Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating the individual benefit of immediate treatment or active surveillance for prostate cancer after screen‐detection in older (65+) men

A significant proportion of screen‐detected men with prostate cancer is likely to be overtreated, especially in older age groups. We aim to find which groups of screen‐detected older men (65+) benefit the most from Immediate Radical Treatment or Active Surveillance (AS) for prostate cancer, depending on age, screening history, health status and prostate cancer stage at detection. We used a microsimulation model (MISCAN) of the natural history of prostate cancer based on ERSPC data. Individual life histories are simulated with US comorbidity lifetables based on a random sample of MEDICARE data. Different screening histories are simulated and we count outcomes for men screen‐detected from ages 66 to 72. For immediately treated men with low‐risk disease (≤ T2a, Gleason 6) the probability of overtreatment ranges from 61% to 86% decreasing to between 37 and 46%, if they are assigned to AS. For intermediate risk men (≤T2, Gleason 3 + 4) overtreatment ranges from 23 to 60%, which reduces to between 16 and 31% for AS. For high risk men (T3, or ≥ Gleason 4 + 3), overtreatment ranges from 11 to 51%. The disease stage at screen‐detection is a critical risk factor for overtreatment. For low risk men, AS seems to significantly reduce overtreatment at a modest cost. For intermediate risk men, the decision between immediate treatment or AS depends on age and comorbidity status. Men screen‐detected in a high risk disease stage may benefit from immediate treatment even beyond age 69.
The Motherhood Wage Penalty by Work Conditions: How Do Occupational Characteristics Hinder or Empower Mothers?

Mothers are shown to receive lower wages than childless women across industrial countries. Although research on mothers’ wage disadvantage has noted that the extent of this disadvantage is not universal among mothers, it has paid relatively little attention to how the structural characteristics of jobs moderate the price women pay for motherhood. Using data from 16 waves of the National Longitudinal Survey of Youth that began in 1997, we examine how the pay gap between mothers and non-mothers varies by occupational characteristics. Deriving hypotheses from three prominent explanations for the motherhood wage penalty—stressing work-family conflict and job performance, compensating differentials, and employer discrimination, respectively—we test whether this penalty changes with an occupation’s exposure to hazardous conditions, schedule regularity, required on-the-job training, competitiveness, level of autonomy, and emphasis on teamwork. Results from fixed-effects models show that the wage reduction for each child is less in occupations with greater autonomy and lower teamwork requirements. Moreover, mothers encounter a smaller penalty when their occupations impose less competitive pressure. On the whole, these findings are consistent with the model focusing on job strain and work-family conflict, adding evidence to the importance of improving job conditions to alleviate work-family conflict.
Old and New Insurgency Forms

Abstract : While the study of insurgency extends well over100 years and has its origins in the guerrilla and small wars of the 19th century and beyond, almost no cross modal analysisthat is, dedicated insurgency form typology identificationhas been conducted. Until the end of the Cold War, the study of insurgency focused primarily on separatist and Marxist derived forms with an emphasis on counterinsurgency practice aimed at those forms rather than on identifying what differences and interrelationships existed. The reason for this is that the decades-long Cold War struggle subsumed many diverse national struggles and tensions into a larger paradigm of conflicta free, democratic, and capitalist West versus a totalitarian, communist, and centrally planned East. With the end of the Cold War and the resulting ideological and economic implosion of the Soviet Union, post-Cold War insurgency typologies began to emerge because a need existed to understand where this component of the new global security environment was heading. Over 2 decades of research and writing have been focused on this endeavor by what is a relatively small number of insurgency practitioners and/or theorists. In addition, the works of some contemporary terrorism scholars are also relevant to this topical area of focus. For this monograph to identify what can be considered new forms of insurgency that are developing, an appreciation for and understanding of earlier insurgency forms must also be articulated.
Postoperative Chylothorax Successfully Treated Using Conservative Strategies

