Perfusion-ventilation matching in the lungs requires AMPK-α1 and AMPK-α2 activation downstream of LKB1. Hypoxia amps AMPK Most arteries in the body vasodilate in response to hypoxia. In contrast, pulmonary arteries constrict in response to hypoxia to ensure that blood is diverted to oxygen-rich areas, a process called hypoxic pulmonary vasoconstriction. When this process is prolonged, it can lead to pulmonary hypertension and, ultimately, heart failure. Analysis of genetically manipulated mice by Moral-Sanz et al. showed that hypoxic pulmonary vasoconstriction under mild hypoxia required the α1 subunit of AMPK, which was activated downstream of LKB1 during hypoxia. During severe hypoxia, the α2 subunit of AMPK was also required. AMPK supports hypoxic pulmonary vasoconstriction, in part, by phosphorylating and inhibiting the K+ channel KV1.5 in pulmonary arterial myocytes. By contrast, in most systemic arteries, hypoxia does not inhibit KV, which may aid vasodilation rather than vasoconstriction. These results delineate a key role for LKB1-activated AMPK-α1 and AMPK-α2 in hypoxic pulmonary vasoconstriction. Hypoxic pulmonary vasoconstriction (HPV), which aids ventilation-perfusion matching in the lungs, is triggered by mechanisms intrinsic to pulmonary arterial smooth muscles. The unique sensitivity of these muscles to hypoxia is conferred by mitochondrial cytochrome c oxidase subunit 4 isoform 2, the inhibition of which has been proposed to trigger HPV through increased generation of mitochondrial reactive oxygen species. Contrary to this model, we have shown that the LKB1–AMPK-α1 signaling pathway is critical to HPV. Spectral Doppler ultrasound revealed that deletion of the AMPK-α1 catalytic subunit blocked HPV in mice during mild (8% O2) and severe (5% O2) hypoxia, whereas AMPK-α2 deletion attenuated HPV only during severe hypoxia. By contrast, neither of these genetic manipulations affected serotonin-induced reductions in pulmonary vascular flow. HPV was also attenuated by reduced expression of LKB1, a kinase that activates AMPK during energy stress, but not after deletion of CaMKK2, a kinase that activates AMPK in response to increases in cytoplasmic Ca2+. Fluorescence imaging of acutely isolated pulmonary arterial myocytes revealed that AMPK-α1 or AMPK-α2 deletion did not affect mitochondrial membrane potential during normoxia or hypoxia. However, deletion of AMPK-α1, but not of AMPK-α2, blocked hypoxia from inhibiting KV1.5, the classical "oxygen-sensing" K+ channel in pulmonary arterial myocytes. We conclude that LKB1–AMPK-α1 signaling pathways downstream of mitochondria are critical for the induction of HPV, in a manner also supported by AMPK-α2 during severe hypoxia.


Chronic autoimmune diseases are associated with mutations in PTPN22, a modifier of T cell receptor (TCR) signaling. As with all protein tyrosine phosphatases, the activity of PTPN22 is redox regulated, but if or how such regulation can modulate inflammatory pathways in vivo is not known. To determine this, we created a mouse with a cysteine-to-serine mutation at position 129 in PTPN22 (C129S), a residue proposed to alter the redox regulatory properties of PTPN22 by forming a disulfide with the catalytic C227 residue. The C129S mutant mouse showed a stronger T-cell-dependent inflammatory response and development of T-cell-dependent autoimmune arthritis due to enhanced TCR signaling and activation of T cells, an effect neutralized by a mutation in Ncf1, a component of the NOX2 complex. Activity assays with purified proteins suggest that the functional results can be explained by an increased sensitivity to oxidation of the C129S mutated PTPN22 protein. We also observed that the disulfide of native PTPN22 can be directly reduced by the thioredoxin system, while the C129S mutant lacking this disulfide was less amenable to reductive reactivation. In conclusion, we show that PTPN22 functionally interacts with Ncf1 and is regulated by oxidation via the noncatalytic C129 residue and oxidation-prone PTPN22 leads to increased severity in the development of T-cell-dependent autoimmunity.


Subtitled A Savannah Story, John Berendt's 1994 bestseller Midnight in the Garden of Good and Evil had an immediate impact on the city he depicted, as did the movie version directed by Oint Eastwood and released in 1997. Eight months after the publication of Midnight, tourism in Savannah was up by 46 percent; convention booking grew 40 percent in 1994 and another 30 percent in 1995; and new businesses opened on Broughton Street, where previously empty storefronts had littered Savannah's main shopping thoroughfare. Guided tours led visitors to spots highlighted in Berendt's Savannah stoiy, especially Mercer House, the home of the flamboyant protagonist Jim Williams and the site where the plot of both the book and the film takes off with the midnight murder of Williams's boy toy. Tourists out on their own got lost among identical squares and indistinguishable mansions and inadvertently gave the reception of the bestseller a postmodern twist that Berendt and Eastwood might appreciate. An internet map of the city with Berendt's crucial locations drawn in-from the Old Bonaventure Cemetery to Hard-hearted Hannah's house that exists in blues lyrics only-adds to the general confusion. As the title suggests, Midnight in the Garden of Good and Evil draws on traditional themes and figures familiar to readers of William Faulkner, Flannery O'Connor, William Styron, Walker Percy, and Alice Walker: grotesque characters, gothic settings, North/South dichotomies, southern heroes and belles, racial ambiguities, the importance of place, and more. Yet both book and film versions have a distinctly postmodern flavor. Midnight combines travel narrative, tourist brochure, detective fiction, (auto)biography, and courtroom drama into a tasty gumbo. This mixture of ingredients continues in representations of gender and race, for example with the provocative figure of the Lady Chablis, an African American transvestite intermittently named Frank, who turns into a southern belle with a knack for dresses, strip shows, and generous gentlemen of whatever race and gender. The shooting of other films at Mercer House and Lafayette Square, empty signif iers like Nazi flags hung for decoration or subversion, as well as the mixture of real and reel characters, contributes to postmodern confusions and delights. The southern gothic a la Berendt adds spice to both versions of the Savannah narrative. Rich with writerly and readerly possibilities, Berendt's Savannah becomes a hyperreality, where southernness constitutes a series of interrelated discourses about the South and where comfortable notions of fact and fiction, acting and reality, class, gender, and truth no longer fit, or matter. Midnight as book and film stirs up southern fictions, which the two media address in overlapping but different ways. Unlike Jim Williams, who shifts friends and enemies from the Out to the In box for his Christmas party invitations, Midnight in the Garden of Good and Evil invites and welcomes all variations of bodies and behaviors, as southern, homosexual, postmodern, and real as John Berendt's simulacrum Savannah. Williams inhabits a text and a city as southern as John Pendleton Kennedy's Swallow Barn (1832). As the owner of Mercer House, run like a model plantation, he embodies the southern gentleman, adept at manners and decorum, and with a collection of vices and Faberge objects worthy of his position. His casual decadence flourishes at his gentlemen-only Christmas party, catered, like his regular Christmas party, by Lucille Wright, an African American cook he keeps as busy as any leisured nineteenth-century slaveholder would. He enjoys a good neighborly feud, but stays away from cruder activities such as public gambling and car racing, along with sex, his young lover's favorite pastimes. Danny Hansford plays the part of the Southern Hero in Berendt's and Eastwood's scripts, as passionate, violent, anti-intellectual, and self-destructive as Kate Chopin's Armand Aubigny. …


X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene encoding a peroxisomal ABC transporter. In this review, we compare estimates of incidence derived from different populations in order to provide an overview of the worldwide incidence of X-ALD. X-ALD presents with heterogeneous phenotypes ranging from adrenomyeloneuropathy (AMN) to inflammatory demyelinating cerebral ALD (CALD). A large number of different mutations has been described, providing a unique opportunity for analysis of functional domains within ABC transporters. Yet the molecular basis for the heterogeneity of clinical symptoms is still largely unresolved, as no correlation between genotype and phenotype exists in X-ALD. Beyond ABCD1, environmental triggers and other genetic factors have been suggested as modi-fiers of the disease course. Here, we summarize the findings of numerous reports that aimed at identifying modifier genes in X-ALD and discuss potential problems and future approaches to address this issue. Different options for prenatal diagnosis are summarized, and potential pitfalls when applying next-generation sequencing approaches are discussed. Recently, the measurement of very long-chain fatty acids in lysophosphatidylcholine for the identification of peroxisomal disorders was included in newborn screening programs.


Background Little is known about the prevalence proportion of sports injuries in Denmark. In addition, the beliefs amongst athletes regarding injury-preventive training regimes and the association with injury risk are lacking. Objective To examine the prevalence proportion of injured athletes in a population-based sample and to describe beliefs regarding their ability to prevent injuries through proper training. Design Population-based sample interviews. Setting Denmark, March 2016. Participants A random sample of 1059 persons from the Danish population above 18 years. Assessment of Risk Factors During the interview, the following questions were asked: Are you sports active? Have you sustained any sports-related injury within the past 3 years that prevented sports activity for a shorter or longer period? Do you know how to train properly to prevent injury? In addition, assessment of demographics included: age, sex, social class, income, education, number of children, county, union member and unemployment fund. Main measurements Sports active, injury within 3 years and prevention knowledge. Results The prevalence proportion of sports active was 60.9% [95% CI: 57.9–63.9]. A majority (61.8% [95% CI: 58.3–65.2]) reported to be aware of proper injury-preventive training, whereas 25.4% [95% CI: 22.0–28.9] sustained an injury within 3 years. Sports activity increased with education (OR=1.17 [95% CI: 1.1–1.23], P=0.0001). Risk of injury decreased with increasing age (OR=0.64 [95% CI: 0.54–0.74], P<0.0001) and female sex (OR=1.61 [95% CI: 1.11–2.35], P=0.013). Knowledge of injury prevention increased with age (OR=1.15 [95% CI: 1.02–1.3], P=0.022) and female sex (OR=1.35 [95% CI: 1.13–1.51], P=0.004). No association of preventive training on injury (OR=1.07 [95% CI: 0.71–1.67]) Conclusions The prevalence proportion of injuries seems to be a public-health issue. A majority believe they know how to train properly to prevent injuries. However, awareness of preventive training was not associated with decreased injury risk.


