Miracle-dz/UniFAR-FTUs huggingface dataset:
Voriconazole pharmacokinetics and pharmacodynamics in children.

BACKGROUND Voriconazole pharmacokinetic and pharmacodynamic data are lacking in children. METHODS Records at the Childrens Hospital Los Angeles were reviewed for children with > or =1 serum voriconazole concentration measured from 1 May 2006 through 1 June 2007. Information on demographic characteristics, dosing histories, serum concentrations, toxicity and survival, and outcomes was obtained. RESULTS A total of 207 voriconazole measurements were obtained from 46 patients (age, 0.8-20.5 years). A 2-compartment Michaelis-Menten pharmacokinetic model fit the data best but explained only 80% of the observed variability. The crude mortality rate was 28%, and each trough serum voriconazole concentration <1000 ng/mL was associated with a 2.6-fold increased odds of death (95% confidence interval, 1.6-4.8; P=.002). Serum voriconazole concentrations were not associated with hepatotoxicity. Simulations predicted an intravenous dose of 7 mg/kg or an oral dose of 200 mg twice daily would achieve a trough >1000 ng/mL in most patients, but with a wide range of possible concentrations. CONCLUSIONS We found a pharmacodynamic association between a voriconazole trough >1000 ng/mL and survival and marked pharmacokinetic variability, particularly after enteral dosing, justifying the measurement of serum concentrations.
[Sequence analysis of ITS2 and CO1 genes of Paragonimus harinasutai].

OBJECTIVE To identify Paragonimus harinasutai from Ninghai, Zhejiang Province, China. METHODS Metacercariae were collected from the crabs Sinopotamon chekiangenes in Xixi village of Ninghai County for ITS2 sequence analysis, CO1 sequence analysis and endonuclease BsaHI and StuI analysis by PCR-RFLP. Results The fingerprintings of PCR-RFLP were virtually same to the isolate from Thailand (Nakorn-nayok). The ITS2 sequence with 366 bp and CO1 sequence with 390 bp of the metacercariae collected from Ninghai revealed a nucleotide identity 95.6% and 89.5% respectively to the Thai isolate. CONCLUSION The study confirmed that Paragonimus harinasutai is present in Ninghai, China, with certain variation on molecular biology in comparison to the Thai isolate.
Dealing with allegations of violence against women in a multicultural environment: Consideration of approach(es) and procedure(s) with regards to abuse allegations of women of an Asian, African and Middle Eastern origin in New Zealand

New Zealand has become increasingly multicultural and continues to accept a large number of migrants every year. This adds a duty on its legal system to ensure that its current laws can protect minority groups and adequately deal with culturally specific issues that arise due to different cultural norms. Many argue that the current legal system fails to provide adequate protection for girls and women from an Asian, African and Middle Eastern (AAM) origin; this is due to a lack of multicultural consideration and the addressing of specific issues linked to these ethnic groups. One such issue is the problem of forced marriages among AAM communities living in New Zealand. This article argues that New Zealand's laws and processes do not adequately protect women of an AAM background due to a lack of specific laws and policies that can protect against culturally specific abuse. This argument is reached through the consideration of approaches and procedures through socio-legal methodology. This includes the review of governmental documents, semi-structured interviews with relevant organisations and experienced individuals in the field, case studies and independent research. I will conclude that there is a lack of cultural understanding within support organizations and public institutions regarding the forced marriage issues. Moreover AAM women are also not completely aware of their rights and the available support. Finally, I will provide some recommendations based on knowledge I have gained while conducting my research.
Gender differences in airway resistance during sleep.

At the onset of non-rapid-eye-movement (NREM) sleep there is a fall in ventilation and an increase in upper airway resistance (UAR). In healthy men there is a progressive increase in UAR as NREM sleep deepens. This study compared the pattern of change in UAR and ventilation in 14 men and 14 women (aged 18-25 yr) both during sleep onset and over the NREM phase of a sleep cycle (from wakefulness to slow-wave sleep). During sleep onset, fluctuations between electroencephalographic alpha and theta activity were associated with mean alterations in inspiratory minute ventilation and UAR of between 1 and 4.5 l/min and between 0.70 and 5.0 cmH2O . l-1 . s, respectively, with no significant effect of gender on either change (P > 0.05). During NREM sleep, however, the increment in UAR was larger in men than in women (P < 0.01), such that the mean levels of UAR at peak flow reached during slow-wave sleep were approximately 25 and 10 cmH2O . l-1 . s in men and women, respectively. We speculate that the greater increase in UAR in healthy young men may represent a gender-related susceptibility to sleep-disordered breathing that, in conjunction with other predisposing factors, may contribute to the development of obstructive sleep apnea.
NOTCH and phosphatidylinositide 3-kinase/phosphatase and tensin homolog deleted on chromosome ten/AKT/mammalian target of rapamycin (mTOR) signaling in T-cell development and T-cell acute lymphoblastic leukemia

