Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment with oral paricalcitol in daily clinical practice for patients with chronic kidney disease stage 3–4: a preliminary study

Background Active vitamin D is an effective treatment for secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients often complicated by hypercalcaemia and hyperphosphataemia. Treatment with paricalcitol, a selective vitamin D receptor activator, has shown benefits by adequately reducing parathyroid hormone (PTH) levels with minimal changes in serum calcium (Ca) and phosphorus (P). The purpose of this study is to present data on the use of oral paricalcitol in real-life clinical practice in patients with CKD stage 3–4 and SHPT. Methods We studied 43 patients, M/F: 25/18, median age: 74 years (47–87), CKD stage 3/4: 16/27, with SHPT, who were prescribed oral paricalcitol at recommended doses for 6 months. Monthly measurements of serum intact PTH (iPTH), Ca, P, alkaline phosphatase (ALP), haemoglobin, albumin (ALB), lipid profile, proteinuria and 24-h urine creatinine clearance were performed 3 months before and 6 months after treatment initiation. Results Paricalcitol induced a significant, early and sustained, through the end of follow-up period, decrease in iPTH and ALP levels and an increase in serum ALB. No significant increase in Ca and P levels as well as in Ca × P product was observed during the study period. No significant changes were found in protein excretion, kidney function and the other measured parameters between baseline and last evaluation. Paricalcitol final median dose was 5 μg/week ranging between 3 and 7 μg/week. Conclusions In the context of real-life clinical practice, oral paricalcitol for 6 months is an effective, well-tolerated treatment of SHPT in CKD stage 3–4 with minimal effects on calcium and phosphorus metabolism.
Vaccination with Heat-Killed Listeria as Adjuvant Reverses Established Allergen-Induced Airway Hyperreactivity and Inflammation: Role of CD8+ T Cells and IL-181

Asthma is a respiratory disorder characterized by airway hyperreactivity (AHR) and inflammation and is associated with high serum IgE and overproduction of IL-4, IL-5, and IL-13 by allergen-specific Th2 cells. Our previous studies demonstrated that heat-killed Listeria monocytogenes (HKL) as an adjuvant in immunotherapy successfully reversed ongoing Ag-specific Th2-dominated responses toward Th1-dominated responses, but it was unclear if such immune modulation could reverse ongoing, established disease in target organs such as the lung. In this paper we show that a single dose of Ag plus HKL as adjuvant significantly reduced AHR in a murine model for asthma and reversed established AHR when given late after allergen sensitization. HKL as adjuvant also dramatically inhibited airway inflammation, eosinophilia, and mucus production, significantly reduced Ag-specific IgE and IL-4 production, and dramatically increased Ag-specific IFN-γ synthesis. The inhibitory effect of HKL on AHR depended on the presence of IL-12 and CD8+ T cells and was associated with an increase of IL-18 mRNA expression. Thus, our results demonstrate that HKL as an adjuvant for immunotherapy mediates immune deviation from a pathological Th2-dominated response toward a protective immune response in peripheral lymphoid tissues and in the lungs and may be clinically effective in the treatment of patients with established asthma and allergic disease.
Different Alcohol Drinking and Blood Pressure Relationships in France and Northern Ireland: The PRIME Study

To assess the effect of alcoholic beverages consumed on blood pressure levels by day of the week, baseline data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME), including 6523 male subjects who drank at least once a week (5156 in France and 1367 in Northern Ireland), were analyzed. In France, alcohol consumption was rather homogeneous throughout the week, with a slight increase during weekends, whereas in Northern Ireland, Fridays and Saturdays accounted for 66% of total alcohol consumption. After adjustment for age, body mass index, heart rate, tobacco smoking, educational level, marital status, and professional activity, blood pressure levels were higher in Northern Irish drinkers on Monday and decreased until Thursday, whereas blood pressure levels were constant throughout the week for French drinkers (day×country interactions, P <0.05). Conversely, no between-day differences were found regarding teetotalers in both countries. In drinkers, between-day differences and day×country interactions were suppressed after adjustment for the average alcohol consumption of the third day before measurement. We conclude that the binge-drinking pattern observed among Northern Irish drinkers leads to physiologically disadvantageous consequences regarding blood pressure levels, whereas no such fluctuations in blood pressure levels are found for regular consumption.
A Digital Signature Scheme Secure Against Adaptive Chosen-Message Attacks