Purpose. The aim of this study was to identify predicting factors for successful vocational rehabilitation for people with back pain problems. Method. The study was based on data from 347 long-term sick-listed clients collected at the onset of vocational rehabilitation. The outcome was measured 6 months after the conclusion of rehabilitation. Results. In a first bi-variate analysis, a considerable number of variables were associated with the rehabilitation outcome. In a second multivariate analysis, only four associations remained. These were age, general health, vitality and internal locus of control. Young vital clients in good general health, with a high internal locus of control were more likely than others to return to work. Conclusion. The findings regarding age, general health and vitality are well in line with previous studies. The findings regarding internal locus of control are more unique.


Incz N. McF~ Dansvllle (N. Y.): F. A. Owen Publishing Company. Paper. 166 PP. Prlce, 25 cents. The full name t)f "thrs geographical volume Is "OutUnes, Devices. and Recreations In United States Geography," And the plan suggested by this ampler name is manltest all throngh the work. The book Is not a mass of dry details. I·'eatllres are Introduced that relieve the tension of study, and yet greatly assist the pupil In apprectattne and appropriating the facts under survey. In th~ Iesscn ou Mlchl<:l\n. for Instance, the song, "Michigan. mv Mlchl~n," Is Introduced, and readings, such as "The Rover &ys on the Great Lakes...• are given. Nlokand freerlom of woman. if It gtves her one hour more of pure air and sunshine. If It glvea her new thoughts, new dreams. new hopes with which she may endow the race to be, If but In rlreams It shifts the scene from four dark walls hung with pots and bones to gardens and fields. where nature's bounteous store of purple and red is swung with prodigal hand In sunshine and autumn leaves, wavlnp; and wsltlng to mingletheir lift> with hers; if It brings ber more youth and years, less sorrow and tears, If this book In the least lightens the leaden load that has been laid upon her by our clvlllzallon,-If In all the world It changes one hour of aulf..rlng to sn hour of peace or pleasure, we wlll be repaid."


We analyze the maintenance strategy for a complex system consisting of two types of components: non-monitored and monitored. Non-monitored components can only be maintained correctively upon failure. Monitored components are monitored continuously and are maintained when they become too degraded, i.e., just before its degradation level hits a threshold. There is an economic dependence between the components, which means that a maintenance intervention for one component can be used as an opportunity for preventive maintenance of monitored components: If the degradation level of a monitored component exceeds a preventive threshold at the time of another maintenance intervention, this component is maintained preventively. Evaluating the costs of a given maintenance strategy is time consuming, especially for a large number of monitored components. However, using semi-regenerative techniques instead of renewal techniques, we are able to drastically shorten the required computation time: For a system with ten monitored components, the computation time to evaluate the optimal maintenance strategy goes from more than a day to few seconds. We give numerical examples to illustrate our results.


This article empirically studies current claims that patent trolls, also known as patent assertion entities (PAEs) or non-practicing entities (NPEs), behave badly in litigation by bringing frivolous patent infringement suits and seeking nuisance fee settlements. The study explores these claims by examining the relationship between the type of patentee-plaintiffs and litigation outcomes (e.g., settlement, grant of summary judgment, trial, and procedural dispositions), while taking into account, among other factors, the technology of the patents being asserted and the identity of the lawyers and judges. The study finds significant heterogeneity among different patent holder entity types with individual inventors, failed operating companies, patent holding companies, and large patent aggregators each having distinct litigation strategies largely consistent with their economic posture and incentives. These PAEs appear to litigate differently from each other and from operating companies. Accordingly, to the extent any patent policy reform targets specific patent plaintiff types, such reforms should go beyond the practicing entity versus non-practicing entity distinction and understand how the proposed legislation would impact more granular and meaningful categories of patent owners.


INTRODUCTION
Hospital-acquired acute renal failure increased in the last years from about 5 to 6.4%, while mortality remained high and according to newest investigations it is about 60% on average. Radiocontrast-induced nephropathy is the third cause of death in hospital-acquired acute renal failure. RISK FACTORS FOR RADIOCONTRAST-INDUCED NEPHROPATHY: Risk factors for radiocontrast-induced nephropathy include: the existing kidney disease, diabetes, dehydratation, multiple myeloma, older age and earlier kidney damage by contrast substances. COURSE OF RADIOCONTRAST-INDUCED NEPHROPATHY: The clinical course of radiocontrast-induced nephropathy may manifest from asymptomatic picture to development of oliguric form of acute renal failure. PREVENTION AND TREATMENT MODALITIES OF RADIOCONTRAST-INDUCED NEPHROPATHY: Modalities of prevention and treatment of radiocontrast-induced nephropathy are as follows: adequate hydration of patients, appropriate application of diuretics, calcium channel blockers nonionizing radiocontrast and preventive haemodialysis. EXPERIMENTAL STUDIES IN PREVENTION AND TREATMENT OF RADIOCONTRAST-INDUCED NEPHROPATHY: Experimental studies indicate application of atrial natriuretic peptide, endothelin, prostaglandin.

CASE REVIEW
Two patients treated at the Clinic for Nephrology and Clinical Immunology in Novi Sad, presented with radiocontrast-induced nephropathy. In one patient it appeared after panaortography and in the second after computerized tomography of the abdomen. In both cases aggravation occurred due to already existing renal failure caused by radiocontrast substances.

CONCLUSION
The problem is particularly important because there is a large number of patients in whom there is a risk of radiocontrast-induced nephropathy and it is necessary to carry out adequate prophylaxis and accurate assessment of kidney function before application of radiocontrast substances.


Over half of all infant formula sold in the United States is purchased through the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Typically, WIC State agencies obtain substantial discounts in the form of rebates from infant formula manufacturers for each can of formula purchased through the program. The cost to WIC for each can of formula provided through the program has two components: (1) net wholesale price, which is equal to the wholesale price of formula minus the amount of the rebate; and (2) retail markup, which is equal to the retail price minus the wholesale price. This analysis suggests that retail markup accounts for most of the cost to WIC of infant formula in most States. However, both cost components have increased over time. The recent increase in both net wholesale price and retail markup coincides with the introduction of higher priced supplemented infant formulas. Conditions may change after the market adjusts to these new formulas.


Conventional rodent models of respiratory allergy that employ intraperitoneal sensitization to aeroallergen plus adjuvant, have offered greatly to our current knowledge of the pathophysiology of allergic airway diseases. Notwithstanding this significant contribution, non‐adjuvant aided sensitization via respiratory presentation of the allergen, is more naturally relevant and more closely mimics the human exposure. Nevertheless, in the experimental setting, primary respiratory exposure to inert antigen is likely to lead to inhalation tolerance. Inasmuch as divergent and discrepant results are often reported in experimental models employing this method of sensitization, we set out to review the relative literature and identify and discuss factors that are liable to interfere in such protocols and modify the immune response, hence leading to variable outcomes. Protocol design features (including the use of anaesthesia, the nature and dosage of the antigen and the strain/age/sex and handling of the animals) as well as environmental factors (including airborne substances, viruses and lipopolysaccharide) have been identified as key modulators of the immune response that evolves, following primary airway exposure of laboratory rodents to aeroallergen. Delineation of the effect of those factors to induction or abrogation of inhalation tolerance can have important implications in the design of both improved experimental protocols of respiratory allergy and methods to intercept sensitization to inert aeroallergens in the clinical field.


Context.Surface magnetic fields have been detected in 5–10% of isolated massive stars, hosting outer radiative envelopes. They are often thought to have a fossil origin, resulting from the stellar formation phase. Yet, magnetic massive stars are scarcer in (close) short-period binaries, as reported by the BinaMIcS (Binarity and Magnetic Interaction in various classes of Stars) Collaboration.Aims.Different physical conditions in the molecular clouds giving birth to isolated stars and binaries are commonly invoked. In addition, we propose that the observed lower magnetic incidence in close binaries may be due to nonlinear tides. Indeed, close binaries are probably prone to tidal instability, a fluid instability growing upon the equilibrium tidal flow via nonlinear effects. Yet, stratified effects have hitherto been largely overlooked.Methods.We theoretically and numerically investigate tidal instability in rapidly rotating, stably stratified fluids permeated by magnetic fields. We use the short-wavelength stability method to propose a comprehensive (local) theory of tidal instability at the linear onset, discussing damping effects. Then, we propose a mixing-length theory for the mixing generated by tidal instability in the nonlinear regime. We successfully assess our theoretical predictions against proof-of-concept, direct numerical simulations. Finally, we compare our predictions with the observations of short-period, double-lined spectroscopic binary systems.Results.Using new analytical results, cross-validated by a direct integration of the stability equations, we show that tidal instability can be generated by nonlinear couplings of inertia-gravity waves with the equilibrium tidal flow in short-period massive binaries, even against the Joule diffusion. In the nonlinear regime, a fossil magnetic field can be dissipated by the turbulent magnetic diffusion induced by the saturated tidal flows.Conclusions.We predict that the turbulent Joule diffusion of fossil fields would occur in a few million years for several short-period massive binaries. Therefore, turbulent tidal flows could explain the observed dearth of some short-period magnetic binaries.


Nursing is a profession based on the interaction with others therefore caring appears as one of its central concepts. The research around the concept is undervalued by the importance given to the technical and instrumental behaviours in nursing practice. A review of literature was undertaken on 20 articles published on a Portuguese nursing journal over ten years (1995-2005). The main purpose was to identify the conceptualizations underlying the concept of caring present in those articles. Caring appears to be inherent to nursing practice and arises from respect and concern for the patient. It's a skill that evolves with experience and, above all, with the reflection about that experience. Caring implies an intentional activity, and attitudes and feelings that shape the professional interaction established between nurse and patient. We consider that research around the concept of caring is important in order to reveal its patterns and processes and to enhance the knowledge about the caring phenomenon.


IMPORTANCE
Diabetic macular nonperfusion leads to decreased perifoveal capillary blood flow, which in turn causes chronic ischemia of the retinal tissue. Using point-to-point correlation between spectral-domain optical coherence tomography (SD-OCT) and nonperfusion on fluorescein angiography, we observed that retinal capillary nonperfusion is associated with photoreceptor compromise on OCT. This study highlights a new concept of a possible contribution of the retinal deep capillary plexus to photoreceptor compromise in diabetic retinopathy in the absence of diabetic macular edema.