The anatomy of the thoracic duct varies considerably, rendering it prone to disruption during thoracic surgery. Chylothorax complicates up to 0.5% of all intrathoracic procedures, its morbidity requiring the surgeon's vigilance throughout the entire course of the patient's illness. The natural history of chylothorax includes cardiopulmonary dysfunction, immunosuppression, nutritional and electrolyte derangements, and, ultimately, sepsis and death. General criteria for conservative management of thoracic duct injuries have been described in surgical literature, yet in selecting the best treatment for the patient, surgeons rely heavily on their own experience and the patient's unique presentation. A variety of conservative strategies may be implemented with success in approximately 50% of all cases. The duration of conservative treatment may vary, but the futility of conservative efforts should be recognized early and surgical intervention not delayed. We report a case of a 42-year-old man who presented at our institution with chylothorax after posterior mediastinal mass resection. The patient was treated successfully by withholding oral food and fluids, instituting total parenteral nutrition, and draining with a thoracostomy tube. He was discharged home with a complete resolution of chylothorax on hospital day 8. We describe the patient's illness course and discuss current strategies in the conservative management of thoracic duct injury after mediastinal resection.
Multi-Level Coded Modulation for 16-ary Constellations in Presence of Phase Noise

Application of multi-level coded modulation (MLCM) for 16-ary constellations in coherent systems is studied. An MLCM system with Reed-Solomon component codes and multi-stage decoder is considered. A systematic numerical method for finding set-partitioning and optimal code rates is presented. The method only requires the probability density function of received samples and can be applied to any constellation regardless of irregularity or lack of symmetry. Performance of the designed MLCM system is verified in presence of nonlinear phase noise and normal phase noise. For nonlinear phase noise limited system, it is shown that the block error rate (BLER) of the system can be improved using our approach for set-partitioning. For phase noise limited system, both BLER and bit error rate (BER) are studied for a phase noise optimized and square 16-quadrature amplitude modulation (16QAM). Post forward-error correction (FEC) BER performance of the optimized constellation over square 16QAM is studied for different levels of phase noise. It is shown that the optimized constellation along with MLCM system decreases the required signal-to-noise ratio by several dB at high phase noise regime and low post FEC BER.
Impact of a hybrid TGfU-Sport Education unit on student motivation in physical education

The Teaching Games for Understanding (TGfU) and Sport Education (SE) pedagogical models share several objectives and pedagogical processes. Despite this seemingly uncanny relationship, few studies have examined the efficacy of a hybrid TGfU/SE pedagogical model, particularly how a teacher’s utilization of such a model impacts on student motivation. The purpose of the current study was to investigate the effect a hybrid TGfU/SE unit, in comparison to direct instruction, on students’ perceptions of various aspects of their motivation to engage in physical education (autonomous motivation, basic psychological needs, enjoyment and intention to be physically active). A crossover design was utilized, using the technique of counterbalancing. One group experienced a hybrid SE/TGfU unit first, followed by a unit of direct instruction. A second group experienced the units in the opposite order. Participants were 55 students. The intervention was conducted over a total of 16 lessons. The hybrid unit was designed according to the characteristics of SE by using seasons, roles, persistent teams, etc. Learning tasks set by the teacher during individual lessons, however, were designed according to the pedagogical principles of TGfU. Student motivation data was generated using validated questionnaires. Results showed that regardless of the order of intervention, the two groups showed significant improvements in autonomy, competence and enjoyment when they were taught using the hybrid model. Instead, in the variables autonomous motivation, relatedness and intention to be physically active there were no significant improvements in one group. These results demonstrate that it is possible to design varied learning situations in which affiliation, leadership and trust are fostered, while tasks are adapted to the characteristics of the students. All this can cause greater autonomous motivation, and consequently, perceived competence in the student, a positive image of the sport to practice, and therefore greater enjoyment and to be physically active.
Lethal pancreatitis.

