Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of non-compliance on the cost-effectiveness of pharmaceuticals: a review of the literature.

Non-compliance with drug therapies not only limits their effectiveness, but in some instances, is associated with grave clinical sequelae and substantial economic burden. It is important, therefore, to consider non-compliance in economic evaluations. A review of pharmacoeconomic evaluations, which have applied sensitivity analysis to non-compliance rates, was undertaken to evaluate the impact of non-compliance on the cost-effectiveness of different drug therapies. Although 22 evaluations satisfied the inclusion criteria, additional information was obtained from the authors of most studies, as the published details were inadequate. The majority of evaluations assumed altered effectiveness owing to reduced compliance in the absence of supportive clinical evidence. Because of the disparity in the nature of the outcomes, the measures of non-compliance and the time horizon of the studies evaluated, it was not possible to compare the magnitude of the impact of non-compliance among different drug-disease combinations. However, it was evident that non-compliance always results in a reduction in efficacy, but its impact on costs varied substantially. The importance of incorporating measures of compliance is highlighted, as failing to account for 'real world' compliance rates in pharmacoeconomic evaluations may lead to selection of sub-optimal treatment strategies.
Pseudoxanthoma Elasticum

P elasticum (PXE) is a hereditary disorder of abnormal calcification of the skin, eyes, and cardiovascular system producing pathognomonic skin lesions in flexural sites, retinopathy secondary to calcification of Bruch's membrane, and a clinical spectrum of cardiovascular manifestations comparable to those of ordinary non-PXE arteriosclerosis. This brief treatise on PXE is based on a recently completed long-term study of 100 patients with PXE. A detailed clinical and statistical account of all aspects of the disorder including therapeutic recommendations is being published shortly. ^ The last major reviews or studies of PXE involving more than isolated case reports were published more than two decades
Quantum jumps of the micromaser field: Dynamic behavior close to phase transition points.

The field of the one-atom maser, or micromaser, shows strong variations in certain parameter regions usually identified as phase transitions. In this paper the time development of the field in the vicinity of those regions is investigated. Depending on the parameters, spontaneous jumps or slow transitions between two metastable field values can be observed. Hystersis behavior also occurs. The results are explained by means of a quantum Monte Carlo simulation of the maser field as well as a Fokker-Planck description used earlier in micromaser theory.
Lattice Strain Measurements in Hydrogen Implanted Materials for Layer Transfer Processes

The ion implantation technique introduces atomic species in a material in order to modify its electronic, optical, and / or structural properties. The beam of species is accelerated through an electric field and thus bombards the target material with an electron-volt to mega-electron-volt energy range. Depending on the nature of the ions, their quantity and their energy, the properties of the target material are modified leading to different applications. This chapter is focused on one of these applications, which is the semiconductor slicing generated by ion implantation.
Regulatory T cells attenuate mycobacterial stasis in alveolar and blood-derived macrophages from patients with tuberculosis.

RATIONALE There are hardly any data about the frequency of CD4(+)CD25(+)Foxp3(+) regulatory T cells (T-Regs) in the lungs of patients with active tuberculosis (TB). OBJECTIVES To obtain data about the frequency of CD4(+)CD25(+)Foxp3(+) T-Regs, and their impact on mycobacterial containment, in the lungs of patients with active TB. METHODS Patients with pulmonary TB (n = 49) and healthy volunteers with presumed latent TB infection (LTBI; n = 38) donated blood and/or bronchoalveolar lavage (BAL) cells obtained by bronchoscopy. T-cell phenotype (Th1/Th2/Th17/T-Reg) and functional status was evaluated using flow-cytometry and (3)H-thymidine proliferation assays, respectively. H37Rv-infected alveolar and monocyte-derived macrophages were cocultured with autologous T-Regs and purified protein derivative (PPD) preprimed T-Reg-depleted effector cells. Mycobacterial containment was evaluated by counting CFUs. MEASUREMENTS AND MAIN RESULTS In blood and BAL T-Reg levels were higher in TB versus LTBI (P < 0.04), and in TB the frequency of T-Regs was significantly higher in BAL versus blood (P < 0.001). T-Reg-mediated suppression of T-cell proliferation in blood and BAL was concentration-dependent. Restriction of mycobacterial growth in infected alveolar and monocyte-derived macrophages was significantly diminished, and by up to 50%, when T-Regs were cocultured with PPD-primed CD4(+) effector T cells. The levels of CD8(+) T-Regs (CD8(+)CD25(+)Foxp3(+)), IL-17-producing T-Regs (IL-17(+)CD4(+)CD25(+)Foxp3(+)), and IL-17-producing T cells were similar in BAL-TB versus BAL-LTBI. Within the TB group compartmentalization of responses was prominent (T-Reg, IFN-γ, tumor necrosis factor-α, IL-17, and IL-22 significantly higher in BAL vs. blood). CONCLUSIONS In patients with TB the alveolar compartment is enriched for CD4(+) T-Regs. Peripheral blood-derived T-Regs decrease the ability of alveolar and monocyte-derived macrophages to restrict the growth of Mycobacterium tuberculosis in the presence of effector cells. Collectively, these data suggest that CD4(+)CD25(+)FoxP3(+) T-Regs subvert antimycobacterial immunity in human TB.
Pretreatment frequency of circulating IL‐17+CD4+ T‐cells, but not Tregs, correlates with clinical response to whole‐cell vaccination in prostate cancer patients