OBJECTIVE
To report outer retinal structural changes associated with enlargement of the foveal avascular zone and/or capillary nonperfusion in the macular area of diabetic patients.

DESIGN, SETTING, AND PARTICIPANTS
Retrospective observational cross-sectional study in 9 patients who were diagnosed as having diabetic retinopathy without diabetic macular edema and underwent fluorescein angiography and SD-OCT for diabetic retinopathy from July 8, 2014, to December 1, 2014, at a tertiary academic referral center. This analysis was conducted between December 2, 2014, and January 31, 2015.

MAIN OUTCOMES AND MEASURES
Outer retinal changes on SD-OCT in areas of macular ischemia.

RESULTS
The study included 13 eyes of 9 diabetic patients (4 men and 5 women aged 34-58 years) with a mean duration of diabetes mellitus of 14.5 years. Nine eyes showed outer retinal disruption revealed by SD-OCT that colocalized to areas of enlargement of the foveal avascular zone and macular capillary nonperfusion. Four fellow eyes with normal foveal avascular zones did not show any retinal changes on SD-OCT.

CONCLUSIONS AND RELEVANCE
Macular ischemia in diabetic patients can be associated with photoreceptor compromise. The presence of disruption of the photoreceptors on OCT in diabetic patients can be a manifestation of underlying capillary nonperfusion in eyes without diabetic macular edema. Ischemia at the deep capillary plexus may play an important role in these outer retinal changes.


In this paper, we focus on the net changes in attributes across versions of OSS and use net class change data (class additions and deletions) as well as refactoring data from a previous study to inform our understanding of how those three systems evolved as they did. While the majority of new attributes were added at levels 1 and 2 of the inheritance, these patterns were not consistent. The research question addresses the evolutionary relationship between classes and attributes as well as the connection between those changes and refactorings. Although some evidence of attributes following patterns conformant with class additions was found, we also identified occurrences of attributes being added unilaterally. A strong correspondence was also found between attribute addition and the refactoring data. Finally, we explore features of a fourth system with seven inheritance levels for similar characteristics.


Post-traumatic stress disorder (PTSD) is associated with impaired memory performance coupled with functional changes in brain areas involved in declarative memory and emotion regulation. It is not yet clear how symptom severity and comorbidity affect neurocognitive functioning in PTSD. We performed a functional magnetic resonance imaging (fMRI) study with an emotional declarative memory task in 28 Complex PTSD patients with comorbid depressive and personality disorders, and 21 healthy non-trauma-exposed controls. In Complex PTSD patients--compared to controls--encoding of later remembered negative words vs baseline was associated with increased blood oxygenation level dependent (BOLD) response in the left ventral anterior cingulate cortex (ACC) and dorsal ACC extending to the dorsomedial prefrontal cortex (dmPFC) together with a trend for increased left hippocampus activation. Patients tended to commit more False Alarms to negative words compared to controls, which was associated with enhanced left ventrolateral prefrontal and orbitofrontal cortex (vlPFC/OFC) responses. Severity of child abuse was positively correlated with left ventral ACC activity and severity of depression with (para) hippocampal and ventral ACC activity. Presented results demonstrate functional abnormalities in Complex PTSD in the frontolimbic brain circuit also implicated in fear conditioning models, but generally in the opposite direction, which may be explained by severity of the trauma and severity of comorbid depression in Complex PTSD.


Java is becoming the predominant language for defining and deploying complex business logic across all tiers of the enterprise. Java is uniquely suited to distributed information systems, and clearly critical to the success of Oracle's network computing initiative. No other language combines the features required in these environments. This paper surveys five aspects of our Java product strategy. Unless otherwise stated, these components are included in the Oracle 8.1 software development kit, SDK2, which is under test at a small number of sites. Over the past 20 years, SQL has become the "shape" of the world's store of data. In many ways, Java represents a practical, ubiquitous means for augmenting this structure with the arbitrarily complex operational semantics that only a general-purpose, object-oriented programming language can provide. Such logic is inherently distributed, and may be freely deployed on any network computing tier. The combination of ubiquitous SQL data and Java behavior will generalize relational database management systems into the information servers that are so critical to the future of network computing.


We study the mapping from Lagrangian to Eulerian space in the context of the Effective Field Theory (EFT) of Large Scale Structure. We compute Lagrangian displacements with Lagrangian Perturbation Theory (LPT) and perform the full non-perturbative transformation from displacement to density. When expanded up to a given order, this transformation reproduces the standard Eulerian Perturbation Theory (SPT) at the same order. However, the full transformation from displacement to density also includes higher order terms. These terms explicitly resum long wavelength motions, thus making the resulting density field better correlated with the true non-linear density field. As a result, the regime of validity of this approach is expected to extend that of the Eulerian EFT, and match that of the IR-resummed Eulerian EFT. This approach thus effectively enables a test of the IR-resummed EFT at the field level. We estimate the size of stochastic, non-perturbative contributions to the matter density power spectrum. We find that in our highest order calculation, at redshift z = 0 the power spectrum of the density field is reproduced with an accuracy of 1% (10%) up to k = 0.25 hMpc−1 (k = 0.46 hMpc−1). We believe that the dominant source of the remaining error is the stochastic contribution. Unfortunately, on these scales the stochastic term does not yet scale as k4 as it does in the very low k regime. Thus, modeling this contribution might be challenging.


This paper examines whether, when, and why job seekers use firms' financial information in the job search process. We find first evidence of financial information's relevance to job seekers by documenting a substantial increase in job search activity around earnings announcements in the spirit of Beaver (1968). We also find that financial information acquisition by job seekers is positively related to both job postings and interviews at the firm-county-month level. Spurred by this finding, we develop a theoretical model of job search paired with firms' heterogeneous earnings to better understand job seeker's information acquisition behavior. Our model predicts that job seekers trade off the probability of an offer with the value of the employment contract and intensify information acquisition as the number of available positions shrinks relative to the pool of job seekers. Consistent with these predictions, we find that firm performance is positively correlated with both job seekers' search activities and employers' posted wages. We also find that the positive association between financial information acquisition and interviews is stronger when the job market is more competitive. Overall, these results indicate that, like capital market participants, job seekers value and use financial reporting.


Objective: The purpose of this study was to compare etomidate-lipuro and propofol and 50%, (1:1) admixture of these agents at induction with special reference to injection pain, hemodynamic changes, and myoclonus. Methods: Ninety patients were assigned at random to three groups in which induction was performed with either etomidate-lipuro, propofol or etomidate-lipuro–propofol admixture. After monitorization with bispectral index (BIS) all agents were given with infusion with a perfuser at a constant rate of 200 ml/min till the BIS values decreased to 40. Blood pressure and heart rate were measured every 30 s at this period. Patients were asked for pain at the injection site and observed visually for myoclonus. The time BIS values decreased to 40 (BIS 40 time) and total amounts of induction doses were measured. Results: BIS 40 time measurements were P > E > PE (199.4 ± 40.9, 176.9 ± 31.6, 163.5 ± 20.6 s). The hemodynamic (systolic, diastolic and mean blood pressures, heart rate) changes were minimal in group PE than other two groups (P = 0.017). The intensity of myoclonus was graded as mild in 9, moderate in 12, and severe in 5 patients in the group E (76.3%). Myoclonus was not observed in group PE and group P. There were no injection pain in group PE as the incidence were (83.8%) in group P and in (63.2%) group E. Conclusion: Incidence of hemodynamic changes, myoclonus, and injection pain is significantly lower in group PE. BIS 40 times is least in group PE. We concluded that 1:1 admixture of etomidate-lipuro and propofol is a valuable agent for induction.


The aim of this investigation was to study the total replacement of powder milk protein (SL) for hydrosoluble soybean extract (EHS) in feeding 5-day-old Holstein male calves. The experiment was carried out using 3 treatment throughout the period of milk intake (5 to 90 days of life). In treatment I, SL was supplied from the 5th to 90th day of life. In treatment II, SL was supplied until the 29 th day, and, from the 30th to 90th day, EHS was supplied. In treatment III, EHS was supplied from the 5th day of life. After this period the calves were weaned and received the same hay and concentrate feed as in the milk intake period, up to 180 days. During the milk intake period, the animals of treatment II, showed in average lower food intake, decreased daily weight gain and poorer digestibility of nutrients than animals from treatment I (P<0.05). In the post-weaning period food intake and average daily gain were similar. Calves of treatment III lost weight throughout the experiment, showed very weak body condition and were sacrified.


'Blue' is one of the 11 basic colour terms (BCTs) in languages with a developed colour term inventory [1]. In a challenge to the Berlin-Kay model, Italian appears to require more than one BCT to name the blue area: blu 'dark blue', azzurro 'light (-and-medium) blue' and celeste 'light blue'. We addressed the proposition of multiple Italian 'blue' BCTs in a psycholinguistic study. Eight Munsell charts embracing the BLUE area of colour space (7.5BG-5PB, Value 2-9, Chroma 2-12) were employed to explore colour name mapping in Italian speakers compared to English speakers. Participants were Italian monolinguals (N=13, Alghero; N=15, Verona) and English monolinguals (N=19; Liverpool). An unconstrained colour naming method was used; this was followed by indicating the best example (focal colour) of blu, azzurro and celeste (Italian) or blue and light blue (English). Choices of focal colours, in Munsell notation, are reported for each of the terms. In addition, distances between centroids of the focal colours, in CIELAB notation, are reported for each of the three participant groups. The dominant focal English blue and Italian blu appeared to concur in Hue (2.5PB, 5PB), but not in lightness (blue: Value 5; blu: Value 2-3). Italian speakers required, in addition, the azzurro term for naming light/medium blue colours. Notably, for the Algherese, azzurro indicates the 'medium blue' and is complemented by celeste for denoting light blue shades, similar to English light blue. In contrast, the Veronese use azzurro for 'light-and-medium blue'; celeste was named conspicuously less frequently, overlapping with azzurro. The present study adds to psycholinguistic evidence that Italian possesses two BCTs, blu and azzurro, differentiating 'blues' along the lightness dimension. Celeste is a contender for a third BCT for the Alghero speakers. Cognitive representation (i.e. prototype) of azzurro as well as the status of celeste appear to vary markedly across Italian dialects.


