Miracle-dz/UniFAR-FTUs huggingface dataset:
Skewed X-Chromosome Inactivation in Greek Women with Idiopathic Recurrent Miscarriage

Objectives: To investigate if skewed X-chromosome inactivation (XCI) is associated with unexplained recurrent miscarriage (RM) in Greek women. Methods: This was a prospective case-control study. A methylation-sensitive assay was used to investigate the X-inactivation pattern of women with unexplained RM and controls. Results: Fifty-six of the 74 patients (75.7%) and 55 of 80 controls (68.8%) were informative. Among the informative cases, 6/56 (10.7%) women showed extreme XCI (>90%) and among the informative controls, 2/55 (3.6%) showed extreme XCI. Conclusions: In the present study, women with unexplained RM showed a statistically nonsignificant increase in skewed XCI prevalence (10.7%) compared with control women (3.6%; p = 0.271).
Combination immunotherapy with soluble tumor necrosis factor receptors plus interleukin 1 receptor antagonist decreases sepsis mortality

ObjectiveInhibition of tumor necrosis factor (TNF) or interleukin 1 (IL-1) alone has not improved sepsis survival in human clinical trials; therefore, it has been suggested that blockade of both may be successful. We tested whether combination immunotherapy would improve survival in mice subjected to a lethal lipopolysaccharide (LPS) challenge or the sepsis model of cecal ligation and puncture. DesignMice were treated with the combination immunotherapy and challenged with either a lethal dose of lipopolysaccharide or a septic challenge induced by cecal ligation and puncture. SettingUniversity research laboratory. SubjectsAdult, female Balb/c mice. InterventionsMice were treated with the combination of the IL-1 receptor antagonist plus a polyethylene glycol-linked dimer of the TNF soluble receptor. Measurements and Main Results LPS lethality was reduced in the treated mice with a decrease in biologically active TNF in the plasma and peritoneal fluid. In the cecal ligation and puncture (CLP) model of sepsis, this combination immunotherapy for 1 day decreased plasma and peritoneal levels of IL-6 and the murine chemokines KC and MIP-2. However, treatment did not result in a reduction in the hypothermia or peripheral blood alterations that occur after CLP, and the 1-day therapy did not result in an improvement in survival. In contrast, when combination immunotherapy was extended to 3 days there was a significant improvement in survival. ConclusionsThese data demonstrate that inhibition of both TNF and IL-1 will decrease the lethality of sepsis initiated by CLP if the combination immunotherapy is provided for a sufficient amount of time.
Study Designs and Tests for Comparing Resource Use and Availability II

Abstract We review 87 articles published in the Journal of Wildlife Management from 2000 to 2004 to assess the current state of practice in the design and analysis of resource selection studies. Articles were classified into 4 study designs. In design 1, data are collected at the population level because individual animals are not identified. Individual animal selection may be assessed in designs 2 and 3. In design 2, use by each animal is recorded, but availability (or nonuse) is measured only at the population level. Use and availability (or unused) are measured for each animal in design 3. In design 4, resource use is measured multiple times for each animal, and availability (or nonuse) is measured for each use location. Thus, use and availability measures are paired for each use in design 4. The 4 study designs were used about equally in the articles reviewed. The most commonly used statistical analyses were logistic regression (40%) and compositional analysis (25%). We illustrate 4 problem areas in resource selection analyses: pooling of relocation data across animals with differing numbers of relocations, analyzing paired data as though they were independent, tests that do not control experiment wise error rates, and modeling observations as if they were independent when temporal or spatial correlations occurs in the data. Statistical models that allow for variation in individual animal selection rather than pooling are recommended to improve error estimation in population-level selection. Some researchers did not select appropriate statistical analyses for paired data, or their analyses were not well described. Researchers using one-resource-at-a-time procedures often did not control the experiment wise error rate, so simultaneous inference procedures and multivariate assessments of selection are suggested. The time interval between animal relocations was often relatively short, but existing analyses for temporally or spatially correlated data were not used. For studies that used logistic regression, we identified the data type employed: single sample, case control (used–unused), use–availability, or paired use–availability. It was not always clear whether studies intended to compare use to nonuse or use to availability. Despite the popularity of compositional analysis, we do not recommend it for multiple relocation data when use of one or more resources is low. We illustrate that resource selection models are part of a broader collection of statistical models called weighted distributions and recommend some promising areas for future development.
Myocardial and Skeletal Muscle Concentrations of Digoxin in Patients on Long-term Therapy

