Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of inhibitors in patients with haemophilia from India

Four hundred and seven patients (352 haemophilia A and 55 haemophilia B) were investigated for the presence of factor VIII and IX inhibitors. Twenty‐four out of 292 severe and two out of 36 moderate haemophilia A patients showed the presence of inhibitors. The mean age at development of inhibitors was 17.7 years (range 6–52 years). In 12 patients the inhibitors were detected due to suboptimal response to factor replacement therapy (symptomatic) and in the remaining 14 patients the inhibitors were detected during the routine screening of the patients’ samples for inhibitors. They had, however, responded well to the usual doses of factor concentrates and there was no suspicion in these patients that they had developed an inhibitor (asymptomatic). There were two families in which the inhibitors were detected in more than one family member. The level of inhibitors in symptomatic patients ranged from 2.2 Bethesda units (BU) mL–1 to 460.6 BU mL–1, and in asymptomatic patients it ranged from 0.8 BU mL–1 to 3.2 BU mL–1. The inhibitors persisted in all patients except one, who developed an inhibitor postoperatively for a brief period of 3 months. All these patients were followed up from first factor exposure and were tested for inhibitors at least twice a year. The mean number of exposure days before they developed inhibitors was 47.5 exposure days (range 17–98 exposure days). No inhibitors appeared after more than 100 exposure days in any of the patients. When 50 consecutive patients were investigated for intron 22 inversions of the factor VIII gene, 17 patients were found to be positive for inversions (10 proximal inversion; seven distal inversion) out of whom four patients developed inhibitors, three patients belonging to the same family. Out of 35 haemophilia B patients, only one patient developed an inhibitor. The overall prevalence of inhibitors was thus 8.2%, which is similar to the reports from western countries, prior to the introduction of highly purified factor concentrate therapy.
Ric1p and Rgp1p form a complex that catalyses nucleotide exchange on Ypt6p

Cells lacking the GTPase Ypt6p have defects in intracellular traffic and are temperature sensitive. Their growth is severely impaired by additional mutation of IMH1, which encodes a non‐essential Golgi‐associated coiled‐coil protein. A screen for mutants that, like ypt6, specifically impair the growth of imh1 cells led to the identification of RIC1. Ric1p forms a tight complex with a previously uncharacterized protein, Rgp1p. The Ric1p–Rgp1p complex binds Ypt6p in a nucleotide‐dependent manner, and purified Ric1p–Rgp1 stimulates guanine nucleotide exchange on Ypt6p in vitro. Deletion of RIC1 or RGP1, like that of YPT6, blocks the recycling of the exocytic SNARE Snc1p from early endosomes to the Golgi and causes temperature‐sensitive growth, but this defect can be relieved by overexpression of YPT6. Ric1p largely colocalizes with the late Golgi marker Sec7p. Ypt6p shows a similar distribution, but this is altered when RIC1 or RGP1 is mutated. We infer that the Ric1p–Rgp1p complex serves to activate Ypt6p on Golgi membranes by nucleotide exchange, and that this is required for efficient fusion of endosome‐derived vesicles with the Golgi.
Educating children and youth in care in Alberta: a scoping review

Alberta Education and Alberta Children Services have reported consistent low achievement in school by children and youth in care, especially those in residential group care. This article provides the current picture of research and practice (policy) regarding the learning experience of children and youth in care. Utilizing a scoping review of local and international research studies, the paper argues that the education of children in care in Alberta is not considered an important issue. The dominance of the social work paradigm in children and family services is exposed as inadequate, and hence the call for social pedagogy to be adopted. Determinants of educational achievement for children and youth in care are examined and using these attainment factors, the article identifies and recommends areas that Alberta Education and Alberta Children Services need to consider with urgency if children and youth in care are to benefit from schooling like all other children.
Alcohol-Induced Adipogenesis in Bone and Marrow: A Possible Mechanism for Osteonecrosis