Spinal cord infarction is a well-known entity in adult medicine, but remains exceedingly rare in children quite more so when considered by causation of trauma. This is the case of a 16-month old Hispanic child who presented to the emergency department greater than 24 hours after an unwitnessed fall from a table found to have a traumatic spinal cord infarction. The father initially voiced concern of the child vomiting and "not acting right." The child had a previous history of non-accidental trauma and initial plan of care reflected a suspicion of head injury in the absence of obvious external injuries. Subsequent examination and history would yield that the child had paraplegia with MRI showing acute/subacute infarction of thoracic spinal cord without obvious extraneural pathology. The patient had no worsening or improvement in symptoms and at 7 months after presentation would remain a paraplegic. Investigation by child protective services determined father neglected to seek care for >24 hours after the accident. The child was removed from his home and the father imprisoned on charges of child abuse. This case highlights the importance of early recognition of injury, detailed and specific history taking, and completeness of exam in setting of suspected abuse.


After the cultural explosion of Web 2.0, digital culture reveals an apparently semiotic paradox associated with the incredibly widespread use of images of faces, while at the same time the reason to trust in the authenticity of these faces is constantly declining. This is because graphic technology has made the sophisticated manipulation of images both possible and easy. After a review of the existing semiotic models and considerations of trust, I am proposing a new approach which emphasizes the value-generating properties of trust by analogy with the money sign, seen as "trust inscribed". Research from the neurosciences supports the hypothesis that the trustworthiness of the face is judged pre-reflexively and primordially. This, therefore, means that a trustworthy face is a premise for more successful communication than an untrustworthy one, notwithstanding the object of discussion and the cultural context. An example concerning social media influencers serves to show that in the internet-dominated globalizing culture, trustworthy faces are a multipurpose communicative asset that makes a difference.


Driving is an important task that demands the full attention of the driver. There are many different factors that can compromise driving performance and lead to vehicle crashes. Perhaps two of the most common, yet also the most dangerous, are drug (including alcohol) influences on driving and distractions using handheld devices like cell phone calls and/or texting. Although each of these driving disruptors has been studied separately and has been shown to adversely affect driving performance, there is a paucity of data regarding the effects of these driving disruptors when combined. Given the explosion of handheld electronic devices, and the likelihood that drivers are using these devices when they are driving, it is not surprising that reports of crashes relating to this 'triple threat' combination of drugs (including alcohol), texting and driving are on the rise and in the news. Clearly, this 'triple threat' of texting, drugs and driving is a problem that requires research attention.


Variations in the strontium isotope ratio ( 87 Sr/ 86 Sr) of tooth enamel are used to examine the migration patterns of late Pleistocene mammoths and mastodons from Florida. An animal's 87 Sr/ 86 Sr ratio tracks the ratios of its environment, which vary with differences in bedrock and soil. Consequently, the environmentally controlled differences in 87 Sr/ 86 Sr ratio recorded in mineralized tissue, such as tooth enamel, may be used to reconstruct the movement patterns of an individual. We map variations in local 87 Sr/ 86 Sr ratios across modern Florida and Georgia through analysis of rodent teeth, plants, and surface water, then use this map to interpret the movement patterns of extinct mammals. Mastodons from northern and central Florida have higher 87 Sr/ 86 Sr ratios than both modern environmental samples from Florida and fossils from nonmigratory species, suggesting that mastodons migrated north into Georgia. Mammoths display ratios similar to those of environmental samples and resident species, suggesting that they did not migrate outside Florida.


We developed and herein introduce a new microscopic system for automatic acquisition of timelapse images of both brightfield images and four kinds of fluorescence images. We combined an inverted incident-light fluorescence microscope with an incubation system, a Hoffman Modulation Contrast device, a color chilled 3CCD camera, and an automatic excitation-filter exchanger. The light source switching for brightfield imaging was controlled automatically by a computer. Cells were maintained in 5% CO2 plus 95% air at 37°C on a microscopic stage with an incubation system, which consists of a gas-regulatory system and two separate temperature-control devices. The fluorescence of annexin V (AV)-enhanced green fluorescent protein (EGFP), AV-fluorescein isothiocyanate, and propidium iodide (PI) diminished 3%, 77%, and 28%, respectively, at 24 hours during time-lapse observation using this system. Time-lapse observation of individual Jurkat cells using this system confirmed that anti-Fas antibody-mediated apoptotic cells occurred at first budding and were stained with AV-EGFP alone, and thereafter were also stained with PI when the cells became flat as a result of ruptures of the plasma membrane. These results present direct evidence that apoptotic cells undergo secondary necrosis, which could be recognized based on PI staining. There was a significantly long time interval between the staining of individual cells with AVEGFP, indicating apoptosis, and the staining of these cells with PI, which indicated the occurrence of secondary necrosis. On the other hand, most of the cells that underwent necrosis were detected simultaneously with AVEGFP and PI. The microscopic system we developed allows time-lapse and simultaneous observation of individual cells for changes in both morphology and staining pattern of fluorescent dyes that allow the visualization of cellular function. This system might be a useful tool for research in radiation biology.


A body of evidence has emerged in the literature on intergenerational mobility documenting that countries with large income differences also have less intergenerational mobility: a relationship known as the Great Gatsby Curve. In this paper, I estimate the Great Gatsby Curve within Sweden exploiting both cross-sectional and longitudinal variation. I find that men who grew up in regions or periods with high levels of income inequality experienced less intergenerational mobility as adults, thereby confirming the existence of a Great Gatsby Curve in Sweden. I also present new evidence on the underlying mechanisms of the Great Gatsby Curve. By decomposing intergenerational mobility into separate transmission channels, I find that the mediating effects that educational attainment and cognitive and non-cognitive skills have on the persistence of socioeconomic status across generations drive the Great Gatsby Curve.


: Construction of road or building on soft soil, especially on peat soil, is the most challenging condition where there are consequences that engineers may have faced. Peat has excellent water-holding characteristics, highly fibrous due to the presence of a lot of decomposed materials and organic matter, which makes it highly compressible, weak at shear strength, and low in bearing capacity. This characteristic makes it unsuitable for use as foundation or sub-grade since it would have a large impact on deformation and settlement if not treated very well. Due to the excellent effects, soil reinforcement has been seen as a relevant method in various infrastructural projects in recent years since this technique is the most practical application to improve the strength and stiffness of peat soil by using various methods, including bamboo technology. This paper highlights some of the alternative methods in peat soil reinforcement technology. It combines several techniques based on the floating concept bamboo insights that effectively distributed the load on the embankment over the peat soil. In this strategy, it is observable to reduce the impact of deformation and settlement on peat soil.


Environmental policy traditionally relies on financial incentives and direct regulation to achieve desirable outcomes in terms of conservation and pro-environmental behavior. Empirical research has shown that market based approaches are more cost-effective than direct regulation. However, experimental research has demonstrated that a combination of financial and non-financial incentives (specifically empathy nudging) is, on average, even more effective than a financial nudge, or empathy nudge, individually. The current study looks at environmental policy, specifically financial and empathy nudging, in the agricultural context. The increase of the number of farms headed by females raises the question whether previous findings of the effectiveness of these nudges are gender specific or gender neutral. We investigate this question using data from a framed laboratory experiment in the context of farmers' conservation behavior. Specifically, we compare the change in conservation efforts of females and males in response to financial incentives and empathy nudging applied separately and at the same time. Our findings show that both females and males are moderately affected by financial nudges, but only females are affected by empathy nudges separately. The combination of both nudges is economically and statistically significantly higher than each nudge individually, and substantially higher for females than for males. This implies that policy makers could increase the effectiveness of environmental policy by accounting for these gender specific differences in the policy design.


B cell stimulatory factor 2 receptors (BSF-2-R) were studied using radioiodinated recombinant BSF-2 with a specific activity of 6.16 X 10(13) cpm/g. Kinetic studies showed that binding of 125I-BSF-2 to CESS cells reached maximum level within 150 min at 0 degrees C. There was a single class of receptors with high affinity (Kd 3.4 X 10(-10) M) on CESS, and the number of receptors was 2,700 per cell. Binding of 125I- BSF-2 to CESS was competitively inhibited by unlabeled BSF-2 but not by IL-1, IL-2, IFN-beta, IFN-gamma, and G-CSF, indicating the presence of the receptors specific for BSF-2. EBV-transformed B lymphoblastoid cell lines (CESS, SKW6-CL4, LCL13, and LCL14) expressed BSF-2-R, whereas Burkitt's lines did not. EBV or EBNA2 did not induce the expression of the receptors on Burkitt's cells. The plasma cell lines (ARH-77 and U266) expressed BSF-2-R, fitting the function of BSF-2 as plasma cell growth factor. Several other cell lines, the histiocytic line U937, the promyelocytic line HL60, the astrocytoma line U373 and the glioblastoma line SK-MG-4, in which BSF-2 was inducible with IL-1 or TPA, displayed BSF-2-R with Kd in the range of 1.3-6.4 X 10(-10) M, suggesting the autocrine mechanism in BSF-2 function. The four T cell lines (CEM, HSB, Jurkat, and OM 1) did not express a detectable number of receptors, but normal resting T cells expressed 100-1,000 receptors per cell. BSF-2-R were not present on normal resting B cells but expressed on activated B cells with a Kd of 3.6-5.0 X 10(-10) M, fitting the function of BSF-2, which acts on B cells at the final maturation stage to induce immunoglobulin production.


Sensitive reverse transcriptase assay was applied to human immunodeficiency virus type 2. The kinetics of this assay, stability of the enzyme and the effect of BSA to this assay indicated that the condition of this assay should be 37 degrees C in reaction temperature. The sensitivity of this assay increased by adding more than 10 micrograms/ml of BSA. The sensitivity of this assay is at least four times more than that of CPE assay using Molt-4 cell. Other HIV-2 isolate, LAV-2 in culture medium was also detectable in this condition. Moreover reverse transcriptase inhibiting antibody that specifically inhibits HIV-2 reverse transcriptase was found by this assay.