The digoxin content was measured in samples of left ventricular papillary muscle, skeletal muscle, and plasma obtained during mitral valve replacement from eight patients on maintenance treatment with the drug. The content in papillary muscle ranged from 15·5 to 132 ng/g (mean 77·7) and in skeletal muscle from 7·5 to 23 ng/g (mean 11·3). The ratio of myocardial digoxin concentration to plasma concentration varied between patients from 39:1 to 155:1. No simple relationship exists between plasma levels of digoxin and its concentration in the heart muscle, but total myocardial concentration may not accurately reflect therapeutic activity.
Individual differences in substance dependence: at the intersection of brain, behaviour and cognition

Recent theories of drug dependence propose that the transition from occasional recreational substance use to harmful use and dependence results from the impact of disrupted midbrain dopamine signals for reinforcement learning on frontal brain areas that implement cognitive control and decision‐making. We investigated this hypothesis in humans using electrophysiological and behavioral measures believed to assay the integrity of midbrain dopamine system and its neural targets. Our investigation revealed two groups of dependent individuals, one characterized by disrupted dopamine‐dependent reward learning and the other by disrupted error learning associated with depression‐proneness. These results highlight important neurobiological and behavioral differences between two classes of dependent users that can inform the development of individually tailored treatment programs.
PRODUCT AND INTERNATIONAL DIVERSIFICATION AMONG JAPANESE MULTINATIONAL FIRMS

This paper examines the relationship of performance with product and international diversification on Japanese multinational firms from 1977 to 1993. We show the relationships between diversification and performance change over time through the use of multiple time periods and accounting for keiretsu membership. Results show that while diversity strategies vary between keiretsu and non-keiretsu firms, performance is not much different. Across time periods, performance varies considerably, but strategies are less variable. Product diversity has weak effects on firm performance only in one time period, while international diversification has negative profitability and positive growth consequences in in some periods. These results suggest first that diversification strategies and their effects on performance vary across time periods and generally produce some unexpected findings. We do not find strong interactive diversity effects. Copyright © 2000 John Wiley & Sons, Ltd.
Cardiac myxoma is rich in factor XIIIa positive dendrophages: immunohistochemical study of four cases

Cardiac myxoma is an enigmatic tumour thought to arise from primitive cardiac mesenchymal cells. Factor XIIIa+ dendrophages are tissue histiocytes that are active in tissue repair and thrombosis. To explore whether factor XIIIa+ dendrophages play a role in cardiac myxoma morphogenesis, we stained four cases with an antiserum against coagulation factor XIIIa (FXIIIa). We also used antibodies recognizing CD34, CD31, and S‐100 protein. Samples of valvular endocardium from 12 and 16 week fetuses and two adult autopsies were compared with the four myxomas. All cardiac myxomas had rounded and dendritic FXIIIa+ cells admixed with more numerous CD34+ spindle and stellate myxoma cells. The CD34+ cells formed multicellular syncytia and capillary sprouts. Many of these syncytial structures also expressed CD31 and, to a lesser extent, S‐100 protein, strongly in two cases and more focally in two. Fetal subendocardium was composed of CD34+ stellate fibroblast‐like cells invested with scattered FXIIIa+ histiocytes; no S‐100+ cells were detected. Our findings confirm that cardiac myxomas are composed of CD34+ primitive subendocardial cells. These cells show a capacity for CD31+ endothelial differentiation. In cardiac myxoma, the CD34+ myxoma cells are accompanied by numerous FXIIIa+ dendrophages, the presence of which suggests abnormal organizing thrombus‐like differentiation in cardiac myxoma morphogenesis.
Prognostic relevance of anemia in myelodysplastic syndromes

