A cross-sectional study to ascertain what the Singapore population would regard as material risk in the anaesthesia consent-taking process and identify demographic factors that predict patient preferences in medical decision-making to tailor a more patient-centered informed consent. A survey was performed involving patients 21 years old and above who attended the pre-operative evaluation clinic over a 1-month period in Singapore General Hospital. Questionnaires were administered to assess patients’ perception of material risks, by trained interviewers. Patients’ demographics were obtained. Mann–Whitney U (...) test and Kruskal-Wallis one-way analysis of variance was used. Statistical significance was taken at p < 0.05. Four hundred fourteen patients were eligible of which 26 refused to participate and 24 were excluded due to language barrier. 364 patients were recruited. A higher level of education, being employed and younger age group are factors identified in patients who wanted greater participation in medical decisions. Gender, marital status, type of surgery, and previous surgical history did not affect their level of participation. The complications most patients knew about were Nausea, Drowsiness and Surgical Wound Pain. Patients ranked Heart Attack, Death and Stroke as the most significant risks that they wanted to be informed about in greater detail. Most patients wanted to make a joint decision with the anaesthetist, instead of letting the doctor decide or deciding for themselves. Discussion with the anaesthetist is the preferred medium of communication compared to reading a pamphlet or watching a video. Age and educational level can influence medical decision-making. Despite the digital age, most patients still prefer a clinic consult instead of audio-visual multimedia for pre-operative anaesthetic counselling. The local population appears to place greater importance on rare but serious complications compared to common complications. This illustrates the need to contextualize information provided during informed consent to strengthen the doctor-patient relationship. (shrink)

Previous research has found that funding disparities are driven by applications’ final impact scores and that only a portion of the black/white funding gap can be explained by bibliometrics and topic choice. Using National Institutes of Health R01 applications for council years 2014–2016, we examine assigned reviewers’ preliminary overall impact and criterion scores to evaluate whether racial disparities in impact scores can be explained by application and applicant characteristics. We hypothesize that differences in commensuration—the process of combining criterion scores into (...) overall impact scores—disadvantage black applicants. Using multilevel models and matching on key variables including career stage, gender, and area of science, we find little evidence for racial disparities emerging in the process of combining preliminary criterion scores into preliminary overall impact scores. Instead, preliminary criterion scores fully account for racial disparities—yet do not explain all of the variability—in preliminary overall impact scores. (shrink)

We report a detection of the baryon acoustic oscillation feature in the three-dimensional correlation function of the transmitted flux fraction in the Lya forest of high-redshift quasars. The study uses 48 640 quasars in the redshift range 2.1 = z = 3.5 from the Baryon Oscillation Spectroscopic Survey of the third generation of the Sloan Digital Sky Survey. At a mean redshift z = 2.3, we measure the monopole and quadrupole components of the correlation function for separations in the range (...) 20 h-1 Mpc < r < 200 h-1 Mpc. A peak in the correlation function is seen at a separation equal to times the distance expected for the BAO peak within a concordance.CDM cosmology. This first detection of the BAO peak at high redshift, when the universe was strongly matter dominated, results in constraints on the angular diameter distance DA and the expansion rate H at z = 2.3 that, combined with priors on H0 and the baryon density, require the existence of dark energy. Combined with constraints derived from cosmic microwave background observations, this result implies H = km s-1 Mpc-1, indicating that the time derivative of the cosmological scale parameter.a = H/ is significantly greater than that measured with BAO at z ∼ 0.5. This demonstrates that the expansion was decelerating in the range 0.7 < z < 2.3, as expected from the matter domination during this epoch. Combined with measurements of H0, one sees the pattern of deceleration followed by acceleration characteristic of a dark-energy dominated universe. © 2013 ESO. (shrink)

Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, (...) NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity. (shrink)