We present a digital signature scheme based on the computational difficulty of integer factorization. The scheme possesses the novel property of being robust against an adaptive chosen-message attack: an adversary who receives signatures for messages of his choice (where each message may be chosen in a way that depends on the signatures of previously chosen messages) cannot later forge the signature of even a single additional message. This may be somewhat surprising, since in the folklore the properties of having forgery being equivalent to factoring and being invulnerable to an adaptive chosen-message attack were considered to be contradictory. More generally, we show how to construct a signature scheme with such properties based on the existence of a "claw-free" pair of permutations--a potentially weaker assumption than the intractibility of integer factorization. The new scheme is potentially practical: signing and verifying signatures are reasonably fast, and signatures are compact.
Endothelial Activation Microparticles and Inflammation Status Improve with Exercise Training in African Americans

African Americans have the highest prevalence of hypertension in the world which may emanate from their predisposition to heightened endothelial inflammation. The purpose of this study was to determine the effects of a 6-month aerobic exercise training (AEXT) intervention on the inflammatory biomarkers interleukin-10 (IL-10), interleukin-6 (IL-6), and endothelial microparticle (EMP) CD62E+ and endothelial function assessed by flow-mediated dilation (FMD) in African Americans. A secondary purpose was to evaluate whether changes in IL-10, IL-6, or CD62E+ EMPs predicted the change in FMD following the 6-month AEXT intervention. A pre-post design was employed with baseline evaluation including office blood pressure, FMD, fasting blood sampling, and graded exercise testing. Participants engaged in 6 months of AEXT. Following the AEXT intervention, all baseline tests were repeated. FMD significantly increased, CD62E+ EMPs and IL-6 significantly decreased, and IL-10 increased but not significantly following AEXT. Changes in inflammatory biomarkers did not significantly predict the change in FMD. The change in VO2 max significantly predicted the change in IL-10. Based on these results, AEXT may be a viable, nonpharmacological method to improve inflammation status and endothelial function and thereby contribute to risk reduction for cardiovascular disease in African Americans.
Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis

Objective To assess whether it is feasible to establish specific cut-off values able to discriminate ‘physiological’ or ‘pathological’ brain volume rates in patients with multiple sclerosis (MS). Methods The study was based on the analysis of longitudinal MRI data sets of patients with MS (n=206, 87% relapsing–remitting, 7% secondary progressive and 6% primary progressive) and healthy controls (HC; n=35). Brain atrophy rates were computed over a mean follow-up of 7.5 years (range 1–12) for patients with MS and 6.3 years (range 1–12.5) for HC with the SIENA software and expressed as annualised per cent brain volume change (PBVC/y). A weighted (on the follow-up length) receiver operating characteristic analysis and the area under the curve (AUC) were used for statistics. Results The weighted PBVC/y was −0.51±0.27% in patients with MS and −0.27±0.15% in HC (p<0.0001). There was a significant age-related difference in PBVC/y between HC older and younger than 35 years of age (p=0.02), but not in patients with MS (p=0.8). The cut-off of PBVC/y, as measured by SIENA that could maximise the accuracy in discriminating patients with MS from HC, was −0.37%, with 67% sensitivity and 80% specificity. According to the observed distribution, values of PBVC/y as measured by SIENA that could define a pathological range were above −0.52% with 95% specificity, above −0.46% with 90% specificity and above −0.40% with 80% specificity. Conclusions Our evidence-based criteria provide values able to discriminate the presence or absence of ‘pathological’ brain volume loss in MS with high specificity. Such results could be of great value in a clinical setting, particularly in assessing treatment efficacy in MS.
Modeling the grid synchronization induced negative-resistor-like behavior in the output impedance of a three-phase photovoltaic inverter

Photovoltaic power has to be converted from DC into AC in grid-connected applications. The conversion is done by using a single or three-phase inverter. Phase angle and frequency of the injected current and the grid voltage have to match to achieve unity power factor. This has been commonly accomplished by using a phase-locked-loop (PLL). The PLL has a tendency to make the output impedance of the inverter to appear as a negative resistor which can introduce harmonics in the grid current or even make the inverter-grid interface unstable. This paper presents a general small-signal model of a PV inverter in the synchronous reference frame which includes the PLL. Due to the negative resistance, the inverter can become unstable when the grid has high inductance. The derived small-signal model can be used to predict the exact conditions where the instability will take place by utilizing the impedance ratio and Nyquist stability criterion.
Automorphic Representations, Shimura Varieties, and Motives. Ein Marchen*