Responding to children and young people with sexualised or sexual offending behaviours presents significant challenges across the allied health, child protection, education and juvenile justice sectors. This report maps the specialised therapeutic services designed to effect positive behavioural change and thus divert young people with sexualised behaviours from the juvenile justice system. Accurate numbers on children with sexualised or sexual offending behaviours are difficult to determine.  There are several factors  contributing to this gap in understanding. These include entrenched ideals about children as inherently innocent, widespread ignorance about developmental sexuality, and the tendency of both young people and parents to deny or minimise incidents when they do occur. In Australia, data on children with sexualised behaviours are not collected uniformly and nondisclosure contributes to what might be large numbers of offences going undetected. Mandatory reporting requirements apply where children display sexualised behaviours and are thought to be at risk of harm. Yet a general lack of knowledge as to what constitutes appropriate behaviour means that many may respond inappropriately to incidents of sexualised behaviours. This context of confusion, denial and non-disclosure creates a hidden population of children that continues to be at risk. Attention to redressing the contexts for non-disclosure is urgently required to ensure that children in need are provided with specialised therapeutic care. This report presents qualitative data from interviews with specialised clinicians as well as submissions from service providers in both community and youth justice settings. In mapping the availability of therapeutic services, this report highlights a number of geographic and demographic gaps in service provision, including difficulties with eligibility criteria, referral pathways, funding arrangements and specialised workforce development.  There are multiple challenges facing the tertiary services sector, yet the comprehensive provision  of specialised services is just one part of the response required. This study emphasises the need for effective primary and secondary prevention to effect a reduction in the numbers of young people requiring counselling in the future. Consistent with the public health model, this report prioritises professional and community education strategies that would ultimately necessitate fewer tertiary services for young people and fewer places in juvenile detention centres.


Nowadays Progressive weight loss, common reduces performance and quality of life in patients with advanced lung cancer. However, there is a paucity of studies that focus on nutritional status and quality of life of non-small cell lung cancer (NSCLC) patients. The present study seeks to determine the nutritional status, and its relation to quality of life, of NSCLC patients. One hundred NSCLC patients (mean age 60,1 years) were evaluated during therapy at the Lower Silesian Center of Lung Diseases in Thai Nguyen – Vietnam. Nutritional status was evaluated by means of the Mini-Nutritional Assessment (MNA) and quality of life by means of two instruments developed by the European Organization for the Research and Treatment of Cancer (EORTC): QLQ-C30 and QLQ-LC13 questionnaires. The MNA revealed that up to 49,1% of patients were undernourished, 24,9% were at risk of malnutrition, and only 26.0% showed a normal nutrition. The well-nourished respondents evaluated their quality of life better in all functional scaQLQ-C30 and specific LC13 questionnaires. In univariate analysis, malnutrition significantly correlated with decreased quality of life and the intensity of symptoms in both questionnaires. In multivariate analysis, malnutrition was an independent determinant of decreased quality of life in physical functioning domain (β ¼ 0.015; p < 0.001). We conclude that malnutrition has an impact on quality of life and on the presentation of symptoms in NSCLC patients. Therefore, nutritional care should be integrated into the global oncology as an adjunct to symptomatic treatment. les (33.3 vs. 41.7 vs. 66.7, respectively) and presented less intensive symptoms in general, research has contributed to the current viewpoint cancer treatment.


We document a robust relation between corporate tax differentials and U.S. international financial integration (IFI). While this is the case for traditional IFI based on cross-border positions, the positive link also emerges for its larger consolidated-by-nationality version. The gap between these IFI measures, the key outcome variable in our analysis, exhibits a strong positive correlation with tax differentials too. This is in part due to consolidated assets of multinational enterprises being more strongly correlated with tax differentials than their cross-border counterpart. We interpret this as indirect evidence of U.S. multinationals taking advantage of tax differentials in ways that go beyond what is captured by traditional Balance of Payments procedures.


This is the third paper in a series aimed at finding reionization-era quasars with the combination of DESI Legacy imaging Surveys (DELS), the Pan-STARRS1 (PS1) Survey, and near-infrared imaging surveys, such as the UKIRT Hemisphere Survey (UHS), as well as the Wide-field Infrared Survey Explorer (WISE) mid-infrared survey. In this paper, we describe the updated quasar candidate selection procedure, report the discovery of 16 quasars at 6.4 ≲ z ≲ 6.9 from an area of ∼13,020 deg2, and present the quasar luminosity function (QLF) at z ∼ 6.7. The measured QLF follows in the magnitude range −27.6 < M1450 < −25.5. We determine the quasar comoving spatial density at = 6.7 and M1450 < −26.0 to be 0.39 ± 0.11 Gpc−3 and find the exponential density evolution parameter to be k = −0.78 ± 0.18 from z ∼ 6 to z ∼ 6.7, corresponding to a rapid decline by a factor of ∼6 per unit redshift toward earlier epochs. This indicates that the rapid decline of quasar spatial density at z > 5 that was found by previous works continues to z > 6, at a rate significantly faster than the average decline rate between z ∼ 3 and 5. We measured quasar comoving emissivity at z ∼ 6.7, which indicates that high-redshift quasars are highly unlikely to make a significant contribution to hydrogen reionization. The broad absorption line quasar fraction at z ≳ 6.5 is measured to be ≳22%. In addition, we also report the discovery of six additional quasars at z ∼ 6 in the Appendix.


Introduction
 Autologous T cells expressing a CD19-specific chimeric antigen receptor (CAR) have produced impressive minimal residual disease-negative complete remission (MRD-neg CR) rates in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) patients (pts). Factors associated with durable remission in pts achieving MRD-neg CR after immunotherapy with T cells engineered with a CD19 CAR (FMC63.41bb.3ζ) have not been elucidated.
 Methods
 We studied factors impacting disease-free survival (DFS) of adults with B-ALL treated with lymphodepletion chemotherapy and CD19 CAR-T cells in a phase I/II clinical trial (NCT01865617). Pts were eligible for this analysis if they had bone marrow leukemia identified by flow cytometry and/or extramedullary disease before CAR-T cell therapy, and received CAR-T cells at or below the previously determined maximum tolerated dose (MTD; Turtle, JCI 2016). Anti-tumor response after CAR-T cell infusion was assessed by bone marrow aspiration and biopsy, with PET-CT performed in pts with extramedullary disease. High resolution (1:10,000) flow cytometry was used to identify marrow MRD, and marrow from pts in MRD-neg CR was evaluated by high throughput sequencing (HTS) of IGH, IGK, TRB, TRD, and TRG genes. Cox regression univariate and stepwise multivariable modeling were performed to identify factors associated with DFS.
 Results
 Of 57 pts who received lymphodepletion and CD19 CAR-T cells, 53 were evaluable for response and 4 were not evaluable (one MRD-neg CR before CAR-T cell infusion; 2 received CAR-T cells above the MTD; one fatal neurotoxicity prior to restaging).
 Forty-five of 53 restaged pts (85%) achieved MRD-neg CR after CAR-T cell therapy. With a median follow-up of 30.9 months, DFS and overall survival (OS) were longer in pts who achieved MRD-neg CR compared to those who did not (Fig 1A; median DFS, 7.6 vs 0.8 months, P < .0001; median OS, 20.0 vs 5.0 months, P = .014). Twenty-eight of the 45 pts who achieved MRD-neg CR had a leukemic clone identified by HTS prior to CAR-T cell infusion, and in 20 of these pts (71%), the leukemic clone was not detected in marrow 3 weeks after CAR-T cell infusion. DFS was better in MRD-neg CR pts with no detected malignant clone compared to those with a persistent clone by HTS (Fig 1B; median DFS, 8.4 vs 3.6 months, P = .036).
 We then used stepwise multivariable modeling to determine factors impacting DFS in the pts who achieved MRD-neg CR (n = 45). Better DFS was seen in pts with a higher pre-lymphodepletion platelet count (hazard ratio, HR 0.65 [95% CI; 0.47-0.88] per 50,000/μL increment P = .006), lower pre-lymphodepletion LDH (HR 1.39 [1.12-1.74] per 100 U/L increment, P = .003), and with incorporation of fludarabine into the cyclophosphamide-based lymphodepletion (Cy/Flu; HR 0.34 [0.15-0.78], P = .011). Similar findings were noted in analysis of MRD-neg CR pts who had no malignant clone by HTS after CAR-T cells. Pts with platelets ≥100,000/μL and normal LDH before lymphodepletion who received Cy/Flu (good risk, n = 15) had 2-year point estimates of DFS and OS of 78% and 86%, respectively.
 Allogeneic hematopoietic cell transplantation (HCT) is standard of care in suitable R/R adult B-ALL pts after achieving MRD-neg CR. Eighteen pts in MRD-neg CR after CAR-T cells underwent HCT a median of 2.3 months after CAR-T cell infusion. We analyzed the effect on DFS of HCT after CAR-T cell therapy by treating HCT as a time-dependent covariate. After adjusting for LDH, platelets, and Cy/Flu lymphodepletion, pts undergoing HCT after CAR-T cell therapy had lower risk of failure for DFS compared to those who did not undergo HCT (Table 1). No significant interaction effect was seen between HCT and risk group (P = .51). With a median follow-up of 28.4 months after HCT, 2-year point estimates of DFS and OS were 61% and 72% respectively. The 2-year cumulative incidence of relapse was 17% and non-relapse mortality was 23%.
 Conclusion
 A high rate of MRD-neg CR was seen following CD19 CAR-T cell therapy in adult B-ALL pts and is associated with improved DFS and OS. Absence of the index clone by HTS after CAR-T cells was associated with better DFS, suggesting deeper responses are associated with improved outcomes. Stepwise multivariable modeling identifies better DFS in pts with higher pre-lymphodepletion platelet count and lower LDH, and with use of Cy/Flu lymphodepletion. After adjusting for these factors, HCT after CD19 CAR-T cells may also be associated with better DFS.