In the management and business ethics literatures, stakeholder engagement has been demonstrated to lead to more ethical management practices. However, there may be limits on the extent to which stakeholder engagement can, as currently conceptualized, resolve some of the more difficult ethical challenges faced by managers. In this paper we argue that stakeholder engagement, when seen as a way of reducing five types of knowledge problems—risk, ambiguity, complexity, equivocality, and a priori irreducible uncertainty—can aid managers in resolving such ethical challenges. (...) Using a practical illustration of the ethical challenges surrounding the development and application of genetic modification technologies, we demonstrate how stakeholder engagement enables managers to better address these knowledge problems, thereby to manage more ethically. In this way, we suggest that stakeholder engagement has an even more crucial role to play in business ethics research and practice. (shrink)

In this article, we use ideas from stakeholder capital maintenance theory to address tensions in allocating firm profits between stockholders and other stakeholders. We utilize a mediative thought experiment to conceptualize how multiple stakeholder interests might better be served, such that genuine firm profits (from new value creation) versus artificial firm profits (from non-wealth-producing transfers) may be identified and incentivized. We thereby examine how such accounting transfers can be envisioned as stakeholder capital to be maintained for the benefit of both (...) the firm and the economy. We present examples to illustrate the hypothetical model proposed and its implications. (shrink)

Introduction Future HIV vaccine efficacy trials with adolescents will need to ensure that participants comprehend study concepts in order to confer true informed assent. A Hepatitis B vaccine trial with adolescents offers valuable opportunity to test youth understanding of vaccine trial requirements in general. Methods Youth reviewed a simplified assent form with study investigators and then completed a comprehension questionnaire. Once enrolled, all youth were tested for HIV and confirmed to be HIV-negative. Results 123 youth completed the questionnaire (mean age=15 (...) years; 63% male; 70% Hispanic). Overall, only 69 (56%) youth answered all six questions correctly. Conclusions Youth enrolled in a Hepatitis B vaccine trial demonstrated variable comprehension of the study design and various methodological concepts, such as treatment group masking. (shrink)

This breakthrough volume integrates European, British, and American scholarship in advanced areas of philosophy and decision theory. Contributions cover a broad area of economics--from criticism of institutional economics to examination of the role of induction in economic forecasting.

Medium- and high-spin states of Pr-134 were populated using the Cd-116(Na-23, 5n) reaction and studied with the GAMMASPHERE spectrometer. Several new bands have been found in this nucleus, one of them being linked to the previously observed chiral-candidate twin-band structure. The ground state of Pr-134 could be determined through establishing a level structure that connects the two previously known long-lived isomeric states. Unambiguous spin-parity assignments for the excited states could be performed based on the known 2(-) spin-parity of the ground (...) state combined with the present experimental data. Intrinsic single-particle configurations have been assigned to the newly observed bands on the basis of the measured B(M1)/B(E2) ratios, alignments, band-crossing frequencies, bandhead spins, the observed single-particle configurations in the neighboring nuclei, and taking into account the predictions of total Routhian surface and tilted-axis cranking calculations. (shrink)

Elephants show a rich social organization and display a number of unusual traits. In this paper, we analyse reports collected over a thirty-five year period, describing behaviour that has the potential to reveal signs of empathic understanding. These include coalition formation, the offering of protection and comfort to others, retrieving and 'babysitting' calves, aiding individuals that would otherwise have difficulty in moving, and removing foreign objects attached to others. These records demonstrate that an elephant is capable of diagnosing animacy and (...) goal directedness, and is able to understand the physical competence, emotional state and intentions of others, when they differ from its own. We argue that an empathic understanding of others is the simplest explanation of these abilities, and discuss reasons why elephants appear to show empathy more than other non-primate species. (shrink)