1. Introduction. It had been my intention to survey the problems posed by the study of zetafunctions of Shimura varieties. But I was too sanguine. This would be a mammoth task, and limitations of time and energy have considerably reduced the compass of this report. I consider only two problems, one on the conjugation of Shimura varieties, and one in the domain of continuous cohomology. At first glance, it appears incongruous to couple them, for one is arithmetic, and the other representationtheoretic, but they both arise in the study of the zeta-function at the infinite places. The problem of conjugation is formulated in the sixth section as a conjecture, which was arrived at only after a long sequence of revisions. My earlier attempts were all submitted to Rapoport for approval, and found lacking. They were too imprecise, and were not even in principle amenable to proof by Shimura’s methods of descent. The conjecture as it stands is the only statement I could discover that meets his criticism and is compatible with Shimura’s conjecture. The statement of the conjecture must be preceded by some constructions, which have implications that had escaped me. When combined with Deligne’s conception of Shimura varieties as parameter varieties for families of motives they suggest the introduction of a group, here called the Taniyama group, which may be of importance for the study of motives of CM-type. It is defined in the fifth section, where its hypothetical properties are rehearsed. With the introduction of motives and the Taniyama group, the report takes on a tone it was not originally intended to have. No longer is it simply a matter of formulating one or two specific conjectures, but we begin to weave a tissue of surmise and hypothesis, and curiosity drives us on. Deligne’s ideas are reviewed in the fourth section, but to understand them one must be familiar at least with the elements of the formalism of tannakian categories underlying the conjectural theory of motives, say, with the main results of Chapter II of [40]. The present Summer Institute is predicated on the belief that there is a close relation between automorphic representations and motives. The relation is usually couched in terms of L-functions, * First appeared in Automorphic forms, representations, and L-functions, Proc. of Symp. in Pure
Spatiotemporal relationships between climate and whitebark pine mortality in the greater Yellowstone ecosystem

Whitebark pine (Pinus albicaulis) serves as a subalpine keystone species by regulating snowmelt runoff, reducing soil erosion, facilitating the growth of other plants, and providing food for wildlife. Mountain pine beetle (Dendroctonus ponderosae) is an ideal bioindicator of climate change, because its life cycle is temperature-dependent. Western North America is currently experiencing the largest outbreak of mountain pine beetle on record, and evidence suggests that a changing climate has accelerated the life cycle of this bark beetle. This study explored the relationships between climate, mountain pine beetles, and whitebark pine mortality in the Greater Yellowstone Ecosystem. A time series of Landsat satellite imagery (nine images) was used to monitor whitebark pine mortality in the Greater Yellowstone Ecosystem from 1999 to 2008. The patterns of mortality were analyzed with respect to monthly climate variations over the 9-year period. The impacts of topography and autocorrelation (both spatial and temporal) were also analyzed. The most important predictor variables were autocorrelation terms, indicating a strong host-tree depletion effect. Both drier and warmer climatic conditions favored increased whitebark pine mortality. These results show for the first time a statistical link between climate variability and whitebark pine mortality, probably mediated by mountain pine beetles. FOR . S CI. 57(4):320-335.
Neuroanatomic deficits in congenital central hypoventilation syndrome

Congenital Central Hypoventilation Syndrome (CCHS) patients exhibit compromised autonomic regulation, reduced breathing drive during sleep, diminished ventilatory responses to chemoreceptor stimulation, and diminished air hunger perception. The syndrome provides an opportunity to partition neural processes regulating breathing and cardiovascular action. No obvious lesions appear with conventional magnetic resonance imaging; however, T2 relaxometry procedures can detect reduced cell or fiber density or diminished myelination not found with routine evaluation. High‐resolution T1, proton density, and T2‐weighted brain images were collected from 12 patients and 28 age‐ and gender‐matched controls. Voxel‐by‐voxel T2 maps were generated from the proton density and T2‐weighted images and evaluated by voxel‐based‐relaxometry procedures. Normalized and smoothed T2 maps were compared between groups using analysis of covariance at each voxel, with age and ventricle size included as covariates. Patients showed damaged or maldeveloped tissue, principally right‐sided, including white matter from the level of the anterior cingulate cortex caudally to the level of the posterior cingulate and laterally to the posterior superior temporal cortex. Portions of the posterior, mid, and anterior cingulate, as well as the internal capsule, putamen, and globus pallidus and basal forebrain extending to the anterior and medial thalamus were affected. Deficits in the cingulum bundle and mid‐hippocampus and ventral prefrontal cortex appeared, as well as the right cerebellar cortex and deep nuclei. Neuroanatomic deficiencies in limbic structures suggest a structural basis for reduced air hunger perception, thermoregulatory and autonomic deficiencies in the syndrome, while cerebellar deficits may also contribute to breathing and cardiovascular dysregulation. J. Comp. Neurol. 487:361–371, 2005. © 2005 Wiley‐Liss, Inc.
Architectural implications of a family of irregular applications