Activating mutations in NOTCH1 consitute the most prominent genetic abnormality in T-cell acute lymphoblastic leukemia (T-ALL). However, most T-ALL cell lines with NOTCH1 mutations are resistant to treatment with γ-secretase inhibitors (GSIs). The spotlight is now shifting to the phosphatidylinositide 3-kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome ten (PTEN)/AKT/mammalian target of rapamycin (mTOR) pathway as another key potential target. These two signaling routes are deregulated in many types of cancer. In this review we discuss these two pathways with respect to their signaling mechanisms, functions during T-cell development, and their mutual roles in the development of T-ALL.
Combined flow and absorption DNA measurements of [3H]TdR‐labelled tumour cells. I. Studies of MCa‐11 cells grown as tumours in vivo and as exponential cultures in vitro *

Abstract. Flow cytometry of cellular DNA content provides rapid estimates of DNA distributions, i.e. the proportions of cells in the different phases of the cell cycle. Measurements of DNA alone, however, yield no kinetic information and can make it difficult to resolve the cell cycle distributions of normal and transformed cells present in tumour biopsy specimens. The use of absorption cytophotometry of the Feulgen DNA content and [3H]TdR labelling of the same nuclei provides objective criteria to distinguish the ranges of DNA content for G0/G1, S, and G2/M cells. We now report on a study in which we combined flow and absorption cytometry to resolve the cell cycle distributions of host and tumour cells present in biopsy specimens of MCa‐11 mouse mammary tumours labelled in vivo for 0.5 hr with [3H]TdR. A similar analysis of exponential monolayer cultures, labelled for 5 min with [3H]TdR under pulse‐chase conditions, revealed a highly synchronous traversal of almost all cells through the different phases of the cell cycle. Combination of the flow and absorption methods also allowed us to detect G2 tumour cells in vivo and a minor tumour stem‐line in vitro, to show that these two techniques are complementary and yield new information when they are combined.
Prospective comparative study of endoscopic papillary large balloon dilation and endoscopic sphincterotomy for removal of large bile duct stones in patients above 45 years of age

Abstract Objective. Although endoscopic papillary large balloon dilation (EPLBD) with limited endoscopic sphincterotomy (ES) showed excellent outcomes for treatment of large bile duct stones, hemorrhage and recurrence of stones are problematic complications. Recent studies suggest that EPLBD alone is safe and effective for removal of large bile duct stones. This study aimed to determine the therapeutic outcomes and safety of EPLBD, compared with ES, for removal of large bile duct stones. Material and methods. Eighty-three patients above 45 years of age with bile duct stones >1 cm in diameter were randomized to EPLBD and ES groups for removal of common bile duct stones from September 2010 to August 2011. Prophylactic gabexate mesilate was given to all patients. Results. Baseline characteristics were not significantly different, except diabetes and gallbladder stones between the EPLBD group (n = 40) and ES group (n = 43). The overall complete stone removal rate in each group was 97.5% (39/40) and 95.3% (41/43), respectively (p = 0.600). Requirement of mechanical lithotripsy was not significantly different between the EPLBD and ES group (10% vs. 21%, p = 0.171). Complete ductal clearance in one session was achieved in 82.4% and 81.4% of cases in each group, respectively (p = 0.577). There were no differences in complication rates between the EPLBD and ES group; pancreatitis, 5.0% vs. 7.0%; hemorrhage, 10.0% vs. 16.3%; acute cholangitis, 5.0% vs. 2.3%, and perforation, 2.5% vs. 0%. Conclusions. The therapeutic outcomes and complications of EPLBD for removal of large bile duct stones are comparable to those of ES.
The Contribution of Project Management and Change Management to Project Success

Project Management and Change Management are two management disciplines that contribute to the delivery of organizational changes. However, there is a lack of clarity about how these disciplines should work together, and evidence that there is some rivalry about which discipline should be managing organizational change projects. This research has analysed the responses of project managers and change managers to an online survey regarding each discipline’s influence over factors that have been identified as critical to project success. The results have been used to determine factors that were more typically influenced by each discipline. Significant differences of opinion about how these disciplines perceived the other’s contribution were also identified from the results, suggesting possible sources of conflict between the disciplines. These results were used to create a framework to determine project manager and change manager responsibility for aspects of the delivery of a project, based on where significant project risks are anticipated.
Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia.