 Hay: DAVA Oncology: Honoraria. Hirayama:DAVA Oncology: Honoraria. Li:Juno Therapeutics: Employment, Equity Ownership. Till:Mustang Bio: Patents & Royalties, Research Funding. Kiem:Rocket Pharmaceuticals: Consultancy; Homology Medicine: Consultancy; Magenta: Consultancy. Ramos:Seattle Genetics: Employment, Equity Ownership. Shadman:Qilu Puget Sound Biotherapeutics: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Research Funding; Genentech: Consultancy; Mustang Biopharma: Research Funding; AbbVie: Consultancy; Celgene: Research Funding; Verastem: Consultancy; Acerta Pharma: Research Funding; Genentech: Research Funding; TG Therapeutics: Research Funding; Beigene: Research Funding; Gilead Sciences: Research Funding. Cassaday:Adaptive Biotechnologies: Consultancy; Amgen: Consultancy, Research Funding; Incyte: Research Funding; Seattle Genetics: Other: Spouse Employment, Research Funding; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Research Funding; Pfizer: Consultancy, Research Funding; Merck: Research Funding. Acharya:Juno Therapeutics: Research Funding; Teva: Honoraria. Riddell:Adaptive Biotechnologies: Consultancy; NOHLA: Consultancy; Juno Therapeutics: Equity Ownership, Patents & Royalties, Research Funding; Cell Medica: Membership on an entity's Board of Directors or advisory committees. Maloney:Seattle Genetics: Honoraria; Roche/Genentech: Honoraria; GlaxoSmithKline: Research Funding; Janssen Scientific Affairs: Honoraria; Juno Therapeutics: Research Funding. Turtle:Adaptive Biotechnologies: Consultancy; Eureka Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics / Celgene: Consultancy, Patents & Royalties, Research Funding; Gilead: Consultancy; Nektar Therapeutics: Consultancy, Research Funding; Caribou Biosciences: Consultancy; Precision Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Consultancy; Aptevo: Consultancy.


Currently, emulsification-templated nanoencapsulation techniques (e.g., nanoprecipitation) have been most frequently used to prepare poly-d,l-lactide-co-glycolide (PLGA) nanoparticles. This study aimed to explore a new top-down process to produce PLGA nanoparticles. The fundamental strategy was to prepare spongelike PLGA microspheres with a highly porous texture and then crush them into submicron-sized particles via wet milling. Therefore, an ethyl formate-based ammonolysis method was developed to encapsulate progesterone into porous PLGA microspheres. Compared to a conventional solvent evaporation process, the ammonolysis technique helped reduce the tendency of drug crystallization and improved drug encapsulation efficiency accordingly (solvent evaporation, 27.6 ± 4.6%; ammonolysis, 65.1 ± 1.7%). Wet milling was performed on the highly porous microspheres with a D50 of 64.8 μm under various milling conditions. The size of the grinding medium was the most crucial factor for our wet milling. Milling using smaller zirconium oxide beads (0.3~1 mm) was simply ineffective. However, when larger beads with diameters of 3 and 5 mm were used, our porous microspheres were ground into submicron-sized particles. The quality of the resultant PLGA nanoparticles was demonstrated by size distribution measurement and field emission scanning electron microscopy. The present top-down process that contrasts with conventional bottom-up approaches might find application in manufacturing drug-loaded PLGA nanoparticles.


Several methods have been used to relieve pain in neonates. The objective of this study was to assess the analgesic effect of 50% glucose and water during hepatitis B vaccination. In this randomized controlled trial, 90 term neonates were studied. Infants were randomly assigned to one of the three equal sized groups. First, heart rates were measured by EKG monitor. Then, 2mL of either 50% glucose or sterile water was administered into the mouths of infants in groups one and two, respectively. No intervention was done for group three. During vaccination until three minutes after, crying of babies was taped. Heart rates were measured during injection until 60 seconds. Mean values of duration of crying for glucose, water, and no intervention groups were 21.1 s, 33.3 s, and 56.9 s, respectively, which were significantly different ( P = 0.0003). Post hoc test revealed substantial differences between groups one and three ( P = 0.0001) and between groups two and three ( P = 0.006). However, groups one and two were not statistically different ( P = 0.19). Moreover, heart rate did not rise significantly in any of those groups. Both 50% glucose and water showed analgesic effects in neonates.


Typical multimedia applications require highly reliable connections and should not depend upon a single link. On-demand multipath routing protocols for mobile ad-hoc networks, therefore, are crucial in providing resilience to route failures and to successful load balancing. Performance evaluations of on-demand multipath routing protocols have been carried out and contrasted with traditional single-path routing protocols. Results show the superiority of multipath routing protocols under certain scenarios in terms of goodput, average end-to-end delay and routing overheads. Based on the observations, we make recommendations about how the performance of the on-demand multipath routing protocols can be improved.


The authors describe the development of software for the computation of electromagnetic field strengths in complex systems. The code MESAF (multilevel EMC system analysis framework) offers a different way to approach the analysis of EMC problems, particularly susceptibility. It occupies the intermediate level between 'back of the envelope' calculations for simple geometries and the complexity of a full computational electromagnetics solution. It can also encompass the statistical variations found in real product geometries and layouts. Users are expected to be electromagnetic compatibility design engineers working in industry. The software is based on the concept of electromagnetic topology. The user defines the system electromagnetic topology, so precise geometrical details are not required, and the code then automatically generates the network of field ingress paths to a given unit in the system. A link to a transfer function database enables signal levels along these paths to be computed, so the susceptibility of the unit can be assessed. With MESAF it is possible to model the effect of design changes on the system susceptibility and to model products throughout the design cycle, with increasing accuracy as the design evolves.


Due to the advances of sensing and storage technologies, a tremendous amount of data becomes available and, it supports the phenomenal growth of artificial intelligence (AI) techniques especially, deep learning (DL), in various application domains. While the data sources become valuable assets for enabling the success of autonomous decision-making, they also lead to critical vulnerabilities in privacy and security. For example, data leakage can be exploited via querying and eavesdropping in the exploratory phase for black-box attacks against DL-based autonomous decision-making systems. To address this issue, in this work, we propose a novel data encryption method, called AdvEncryption, by exploiting the principle of adversarial attacks. Different from existing encryption technologies, the AdvEncryption method is not developed to prevent attackers from exploiting the dataset. Instead, our proposed method aims to trap the attackers in a misleading feature distillation of the data. To achieve this goal, our AdvEncryption method consists of two essential components: 1) an adversarial attack-inspired encryption mechanism to encrypt the data with stealthy adversarial perturbation, and 2) a decryption mechanism that minimizes the impact of the perturbations on the effectiveness of autonomous decision making. In the performance evaluation section, we evaluate the performance of our proposed AdvEncryption method through case studies considering different scenarios.


Consumer behaviour and perceptions evolve over time and affect credit usage from the financial service providers. We use the 2016 FinAccess Household survey data of 2015 from 8665 households to examine how perceptions and behaviour of un(der) banked consumers can shape their dynamics towards credit usage. The perceptions and behaviour are based on source of financial advice, trust of the institutions, characteristics of the financial instrument and cost of credit. The multinomial logistic regression model predicts the odds of credit usage based on perceptions and behaviour of the consumers. The categories for the credit usage are: have credit, used to have credit and never had credit. Consumer perceptions and behaviour based on cost of credit and trust increase credit usage, while source of financial advice had minimal influence on credit usage. The characteristics of the financial instrument are catering to emergencies and being safe to use increased credit usage. The Savings and Credit Cooperative Organizations and microfinance are the most trusted financial institutions by the consumers, while shylock has the highest cost of credit. Radio as a source of financial advice reduced credit usage. The dynamics of credit usage are shaped by the perceptions and behaviour of the consumers.


Although permeable pavements have been used all over the world in recent years to infiltrate and treat stormwater, only limited research has been undertaken to investigate and compare the long-term performance of these sustainable urban drainage system devices. This paper presents the results of an extensive international review of research on the reduction of infiltration capacity of permeable pavements over time. The results of these studies, coupled with specific knowledge of the key environmental factors on the individual research locations and infiltration testing methods used, enables the maintenance of these SUDS to be strategically planned in order to meet specific European and international infiltration capacity guidelines.


The role of the Notch pathway during the lateral inhibition that underlies binary cell fate choice is extensively studied, but the context specificity that generates diverse outcomes is less well understood. In the peripheral nervous system of Drosophila melanogaster, differential Notch signaling between cells of the proneural cluster orchestrates sensory organ specification. Here we report functional analysis of Drosophila Ataxin 2-binding protein 1 (A2BP1) during this process. Its human ortholog is linked to type 2 spinocerebellar ataxia and other complex neuronal disorders. Downregulation of Drosophila A2BP1 in the proneural cluster increases adult sensory bristle number, whereas its overexpression results in loss of bristles. We show that A2BP1 regulates sensory organ specification by potentiating Notch signaling. Supporting its direct involvement, biochemical analysis shows that A2BP1 is part of the Suppressor of Hairless [Su(H)] complex in the presence and absence of Notch. However, in the absence of Notch signaling, the A2BP1 interacting fraction of Su(H) does not associate with the repressor proteins Groucho and CtBP. We propose a model explaining the requirement of A2BP1 as a positive regulator of context-specific Notch activity. Summary: Drosophila A2BP1 regulates sensory organ specification by potentiating Notch signaling, forming part of the Suppressor of Hairless complex and acting in a context-dependent manner.


Abstract. The effect of particulate matter is increasingly gaining significance due to its harmful effects on human and urban ecosystems. In view of it, many communities worldwide are collecting air quality data privately to influence their policy makers to make stricter provisions for reducing harmful emissions and thereby improving their quality of life. Likewise, in many German cities, a community of air quality monitors which rely on low-cost PM Sensors is gathering momentum. Such communities possess privately-owned & low-cost air quality monitoring devices that claim to accurately measure PM concentrations and are openly accessible via internet. One such initiative is an air quality monitoring network viz. "luftdaten.info", which contains of more than 300 low-cost sensors that consistently obtains PM data, colloquially referred as fine dust, in the city of Stuttgart as well as its surrounding districts. Besides, eight stations are continuously monitoring PM concentration in Stuttgart; these are operated by the State Environmental Agency (LuBW- Landesanstalt für Umwelt Baden-Württemberg). Stuttgart University of Applied Sciences (HFT) has currently installed 7 low-cost PM sensors to monitor and study PM concentration in one of its projects. This study endeavors to relate PM 2.5 and PM 10.0 using low-cost sensors. It intends to investigate the reliability of the measured PM concentration using such low-costs sensors once these are placed horizontally and vertically apart and comparing the measures of the 7 sensors. Another objective is to compare the PM concentration measurements with a meteorological station operated by the State of Baden-Wuerttemberg in the vicinity. A correlation analysis is performed to develop understanding of relationships of PM concentration with meteorological parameters, viz. with respect to ambient temperature, air pressure, humidity, wind speed and wind direction. Furthermore, it attempts to develop a regression model using above listed meteorological parameters. Finally, deficiencies in the measurement of low-costs and its placement effects are commented. Further suggestions are made for improving the data capturing and analytical procedures while using low-cost sensors.