The aim of this study was to determine the prognostic implications of the pretreatment level of Th17 cells compared with regulatory T‐cell status in prostate cancer patients receiving active whole cell immunotherapy. Ten‐color flow cytometry was used to analyze IL‐17‐producing CD4+ T‐cells in the peripheral blood of hormone‐resistant non‐bone metastatic prostate cancer patients prior to immunotherapy with an allogeneic whole‐cell vaccine. Surface expression of the chemokine receptors CCR4 and CCR6 was used to further subdivide IL‐17‐producing cells into subsets with distinct homing properties. The frequency of circulating regulatory T‐cells (Tregs), defined as CD3+CD4+CD127loFoxp3+CD25+ was compared in the same patients. The frequency of CCR4−IL‐17+CD4+ T‐cells prevaccination inversely correlated with time to disease progression (TTP) in 23 prostate cancer patients. Furthermore, responder (R) patients with statistically significant reductions in PSA velocity (PSAV) in response to the immunotherapy (n = 9), showed a Th17 profile similar to healthy male controls and significantly different from non‐responder (NR) patients (n = 14) (i.e., those without any significant reduction in PSAV). In contrast, the frequency of Tregs in peripheral blood in PSA‐R (n = 11) and ‐NR (n = 14) patients was similar (but in both cases, significantly higher than in age‐matched healthy men). Accordingly, there was no significant correlation between frequency of Tregs and TTP in these late‐stage prostate cancer patients undergoing active immunotherapy. These data imply an important role for IL‐17‐producing helper T‐cells in cancer immunology and highlight their potential use as a pretreatment screen to ensure appropriate treatment is offered to hormone‐resistant prostate cancer patients. © 2009 UICC
Effect of Radiation Techniques in Treatment of Oropharynx Cancer

Objectives: To compare the toxicity and outcomes of three radiotherapy techniques—three‐dimensional conformal (3D‐RT), accelerated fractionation with concomitant boost (AFxCB), and intensity modulated radiotherapy (IMRT)—in the combined modality treatment of stage III–IV squamous cell carcinoma (SCC) of the oropharynx.
Synthesis and characterization of functional elastomeric poly(ester amide) co-polymers

A new family of random co-poly(ester amides)s (co-PEAs) having reactive pendant functional carboxylic acid groups were synthesized by co-polycondensation of di-p-toluenesulfonic acid salts of bis-(L-α-amino acid (L-leucine and/or L-phenylalanine)) α,ω-alkylene diesters with active diesters of dicarboxylic acids using di-p-toluenesulfonic acid salt of L-lysine benzyl ester as a co-monomer. The lateral benzyl ester groups in the L-lysine segment of co-PEAs were subsequently transformed into free COOH groups by catalytic hydrogenolysis using Pd black as a catalyst. The co-PEA-based polyacids obtained, as well as the original co-PEA having lateral benzyl ester groups were characterized by standard methods. In vitro biodegradation studies in the presence of hydrolases like α-chymotrypsin and lipase showed significant enzymatic-catalyzed biodegradation of these co-PEAs. These co-PEA-based polyacids were used for covalent attachment of iminoxyl radicals (4-amino-TEMPO) and in vitro biodegradation of 4-aminoTEMPO attached polymer was studied along with releasing kinetic of iminoxyl radical.
Adaptive motion control of rigid robots: a tutorial

