Miracle-dz/UniFAR-FTUs huggingface dataset:
Physician Practice Consolidation Driven By Small Acquisitions, So Antitrust Agencies Have Few Tools To Intervene.

The growing concentration of physician markets throughout the United States has been raising antitrust concerns, yet the Department of Justice and the Federal Trade Commission have challenged only a small number of mergers and acquisitions in this field. Using proprietary claims data from states collectively containing more than 12 percent of the US population, we found that 22 percent of physician markets were highly concentrated in 2013, according to federal merger guidelines. Most of the increases in physician practice size and market concentration resulted from numerous small transactions, rather than a few large transactions. Among highly concentrated markets that had increases large enough to raise antitrust concerns, only 28 percent experienced any individual acquisition that would have been presumed to be anticompetitive under federal merger guidelines. Furthermore, most acquisitions were below the dollar thresholds that would have required the parties to report the transaction to antitrust authorities. Under present mechanisms, federal authorities have only limited ability to counteract consolidation in most US physician markets.
Feasibility and Acceptability of Google Glass for Emergency Department Dermatology Consultations.

that approximately 20 to 30 NMEs were approved each year from 2000 through 2013. Topical NMEs are developed at a much lower rate (0.9 NMEs per year). These findings are consistent with prior studies5 illustrating the underrepresentation of all drugs developed for primarily dermatological uses. Dermatological illnesses are not often fatal and may be considered lower priority by policymakers. Priority designations are assigned by the US Food and Drug Administration to new drugs that represent significant improvements over existing options and command more resource investment and regulatory attention. Only 5 total topical applications and 1 topical NME were given the priority review designation compared with 45% of all pharmaceutical and biological NMEs from 2000 through 2009.6 Beyond being considered lower priority, traditional metrics of blood and urine drug levels often do not apply to topical therapies. The lack of accepted surrogate end points may explain why the median approval time for topical medications is comparable with oral and intravenous therapies despite representing a lower systemic risk. Given these regulatory challenges, the low number of active companies with the necessary expertise to develop topical therapeutics likely contributes to the continued high cost and low availability of these drugs. Prior studies on medical innovation of devices, small molecules, and biotechnology suggest a multifaceted approach to spur future development.7 Strategies most likely to succeed include continued research funding to study diseases that are likely to be responsive to topical therapeutics and increased collaboration between academic and industry professionals. In the short term, adoption of more surrogate end points reduces the regulatory burden and may encourage companies to invest more resources in this underserved area.
The mechanism and significance of the slow changes of ventricular action potential duration following a change of heart rate

This article reviews the effects of changes of heart rate on the ventricular action potential duration. These can be divided into short term (fractions of a second), resulting from the kinetics of recovery of membrane currents, through to long term (up to days), resulting from changes of protein expression. We concentrate on the medium‐term changes (time course of the order of 100 s). These medium‐term changes occur in isolated tissues and in the intact human heart. They may protect against cardiac arrhythmias. Finally, we discuss the cellular mechanisms responsible for these changes.
Protandric simultaneous hermaphroditism in the shrimps Lysmata bahia and Lysmata intermedia

Abstract. The sexual system of two peppermint shrimps, Lysmata bahia and Lysmata intermedia, inhabiting intertidal fossil coral terraces at Bocas del Toro, on the Caribbean coast of Panama, was examined. Dissections suggested that the population of each species consisted of functional males and functional simultaneous hermaphrodites. Males have cincinulli and appendices masculinae on the first and second pair of pleopods, respectively, gonopores located at the coxae of the third pair of walking legs, and ovotestes with a well-developed male portion full of sperm, but an undeveloped female portion. Hermaphrodites lacked appendices masculinae and cincinulli. However, they have male gonopores and ovotestes with well-developed ovaries full of mature oocytes and testes with sperm. When hermaphrodites were maintained in pairs, both molted and spawned eggs (to beneath abdomen) that continued developing after 3 d, demonstrating that hermaphrodites can reproduce as males and inseminate other hermaphrodites acting as females. The possibility of self-fertilization or parthenogenetic reproduction was tested and disregarded, because hermaphrodites reared in isolation spawned oocytes that failed to develop, disappearing from the abdomen after 2 d. Males reared in pairs mature as hermaphrodites in <50 d, showing the ability of males to mature as hermaphrodites. These results demonstrate that L. bahia and L. intermedia are protandric simultaneous hermaphrodites, as reported for all species of this genus whose sexual system has been examined. However, the studied species featured a lifestyle, termed “tropical-low abundance,” here not recognized previously for the genus; they occur in low abundances in tropical environments, they do not develop symbiotic associations with sessile invertebrates, and they are not conspicuously colored. Information on the sexual systems and lifestyles of more species needs to be examined before these observations can be placed into a comparative context within the genus.
The effects of melatonin on sperm motility in vitro in Wistar rats