The effect of alcohol on rabbit bone marrow and on the differentiation of mouse bone marrow stromal cells was investigated. Alcohol was administered intragastrically at a dose of 10mL/kg/day for 1 to 6 months. Alcohol induced a significant increase in serum lipid peroxides, triglyceride, and cholesterol, and a reduction in superoxide dismutase activity. Fatty infiltration in the liver and adipogenesis in bone marrow were found histologically after alcohol administration. Fat cell hypertrophy and proliferation and diminished hematopoiesis in the subchondral area of the femoral head were observed. Triglycerides were deposited in osteocytes, which became pyknotic, and the percentage of empty osteocyte lacunae increased. None of these abnormal changes were detectable in the control group. In the in vitro study, the marrow stromal cells were treated with increasing (0.03, 0.09, and 0.15 mol/L) concentrations of ethanol for 4 to 21 days. Alcohol induced the differentiation of the cells into adipocytes. The number of adipocytes increased with longer durations of exposure to ethanol and with higher concentrations. Cells treated with ethanol also showed diminished alkaline phosphatase activity and expression of osteocalcin. These novel findings indicate that alcohol can directly induce adipogenesis, decrease osteogenesis in bone marrow stroma, and produce intracellular lipid deposits resulting in the death of osteocytes, which may be associated with the development of osteonecrosis, especially in patients with long-term and excessive use of alcohol.
Evaluation of schistocyte monitoring after haematopoietic stem cell transplantation

Introduction: Observation of schistocytes on the peripheral blood following haematopoietic stem cell transplantation (SCT) is a common finding. As their presence is not specific to the onset of SCT‐related thrombotic microangiopathy, we evaluated the interest of schistocyte measurement twice a week during the entire follow‐up of 195 patients undergoing SCT, particularly focussing on the 125 allogeneic SCT.
Voting on Behalf of a Future Generation: A Laboratory Experiment

This paper investigates a new voting rule wherein some people are given extra votes to serve as proxies for future generations. We predict that this voting scheme affects the voting behavior of those who do not receive an extra vote (i.e., single-ballot voters) because they are less likely to become a pivot, while proxy voters are expected to behave in support of the future generation. To test this prediction, we compare three scenarios wherein single-ballot voters would cast a vote: (a) one-voter-one-vote scenario wherein all voters cast only a single ballot; (b) a standard proxy-voting scenario wherein other voters cast two ballots, and the second vote is to cast for the benefit of a future generation; and (c) a non-proxy-voting scenario wherein other voters cast two ballots with no explanation for the second vote. The result shows that single-ballot voters are less inclined to vote for the future-oriented option in (c) than in (a). This indicates the potential drawback of the new voting scheme. However, there is no difference in the single-ballot voters’ decision between (a) and (b), indicating that the explanation of the second ballot as the proxy is important for reducing the intergenerational inequality through this voting reform.
Highlights of Educational Research on Leadership Mentoring: One and a half decades of Singapore experience

This purpose of this paper is to surface findings from a review of pertinent major research in Singapore and highlight the system-wide impact of in-service leadership mentoring over a sustained period of time. Beyond the transmission of knowledge and experience, sustained leadership mentoring generates a pervasive network to create learning in the development of aspiring school principals. Findings also reveal that protégés appreciate the role-modeling of their mentor principal in relation to service in leadership and the facilitation of learning. The nurturing and consolidation of relationships in mentoring actively promote interactions among peers in educational administration and leadership. The impact of leadership mentoring on the education system in influencing school leaders is substantial, over and beyond the period of its structured implementation.
Priming voluntary autobiographical memories: Implications for the organisation of autobiographical memory and voluntary recall processes

The goal of this study was to show that voluntary autobiographical memories could be primed by the prior activation of autobiographical memories. Three experiments demonstrated voluntary memory priming with three different approaches. In Experiment 1 primed participants were asked to recall memories from their elementary school years. In a subsequent memory task primed participants were asked to recall memories from any time period, and they produced significantly more memories from their elementary school years than unprimed participants. In Experiment 2 primed participants were asked to recall what they were doing when they had heard various news events occurring between 1998 and 2005. Subsequently these participants produced significantly more memories from this time period than unprimed participants. In Experiment 3 primed participants were asked to recall memories from their teenage years. Subsequently these participants were able to recall more memories from ages 13–15 than unprimed participants, where both had only 1 second to produce a memory. We argue that the results support the notion that episodic memories can activate one another and that some of them are organised according to lifetime periods. We further argue that the results have implications for the reminiscence bump and voluntary recall of the past.
Predicting substance use in late adolescence: results from the Ontario Child Health Study follow-up.