OBJECTIVE We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. METHOD This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004. RESULTS Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = . 743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = . 366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = . 011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = . 811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score. CONCLUSIONS Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00014001.
Nitrogen retention by lambs fed oscillating dietary protein concentrations.

Nitrogen excreted by beef cattle can be retained in manure or lost by volatilization to the atmosphere or by runoff and percolation into surface or ground water. Increasing the retention of dietary N should decrease environmental losses. To this end, the effects of oscillating concentrations of dietary CP on nutrient retention were determined using lambs fed a 90% concentrate diet. Ten St. Croix lambs (average BW = 27 kg) were used in two 5x5 Latin square experiments. Dietary treatments were as follows: 1) 10% CP, 2) 12.5% CP, 3) 15% CP, 4) 10% and 15% CP diets oscillated at 24-h intervals, and 5) 10% and 15% CP diets oscillated at 48-h intervals. Supplemental N was provided by cottonseed meal in Trial 1 and by a 50:50 (N basis) blend of cottonseed meal and urea in Trial 2. Each period of the Latin square lasted 35 d, with excreta collection the final 8 d. Nitrogen retention increased linearly (P<.01) with increasing N intake in both trials (.77, 1.33, and 1.89 g/d for 10, 12.5, and 15% CP, respectively, in Trial 1; .94, 1.78, and 2.19 g/d for 10, 12.5, and 15% CP, respectively, in Trial 2). Compared with continuously feeding the 12.5% CP diet, oscillating the 10 and 15% CP diets on a 24-h basis did not affect N retention (P>.10) in either trial (1.62 and 1.56 g/d for Trials 1 and 2, respectively). Oscillating dietary CP at 48-h intervals did not affect N retention in Trial 2 (1.82 g/d) but increased (P<.05) N retention by 38% in Trial 1 (1.87 g/d). Phosphorus, K, and Na retention and excretion were not affected by dietary treatments in Trial 1. In Trial 2, P retention increased (linear, P<.05) with increasing dietary CP and was greater (P<.05) in lambs on the 48-h oscillation treatment than in lambs fed the 12.5% CP diet. These results suggest that oscillating the dietary CP concentrations might potentially increase the utilization of N by ruminants fed high-concentrate diets.
Refining a Polarimetric Decomposition of Multi-Angular UAVSAR Time Series for Soil Moisture Retrieval Over Low and High Vegetated Agricultural Fields

The model-based polarimetric decomposition under multi-angular condition is refined to estimate soil moisture over agricultural fields covered by different crops from Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) time series. The approach allows to disentangle the vegetation and ground scattering components in order to invert the latter for the retrieval of soil moisture. For the vegetation volume separation, the crop orientations were estimated from SAR observations acquired at different incidence angles, and the associated volume scattering component was subtracted from each acquisition individually. Afterward, the soil moisture was retrieved from both ground scattering components (surface, dihedral), using the developed multi-angular cost functions comprised of dominant Bragg surface (β) or Fresnel dihedral (α) scattering parameters. Compared to former soil moisture retrievals from model-based decomposition of multi-angular polarimetric SAR data, the present refined approach that integrated both ground components, surface and dihedral, is independent of the power attenuation and loss during the microwave propagation through the vegetation. In this way, the ambiguity in the dihedral scattering component (most prominent around 45° incidence angle) was overcome, enabling a more robust retrieval methodology by clearly decoupling the soil and vegetation dielectric constants. The proposed multi-angular approach for soil moisture retrieval was validated with respect to the ground measurements conducted during the Soil Moisture Active Passive Validation Experiment in 2012. Due to the increased number of valid dominant surface/dihedral components which are used to retrieve the soil moisture in the multi-angular approach, an overall retrieval rate of 90%, significantly higher than that of the single-angular condition (50%), is obtained. The results indicate an overall retrieval rmse of 0.07–0.09 m3/m3 for the early crop growth stage, and a rmse of 0.09–0.12 m3/m3 for the later crop development until mature stage. However, the retrieval performance is highly dependent on the crop structure and phenological development stages, but the multi-angular rmse range is mostly lower than all single-angular rmses, indicating better quality of the multi-angular inversion than the single-angular one.
Sophisticated Electoral Accountability: A Political Psychology Agency Theory

