Miracle-dz/UniFAR-FTUs huggingface dataset:
Measurement of airway hyperresponsiveness: new considerations

Since its initial descriptions in 1946,1 the measurement of airway responsiveness with inhaled bronchoconstrictor stimuli such as methacholine or histamine has become routine practice in the diagnosis and follow up of asthmatic patients. Practically, this involves the patient inhaling increasing doses or concentrations of a stimulus until a given level of bronchoconstriction is achieved, typically a 20% fall in forced expired volume in one second (FEV1). Airway responsiveness is then expressed as the provocative dose or concentration of the stimulus required to achieve this degree of bronchoconstriction (PD20 and PC20, respectively). The term “airway responsiveness” is preferred when discussing PD20 and PC20 measurements as this is a non-specific term that encompasses the underlying mechanisms that may be responsible for differences in these measurements either between individuals or within an individual over time2. This is best illustrated in fig 1 where it can be seen that a decrease in PC20 may be due to a steeper dose-response curve (hyperreactivity) or to a shift in the curve to the left (hypersensitivity), or both. Thus, when an individual displays a decreased PC20 it is usually not known whether this is due to hyperreactivity or hypersensitivity although it is certainly one, the other, or both—all of which are covered by the term airway “hyperresponsiveness”. Figure 1 Changes in FEV1 induced by increasing doses of a bronchoconstrictor stimulus such as histamine or methacholine. Bronchial hyperresponsiveness, defined as the dose causing a 20% fall in FEV1, can be induced by airway hypersensitivity (shift to the left of the dose-response curve) or airway hyperreactivity (steeper slope of the dose-response curve). This figure illustrates how either of these two different mechanisms may result in the same degree of hyperresponsiveness (as measured by a shift in PC …
Association of angiotensin I‐converting enzyme gene polymorphisms with aspirin intolerance in asthmatics

Background Aspirin‐intolerant asthma (AIA) refers to the development of bronchoconstriction in asthmatic individuals following the ingestion of aspirin or other non‐steroidal anti‐inflammatory drugs (NSAIDs). Angiotensin I‐converting enzyme (ACE), a membrane‐bound peptidase present in the lung, plays a pivotal role in the metabolism of the endogenous peptides involved in the pathogenesis of asthma.
Chemotherapy with Benznidazole and Itraconazole for Mice Infected with Different Trypanosoma cruzi Clonal Genotypes

ABSTRACT The benznidazole (BZ) and itraconazole (ITC) susceptibilities of a standard set of Trypanosoma cruzi natural stocks were evaluated during the acute phase and the chronic phase of experimental chagasic infection in BALB/c mice. Twenty laboratory-cloned stocks representative of the total phylogenetic diversity of T. cruzi, including genotypes 20 and 19 (T. cruzi I) and genotypes 39 and 32 (T. cruzi II), were analyzed. Our results demonstrate important differences among stocks that could be pointed out as markers of biological behavior. Members of the T. cruzi I group were highly resistant to both BZ and ITC, whereas members of the T. cruzi II group were partially resistant to both drugs, despite their susceptibilities to ITC during the chronic phase of infection. The resistance to BZ observed for T. cruzi I was mainly triggered by genotype 20 isolates, whereas resistance to ITC was due to both genotype 20 and 19 isolates. Two polar patterns of response to BZ observed for genotype 39 isolates had a major impact on the partial resistance pattern observed for members of the T. cruzi II group. Genotype 32 isolates showed a typical profile of susceptibility. The correlation between the response to treatment and phylogenetic classification of T. cruzi stocks was clearer for ITC than for BZ. In conclusion, the data presented show a correlation between phylogenetic divergence among T. cruzi stocks and their susceptibilities to chemotherapeutic agents in vivo. Our results warn of the necessity to take into account the lesser genetic subdivisions of T. cruzi stocks since the upper subdivisions (T. cruzi I and II) show a great deal of heterogeneity for in vivo drug susceptibility.
Association between antibiotic use and risk of prostate cancer