Primary myelodysplastic syndromes are acquired disorders of hematopoietic stem cells occurring in older persons and characterized by bone marrow failure and a substantial risk of progression into acute myeloid leukemia [1]. These disorders show impressive clinical heterogeneity, ranging from indolent conditions spanning years—like the myelo-dysplastic syndrome with isolated 5q deletion or refractory anemia with ringed sideroblasts—to forms with a rapid evolution into acute myeloid leukemia. The World Health Organization (WHO) classiﬁcation of myeloid neoplasms [2] provides clinicians with a very useful tool for deﬁning the different subtypes of myelodysplastic syndromes. This clas-siﬁcation is not only useful for diagnostic purposes but also has a relevant prognostic value, and it can therefore be used to facilitate clinical decision-making in the individual patient [3,4]. Among patients with myelodysplastic syndromes without excess blasts, in particular, the isolated involvement of the erythroid lineage as compared with bi-or tri-lineage marrow dysplasia is associated with a signiﬁ-cantly better prognosis in terms of both overall survival and leukemia-free survival. A risk-adapted
Frequency, Risk, and Cost of Gout-related Episodes Among the Elderly: Does Serum Uric Acid Level Matter?

Objective. We examined the association between serum uric acid (SUA) level and the frequency, risk, and cost of gout flares among the elderly. Methods. Data were extracted from the Integrated Healthcare Information Services claims database (1999–2005). Patients were included if they had gout, were aged 65 years and older and had both medical and pharmacy benefits, and electronic laboratory data. Patients with gout and gouty episodes were identified using algorithms based on ICD-9-CM codes and medications. Logistic regression and negative binomial regressions were used to study the relationship between SUA concentration and the annual frequency and one-year risk of gout episodes. Generalized linear models were used to examine the direct healthcare costs associated with gout episodes in the 30 days following each episode. Results. Elderly patients with gout (n = 2237) with high (6–8.99 mg/dl) and very high (> 9 mg/dl) SUA concentrations were more likely to develop a flare within 12 months compared to patients with normal (< 6 mg/dl) SUA levels (OR 2.1, 95% CI 1.7–2.6; OR 3.4, 95% CI 2.6–4.4, respectively). In multivariate regressions, the average annual number of flares increased by 11.9% (p < 0.001) with each unit-increase in SUA level above 6 mg/dl (p < 0.001). Among patients with very high SUA levels, average adjusted total healthcare and gout-related costs per episode were $2,555 and $356 higher, respectively, than those of patients with normal SUA levels (both p < 0.001). Conclusion. Higher SUA levels are associated with increased frequency and risk of gout episode, and with higher total and gout-related direct healthcare costs per episode.
Differences that make the difference: a study of functionalities in synchronous CMC

Abstract This paper has a dual aim: to situate functionalities among the complex of factors that help shape online interactions and to explore the heterogeneity of audio conferencing and its implications. Following a critical discursive synthesis of the treatment of variables in the literature, attention focuses on the distinctive and diverse characteristics of synchronous audio environments. The existence of a synchronous-asynchronous dichotomy is questioned and the effects of a number of differences are highlighted. As a further illustration, the paper next undertakes a comparison of Lyceum and Wimba Voice Direct. The main features of the two environments are introduced and a detailed analysis of their text and voice chat facilities is carried out. In the last section the benefits of text-based CMC are revisited through the lens of voice chat technology. It is concluded that the benefits of CMC appear to have been overstated and that no general claims can be made about voice CMC, but that collectively, well documented studies could provide a useful source of information on the level of contingency of particular findings.
p53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma.