Thirty-two patients died of pancreatitis and its complications over a 10-year period. Infection (bacteremia, fungemia, or pancreatic abscess) was the major cause of death in 80%. In the remaining 20%, refractory hypotension or respiratory failure were the lethal mechanisms. In only 78% of patients was the correct diagnosis made before death. Ninety-four percent of those who died did so during their first clinical episode of pancreatitis. Prophylactic antibiotics did not prevent the development of pancreatic abscesses and organisms resistant to the antibiotics used often became the primary pathogens. Certain prognostic factors reliably separated those who died from those who lived. Peritoneal lavage and dialysis may be helpful in both the early diagnosis and therapy of severe acute pancreatitis.
Essays on international macroeconomics

Paper 1: We investigate the international distribution of external balances using a world economy model featuring country-specific macroeconomic uncertainty. Incomplete international financial markets and a collateral constraint on borrowing both serve to limit risk-sharing opportunities. In this environment, insurance against uncertainty takes the form of physical capital accumulation and intertemporal trade between countries. The cross-country dispersion of net foreign assets is close to its empirical counterpart. Macroeconomic uncertainty accounts for about one third of the international variation of cross-border asset holdings in the model. Approximations suggest that decreases in financial frictions were an important driver of increases in the international dispersion of external balances observed in the data. Paper 2: I investigate the effect of real exchange rate movements on the international distribution of external balances in a model world economy featuring incomplete markets. Intertemporal trade between nations is the only means of insuring against country-specific uncertainty. By changing the return to delaying consumption, fluctuations in the real exchange rate influence the accumulation of foreign assets. In a plausibly calibrated approximation of the model, the proportion of the cross-country dispersion of net foreign assets, the current account and the trade balance that can be attributed to the effect of real exchange rate movements is 23, 35 and 53 percent respectively. Paper 3: The link between exchange rate flexibility, the international balance sheet and economic recoveries is analysed in this paper through the application of OLS and two-stage least squares estimators to a dataset covering 201 recovery episodes occurring between 1971 and 2007. An instrument representing the history of exchange rate regime choice in the years immediately preceding the recovery is used to identify exogenous variation in exchange rate flexibility for the two-stage least squares procedure. Our results suggest that when external foreign currency denominated debt liabilities are relatively large, a pegged regime is associated with significantly faster real GDP growth than a non-pegged arrangement during a recovery. This finding can be rationalised on the basis that when external foreign currency denominated borrowing becomes sufficiently large, the adverse balance sheet effects associated with higher levels of exchange rate flexibility begin to significantly outweigh the beneficial expenditure switching effects.
Candida vaginitis in non-pregnant patients: A study of antifungal susceptibility testing and virulence factors

Vulvovaginal candidosis (VVC) is a major problem for the female population worldwide, and considerably little is known about the difference between acute VVC (AVVC) and recurrent VVC (RVVC). We investigated the susceptibility to six antifungal agents and boric acid of Candida spp. isolated from vaginal cultures, as described in the CLSI document M27-A3, from 228 non-pregnant sexually active women (aged 18–49 years), and the virulence factors of these isolates. The isolates were derived from patients with AVVC (n = 64), those with RVVC (n = 125) and those without signs or symptoms (n = 39). In total, C. albicans was the most commonly isolated species (50%), followed by C. glabrata (35.5%) and other Candida spp. (14.5%). We observed slightly different minimum inhibitory concentration (MICs) for various antifungals among the species and study groups that could have potential therapeutic benefits for the treatment. Analysis of the virulence factors revealed that haemolytic activity is not involved in VVC pathogenesis but that germ-tube formation, adhesion to VECs, and proteinase and phospholipase production may be important in the pathogenesis of VVC.
Human Bronchial Epithelial Cells Secrete Laminin 5, Express Hemidesmosomal Proteins, and Assemble Hemidesmosomes