The association between antibiotics and risk of cancer has been addressed in different studies, most of which were addressing breast cancer. The objective of this study was to assess the association between antibiotics use and risk of prostate cancer. We carried out a population‐based case‐control study using data from Saskatchewan Health administrative databases (Canada) between the years 1981 and 2000. Cases identified by the Saskatchewan Cancer Agency were matched to 4 controls, using incidence density sampling. The effect of dosage and timing of antibiotic use, over a minimum of 15 years before diagnosis, on prostate cancer risk was assessed. Number of prescriptions and number of tablets were used as exposure definitions. Moreover, the effect of different classes of antibiotics on prostate cancer was also studied. A total of 4,052 prostate cancer cases and 16,208 matched controls were included in this study. Antibiotics exposure (number of prescriptions) during the period of 1–15 years in the past was significantly associated with an increased risk of prostate cancer; RR = 1.69, 2.61, 2.71, and 2.83 for the 4 quartiles, respectively, p‐trend = 0.0001. When number of units was taken as the exposure definition, similar results were found. We did not find any effect of the timing or class of antibiotic exposure on prostate cancer risk. We found a dose‐dependent association between antibiotics exposure up to 15 years in the past and risk of prostate cancer. However, the lack of temporal trends and the absence of class specific effects suggest a noncausal relationship.
An Analysis of the Work-Care Experiences of Out-of-Work Partnered Parents in France and the UK: Ideals, Practice and Policy Learning

This thesis analyses the work-care experiences of out-of-work partnered parents in France and the United Kingdom (UK). It aims to understand how activation policy could be improved by recognising the importance of work-family reconciliation issues for out-of-work couples. Based on interviews with thirty-six families in Lille and Sheffield, it contributes to knowledge through increasing awareness of how work-care issues play out within couples and by questioning assumptions among policy makers that such issues are unimportant to out-of-work parents. It differs from existing research by examining the experiences of mothers as carers and potential workers; and fathers as workers and potential carers. The cross-national aspect - with a particular focus on policy learning - evaluates how differences in labour market structures, working time regimes and work-family reconciliation policy in France and the UK are borne out in parental experiences. The ideal work-care scenarios of the parents interviewed are outlined and their experiences of seeking to obtain these models investigated. Respondents were found to have a strong commitment to employment. Personal, activation-side, neighbourhood, societal and (especially for mothers) care factors all contributed to why they were not in work. Differences are identified in the influencing factors cross-nationally between parents. In the UK, even where mothers might find work more easily than fathers, respondents maintained traditional models of whom to prioritise for employment. Parents’ ideals and experiences are analysed in relation to six fields of macro and micro-level literature. Among other contributions, the findings notably allow the development of activation regime theory by fronting the role of care and the extension of ‘gendered moral rationalities’ theory to couples cross-nationally. Discord was found to exist between policy objectives and the ideals of some out-of-work parents in both countries. New policy directions are identified.
The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+,Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells.

We examined the effects of a variety of ligands/activators of the peroxisome proliferator-activated receptor (PPAR) on the expression of the superoxide scavenger enzyme, Cu2+,Zn2+-superoxide dismutase (CuZn-SOD), and the superoxide generating enzyme nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase in primary cultures of human umbilical vein endothelial cells (HUVEC) and human aorta endothelial cells (HAEC). Our data show that 3 types of PPARs, PPARalpha, PPARbeta/delta/Nuc1, and PPARgamma are expressed in endothelial cells. Bezafibrate, which is a ligand/activator for PPARalpha, increased the CuZn-SOD gene expression and protein levels in endothelial cells. Troglitazone and pioglitazone, which are ligands/activators for PPARgamma, also induced PPARalpha gene and protein expression and increased CuZn-SOD gene expression and protein levels in addition to increasing PPARgamma gene and protein expression in endothelial cells. Moreover, with treatment of monounsaturated and polyunsaturated fatty acids (PUFA), the CuZn-SOD mRNA levels were positively correlated with PPARalpha mRNA levels (r = .872, P < .0001) in primary endothelial cells. In addition, the phorbol myristate acetate (PMA)-stimulated or PMA-nonstimulated 22-kd a-subunit (p22phox) mRNA levels and 47-kd a-subunit (p47phox) protein levels in NADPH oxidase were decreased by treatment with PPARalpha and PPARgamma ligands/activators. These results suggest that PPARalpha and PPARgamma gene and protein expression in endothelial cells may play a physiologic role as radical scavengers, although the details of these mechanisms remain to be established.
On the Determination of Appropriate Profit Margins in Insurance Industry Regulation