Japan is the country with the longest history of implementing unconventional monetary policies, which were first introduced 15 years ago and have since been expanded several times. A case in point is the quantitative and qualitative monetary easing (QQE) policy introduced by the Bank of Japan (BOJ) in early 2013 along with the commitment to continue with the program as long as necessary to achieve a 2% price stability target. This study attempts to assess the overall macroeconomic effects of Japan's unconventional monetary policies, with an emphasis on the recent QQE program. Using a stylized block-recursive vector autoregression (VAR) framework, the analysis suggests that expansionary unconventional monetary policy shocks have clear macroeconomic effects, leading to a persistent rise in real output and inflation in Japan. The evidence also suggests that these macroeconomic effects became larger and more persistent after the introduction of QQE. A formal analysis that allows for a regime shift based on a smooth-transition VAR model supports these findings.


Cropping systems with high phosphorus (P) inputs may constitute a risk of P leaching, which contributes to eutrophication. The main objective of this study was to identify P leaching risks associated with three long-term fertilization regimes in separately tile-drained plots on a sandy soil in southwest Sweden. The three regimes resulted in different annual P surpluses of, on average, 16 kg P ha−1 (14 lb P ac−1) in mineral form and 18 kg P ha−1 (16 lb P ac−1) and 37 kg P ha−1 (33 lb P ac−1) as pig slurry. The importance of different soil characteristics (soil P, iron, aluminum, and calcium content, and degree of P saturation [DPS]) and processes (water flow and P sorption/desorption) was examined using 15 years (1989 to 2003) of P leaching measurements and simulations with the ICECREAM model. Measurements of high soil P content and DPS values in the topsoil, in combination with high precipitation and rapid water flow, indicated a high potential for P losses, which was confirmed by the model simulations. However, the model considerably overestimated total P leaching by a factor of 5 to 9 since measured P leaching was small for all treatments. Measured mean annual total P leaching and total P concentration ranged respectively from 0.14 kg ha−1 (0.12 lb ac−1) and 0.06 mg L−1 (3.75 × 10−6 lb ft−3) at a high rate of slurry application to 0.20 kg ha−1 (0.18 lb ac−1) and 0.08 mg L−1 (4.99 × 10−6 lb ft−3) in the mineral P treatment. The differences in concentration were statistically significant (p < 0.001). A main conclusion from this 15-year study was that annual pig slurry application rates of 37 to 58 kg P ha−1 (33 to 52 lb P ac−1) did not increase P leaching. High sorption capacity of the subsoil, caused by Fe, Al, and Ca, was obviously very important for controlling P losses. Thus, information on soil P content and fertilization must be supplemented with estimates of soil P sorption capacity when evaluating the risk of P leaching for different soils. This must also be considered in models used for assessment of P leaching from arable land. The current ICECREAM model does not include appropriate functions for describing P sorption/desorption processes in this type of soil and needs further development.


The transforming growth factor-β (TGF-β) signaling pathway regulates various cellular processes during tissue and organ development and homeostasis. Deregulation of the expression and/or functions of TGF-β ligands, receptors or their intracellular signaling components leads to multiple diseases including vascular pathologies, autoimmune disorders, fibrosis and cancer. In vascular development, physiology and disease TGF-β signaling can have angiogenic and angiostatic properties, depending on expression levels and the tissue context. The objective of this chapter is to analyze the mechanisms that contribute to the activation and signaling of TGF-β in developmental, physiological and pathological angiogenesis, with a particular emphasis on the importance of TGF-β signaling in the mammalian central nervous system (CNS).


The institution of the office of elder in the Reformed Church in the sixteenth century was an innovation in the traditional structure of the western Catholic Church and the canonical pattern of its ministry. There were precedents for something like this in the Waldensian and Bohemian (later Moravian) Communities in the twelfth and fifteenth centuries, and there still are features corresponding to it in the leadership of congregational life in Greek Orthodox Churches arising out of the overlap between the worshipping congregation and the cultural community. In the Reformed Church itself the eldership came to be more closely associated with the ministry of Word and Sacrament which has had the effect of linking together 'clerical' and 'lay' service within the corporate priesthood of the Church and in the operation of its 'sacral courts' at synodal, presbyteral and consistorial levels. The eldership has certainly been a source of inner cohesion and stability in the life of Reformed Churches, leaving upon them characteristics of particular significance in the ecumenical fellowship of Churches.


Objective: Dietary inorganic nitrate, originating from beetroot juice, has been shown to lower brachial blood pressure via bioconversion in the enterosalivary circulation. Its effects on central systolic blood pressure (cSBP) are largely unknown. Design and method: 13 healthy young adults received 180 ml Fit Rabbit (FR) juice, containing 11.2 mmol nitrate, or matched placebo (P), at 8.00 AM in a non-fasting state (but free from coffee). Brachial and central BP was measured with a validated, oscillometric system (mobilograph, Stolberg, Germany) and a transfer function, with a measurement interval of 20 minutes during the day, at baseline (B), following FR and P. Primary endpoint was the change in averaged cSBP between the time interval 7.15–8.30 and 09.00–12.30. Results: From the first to the second time interval, central SBP dropped by 3.3 mm Hg (FR) and 0.2 mm Hg (B) and increased by 1.6 mm Hg (P). The changes in the whole group were statistically significant (p = 0.005), as was the change following FR (p = 0.0003) and the difference between B and FR (p = 0.05). In contrast, we observed only minor changes in brachial SBP at B (−0.8 mm Hg) and following FR (−0.2 mm Hg) and P (+1.2 mm Hg) from the first to the second time interval. The BP changes were accompanied by changes in heart rate (HR): + 4.6 (RF), −3.4 (B) and −2.6 (P) beats per minute, respectively. The changes in the whole group were statistically significant (p = 0.02), as was the change following FR (p = 0.02) and the difference between B and FR (p = 0.01). In exploratory analysis, the results were comparable, when alternative time windows for the second interval were chosen (09.-11.00 or 11.00–12.30, respectively). Conclusions: Our results show that the effects of beetroot juice on systolic blood pressure may be more pronounced on central rather than on brachial blood pressure.


Several studies in linguistics and related disciplines have been extensively exploring sound symbolism, systematic associations between sounds and meanings. Against this theoretical development, research on Pokemon names has shed new light on cross-linguistic similarities and differences in sound symbolic patterns, using similar experimental stimuli across different target languages. A recent experimental study has demonstrated that Brazilian Portuguese speakers sound-symbolically signal evolution when naming Pokemon characters: post-evolution Pokemon characters tend to receive longer names with more voiced obstruents, while pre-evolution characters tend to receive shorter names with fewer voiced obstruents. Other recent studies showed that in Japanese and English, sound symbolism can also signal differences in Pokemon type: evil-looking characters tend to be associated with voiced obstruents, while flying-type characters tend to have names with sibilants. Integrating the insights offered by these two lines of previous studies, the current paper examines whether Brazilian Portuguese speakers are sensitive to these type-related sound symbolic associations. To improve upon previous studies, we used a free-naming task in order to give participants freedom to create new names. This experiment corroborated the associations between voiced obstruents and evil-type characters, but not the association between sibilants and flying-type characters. A follow-up experiment with a forced-choice paradigm, the same method used in earlier work, also failed to reveal systematic connections between sibilants and flying-type characters. These results indicate that this association may not be universal, contrary to the claim made in previous studies.


Background: Contemporary clinical assessments of activity are needed across the age span for children with cerebral palsy (CP). Computerized adaptive testing (CAT) has the potential to efficiently administer items for children across wide age spans and functional levels. Objective: The objective of this study was to examine the psychometric properties of a new item bank and simulated computerized adaptive test to assess activity level abilities in children with CP. Design: This was a cross-sectional item calibration study. Methods: The convenience sample consisted of 308 children and youth with CP, aged 2 to 20 years (X=10.7, SD=4.0), recruited from 4 pediatric hospitals. We collected parent-report data on an initial set of 45 activity items. Using an Item Response Theory (IRT) approach, we compared estimated scores from the activity item bank with concurrent instruments, examined discriminate validity, and developed computer simulations of a CAT algorithm with multiple stop rules to evaluate scale coverage, score agreement with CAT algorithms, and discriminant and concurrent validity. Results: Confirmatory factor analysis supported scale unidimensionality, local item dependence, and invariance. Scores from the computer simulations of the prototype CATs with varying stop rules were consistent with scores from the full item bank (r=.93–.98). The activity summary scores discriminated across levels of upper-extremity and gross motor severity and were correlated with the Pediatric Outcomes Data Collection Instrument (PODCI) physical function and sports subscale (r=.86), the Functional Independence Measure for Children (Wee-FIM) (r=.79), and the Pediatric Quality of Life Inventory–Cerebral Palsy version (r=.74). Limitations: The sample size was small for such IRT item banks and CAT development studies. Another limitation was oversampling of children with CP at higher functioning levels. Conclusions: The new activity item bank appears to have promise for use in a CAT application for the assessment of activity abilities in children with CP across a wide age range and different levels of motor severity.