Epithelial cells attach to the basement membrane through adhesive contacts between the basal cells of the epithelium and the proteins of the extracellular matrix (ECM). The hemidesmosome (HD) is a specialized cell-ECM contact, that mediates the attachment of the epithelial cell basal surface to the ECM. In bronchial epithelial cells, the protein components that constitute the HD have not been demonstrated. Using immunohistochemical techniques, we determined that normal human bronchial epithelial (NHBE) cells express the HD cell surface integrin α6β4 and produce laminin 5, the ECM protein associated with HDs. Furthermore, expression of the HD-associated structural proteins, bullous pemphigoid antigens 1 (BPAG 1) and 2 (BPAG 2), was demonstrated in NHBE cells by immunofluorescence microscopy and immunoblot analyses. In addition, we confirmed the presence of laminin 5 in the basement membrane (BM) of bronchial epithelial biopsy specimens and of BP230, BP180, and the α6β4 integrin heterodimer at the site of bronchial epithelial cell-ECM interaction in vivo. Finally, using electron microscopy, we were able to demonstrate intact HDs in a glutaraldehyde-fixed NHBE cell monolayer. These findings suggest that bronchial epithelium forms HDs and that the laminin 5-α6β4 integrin interaction may be important in stabilizing epithelial cell adhesion to the BM in the lung.
Scientific validation of the antidiabetic effects of Syzygium jambolanum DC (black plum), a traditional medicinal plant of India.

BACKGROUND In spite of the tremendous progress achieved in medical sciences in the last century, the management of diabetes mellitus, a disease as old as mankind, is poor. Diabetes is currently the world's largest endocrine disorder, and estimates are that it affects almost 5% of the population. Ayurveda, the Indian traditional system of medicine, is one of the world's oldest systems to have documented the diagnosis and treatment of diabetes. METHODS Experimental studies performed in accordance with the modern medicine principles have shown that some of the medicinal plants and polyherbal preparations made using the plants used in Ayurveda are effective in preventing both hyperglycemia and its complications. Syzygium jambolanum (Syn Syzygium cumini, Eugenia cumini, Eugenia jambolana), commonly known as black plum and originally indigenous to India, is one of the important antidiabetic plants. RESULTS Jamun has been used in various complementary and alternative systems of medicine and, before the discovery of insulin, was a frontline antidiabetic medication even in Europe. The brew prepared by boiling the Jamun seeds in boiling water has been used in the various traditional systems of medicine in India. CONCLUSIONS This review includes the validated antidiabetic effects of Jamun and some of its compounds. Emphasis is also placed on addressing the various mechanisms of action contributing to the pharmacological effects and the aspects that need future investigations for Jamun to be of clinical use.
Adenovirus E4 open reading frame 4 protein autoregulates E4 transcription by inhibiting E1A transactivation of the E4 promoter

Here we show that the adenovirus early region 4 (E4) open reading frame 4 (ORF4) protein autoregulates its own transcription by inhibiting adenovirus E1A-induced activation of E4 transcription both in transient transfection experiments and during lytic virus growth. The inhibitory activity of E4-ORF4 was selective for E1A-CR3-dependent transactivation and had no effect on CR1 transactivation. The inhibitory activity of E4-ORF4 was relieved by okadaic acid treatment, which inhibits the cellular protein phosphatase 2A (PP2A), suggesting that E4-ORF4 controls the phosphorylated status of transcription factors important for E4 promoter activity. This conclusion agrees with previous demonstrations that E4-ORF4 associates with PP2A and causes a partial dephosphorylation of certain transcription factors, including E1A (U. Müller, T. Kleinberger, and T. Shenk, J. Virol. 66:5869-5878, 1992; T. Kleinberger and T. Shenk, J. Virol. 67:7556-7560, 1993). However, our results indicate that dephosphorylation of E1A itself might not be the primary target for E4-ORF4. Instead, the E4-ORF4-PP2A complex appears to work by dephosphorylation of multiple cellular transcription factors that are involved in E1A transactivation of the E4 promoter.
Spatial and Temporal Brain Responses to Noxious Heat Thermal Stimuli in Burning Mouth Syndrome