PURPOSE The p53 gene plays a critical role in cellular response to DNA damage and has been implicated in the response to platinum compounds in ovarian carcinoma patients. Because taxanes could induce p53-independent apoptosis, we assessed the relevance of p53 gene status to response in ovarian carcinoma patients receiving paclitaxel and platinum-containing chemotherapy. PATIENTS AND METHODS Forty-eight previously untreated patients with advanced disease received standard paclitaxel/platinum-based chemotherapy. In tumor specimens collected at the time of initial surgery, before therapy, p53 gene status and expression were examined by single-strand conformation polymorphism, sequence analysis, and immunohistochemical analysis. Microsatellite instability analysis was performed on available samples from 30 patients. RESULTS Thirty-four (71%) of the 48 patients had a clinical response. Pathologic complete remission was documented in 13 (27%) of 48 patients. p53 mutations were detected in 29 (60%) of 48 tumors. Among the patients with mutant p53 tumors, 25 patients (86%) responded to chemotherapy. Only nine (47%) of 19 patients with wild-type p53 tumors responded to the same treatment. The overall response rate and the complete remission rate were significantly higher among patients with mutant p53 tumors than among patients with wild-type p53 tumors (P: =.008). Most of the tested tumors not associated with complete remission (10 of 12 tumors) were also characterized by microsatellite instability. The complete remission rate was higher among patients with tumors without microsatellite instability (five of seven patients). CONCLUSION In contrast to the limited efficacy of treatment with paclitaxel in combination with standard platinum doses against wild-type p53 ovarian tumors, patients with mutant p53 ovarian tumors were more responsive to paclitaxel-based chemotherapy. The pattern of response to chemotherapy containing paclitaxel is different from that associated with high-dose cisplatin therapy. Determining p53 mutational status can be useful in predicting therapeutic response to drugs effective in ovarian carcinoma.
Physiological evidence of interaction of first‐ and second‐order motion processes in the human visual system: A magnetoencephalographic study

Humans have several mechanisms for the visual perception of motion, including one that is luminance‐based (first‐order) and another that is luminance‐independent (second‐order). Recent psychophysical studies have suggested that significant interaction occurs between these two neural processes. We investigated whether such interactions are represented as neural activity measured by magnetoencephalography (MEG). The second‐order motion of a drifting sinusoidal grating, which is defined by the speed of the dot motion, did not generate a response. Apparent motion (AM) of the square area, defined by the speed of randomly moving dots, evoked a magnetic response whose latency and amplitude changed with the distance that the area moved (a second‐order characteristic), though the response properties were significantly different from those for the first‐order AM. AM, defined by both first‐ and second‐order attributes, evoked an MEG response and the latencies and the amplitudes were distributed between those for the first‐ and second‐order motions. The cortical source of the response was estimated to be around MT+. The results show a distinct difference in the neural processing of the second‐order motion that cannot be explained by the difference in visibility, and they indicate that the interaction of the neural processes underlying first‐ and second‐order motion detection occurs before the MEG response. Our study provides the first physiological evidence of a neural interaction between the two types of early motion detection. Hum. Brain Mapp. 20:158–167, 2003. © 2003 Wiley‐Liss, Inc.
Growth performance, carcass quality, biochemical and haematological traits and immune response of growing rabbits as affected by different growth promoters.

The aim of the article was to study the effect of different growth promoters on growth performance, carcass quality, biochemical and haematological traits and immune response of growing rabbits. A total number of 105 male growing NZW rabbits during 35-91 days of age were randomly distributed among 7 groups fed the same basal diet and submitted to different dietary treatments: the first group was unsupplemented and used as control; the other groups were supplemented respectively with bee pollen and/or propolis at 200 mg/kg BW of each and inulin and/or mannanoligosaccharides (MOS) at 35 mg/kg BW of each. Body weight gain, daily feed intake, feed conversion ratio (FCR), biochemical and haematological blood parameters, carcass characteristics, histological studies of ileum and spleen and economical efficiency were measured. Bee pollen administered alone or with propolis significantly (p < 0.01) the body weight gain and improved FCR in respect of the control group. Inulin with MOS significantly improved just FCR than the control group. Bee pollen with propolis and MOS supplemented-groups resulted in significantly higher (7.96 and 8.41% respectively) white blood cells compared to the control group. Plasma total cholesterol was significantly higher for the MOS group in respect of the control, bee pollen, inulin and inulin with MOS supplemented-groups. Propolis resulted in significantly higher dressed carcass percentage than the control group and higher carcass index than only bee pollen with propolis supplemented-group. Bee pollen, in particular if in combination with propolis, could be used as a supplement in the growing rabbits during days 35-91 of age with positive effects on growth rate and feed conversion ratio.
Tissue culture demyelination by normal human serum