With the advent of Bluetooth and wireless 802.11 Ethernet protocols having transmission speeds up to 54 Mbps, wireless communication for closed-loop control is becoming more and more achievable. Some researchers have utilized Bluetooth networks for wireless control, resulting in successful stabilization of an unstable plant with a network controller. Previously, the authors of this paper developed a novel event-based control with time-based sensing and actuation communication method using 11 Mbps wireless Ethernet with the user datagram protocol (UDP). Near real-time control of an unstable Furuta pendulum with up to 250 Hz closed loop bandwidth was obtained using off the shelf hardware, Matlab, and Windows 2000 operating systems. The present work extends that communication scheme to two independent wireless loops that share a mutual goal, making additional communication between the two controllers advantageous. The communication framework for the coupled control in this ad hoc peer-to-peer network is presented along with some practical limitations. Data from a physical system implementing this framework demonstrates its effectiveness in application. The test plant couples a simple light tracking plant with a Furuta pendulum and a shared goal of maintaining line of sight (LOS) under normal conditions as well as reestablishing LOS in the case of lost contact due to sudden obstacles.Copyright © 2004 by ASME


A brief study has been carried out on the effect of temperature on brick suction or initial rate of absorption (IRA), which is a factor in determining the amount of water extracted from mortar placed between bricks. This is important during cold weather construction when the amount of water extracted determines the pore space available for expansive forces if the remaining water freezes at an early age. The study included extruded clay and shale, dry-press clay, sandlime, and concrete bricks selected to include a range of control IRA (suction) values. Values were determined at 20, 10, −1.5, and −10°C with water at 20°C and at 20°C with water at 10°C. Results indicate a small reduction in suction with dropping temperature for low absorption bricks and a substantial drop for high absorption extruded and dry-press clay bricks at temperatures below 0°C. It is concluded that bricks should be at temperatures above 0°C to ensure maximum potential for reducing the moisture content of mortar during winter construction.


Mechanical loading is essential for the health and homeostasis of articular cartilage, although the fundamental mechanotransduction pathways are unclear. Previous studies have demonstrated that cyclic compression up‐regulates proteoglycan synthesis via an intracellular Ca2+ signalling pathway, mediated by the release of ATP. However, the mechanism(s) of ATP release has not been elucidated. The present study examines expression of the putative mechanosensitive ATP‐release channel, connexin 43 and whether it is expressed on the chondrocyte primary cilium, which acts as a mechanosensor in a variety of other cell types. In addition the study characterized the expression of a range of purine receptors through which ATP may activate downstream signalling events controlling cell function. Bovine articular chondrocytes were isolated by sequential enzyme digestion and seeded in agarose constructs. To verify the presence of functional hemichannels, Lucifer yellow (LY) uptake into viable cells was quantified following treatment with a hemichannel agonist (EGTA) and antagonist (flufenamic acid). LY uptake was observed in 45% of chondrocytes, increasing to 83% following EGTA treatment (P < 0.001). Treatment with the hemichannel blocker, flufenamic acid, significantly decreased LY uptake to less than 5% with and without EGTA. Immunofluorescence and confocal microscopy confirmed the presence of primary cilia and the expression of connexin 43. Approximately 50% of bovine chondrocyte primary cilia were decorated with connexin 43. Human chondrocytes in situ within cartilage explants also expressed connexin 43 hemichannels. However, expression was confined to the upper 200 µm of the tissue closest to the articular surface. Immunofluorescence revealed the expression of a range of P2X and P2Y receptor subtypes within human articular cartilage. In conclusion, the expression of functional hemichannels by articular chondrocytes may represent the mechanism through which mechanical loading activates ATP release as part of a purinergic mechanotransduction pathway. Furthermore, the expression of connexin 43 on the chondrocyte primary cilium suggests the possible involvement of the cilium in this pathway.


The study examined economic effect of land tenure systems on arable crop production in Ekiti State, Nigeria. Attempts were made to examine the type of land ownership rights problems of land acquisition, the pattern of land use and the resource use efficiency of land as a factor of production in arable crop production in the study area. Data were collected from 120 arable farmers randomly selected for interview with the aid of questionnaire were used to analyze. The study revealed that the arable farmers were fairly educated with about 41.7% having secondary education and 16.7% having primary education. The sampled farmers were small holders with 80.8% having less than 4ha of land, this agreed with the fact that most of the arable crop producers were producing for family consumption with the 76.7% of the farmers operated on subsistence basis. It was also indicated that the prevailing tenure type was inheritance ownership right with 60% of the respondents acquiring their land through inheritance. It was also discovered that the prevailing traditional tenure (inheritance, communal) systems has resulted to farmland fragmentation which would not encourage mechanization and commercial agriculture. According to the study, the prevailing land use patterns were the arable cultivation followed by permanent crop cultivation. The production function analysis showed that all the variables were productively used for having positive estimate except fertilizer and agrochemicals that had negative estimate elasticity. Therefore, government must seriously address the issue of land acquisition so that prospective farmers have free access to arable land empowered them to solely make their own production decision (in accordance with the principle of land use) without the dictatorship of the landlords.


Elaboration of new generations of more effective and safer metal-based anticancer agents, has been stimulated by the severe side effects encountered by patients undergoing chemotherapeutic treatments. In this search, ruthenium complexes have shown encouraging potential, demonstrating a wide antiproliferative profile against cancer cells. Seminal studies conducted in our labs have resulted in the development of ruthenium(II)-based new anticancer agents, which showed distinct cytotoxicity mechanisms.
First, a substitutionally-inert bis(dppz)-Ru(II) complex has been synthetized that impairs the mitochondrial membrane potential of cells leading to apoptosis. A follow- up structure-activity relationship analysis investigating the impact of lipophilicity, charge and size-based modification revealed the presence of carboxylic acid functionality as indispensable to confer cytotoxicity to the Ru(II) complex. This complex was successfully inactivated by protecting the carboxylate functionality with a photolabile protecting group. The anticancer activity could be regained by UV-A irradiation (2.58 J/cm2).
Second, a seemingly harmless ruthenium(II) complex was prepared. It targets the cell nucleus and causes significant damage to DNA, such as single-strand breaks (SSBs) and purines oxidation upon UV-A irradiation (1.29 J/cm2). After 24 h, double- strand breaks (DSBs) are also created that lead overall to cell death.
Collectively, these findings are an important progress towards developing a new class of metal-based anticancer agents, which have the potential to overcome the drawbacks of the current platinum-based drugs.


In this paper, we extract for key objects of motion video images (mainly people), then do researches with the technology of object detection and tracking. First, we extract moving object edge and foreground object template with the use of the method of edge detection, and then compare the resulting object template with the original image, thus dye the positions with the colour of the corresponding point coordinates in the original image which belongs to the extent of template filled region. Simulation results show that the proposed algorithm has some advantages and robustness and could meet project needs.


Purpose To assess the association between VKORC1 and CYP2C9 variants and the incidence of adverse drug reactions in warfarin-treated patients in a real-world setting. Materials and Methods This was a register-based cohort study (PreMed) linking data from Finnish biobanks, national health registries and patient records between January 1st 2007 and June 30th 2018. The inclusion criteria were: 1) ≥18 years of age, 2) CYP2C9 and VKORC1 genotype information available, 3) a diagnosis of a cardiovascular disease, 4) at least one warfarin purchase, 5) regular INR tests. Eligible individuals were divided into two warfarin sensitivity groups; normal responders, and sensitive and highly sensitive responders based on their VKORC1 and CYP2C9 genotypes. The incidences of clinical events were compared between the groups using Cox regression models. Results The cohort consisted of 2508 participants (45% women, mean age of 69 years), of whom 65% were categorized as normal responders and 35% sensitive or highly sensitive responders. Compared to normal responders, sensitive and highly sensitive responders had fewer INR tests below 2 (median: 33.3% vs 43.8%, 95% CI: −13.3%, −10.0%) and more above 3 (median: 18.2% vs 6.7%, 95% Cl: 8.3%, 10.8%). The incidence (per 100 patient-years) of bleeding outcomes was 5.4 for normal responders and 5.6 for the sensitive and highly sensitive responder group (HR=1.03, 95% CI: 0.74, 1.44). The incidence of thromboembolic outcomes was 4.9 and 7.8, respectively (HR=1.48, 95% CI: 1.08, 2.03). Conclusion In a real-world setting, genetically sensitive and highly sensitive responders to warfarin had more high INR tests and required a lower daily dose of warfarin than normal responders. However, the risk for bleeding events was not increased in sensitive and highly sensitive responders. Interestingly, the risk of thromboembolic outcomes was lower in normal responders compared to the sensitive and highly sensitive responders. Trial Registration NCT04001166.


Background To support country work to improve national regulation on road traffic injury prevention, we developed various approaches and tools to enhance the capacity of staff in government and civil society organisations, mainly lawyers, to assess and develop evidence-based regulations. We use the term "regulation" in this presentation broadly to include laws that are enacted by national parliament and regulations issued by national or subnational ministerial or other executive branches of government. Methods This presentation describes the approaches used to improve the skills, access to and use of evidence-based interventions to assess and improve regulations on road traffic injury prevention for lawyers and others involved in regulatory processes in public health or road traffic. Results Since 2010, WHO has supported the improvement of road safely legislation in 12 countries with support from Bloomberg Philanthropies. In the early years of the capacity development programme (2012–2014), participants from 9 countries (Brazil, Cambodia, China, India, Kenya, Mexico, Turkey, Russian Federation, Viet Nam) were selected through a nomination process from WHO Regional and Country Offices. This phase focused primarily on providing face-to-face periodic training on skills and information on evidence-based road safety interventions. Starting in 2015 we launched a Legal Development Programme in 4 countries (China, Philippines, Thailand, United Republic of Tanzania) with the objectives of providing a range of learning opportunities for lawyers and other individuals involved in developing regulations and of improving their skills, access to and use of resources on evidence interventions to assess and develop evidence-based regulation. Participants were selected through a semi-competitive process taking into consideration their background, interest in the topic, the nature and extent of their involvement in public health or road safety regulation, and commitment to play an active role in improving legislation in public health or road safety in their country. The level of engagement of the Legal Development Programme members in regulatory mechanisms on the topic in country has also been enhanced. Conclusions During 2012–2014 participants who regularly took part in face-to-face workshops showed longer-term and active involvement in improving road safety regulation in their country. Countries supported also showed better improvement in evidence-based regulation (either in the number of changes or in the extent to which the changes are in line with evidence). Although the impact of the Legal Development Programme has not yet been assessed, it has so far generated greater interest than the previous capacity development programme (through an increase in number of participating members since the launch) as well as more active involvement in various aspects of the road safety regulatory process.