I propose a political agency model where rent-maximizer rulers are constrainedby sophisticated principals/producers that use an awareness-management model A la BA¨nabou and Tirole. In the first part of the paper I empirically test the theoreticalnexus between education and political sophistication by comparing individualswith different education attainments within more than eighty countries and morethat twenty religious groups introduced to capture specic cultural variation inthe results. And elastic (inelastic) political beliefs for respondents with a tertiary(primary) degree according to the quality of political institutions. Motivatedby that, I model Political Psychology predictions by introducing heterogeneity onthe electoral side: producers are endowed with di fferent levels of education, thatincrease over time with human capital investments. I allow education to be boththe engine of growth and a determinant of political participation; in equilibrium,more educated societies are more able to punish politicians that, in turn, investmore in productive public goods such as infrastructure, roads or legal rules forcontracts enforcement. I prove the existence of multiple steady states featuring,respectively, a sophisticated society with congruent politicians in once, and a naivesociety ruled by dissonant politicians. Finally, I address inequality concerns andshow how, for intermediate values, inequality opposingly hits citizens and ruler andonly the latter is found to better or conversely, citizens are averse to inequality,contributing to explain, via sophisticated accountability, why most people dislikeliving in a society which is too unequal.Keywords: political economy, voting, signaling, sophistication, naivet e, human capital,economic growth, inequality.
Corporate parenting for young people in care: : making the difference?

Young people in care and care leavers want to know that their corporate parents (the local authority, collectively with other relevant services) will care for them and do their best for them. In this, one of the largest peer research studies, we report if, and how, this is being achieved. Our research provides an update on corporate parenting from the perspective of policy and senior managers, social workers and leaving care workers, and importantly, of young people themselves. We trained 36 care leavers as peer researchers, carrying out interviews with 579 young people in and from care in 12 local authorities. This created a competent and enthusiastic team and produced a wealth of information on progress and perspectives incorporate parenting.
The evolution of diastolic dysfunction in the hypertensive disease.

AIMS To investigate the effects of cardiac remodelling on left ventricular (LV) diastolic function, as evaluated by tissue Doppler and blood-pool indices, with respect to loading as expressed by wall stress. Cardiac remodelling is the major pathophysiological result of increased blood pressure and manifests as changes in the size, shape, and function of the heart. METHODS AND RESULTS We evaluated 90 hypertensive patients and 30 healthy volunteers. The hypertensive patients were divided into three groups: (i) HTN-N: normal remodelling (n= 30), (ii) HTN-CR: concentric remodelling (n= 30), and (iii) HTN-CH: concentric hypertrophy (n= 30). Mitral annular early diastolic (Ea) velocities were recorded. Filling pressures (E/Ea), relative wall thickness, LV mass index, DT, isovolumic relaxation time (IVRT), E/A ratio, and longitudinal wall stress (LWS) were also measured. Diastolic dysfunction (DD) was diagnosed based on published criteria. Progressive and increased incidence of DD with advancement of LV remodelling and an increase in LV mass was noted. Wall stress-loading was higher in the HTN-N group and lower in the HTN-CR and HTN-CH groups, despite the more deteriorated diastolic function in the latter groups. DD appeared early, even in the HTN-N group, which had a 36.6% incidence of DD compared to a 13% age-related incidence in the control group (P < 0.05). When the control group was used to define the reference values for septal Ea with the cut-off set as 2SD below the mean, the HTN-N, HTN-CR, and HTN-CH groups had abnormal diastolic function at 16.6, 26.6, and 56.6% incidence rates, respectively. Septal (Ea) was correlated with LVMI (r= -0.55), RWT (r= -0.56), Age (r= -0.52), BMI (r= -0.31), SBP (r= -0.54), PP (r= -0.55), and MAP (r= -0.39), all at P < 0.05. The correlations of blood-pool indices (DT, IVRT, and E/A) with the above parameters were less than that of tissue Doppler imaging (Septal and mean Ea). In a multivariate model, LVMI (beta= -0.25), SBP (beta = -0.26), and age (beta= -0.24) R(2)= 0.49 were found to be independent predictors of DD. CONCLUSIONS DD appears early in hypertensive disease, before the onset of abnormal remodelling or LV hypertrophy. With progression of the remodelling process and the advance of LVH, diastolic function progressively deteriorates. Tissue Doppler indices are better correlated with clinical and echocardiographic parameters of LV remodelling compared to blood-pool indices.
Comparison of one week 0900 h serum cortisol, low and standard dose Synacthen tests with a 4 to 6 week insulin hypoglycaemia test after pituitary surgery in assessing HPA axis

To compare the use of 0900 h serum cortisol and both low and standard dose Synacthen tests, one week after pituitary surgery with an insulin hypoglycaemia test performed 4–6 weeks after surgery in assessing the integrity of the hypothalamic–pituitary–adrenal (HPA) axis.