The effects of physiological concentrations of melatonin on motility of spermatozoa from Wistar rats were assessed in vitro. Melatonin had dose‐dependent negative effects on sperm forward progression, the quality of sperm motility and on a sperm motility index. Some, but not all of these effects were due to ethanol (0.5% final concentration) which was used as a solvent for melatonin. Addition of ethanol to the incubation medium altered the pH, and increased pH had a significant negative effect on all aspects of sperm motility. Finally, the overlay of oil, which is a routine part of many sperm culture systems, had an ameliorating effect that was probably because of the lipophilic nature of melatonin.
Spousal military deployment as a risk factor for postpartum depression.

OBJECTIVE To compare the Edinburgh Postnatal Depression Scale (EPDS) results in women whose spouses had deployed during or after pregnancy vs. those whose spouses had not. STUDY DESIGN A chart review of 6-week postpartum visits of women with active-duty spouses was conducted over 10 months. Associations between military deployments and EPDS score were examined by Student's t test, and rates of positive screens (with a cutoff of 12) between groups were compared by odds ratio (OR). Linear regression was used to calculate predictors of EPDS score. RESULTS A total of 415 charts were analyzed. The average EPDS score of women whose partner did deploy during the pregnancy was 7.36 compared to 4.81 for those whose partners did not (p < 0.001). The percentage of positive screens for women whose partner deployed during the pregnancy was 25.27% compared with 10.94% for an OR of 2.75 (p < 0.001). Linear regression showed partner's deployment during pregnancy to be an independent predictor of EPDS score (p < 0.005). CONCLUSION Deployment of a spouse during pregnancy may be a risk factor for depression. Aggressive screening of this at-risk population is recommended.
Mechanics of respiratory system in healthy anesthetized humans with emphasis on viscoelastic properties.

The classic model of the respiratory system (RS) is comprised of a Newtonian resistor in series with a capacitor and a viscoelastic unit including a resistor and a capacitor. The flow interruption technique has often been used to study the viscoelastic behavior under constant inspiratory flow rate. To study the viscoelastic behavior of the RS during complete respiratory cycles and to quantify viscoelastic resistance (Rve) and compliance (Cve) under unrestrained conditions, we developed an iterative technique based on a differential equation. We, as others, assumed Rve and Cve to be constant, which concords with volume and flow dependency of model behavior. During inspiration Newtonian resistance (R) was independent of flow and volume. During expiration R increased. Static elastic recoil showed no significant hysteresis. The viscoelastic behavior of the RS was in accordance with the model. The magnitude of Rve was 3.7 +/- 0.7 cmH2O.l-1 x s, i.e., two times R. Cve was 0.23 +/- 0.051 l/cmH2O, i.e., four times static compliance. The viscoelastic time constant, i.e., Cve.Rve, was 0.82 +/- 0.11s. The work dissipated against the viscoelastic system was 0.62 +/- 0.13 cmH2O x 1 for a breath of 0.56 liter, corresponding to 32% of the total energy loss within the RS. Viscoelastic recoil contributed as a driving force during the initial part of expiration.
Major- and trace-element constraints on Cambrian basalt volcanism in the Southern Oklahoma Aulacogen from well cuttings in the Arbuckle Mountains region, Oklahoma (U.S.A.)