OBJECTIVE The purpose of this study was to evaluate the relationship between use of tobacco, alcohol, marijuana, and hard drugs (substance use) and psychiatric disorder in early adolescence and substance use in late adolescence. METHOD Adolescents included in the study were identified by means of a household sampling frame and participated in the Ontario Child Health Study in 1983 and the follow-up in 1987. There were 726 12-16-year-olds (369 boys and 357 girls) in 1983 who had complete information in 1987. Data on substance use were collected from adolescents by using a structured, self-administered questionnaire. Data on psychiatric disorder were collected in 1983 from both adolescents and their parents by using problem checklists to assess conduct disorder, attention deficit disorder, and emotional disorder. RESULTS Prior substance use in 1983 was associated strongly with subsequent use in 1987. Among the psychiatric disorders assessed in 1983, only conduct disorder made an independent contribution to predicting use of marijuana (relative odds = 3.46) and other hard drugs (relative odds = 6.82) in 1987, after prior use of these substances and coexisting attention deficit and emotional disorders were controlled. Corresponding estimates of attributable risk (the expected contribution of exposure to conduct disorder to the development of substance use) were 5.7% and 11.1%, respectively. CONCLUSIONS Although a statistically significant relationship existed between conduct disorder in early adolescence and use of marijuana and hard drugs in late adolescence, the potential is limited for preventing substance use in the general population by treating conduct disorder early on.
Protection of rat hepatocytes from apoptosis by inhibition of c-Jun N-terminal kinase.

BACKGROUND Apoptotic cell death and c-Jun N-terminal kinase (JNK) activation occur after hepatic ischemia/reperfusion injury. In other cell types, JNK activation was shown to be required for apoptosis. This study tested the hypotheses that JNK contributes to hepatocellular apoptosis, and that inhibition of JNK activity improves cell viability. METHODS Rat hepatocytes were harvested from Sprague-Dawley rats and pretreated with SP600125, a JNK inhibitor. Subsequently, they were exposed to apoptotic stimuli consisting of either the bile salt glycochenodeoxycholic acid (GCDC) or tumor necrosis factor (TNF)-alpha and actinomycin D. RESULTS Western blotting demonstrated specific inhibition of JNK by SP600125. Inhibition of JNK resulted in improved viability measured with crystal violet, decreased in situ DNA nick end labeling positivity, and decreased cleavage of poly (ADP-ribose) polymerase and caspase-3. TNF-alpha and actinomycin D induced apoptosis, upregulated p53, and downregulated expression of the anti-apoptotic protein X-linked inhibitor of apoptosis protein. These effects were abrogated by JNK inhibition. CONCLUSIONS These data show that pharmacologic inhibition of JNK activity reduces bile salt or TNF-alpha-induced apoptosis by maintaining expression of anti-apoptotic proteins. The results indicate that JNK is an important component of the apoptosis signaling cascade and suggest a possible therapeutic strategy in certain liver disorders.
Hyperglycemia stimulates p62/PKCζ interaction, which mediates NF‐κB activation, increased Nox4 expression, and inflammatory cytokine activation in vascular smooth muscle