It is shown that using the CAPM to determine profit margins for property-liability insurance companies presents regulatory commissions with a set of implementation difficulties. These difficulties arise from the unacceptably wide range of acceptable profit margins generated using the CAPM. In particular, if beta is calculated using the appropriate data differencing interval, the confidence intervals may be so wide as to produce unreliable estimates of both beta and profit margin. Use of the Capital Asset Pricing Model (CAPM) has become widespread by regulatory commissions in the rate setting process. Since the Hope decision,' the legal standard for determining rates of return has been that the returns be "'commensurate with returns on investments in other enterprises having corresponding risks. '" It is claimed that the CAPM enables regulators to determine consistent risk adjusted rates of return and commensurate profit margins. Venezian, however, has recently suggested that the CAPM is unsuitable on theoretical grounds for use in insurance industry regulatory proceedings. He cites "circularity in the arguments" made by those using the CAPM since an exogenous rate increase is based upon the results of the CAPM which in turn are based upon the rate increase. Venezian has also recently suggested [1 14 that financial theoretic approaches such as the CAPM lose "relevance in the regulation of businesses which are structured competitively and for whose assets there are viable financial markets. '" While other difficulties have been addressed in using the CAPM in a regulatory framework [ 1,2,3,7,8,9,10], it is still one of the central models upon which allowed rates of return and profit margin are based. Fairley [4] recently proposed an approach to determine equilibrium rates of return and appropriate profit margins for property-liability insurers using the CAPM. His approach calculates the insurer's profit margin as a function of its calculated systematic risk, beta. The purpose of this paper is to show, using Fairley's profit margin model, that in situations where the CAPM is utilized to determine profit margins, the Allen Michel is Associate Professor of Finance at Boston University. James Norris is a Corporate Banking Officer at Bay Bank Harvard Trust Company. The research was completed while the author was associated with the Corporate Research and Planning Group at Liberty Mutual Insurance Company. ' Federal Power Commission v. Hope Natural Gas Co., 320 U.S. 591, 603 (1944). 2Personal communication with Venezian.
Neural Activity in the Medial Temporal Lobe Reveals the Fidelity of Mental Time Travel

Neural circuitry in the medial temporal lobe (MTL) is critically involved in mental time travel, which involves the vivid retrieval of the details of past experience. Neuroscientific theories propose that the MTL supports memory of the past by retrieving previously encoded episodic information, as well as by reactivating a temporal code specifying the position of a particular event within an episode. However, the neural computations supporting these abilities are underspecified. To test hypotheses regarding the computational mechanisms supported by different MTL subregions during mental time travel, we developed a computational model that linked a blood oxygenation level-dependent signal to cognitive operations, allowing us to predict human performance in a memory search task. Activity in the posterior MTL, including parahippocampal cortex, reflected how strongly one reactivates the temporal context of a retrieved memory, allowing the model to predict whether the next memory will correspond to a nearby moment in the study episode. A signal in the anterior MTL, including perirhinal cortex, indicated the successful retrieval of list items, without providing information regarding temporal organization. A hippocampal signal reflected both processes, consistent with theories that this region binds item and context information together to form episodic memories. These findings provide evidence for modern theories that describe complementary roles of the hippocampus and surrounding parahippocampal and perirhinal cortices during the retrieval of episodic memories, shaping how humans revisit the past.
Removal of piperacillin in critically ill patients undergoing continuous venovenous hemofiltration.