Meat is a multi-billion-dollar industry that relies on people performing risky physical work inside meat-processing facilities over long shifts in close proximity. These workers are socially disempowered, and many are members of groups beset by historic and ongoing structural discrimination. The combination of working conditions and worker characteristics facilitate the spread of SARS-CoV-2, the virus that causes COVID-19. Workers have been expected to put their health and lives at risk during the pandemic because of government and industry pressures to keep (...) this “essential industry” producing. Numerous interventions can significantly reduce the risks to workers and their communities; however, the industry’s implementation has been sporadic and inconsistent. With a focus on the U.S. context, this paper offers an ethical framework for infection prevention and control recommendations grounded in public health values of health and safety, interdependence and solidarity, and health equity and justice, with particular attention to considerations of reciprocity, equitable burden sharing, harm reduction, and health promotion. Meat-processing workers are owed an approach that protects their health relative to the risks of harms to them, their families, and their communities. Sacrifices from businesses benefitting financially from essential industry status are ethically warranted and should acknowledge the risks assumed by workers in the context of existing structural inequities. (shrink)

© 2015 Baum et al.; licensee BioMed Central. Background: Malaria is a public health problem in parts of Thailand, where Plasmodium falciparum and Plasmodium vivax are the main causes of infection. In the northwestern border province of Tak parasite prevalence is now estimated to be less than 1% by microscopy. Nonetheless, microscopy is insensitive at low-level parasitaemia. The objective of this study was to assess the current epidemiology of falciparum and vivax malaria in Tak using molecular methods to detect exposure (...) to and infection with parasites; in particular, the prevalence of asymptomatic infections and infections with submicroscopic parasite levels. Methods: Three-hundred microlitres of whole blood from finger-prick were collected into capillary tubes from residents of a sentinel village and from patients at a malaria clinic. Pelleted cellular fractions were screened by quantitative PCR to determine parasite prevalence, while plasma was probed on a protein microarray displaying hundreds of P. falciparum and P. vivax proteins to obtain antibody response profiles in those individuals. Results: Of 219 samples from the village, qPCR detected 25 Plasmodium sp. infections, of which 92% were asymptomatic and 100% were submicroscopic. Of 61 samples from the clinic patients, 27 were positive by qPCR, of which 25.9% had submicroscopic parasite levels. Cryptic mixed infections, misdiagnosed as single-species infections by microscopy, were found in 7 malaria patients. All sample donors, parasitaemic and non-parasitaemic alike, had serological evidence of parasite exposure, with 100% seropositivity to at least 54 antigens. Antigens significantly associated with asymptomatic infections were P. falciparum MSP2, DnaJ protein, putative E1E2 ATPase, and three others. Conclusion: These findings suggest that parasite prevalence is higher than currently estimated by local authorities based on the standard light microscopy. As transmission levels drop in Thailand, it may be necessary to employ higher throughput and sensitivity methods for parasite detection in the phase of malaria elimination. (shrink)

Adding small fractions of cholesterol decreases the interfacial viscosity of dipalmitoylphosphatidylcholine monolayers by an order of magnitude per wt %. Grazing incidence X-ray diffraction shows that cholesterol at these small fractions does not mix ideally with DPPC but rather induces nanophase separated structures of an ordered, primarily DPPC phase bordered by a line-active, disordered, mixed DPPC-cholesterol phase. We propose that the free area in the classic Cohen and Turnbull model of viscosity is inversely proportional to the number of molecules in (...) the coherence area, or product of the two coherence lengths. Cholesterol significantly reduces the coherence area of the crystals as well as the interfacial viscosity. Using this free area collapses the surface viscosity data for all surface pressures and cholesterol fractions to a universal logarithmic relation. The extent of molecular coherence appears to be a fundamental factor in determining surface viscosity in ordered monolayers. © 2014 American Chemical Society. (shrink)