Hyperglycemia leads to vascular smooth muscle cell (VSMC) dedifferentiation and enhances responses to IGF‐I. Prior studies showed that hyperglycemia stimulated NADPH oxidase 4 (Nox4) synthesis, and IGF‐I facilitated its recruitment to a signaling complex where it oxidized src, leading to AKT and MAPK activation. To determine the mechanism that led to these changes, we analyzed the roles of p62 (sequestrosome1) and PKCζ. Hyperglycemia induced a 4.9 ± 1.0‐fold increase in p62/PKCζ association, and disruption of PKCζ/p62 using a peptide inhibitor or p62 knockdown reduced PKCζ activation (78 ± 6%). 3‐Phosphoinoside—dependent protein kinase 1 was also recruited to the p62 complex and directly phosphorylated PKCζ, leading to its activation (3.1 ± 0.4‐fold). Subsequently, activated PKCζ phosphorylated p65 rel, which led to increased Nox4 synthesis. Studies in diabetic mice confirmed these findings (6.0 ± 0.4‐fold increase in p62/PKCζ) and their disruption of attenuated Nox4 synthesis (76 ± 9% reduction). PKCζ/p62 activation stimulated inflammatory cytokine production and enhanced IGF‐I‐stimulated VSMC proliferation. These results define the molecular mechanism by which PKCζ is activated in response to hyperglycemia and suggest that this could be a mechanism by which other stimuli such as cytokines or metabolic stress function to stimulate NF‐κB activation, thereby altering VSMC sensitivity to IGF‐I. —Xi, G. , Shen, X. , Wai, C. , Vilas, C. K. , Clemmons, D. R. Hyperglycemia stimulates p62/PKCζ interaction, which mediates NF‐κB activation, increased Nox4 expression, and inflammatory cytokine activation in vascular smooth muscle. FASEB J. 29, 4772–4782 (2015). www.fasebj. org
High School CPR/AED Training in Washington State

Objective: Describe the rates of CPR/AED training in high schools in the state of Washington after passage of legislation mandating CPR/AED training. Design and Sample: A web‐based survey was sent to administrators at 660 public and private high schools in the state of Washington. Results and Conclusions: The survey was completed by 148 schools (22%); 64% reported providing CPR training and 54% provided AED training. Reported barriers to implementation included instructor availability, cost, and a lack of equipment. Descriptive statistics were used to describe the sample characteristics and implementation rates. Mandates without resources and support do not ensure implementation of CPR/AED training in high schools. Full public health benefits of a CPR mandate will not be realized until barriers to implementation are identified and eliminated through use of available, accessible public health resources.
Theoretical and Empirical Analysis of Economic Resilience Index

Resilience is defined in different ways by different disciplines and different authors but in general resilience may be defined as the ability of a system and its component parts to anticipate, absorb, accommodate, or recover from the effects of a hazardous event in a timely and efficient manner. Resilience is applicable at the micro as macro level, and for this reason, is sometimes defined as the ability of an individual, a household (micro level), a community, a country or a region (macro level) to withstand, cope, adapt, and quickly recover from shocks without compromising long-term development. In this paper economic resilience is defined as the capacity of an economy to resist shocks and withstand the effects of a shock and to avoid the shock altogether. The paper tries to follow the UNDP procedure in presenting Human Development Index , so the same procedure will be followed to provide an Economic Resilience Index (ERI). This resilience index will be applied for a group of developing countries including Iran and the finding will be analyzed.
Activation of Equine Nuclear Transfer Oocytes: Methods and Timing of Treatment in Relation to Nuclear Remodeling1

Abstract Early development of embryos produced by transfer of equine nuclei to bovine cytoplasts is superior to that of intraspecies equine nuclear transfer embryos. This may be related to differences in chromatin remodeling or efficiency of activation between the two oocyte types. The pattern of donor nucleus remodeling was examined in equine-equine and equine-bovine reconstructed oocytes. Chromosome condensation occurred in equine cytoplasts by 2 h but was not seen in bovine cytoplasts until 4 h. We investigated the effect of activation of equine-equine reconstructed oocytes at <30 min or at 2 h after reconstruction. Four activation treatments were evaluated at each time point: injection of sperm extract alone, or in combination with 6-dimethylaminopurine (6-DMAP), cytochalasin B, or 1% dimethylsulphoxide. There was no significant difference in normal cleavage rate or average nucleus number of embryos between equine oocytes activated <30 min or at 2 h after reconstruction. The combination of 6-DMAP with sperm extract significantly (P < 0.01) improved cleavage rate compared with the other three treatments. Activation with sperm extract and 6-DMAP 2 h after donor nucleus injection gave the highest cleavage (79%) and the highest cleavage with normal nuclei (40%). Sperm extract and 6-DMAP also effectively activated oocytes parthenogenetically, yielding 83% cleavage and 73% cleavage with normal nuclei. These results indicate that although nuclear remodeling occurs rapidly in equine cytoplasts, early activation does not improve embryonic development after reconstruction.
The Realizations of Point of Departure of Message in General English Texts