OBJECTIVE Continuous hemofiltration is now widely used in the intensive care unit. Our study aimed to assess the removal of piperacillin under continuous hemofiltration and to define a suitable dosage regimen of administration. DESIGN Prospective study of blood and ultrafiltrate concentrations of piperacillin to assess the pharmacokinetics of the antibiotic. SETTING The medical intensive care unit of a teaching hospital. PATIENTS Ten patients were included in the study. Six patients were receiving their first dose of piperacillin (group 1) and four had already been treated for 2 to 6 days (group 2). The mean Simplified Acute Physiology II score was 74 +/- 6 (SEM), and the number of organ failures was 3.6 +/- 0.3 (range 3 to 5). Renal failure was related to septic shock in seven patients and to cardiogenic shock in three patients. Seven patients were anuric. Hepatic dysfunction was present in four of the ten patients. INTERVENTIONS Patients were treated with continuous venovenous hemofiltration using a hollow polysulfone capillary fiber. Piperacillin (4 g) was injected intravenously over 20 mins. Arterial blood and ultrafiltrate were sampled immediately before the injection and then every hour until 8 hrs after injection time. Piperacillin concentrations were assayed using high performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS In group 1, the mean serum peak concentration of piperacillin was in the normal range (125 +/- 21 mg/L), but trough values were higher (48 +/- 8 mg/L) than in normal subjects. In group 2, trough values before the injection were increased in all patients (188 +/- 71 mg/L). At T1, blood peak concentration reached 470 +/- 127 mg/L. A small amount of piperacillin was retrieved from the ultrafiltrate. The elimination half-life was 5.1 +/- 1.4 and 4.8 +/- 1.4 hrs in groups 1 and 2, respectively. CONCLUSIONS Piperacillin was not removed to a significant extent during continuous hemofiltration. Further, in the intensive care unit, patients in shock with multiple organ failure such as liver failure might behave differently from patients with stable end-stage renal disease. A 4-g dose of piperacillin twice a day is recommended in such patients.
Finally! The structural secrets of a HD‐GYP phosphodiesterase revealed

The major sessility‐motility lifestyle change and additional fundamental aspects of bacterial physiology, behaviour and morphology are regulated by the secondary messenger cyclic di‐GMP (c‐di‐GMP). Although the c‐di‐GMP metabolizing enzymes and many receptors have been readily characterized upon discovery, the HD‐GYP domain c‐di‐GMP phosphodiesterase family remained underinvestigated. In this issue of Molecular Microbiology, Bellini et al. provide an important step towards functional and structural characterization of the previously neglected HD‐GYP domain family by resolving the crystal structure of PmGH, a catalytically active family member from the thermophilic bacterium Persephonella marina. The crystal structure revealed a novel tri‐nuclear catalytic iron centre involved in c‐di‐GMP binding and catalysis and provides the structural basis to subsequently characterize in detail the catalytic mechanism of hydrolysis of c‐di‐GMP to GMP by HD‐GYP domains.
Variational Attention for Sequence-to-Sequence Models

The variational encoder-decoder (VED) encodes source information as a set of random variables using a neural network, which in turn is decoded into target data using another neural network. In natural language processing, sequence-to-sequence (Seq2Seq) models typically serve as encoder-decoder networks. When combined with a traditional (deterministic) attention mechanism, the variational latent space may be bypassed by the attention model, and thus becomes ineffective. In this paper, we propose a variational attention mechanism for VED, where the attention vector is also modeled as Gaussian distributed random variables. Results on two experiments show that, without loss of quality, our proposed method alleviates the bypassing phenomenon as it increases the diversity of generated sentences.
Abnormal haemoglobins in the Sudan savanna of Nigeria. I. Prevalence of haemoglobins and relationships between sickle cell trait, malaria and survival.

The prevalence of different haemoglobins and their interaction with malaria have been studied in Garki, Kano State, Nigeria. Sickle cell trait was present in 24% of newborn and 29% of those aged over five years. Hb.AC was present in 0.7%. Frequency of both haemoglobin variants was greater in Hausa than Fulani. Sickle cell anaemia was almost invariably fatal in early childhood. The distribution curve of percentage of Hb.S in sickle cell trait subjects was normal, and did not demonstrate any high frequency of a gene for alpha-thalassaemia. The presence of beta-thalassaemia minor could not be tested, but Hb.S/beta-thalassaemia was not detected. Hb.S gene frequency appears to have been maintained by a fitness in heterozygotes of 21% over normal homozygotes; increased fertility and high mutation rate did not make any apparent contribution. Hb.AS subjects had on average lower frequency and considerably lower densities of Plasmodium falciparum trophozoites than Hb.AA from the age of 30 to 59 weeks; density was less in sickle cell trait up to age three years in the dry season only. It is suggested that the survival advantage and hence the prevalence of sickle cell trait may be greatest in some hyperendemic areas and less where malaria transmission is extremely high or when it is high and unvaried.
Copeptin: a blood test marker of syncope