An account is given of several adaptive control results for rigid robot manipulators. The intention is to lend some perspective to the growing list of adaptive control results for manipulators by providing a unified framework for comparison of those adaptive control algorithms which have been shown to be globally convergent. In most cases the authors are able to simplify the derivations and proofs of these results as well. <<ETX>>
Energy metabolism in free-living, ‘large-eating’ and ‘small-eating’ women: studies using 2H218O

The doubly-labelled water (2H218O) technique was used to assess the long-term rates of energy expenditure and, after accounting for any changes in body composition, the derived rates of energy intake in weight-stable ‘large-eating’ (n 6) and ‘small-eating’ (n 6) women. The self-reported energy intakes (approximately 11.2 v. 5.6 MJ/d) and energy expenditures (approximately 8.5 v. 12.4 MJ/d) for the ‘large-eating’ and ‘small-eating’ groups respectively, should not be sustainable without significant body-weight changes. 2H218O-assessed rates of energy expenditure for the ‘large-eaters’ (approximately 8.5 MJ/d) and ‘small-eaters’ (approximately 11.3 MJ/d) were in close agreement with the results obtained using 5 d, self-reported activity diaries but the derived rates of energy intake for the ‘large-’ (approximately 8.5 MJ/d) and ‘small-eaters’ (approximately 10.8 MJ/d) were markedly different from those obtained using self-reported, weighed food diaries. When two ‘small-eaters’ were supplied with their self-reported energy intakes (approximately 5 MJ/d) for up to 28 d both subjects lost about 0.75 kg body-weight/week. These results provide no support for the existence of ‘metabolically efficient’ women in the community.
How Selective are Real Wage Cuts? A Micro‐Analysis Using Linked Employer-Employee Data

Using linked employer-employee panel data for Germany, this paper investigates whether firms implement real wage reductions in a selective manner. In line with insider-outsider and several strands of efficiency wage theory, we find strong evidence for selective wage cuts with high-productivity workers being spared even when controlling for permanent differences in firms' wage policies. In contrast to some recent contributions stressing fairness considerations, we also find that wage cuts increase wage dispersion among peers rather than narrowing it. Notably, the same selectivity pattern shows up when restricting our analysis to firms covered by collective agreements or having a works council.
Development of Attention to Faces during the First 3 Years: Influences of Stimulus Type

The development of attention toward faces was explored during the first 3 years of life in 54 children aged between 3 and 36 months. In contrast to previous research, attention to faces was assessed using both static images and a dynamic video sequence in the same participants. Separate analyses at each age and exploratory longitudinal analyses indicate a preference for faces during the first year, followed by a decline during the second year. These results suggest that attention to faces does not follow a linear increasing pattern over development, and that social attention patterns are influenced by stimulus characteristics.
Prevention of ankle sprains

Two different methods for the prevention of ankle joint injuries in soccer were tested. Coordination training on an ankle disk improves functional stabilty and postural control, whereas an orthosis provides mechanical sup port. Both techniques reduce the frequency of ankle sprains in soccer players with previous ankle problems. The orthosis is an alternative to taping, and can be used during the rehabilitation period after injury or when playing on uneven ground. Coordination training on an ankle disk ought to be included in the rehabilitation of ankle injuries to prevent functional instability. It may also be done prophylactically by players with previous ankle problems in order to break the vicious circle of recurrent sprains and feeling of giving way.
Atovaquone Nanosuspensions Show Excellent Therapeutic Effect in a New Murine Model of Reactivated Toxoplasmosis