The Cambrian Southern Oklahoma Aulacogen (SOA) is a >500-km-long northwest-southeast-trending rift zone that extends across southern Oklahoma, Texas, New Mexico, and Colorado (Powell and Phelps, 1977; Larson et al, 1985; Keller and Stephenson, 2007; Thomas, 2011; Hanson et al., 2012). Igneous rocks are grouped within the Wichita Province and include large exposures of tholeiitic gabbros and A-type rhyolite lavas and granites that are well exposed in the Wichita Mountains, Oklahoma (Fig. 1). The origin of the magmas that formed these rocks has been attributed to the formation of the SOA during the Cambrian breakup of the supercontinent Pannotia (Scotese, 2009; Hanson et al., 2012). However, Thomas (2011) proposed an alternative origin for the SOA and suggested that it represents an intracratonic “leaky” transform fault zone. Surface evidence for the SOA is limited in the Arbuckle Mountains region and its existence is based primarily on data from wells penetrating the igneous rocks (Ham et al., 1964; Puckett et al., this guidebook), geophysical anomalies, structural evidence of Cambrian extension and subsequent structural inversion in the late Paleozoic, sparse exposures of northwest-southeast striking Cambrian diabase dikes, and Cambrian Carlton Rhyolite exposures in the Arbuckle Mountains (Ham et al., 1964; Ham, 1969; Denison, 1995; Keller and Stephenson, 2007; Puckett, 2011; Hanson et al., 2012; Eschberger et al. paper, this guidebook). Critical to understanding the entire Wichita Igneous Province is better understanding the Cambrian magmatic record that exists in the subsurface of the Arbuckle Mountains area. During the last ~60 years, wells drilled into the Arbuckle Mountains region for oil and gas exploration encountered thick (>4000 m in the Hamilton Brothers 1A-18 Majorand trace-element constraints on Cambrian basalt volcanism in the Southern Oklahoma Aulacogen from well cuttings in the Arbuckle Mountains region, Oklahoma (U.S.A.)
The Impact of Job Stress on Employee Job Satisfaction A Study on Telecommunication Sector of Pakistan

This paper aims to examine the impact of job stress on employee job satisfaction. A sample of 134 employees from the telecom sector from Pakistan was used for this analysis. Job stress has been measured by conflict at work, workload and physical environment. Prior study indicate that the stressor workload, role conflict, physical environment negatively affect the employee job satisfaction. This study results revealed that stress is negatively related to employee’s job satisfaction which support Caplan (1991) and Keller (1975) result. This study reinforces the importance of employee job satisfaction which is essential for successful firm in current era.
Induction of innate immune responses by Escherichia coli and purified lipopolysaccharide correlate with organ‐ and cell‐specific expression of Toll‐like receptors within the human urinary tract

Mucosal epithelial linings function as physical barriers against microbes. In addition, they participate in the first line of host defence by production of a variety of proinflammatory mediators when exposed to microbes and microbial agents. Here, we use a human urinary tract infection model to demonstrate that organ‐ and cell‐specific innate responses induced by lipopolysaccharides (LPS) present on Gram‐negative bacteria correlates with the expression of Toll‐like receptor 4 (TLR4). The presence of TLR4 on human bladder epithelial cells enables them to rapidly respond to bacterial infections in vitro and in vivo. In contrast, TLR4 is not expressed on human proximal tubule cells isolated from the renal cortex, which may explain the cortical localization of bacteria in pyelonephritis. TLR4‐negative renal epithelial cells, A498, are non‐responsive to purified LPS, however, they respond to viable bacteria via a mannose‐sensitive attachment‐mediated pathway. To identify LPS components recognised by bladder epithelial cells, a bacterial lipid A mutant and LPS of different chemotypes were tested. Full interleukin 8 induction required hexa‐acylated lipid A and was decreased by between 50% and 70% in the presence of O‐antigen. Taken together, we propose that multiple independent pathways, which are organ‐ and cell‐specifically expressed, mediate bacterial recognition and determine the outcome of innate responses to infection.
UvA-DARE ( Digital Academic Repository ) The role of motivation and cultural dialects in the in-group advantage for emotional

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Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas

Objective: Soft tissue sarcomas (STSs) are heterogeneous tumors displaying multiple and complex molecular abnormalities with no specific pattern. Despite current therapeutic advances, the patients with STS still have a poor outcome, which makes it necessary to find out new prognostic markers. The Raf kinase inhibitory protein (RKIP) has been associated with prognosis in several human neoplasms; however, its role in STS is unknown. Methods: In the present study RKIP expression was assessed by immunohistochemistry in a series of 87 STSs, and its expression profile was associated with the patients' pathological parameters. Results: We found that RKIP is expressed in the cytoplasm of the great majority of cases, and absent in only approximately 18% of cases (16/87). Importantly, we observed that loss of RKIP expression was associated with poor outcome, constituting an independent prognostic marker. Conclusion: This is the first study assessing RKIP expression levels in STS. We showed that loss of RKIP expression is present in a small subset of cases; however, its absence was associated with poor survival and may be a potential marker for STS prognosis.
Rapid fault detection and recovery for IP telephony

Short, low-bandwidth keep-alive packets can be injected into VoIP packet streams to rapidly detect faults and deteriorating network conditions (e.g., increasing delay, jitter, or loss). The keep-alive packets can be duplicated and also used to continuously monitor and compare the delay and loss characteristics of primary and alternate network paths, and thereby help control the rapid switchover of calls (in-progress and future) to alternate routing paths (or the circuit-switched PSTN) when faults or deteriorating QoS conditions are detected. By simultaneously transmitting copies of keep-alive packets over multiple paths to make the differential delay measurements and comparisons, the proposed techniques avoid many common synchronization and timing errors. We examine various performance tradeoffs and describe several ways to implement the proposed architectures and techniques.
The ubiquitin‐proteasome system—micro target for macro intervention?

The ubiquitin‐proteasome system is the two sequential labeling and degradation system that accounts for the degradation of 80–90% of all intracellular proteins. Based on the diversity of its substrates, it is integrated in many different biological processes, especially inflammation and cell proliferation. Given the significance of these two processes for primary atherosclerosis and restenosis, the ubiquitin‐proteasome system may be an amendable target in cardiovascular therapy. This review provides background information on the ubiquitin‐proteasome system, currently available data on its involvement in cardiovascular diseases, and a future perspective on the targeted use proteasome inhibitors, including drug‐eluting stents.
Metabolism of P2 Receptor Agonists in Human Airways

Extracellular nucleotides are among the most potent mediators of mucociliary clearance (MCC) in human lungs. However, clinical trials revealed that aerosolized nucleotides provide only a transient improvement of MCC to patients diagnosed with cystic fibrosis (CF). In this study, we identified the mechanism that eliminates extracellular nucleotides from human airways. Polarized primary cultures of human bronchial epithelial cells were impermeable to extracellular nucleotides but rapidly dephosphorylated ATP into ADP, AMP, and adenosine. The half-life of a therapeutic ATP concentration (0.1 mm) was ∼20 s within the periciliary liquid layer. The mucosal epithelial surface eliminated P2 receptor agonists (ATP = UTP > ADP > UDP) at 3-fold higher rates than the serosal surface. We also showed that mucosal (not serosal) ectoATPase activity increases toward areas most susceptible to airway obstruction (nose < bronchi << bronchioles). Bronchial cultures from patients with CF, primary ciliary dyskinesia, or α1-antitrypsin deficiency exhibited 3-fold higher mucosal (not serosal) ectoATPase activity than normal cultures. Time course experiments indicated that CF enhances ATP elimination and adenosine accumulation on the mucosal surface. Furthermore, nonspecific alkaline phosphatase was identified as the major regulator of airway nucleotide concentrations in CF, primary ciliary dyskinesia, and α1-antitrypsin deficiency. The ectoAT-Pase activity and mRNA expression of mucosally restricted nonspecific alkaline phosphatase were 3-fold higher on bronchial cultures from these patients than from healthy subjects. This study demonstrates that the duration of nucleotide-mediated MCC is limited by epithelial ectonucleotidases throughout human airways, with the efficiency of this mechanism enhanced in chronic inflammatory lung diseases, including CF.
Cassava with enhanced β-carotene maintains adequate vitamin A status in Mongolian gerbils (Meriones unguiculatus) despite substantial cis-isomer content