Burning mouth syndrome (BMS) is an idiopathic orofacial pain condition. Although the pathophysiology of BMS is not clearly understood, central and peripheral neuropathic mechanisms are thought to be involved. The authors compared brain response to noxious heat stimuli in 16 right-handed women with primary BMS and 15 sex- and age-matched right-handed healthy female controls. A thermal stimulus sequence of 32 °C to 40 °C to 32 °C to 49 °C was repeated 4 times in a cycle. Warm and noxious heat stimuli were delivered with a Peltier thermode placed on the right palm or right lower lip for 32 s each in a session. Functional magnetic resonance imaging data were obtained by recording echoplanar images with a block design. Statistical Parametric Mapping 8 software was used to analyze the data. Patients and controls both reported feeling more pain during palm stimulation than during lip stimulation. Repetition of noxious heat stimulus on the lower lip but not on the palm induced habituation in brain activity in the cingulate cortex without reduction in pain perception. Multiple regression analysis revealed a correlation between perceived pain intensity and suppression of brain activity in the anterior cingulate cortex when the repeated thermal sequence was applied at the lower lip. Furthermore, the response of the parahippocampal area differed in BMS patients and controls when the same repeated thermal sequence was applied at the palm. The authors’ findings indicate that BMS patients show specific brain responses due to impaired function of the central and peripheral nervous systems (clinical trial registration: UMIN000015002).
Mechanisms regulating the reactions of human hemoglobin with oxygen and carbon monoxide.

The reactions of hemoglobin with oxygen and carbon monoxide are subject to regulation by the heme and the residues surrounding it and by the effectors, also known as heterotopic ligands (H+, Cl-, CO2, and 2,3-diphosphoglycerate), that regulate the equilibrium between its two forms, the oxy or R-structure with high and the deoxy or T-structure with low oxygen affinity. The stereochemical mechanisms of regulation have been studied for many years using a variety of methods. What is new since the subject was last surveyed [1] is determination of the crystal structures at resolutions sufficient to resolve individual atoms of the heme and its surroundings; such structures have now been determined for deoxy, oxy, and carbon monoxyhemoglobin, and for several analogues of transition states in the reaction with oxygen and carbon monoxide. In the past much useful information about the stereochemical mechanism of hemoglobin has come from the study of abnormal human hemoglobins. Now that the genes for the α and s chains of hemoglobin and for the single chain of myoglobin have been cloned in E. coli, directed mutagenesis has provided new tools for probing the reactions of these proteins with ligands. Finally, an (unsuccessful) search for possible antisickling drugs has led to the discovery of a family of compounds which are more powerful allosteric effectors than the natural one, 2,3-diphosphoglycerate, and combine with sites that are far removed from the diphosphoglycerate binding site.
Dichotomous Effects of IFN-γ on Dendritic Cell Function Determine the Extent of IL-12–Driven Antitumor T Cell Immunity

Sustained intratumoral delivery of IL-12 and GM-CSF can overcome tumor immune suppression and promote T cell-dependent eradication of established disease in murine tumor models. However, the antitumor effector response is transient and rapidly followed by a T suppressor cell rebound. The mechanisms that control the switch from an effector to a regulatory response in this model have not been defined. Because dendritic cells (DC) can mediate both effector and suppressor T cell priming, DC activity was monitored in the tumors and the tumor-draining lymph nodes (TDLN) of IL-12/GM-CSF–treated mice. The studies demonstrated that therapy promoted the recruitment of immunogenic DC (iDC) to tumors with subsequent migration to the TDLN within 24–48 h of treatment. Longer-term monitoring revealed that iDC converted to an IDO-positive tolerogenic phenotype in the TDLN between days 2 and 7. Specifically, day 7 DC lost the ability to prime CD8+ T cells but preferentially induced CD4+Foxp3+ T cells. The functional switch was reversible, as inhibition of IDO with 1-methyl tryptophan restored immunogenic function to tolerogenic DC. All posttherapy immunological activity was strictly associated with conventional myeloid DC, and no functional changes were observed in the plasmacytoid DC subset throughout treatment. Importantly, the initial recruitment and activation of iDC as well as the subsequent switch to tolerogenic activity were both driven by IFN-γ, revealing the dichotomous role of this cytokine in regulating IL-12–mediated antitumor T cell immunity.