ABSTRACT Immunocompromised patients are at risk of developing toxoplasma encephalitis (TE). Standard therapy regimens (including sulfadiazine plus pyrimethamine) are hampered by severe side effects. While atovaquone has potent in vitro activity against Toxoplasma gondii, it is poorly absorbed after oral administration and shows poor therapeutic efficacy against TE. To overcome the low absorption of atovaquone, we prepared atovaquone nanosuspensions (ANSs) for intravenous (i.v.) administration. At concentrations higher than 1.0 μg/ml, ANS did not exert cytotoxicity and was as effective as free atovaquone (i.e., atovaquone suspended in medium) againstT. gondii in freshly isolated peritoneal macrophages. In a new murine model of TE that closely mimics reactivated toxoplasmosis in immunocompromised hosts, using mice with a targeted mutation in the gene encoding the interferon consensus sequence binding protein, i.v. -administered ANS doses of 10.0 mg/kg of body weight protected the animals against development of TE and death. Atovaquone was detectable in the sera, brains, livers, and lungs of mice by high-performance liquid chromatography. Development of TE and mortality in mice treated with 1.0- or 0.1-mg/kg i.v. doses of ANS did not differ from that in mice treated orally with 100 mg of atovaquone/kg. In conclusion, i.v. ANSs may prove to be an effective treatment alternative for patients with TE.
B cell receptor editing in tolerance and autoimmunity

Receptor editing is the process of ongoing antibody gene rearrangement in a lymphocyte that already has a functional antigen receptor. The expression of a functional antigen receptor will normally terminate further rearrangement (allelic exclusion). However, lymphocytes with autoreactive receptors have a chance at escaping negative regulation by “editing” the specificities of their receptors with additional antibody gene rearrangements. As such, editing complicates the Clonal Selection Hypothesis because edited cells are not simply endowed for life with a single, invariant antigen receptor. Furthermore, if the initial immunoglobulin gene is not inactivated during the editing process, allelic exclusion is violated and the B cell can exhibit two specificities. Here, we describe the discovery of editing, the pathways of receptor editing at the heavy (H) and light (L) chain loci, and current evidence regarding how and where editing happens and what effects it has on the antibody repertoire.
Quality of life in ovarian cancer patients: comparison of paclitaxel plus cisplatin, with cyclophosphamide plus cisplatin in a randomized study.

PURPOSE Formal quality-of-life (QOL) assessments may contribute important information on patient symptoms. Despite many trials of systemic chemotherapy in ovarian cancer, reports of its effect on QOL are few. PATIENTS AND METHODS QOL was assessed in an Intergroup randomized trial comparing paclitaxel plus cisplatin to cyclophosphamide plus cisplatin in women with advanced ovarian cancer. One hundred fifty-two eligible patients accrued in Canada completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and a trial-specific checklist at baseline (after surgical debulking) and at regular intervals during and after chemotherapy. Mean change scores over time in the two arms were calculated. RESULTS Compliance with QOL questionnaire completion was excellent (81% to 93%). In general, deterioration was seen in the QOL domains immediately after chemotherapy (day 8 of cycle 1), followed by clinically meaningful improvements compared with baseline (change scores > or = 10) in both arms during the treatment period in a number of domains and items, including global QOL, emotional function, social function, fatigue, pain, sleep, constipation, appetite, abdominal swelling, and abdominal cramps. Improvements in global QOL persisted for the duration of follow-up. More neurosensory effects and myalgia were documented in the paclitaxel arm; however, this did not adversely affect global or other domains of QOL and improved once chemotherapy was completed. CONCLUSION Improvement from baseline in QOL measures was seen in both treatment arms. The greater neurologic and muscle toxicity of paclitaxel did not adversely influence QOL. QOL data can contribute useful information on the experience of symptoms and their time course, which may assist patients and physicians in their discussion about the anticipated effects of therapy.
The Role of Neurokinin B Signalling in Reproductive Neuroendocrinology

The KNDy neuropeptides, kisspeptin, neurokinin B (NKB) and dynorphin A (Dyn), have been implicated in regulating pulsatile luteinising hormone (LH) secretion. Studies of the interactions between KNDy signalling systems, however, are currently few. Although the stimulatory effect of kisspeptin and the inhibitory effect of Dyn on the gonadotropin-releasing hormone pulse generator are widely accepted, the effects of NKB in rodents are variable and sometimes controversial. Literature describing increased LH secretion in response to NKB receptor agonism predominates and is in line with human physiology, as well as the pathophysiology of pubertal failure associated with disruption of NKB signalling. However, the robust suppression of the LH pulse, induced by the same treatment under hypoestrogenic conditions, may hold clues as to the mechanisms of reproductive inhibition under pathological conditions. This review discusses the recent evidence for this paradox and outlines a revised working model incorporating the mechanisms by which KNDy neuropeptides modulate the reproductive axis.
Sparse multifocal stimuli for the detection of multiple sclerosis