Irregular applications based on sparse matrices are at the core of many important scientific computations. Since the importance of such applications is likely to increase in the future, high-performance parallel and distributed systems must provide adequate support for such applications. We characterize a family of irregular scientific applications and derive the demands they will place on the communication systems of future parallel systems. Running time of these applications is dominated by repeated sparse matrix vector product (SMVP) operations. Using simple performance models of the SMVP, we investigate requirements for bisection bandwidth, sustained bandwidth on each processing element (PE), burst bandwidth during block transfers, and block latencies for PEs under different assumptions about sustained computational throughput. Our model indicates that block latencies are likely to be the most problematic engineering challenge for future communication networks.
The Pediatrician's Role in Child Maltreatment Prevention

It is the pediatrician's role to promote the child's well-being and to help parents raise healthy, well-adjusted children. Pediatricians, therefore, can play an important role in the prevention of child maltreatment. Previous clinical reports and policy statements from the American Academy of Pediatrics have focused on improving the identification and management of child maltreatment. This clinical report outlines how the pediatrician can help to strengthen families and promote safe, stable, nurturing relationships with the aim of preventing maltreatment. After describing some of the triggers and factors that place children at risk for maltreatment, the report describes how pediatricians can identify family strengths, recognize risk factors, provide helpful guidance, and refer families to programs and other resources with the goal of strengthening families, preventing child maltreatment, and enhancing child development.
Toll-Like Receptor 4 Agonistic Antibody Promotes Innate Immunity against Severe Pneumonia Induced by Coinfection with Influenza Virus and Streptococcus pneumoniae

ABSTRACT Coinfection with bacteria is a major cause of mortality during influenza epidemics. Recently, Toll-like receptor (TLR) agonists were shown to have immunomodulatory functions. In the present study, we investigated the effectiveness and mechanisms of the new TLR4 agonistic monoclonal antibody UT12 against secondary pneumococcal pneumonia induced by coinfection with influenza virus in a mouse model. Mice were intranasally inoculated with Streptococcus pneumoniae 2 days after influenza virus inoculation. UT12 was intraperitoneally administered 2 h before each inoculation. Survival rates were significantly increased and body weight loss was significantly decreased by UT12 administration. Additionally, the production of inflammatory mediators was significantly suppressed by the administration of UT12. In a histopathological study, pneumonia in UT12-treated mice was very mild compared to that in control mice. UT12 increased antimicrobial defense through the acceleration of macrophage recruitment into the lower respiratory tract induced by c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-κB) pathway-dependent monocyte chemoattractant protein 1 (MCP-1) production. Collectively, these findings indicate that UT12 promoted pulmonary innate immunity and may reduce the severity of severe pneumonia induced by coinfection with influenza virus and S. pneumoniae. This immunomodulatory effect of UT12 improves the prognosis of secondary pneumococcal pneumonia and makes UT12 an attractive candidate for treating severe infectious diseases.
Atomic RMI 2: Highly Parallel Pessimistic Distributed Transactional Memory

Distributed Transactional Memory (DTM) is an emerging approach to distributed synchronization based on the application of the transaction abstraction to distributed computation. DTM comes in several system models, but the control flow model (CF) is particularly powerful, since it allows transactions to delegate computation to remote nodes as well as access shared data. However, there are no existing CF DTM systems that perform on par with state-of-the-art systems operating in other models. Hence, we introduce a CF DTM synchronization algorithm, OptSVA-CF. It supports fine-grained pessimistic concurrency control, so it avoids aborts, and thus avoids problems with irrevocable operations. Furthermore, it uses early release and asynchrony to parallelize concurrent transactions to a high degree, while retaining strong safety properties. We implement it as Atomic RMI 2, in effect producing a CF DTM system that, as our evaluation shows, can outperform a state-of-the-art non-CF DTM such as HyFlow2.
Biogeography of Paenibacillus larvae, the causative agent of American foulbrood, using a new multilocus sequence typing scheme

American foulbrood is the most destructive brood disease of honeybees (Apis mellifera) globally. The absence of a repeatable, universal typing scheme for the causative bacterium Paenibacillus larvae has restricted our understanding of disease epidemiology. We have created the first multilocus sequence typing scheme (MLST) for P. larvae, which largely confirms the previous enterobacterial repetitive intergenic consensus (ERIC)–polymerase chain reaction (PCR)-based typing scheme's divisions while providing added resolution and improved repeatability. We have used the new scheme to determine the distribution and biogeography of 294 samples of P. larvae from across six continents. We found that of the two most epidemiologically important ERIC types, ERIC I was more diverse than ERIC II. Analysis of the fixation index (FST) by distance suggested a significant relationship between genetic and geographic distance, suggesting that population structure exists in populations of P. larvae. Interestingly, this effect was only observed within the native range of the host and was absent in areas where international trade has moved honeybees and their disease. Correspondence analysis demonstrated similar sequence type (ST) distributions between native and non-native countries and that ERIC I and II STs mainly have differing distributions. The new typing scheme facilitates epidemiological study of this costly disease of a key pollinator.