Serum from all of 20 normal individuals induced some degree of demyelination when applied to well‐myelinated mouse cerebellum cultures. An intact complement sequence through C5 is required. Demyelinating activity was heat labile at 56°C for 30 minutes but was not destroyed at 50°C for 30 minutes (which inhibits properdin factor B and alternate complement pathway activation, but not the classic complement pathway). Sera from patients with agammaglobulinemia, C4 deficiency, or C6 deficiency all induced demyelination. Our results suggest that tissue culture demyelination results from nonimmunoglobulin activation of the alternate complement pathway and is not limited to sera from patients with neurological disease.
The culture of a trauma team in relation to human factors.

AIM The aim of this ethnographic study was to explore the culture of a trauma team in relation to human factors. BACKGROUND Traumatic injury is the leading cause of death in the first four decades of life in the western world. Evidence suggests that the initial assessment and resuscitation of trauma victims is most successfully carried out by an organized trauma team. Most trauma teams use Advanced Trauma Life Support principles which focus on rapid assessment and management of the patient's injuries. Similarly, most trauma education focuses on Advanced Trauma Life Support principles, concentrating firmly on the patient's physical status. Nevertheless, contemporary literature about emergency teams suggests that human factors, such as communication and interprofessional relationships, can affect the team's performance regardless of how clinically skilled the team members are. METHOD Focused ethnography was used to explore the culture of a trauma team in one teaching hospital. Six periods of observation were undertaken followed by 11 semi-structured interviews with purposively chosen key personnel. Data from transcripts of the observation field notes and interviews were analysed using open coding, followed by formation of categories resulting in the emergence of six central categories. RESULTS Findings suggest that leadership, role competence, conflict, communication, the environment and the status of the patient all influence the culture of the trauma team. Interpretation of these categories suggests that trauma team education should include human factor considerations such as leadership skills, team management, interprofessional teamwork, conflict resolution and communication strategies. RELEVANCE FOR CLINICAL PRACTICE The findings suggest that support systems for role development of junior team leaders should be formalized. The proven airline industry techniques of Crew Resource Management, focusing on teamwork and effective communication, could be implemented into continuing professional development for trauma teams to engender collaboration and interprofessional practice.
Homocysteine concentration in primary and systemic sclerosis associated Raynaud's phenomenon.

OBJECTIVE To investigate whether patients with systemic sclerosis (SSc) have raised homocysteine (Hcy) plasma levels, thought to be an independent risk factor for vascular disease, and to study the relationship between Hcy and endothelial damage, and between Hcy and methylene-tetrahydrofolate reductase (MTHFR) genotypes, and patients' vitamin nutritional status, which are among the more frequent causes of hyperhomocysteinemia. METHODS We measured Hcy, von Willebrand factor (vWF), folic acid, and vitamin B12 plasma levels and analyzed the frequencies of MTHFR mutations in 30 patients with SSc and 12 patients with primary Raynaud's phenomenon (RP); 29 healthy subjects served as controls. RESULTS Patients with SSc had higher Hcy and vWF concentrations than those with RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.02 and p < 0.0001, respectively). Folic acid and vitamin B12 were lower in SSc than in RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.05). MTHFR genotype did not influence Hcy, folate, or vitamin B12 concentrations, but patients homozygous for the mutant gene had higher vWF levels. CONCLUSION Patients with SSc, but not those with RP, had significantly higher Hcy and vWF plasma levels. Nutritional rather than inherited factors seem to have a pathogenic role in SSc hyperhomocysteinemia.