This study aimed to investigate the realization of marked and unmarked theme types as point of departure of message in general English texts. The corpus of this study was 15 general English texts extracted from English general textbooks for university students published in Iran and taught at universities in Iran. The corpus was analyzed based on Halliday’s (1985) framework of thematic organization. Findings suggested the unmarked theme was predominant compared to marked theme. This is due to that writers prefer to use simple structure that help readers to get a better comprehension. Findings also showed that different types of marked theme were used to help in text organization and contribute to better comprehension. In such cases, the writers felt the need to mention some elements in the thematic position other than grammatical subject. The findings highlighted that general English instructors and developers need to take on board the notion of theme and its importance in teaching and developing general English texts.
Outcomes of Carbapenem-Resistant Klebsiella pneumoniae Infection and the Impact of Antimicrobial and Adjunctive Therapies

Background. Carbapenem-resistant Klebsiella pneumoniae is an emerging healthcare-associated pathogen. Objective. To describe the epidemiology of and clinical outcomes associated with carbapenem-resistant K. pneumoniae infection and to identify risk factors associated with mortality among patients with this type of infection. Setting. Mount Sinai Hospital, a 1,171-bed tertiary care teaching hospital in New York City. Design. Two matched case-control studies. Methods. In the first matched case-control study, case patients with carbapenem-resistant K. pneumoniae infection were compared with control patients with carbapenem-susceptible K. pneumoniae infection. In the second case-control study, patients who survived carbapenem-resistant K. pneumoniae infection were compared with those who did not survive, to identify risk factors associated with mortality among patients with carbapenem-resistant K. pneumoniae infection. Results. There were 99 case patients and 99 control patients identified. Carbapenem-resistant K. pneumoniae infection was independently associated with recent organ or stem-cell transplantation (P = .008), receipt of mechanical ventilation (P = .04), longer length of stay before infection (P = .01), and exposure to cephalosporins (P = .02) and carbapenems (P < .001). Case patients were more likely than control patients to die during hospitalization (48% vs 20%; P < .001) and to die from infection (38% vs 12%; P < .001). Removal of the focus of infection (ie, debridement) was independently associated with patient survival (P = .002). The timely administration of antibiotics with in vitro activity against carbapenem-resistant K. pneumoniae was not associated with patient survival. Conclusions. Carbapenem-resistant K. pneumoniae infection is associated with numerous healthcare-related risk factors and with high mortality. The mortality rate associated with carbapenem-resistant K. pneumoniae infection and the limited antimicrobial options for treatment of carbapenem-resistant K. pneumoniae infection highlight the need for improved detection of carbapenem-resistant K. pneumoniae infection, identification of effective preventive measures, and development of novel agents with reliable clinical efficacy against carbapenem-resistant K. pneumoniae.
Dual-Depletion-Region Electroabsorption Modulator With Evanescently Coupled Waveguide for High-Speed (${>}$ 40 GHz) and Low Driving-Voltage Performance

We demonstrate a novel structure of a electroabsorption modulator (EAM) at a 1.55-mum wavelength. By incorporating the epilayer structure of dual-depletion-region EAM with an evanescently coupled optical waveguide, the demonstrated device can achieve low electrical return loss (-20 dB at ~60 GHz), wide 3-dB bandwidth (60 GHz) of electrical transmission loss, wide electrical-to-optical bandwidth (45 GHz), and low 20-dB static driving voltage (V20dB, 1.65 V) with extremely small polarization dependency. This new structure can not only achieve excellent figures-of-merit but release the burden imposed on downscaling the core width or length of high-speed/low driving-voltage EAM without using epitaxial regrowth or ion-implantation techniques to isolate the active and passive regions