We compared the diagnostic capabilities of contrast reversal and sparse pattern pulse stimulation for dichoptic multifocal visual evoked potentials (mfVEPs) measured in normal subjects and multiple sclerosis (MS) patients. Multifocal responses were obtained from 27 normal subjects and 50 relapsing‐remitting patients, 26 of whom had experienced optic neuritis (ON+). The patient groups were matched for length of disease and number of clinical attacks. Compared with the responses of normal subjects those of MS patients had significantly smaller response amplitudes, lower signal‐to‐noise ratios, more complex response waveforms, and longer response delays. The effects were larger for sparser stimuli. Sensitivities and specificities for the different stimulus types were estimated from receiver operator characteristic (ROC) plots. Bootstrap estimates of the accuracies of the ROCs for the most promising measure, the template delays, indicated the sparsest stimulus would deliver 92% sensitivity at a false‐positive rate of 0%. In contrast, at 92% sensitivity the conventional mfVEP stimulus misdiagnosed more than 20% of the normal population. The results were similar for patients with no history of ON (ON−). In performing well in patients with no history of ON, the sparse mfVEPs seem to measure progressive damage associated with axon and gray matter losses rather than damage associated with a history of serious inflammation. Ann Neurol 2005;57:904–913
Evidence for sperm dysfunction as the mechanism of segregation distortion in Drosophila melanogaster.

Drosophila melanogaster males heterozygous for the segregation distorter (SD) second chromosome produce a gross excess of SD-bearing progeny, the percentage of SD progeny in some stocks regularly exceeding 0.99. Sandler, Hiraizumi, and Sandler' have shown the SD phenomenon to be prezygotic; more recent data have shown it to be temperature-sensitive in or near meiosis 1.2 Evidently some critical event occurs at about that time. An early model for the mechanism of SD action involves a fracture of the SD homologue and formation of a reversed sister-chromatid reunion. ' Such a breakage hypothesis received some support when a higher frequency of X-ray-induced meiotic crossing over was found in SD males than in comparable controls.3 The model was frustrated, however, by the failure to observe such cytological abnormalities in melosis. An alternative model, the functional pole hypothesis of Peacock and Erickson,4 proposes first that the primary spermatocyte of normal Drosophila males is polarized, with one of the Anaphase I dyads forming two normal functional sperms, the other dyad forming two morphologically normal but nonfunctional sperms; and secondly that the SD homologue is preferentially directed to the nonfunctional pole. Our subsequent discussion concerns only this latter part of the hypothesis, and not at all whether the spermatocyte is, in fact, normally polarized. Peacock and Erickson have developed an argument for the hypothesis by comparing the number of sperms stored in females with the number of progeny obtained from comparable females inseminated by SD or non-SD males. In both SD and controls only one half of the stored sperms appeared to be capable of fertilization. There are thus two general hypotheses: (1) the sperms receiving the non-SD chromosome are somehow rendered unable to follow the normal course leading ultimately to fertilization, and (2) the sperms receiving the non-SD chromosome are normally destined to be nonfunctional; the primary event here is a preferential chromosome orientation at Metaphase I. We shall call these the dysfunctional sperm and the functional pole hypotheses. The dysfunction hypothesis includes a break as one possibility, but is intended to include any mechanism that interferes with normal sperm development or function. The two hypotheses are not necessarily exclusive: It could be, for example, that only one half of the sperms are normally functional but that SD makes half of these dysfunctional. In this paper we report a negative correlation between the degree of distortion and the number of offspring produced by an SD male under conditions where sperm number appears to be the limiting factor in progeny production. This result argues for the dysfunction hypothesis. Materials. -The original SD chromosomes from nature carry an inversion-linked complex of three separable genetic elements: SD itself and an "activator" (Ac(SD)) both located near the centromere of chromosome II, and a "stabilizer" (St(SD))