 8 early, 6 intermediate, and 11 late CF isolates and 5 environmental strains was assessed by monitoring acute mortality versus survival and P. aeruginosa chronic persistence versus lung clearance in mice of different genetic backgrounds, including CF mice. MEASUREMENTS AND MAIN RESULTS Different patients harbored clonally unrelated strains, but early, intermediate, and late P. aeruginosa isolates from single patients were clonally related, allowing comparative in vivo analysis. Although late isolates were attenuated in causing acute mortality in the mouse models, compared with early and intermediate clonal isolates and environmental strains, they did not differ from early and intermediate clonal isolates in their capacity to establish chronic infection and cause extensive inflammation in the murine respiratory tract. CONCLUSIONS Our findings indicate that clonal expansion of P. aeruginosa strains during microevolution within CF lungs leads to populations with altered but not reduced virulence. These P. aeruginosa clones with adapted virulence play a critical role in the pathogenesis of chronic infections and may serve to define virulence determinants as targets for novel therapies.