Efforts to increase β-carotene in cassava have been successful, but the ability of high-β-carotene cassava to prevent vitamin A deficiency has not been determined. Two studies investigated the bioefficacy of provitamin A in cassava and compared the effects of carotenoid content and variety on vitamin A status in vitamin A-depleted Mongolian gerbils (Meriones unguiculatus). Gerbils were fed a vitamin A-free diet 4 weeks prior to treatment. In Expt 1, treatments (ten gerbils per group) included 45 % high-β-carotene cassava, β-carotene and vitamin A supplements (intake matched to high-β-carotene cassava group), and oil control. In Expt 2, gerbils were fed cassava feeds with 1·8 or 4·3 nmol provitamin A/g prepared with two varieties. Gerbils were killed after 4 weeks. For Expt 1, liver vitamin A was higher (P < 0·05) in the vitamin A (1·45 (sd 0·23) μmol/liver), lower in the control (0·43 (sd 0·10) μmol/liver), but did not differ from the β-carotene group (0·77 (sd 0·12) μmol/liver) when compared with the high-β-carotene cassava group (0·69 (sd 0·20) μmol/liver). The bioconversion factor was 3·7 μg β-carotene to 1 μg retinol (2 mol:1 mol), despite 48 % cis-β-carotene [(Z)-β-carotene] composition in cassava. In Expt 2, cassava feed with 4·3 nmol provitamin A/g maintained vitamin A status. No effect of cassava variety was observed. Serum retinol concentrations did not differ. β-Carotene was detected in livers of gerbils receiving cassava and supplements, but the cis-to-trans ratio in liver differed from intake. Biofortified cassava adequately maintained vitamin A status and was as efficacious as β-carotene supplementation in the gerbil model.
Folate supplementation during the preconception period, pregnancy and puerperium. Polish Society of Gynecologists and Obstetricians Guidelines.

Właściwa podaż folianów w okresie przedkoncepcyjnym, podczas ciąży oraz karmienia piersią w dużej mierze warunkuje prawidłowy rozwój oraz wzrastanie płodu i noworodka. Foliany są jednym z najistotniejszych elementów niezbędnych w szybko dzielących się komórkach, pełniąc między innymi ważną rolę w syntezie DNA. Zwiększone podczas ciąży zapotrzebowanie na niesyntetyzowane w organizmie człowieka foliany tylko częściowo może zostać zaspokojone podażą odpowiednich produktów żywieniowych bogatych w foliany — około 150–250 μg [1]. Niedobór folianów wiąże się z wyższym ryzykiem powstawania wad cewy nerwowej u płodu, jak również rozszczepu wargi i podniebienia oraz zespołu Downa [2]. Zaburzenia metabolizmu folianów mogą prowadzić do hiperhomocysteinemii i częstszego występowania innych powikłań ciąży, takich jak: poronienia nawracające, zahamowanie wzrastania wewnątrzmacicznego płodu oraz stanu przedrzucawkowego [3, 4].
Shear stress during early embryonic stem cell differentiation promotes hematopoietic and endothelial phenotypes

Pluripotent embryonic stem cells (ESCs) are a potential source for cell‐based tissue engineering and regenerative medicine applications, but their translation into clinical use will require efficient and robust methods for promoting differentiation. Fluid shear stress, which can be readily incorporated into scalable bioreactors, may be one solution for promoting endothelial and hematopoietic phenotypes from ESCs. Here we applied laminar shear stress to differentiating ESCs using a 2D adherent parallel plate configuration to systematically investigate the effects of several mechanical parameters. Treatment similarly promoted endothelial and hematopoietic differentiation for shear stress magnitudes ranging from 1.5 to 15 dyne/cm2 and for cells seeded on collagen‐, fibronectin‐ or laminin‐coated surfaces. Extension of the treatment duration consistently induced an endothelial response, but application at later stages of differentiation was less effective at promoting hematopoietic phenotypes. Furthermore, inhibition of the FLK1 protein (a VEGF receptor) neutralized the effects of shear stress, implicating the membrane protein as a critical mediator of both endothelial and hematopoietic differentiation by applied shear. Using a systematic approach, studies such as these help elucidate the mechanisms involved in force‐mediated stem cell differentiation and inform scalable bioprocesses for cellular therapies. Biotechnol. Bioeng. 2013; 110: 1231–1242. © 2012 Wiley Periodicals, Inc.