Copeptin (CPT) is regarded as a stress hormone, and as a novel marker of acute disease, and it has never been tested for a role in diagnosing syncope. The main objectives of the study were to measure CPT in patients suffering from syncope, to determine its diagnostic sensitivity and specificity, and compare it with that in patients with falls and mild trauma. The secondary objective was to determine whether different types of syncope correlate with different levels of CPT.
Screening for trisomy 21 by fetal tricuspid regurgitation, nuchal translucency and maternal serum free β‐hCG and PAPP‐A at 11 + 0 to 13 + 6 weeks

To examine whether in pregnancies with fetal trisomy 21 the level of maternal serum free ß‐human chorionic gonadotropin (ß‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A) at 11 + 0 to 13 + 6 weeks' gestation is independent of the presence or absence of tricuspid regurgitation and to estimate the performance of a screening test that combines tricuspid regurgitation with fetal nuchal translucency (NT) thickness and serum free ß‐hCG and PAPP‐A.
A comparison of ketamine versus etomidate for procedural sedation for the reduction of large joint dislocations

Study Objectives: Ketamine and etomidate are used for procedural sedation (PS) to facilitate the performance of painful procedures. We hypothesized that ketamine produces adequate and comparable sedation conditions for dislocated large joint reduction when compared to etomidate and results in fewer adverse events. Methods: This Institutional Review Board approved prospective trial compared a convenience sample of subjects, who were randomized to receive either ketamine or etomidate for PS to facilitate reduction of large joint dislocations. Following informed consent, subjects were assigned via a computer-generated algorithm to receive either etomidate (0.1 mg/kg) or ketamine (0.5 mg/kg) intravenously; if PS was not sufficient, subjects received repeat doses of etomidate or ketamine until adequate PS was achieved. The protocol's primary endpoint was a successful reduction of dislocated, large joints. Secondary endpoints included alteration in blood pressure, vomiting, recovery agitation, hypersalivation, laryngospasm, myoclonus, hypoxia, airway assistance with chin lift or jaw thrust, bag-valve-mask ventilation, endotracheal intubation, utilization of additional doses of ketamine or etomidate, and recovery time from sedation. Results: Total enrollment was eighty subjects, 46 in the ketamine cohort and 34 in the etomidate cohort. The two PS groups were comparable in terms of gender, age, and weight. There was no significant difference in the primary endpoint of large joint dislocation reduction between the ketamine and etomidate cohorts (46/46, 100%; 32/34, 94.1%; P- 0.1). Shoulder, hip, and ankle joints account for the majority of joint reductions in this trial. Titration of PS was necessary for almost half of each cohort as evidenced by the utilization of additional dosages of the sedative agents: ketamine (22/46, 47.8%) and etomidate (14/34, 41.2%; P- 0.56). Among secondary outcome variables, significant differences between ketamine and etomidate cohorts were myoclonus (1/46, 2.2%, 15/33, 45.5%; P- 0.0001), assisted ventilation with airway manipulation (3/45, 6.7%; 9/33, 27.3%; P- 0.01), and pulsoximetry desaturation < 90% (0/46; 7/34, 20.6%; P- 0.002). There was no significant difference in recovery time from PS between the ketamine and etomidate cohorts (11 min vs. 10 min; P- 0.69). Conclusion: Ketamine produces PS conditions for successful large joint dislocation reduction that are adequate and comparable to etomidate. The increased likelihood of myoclonus, of the requirement for airway assistance, and of hypoxia observed with etomidate suggest potential benefits with the utilization of ketamine for PS for dislocated large joint reduction.