In this consensus report by a diverse group of academics who conduct and/or are concerned about social and behavioral genomics (SBG) research, the authors recount the often‐ugly history of scientific attempts to understand the genetic contributions to human behaviors and social outcomes. They then describe what the current science—including genomewide association studies and polygenic indexes—can and cannot tell us, as well as its risks and potential benefits. They conclude with a discussion of responsible behavior in the context of SBG research. (...) SBG research that compares individuals within a group according to a “sensitive” phenotype requires extra attention to responsible conduct and to responsible communication about the research and its findings. SBG research (1) on sensitive phenotypes that (2) compares two or more groups defined by (a) race, (b) ethnicity, or (c) genetic ancestry (where genetic ancestry could easily be misunderstood as race or ethnicity) requires a compelling justification to be conducted, funded, or published. All authors agree that this justification at least requires a convincing argument that a study's design could yield scientifically valid results; some authors would additionally require the study to have a socially favorable risk‐benefit profile. (shrink)

The Hierarchical Taxonomy of Psychopathology (HiTOP) emerged to address critical shortcomings inherent to traditional psychiatric classification systems such as the Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases, notably their categorical structure, high comorbidity across categories, and within-diagnosis heterogeneity. HiTOP adopts an empirically derived, dimensional, and hierarchical approach, organizing psychopathological phenomena based on their patterns of observed covariation. This paper explores essential conceptual and philosophical considerations around HiTOP, examining its theoretical assumptions about dimensionality and hierarchy, the (...) nature and interpretation of latent variables, the notion of psychopathology, considerations around validity, and the role of epistemic and non-epistemic values in shaping scientific objectivity. HiTOP is a descriptive model based on quantitative evidence (such as taxometric and factor-analytic approaches), but it is also a nosological project that exists within a particular sociocultural and historical context. As an illustration of the role of values, the applicability of HiTOP to marginalized minority populations is discussed, highlighting ongoing efforts toward ensuring inclusivity and representational equity. By addressing these conceptual foundations, this paper lays groundwork essential for future philosophical inquiry, empirical research, and practical applications of the HiTOP framework. (shrink)

In cognitive science, there is a tacit norm that phenomena such as cultural variation or synaesthesia are worthy examples of cognitive diversity that contribute to a better understanding of cognition, but that other forms of cognitive diversity (e.g., autism, attention deficit hyperactivity disorder/ADHD, and dyslexia) are primarily interesting only as examples of deficit, dysfunction, or impairment. This status quo is dehumanizing and holds back much-needed research. In contrast, the neurodiversity paradigm argues that such experiences are not necessarily deficits but rather (...) are natural reflections of biodiversity. Here, we propose that neurodiversity is an important topic for future research in cognitive science. We discuss why cognitive science has thus far failed to engage with neurodiversity, why this gap presents both ethical and scientific challenges for the field, and, crucially, why cognitive science will produce better theories of human cognition if the field engages with neurodiversity in the same way that it values other forms of cognitive diversity. Doing so will not only empower marginalized researchers but will also present an opportunity for cognitive science to benefit from the unique contributions of neurodivergent researchers and communities. (shrink)

The Lee, Oehme and Yang (LOY) theory of time evolution in two state subspace of states of the complete system is discussed. Some inconsistencies in the assumptions and approximations used in the standard derivation of the LOY effective Hamiltonian, HLOY, governing this time evolution are found. Eliminating these inconsistencies and using the LOY method, approximate formulae for the effective Hamiltonian, H||, governing the time evolution in this subspace (improving those obtained by LOY) are derived. It is found, in contradistinction to (...) the standard LOY result, that in the case of neutral kaons (〈K 0 |H|||K 0 〉−〈¯K 0 |H|||¯K 0 〉), cannot take the zero value if the total system the preserves CPT-symmetry. Within the use of the method mentioned above formulae for H|| acting in the three state (three dimensional) subspace of states are also found. (shrink)

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

© 2015 Elsevier Ireland Ltd.The fornix is the primary subcortical output fiber system of the hippocampal formation. In children with 22q11.2 deletion syndrome, hippocampal volume reduction has been commonly reported, but few studies as yet have evaluated the integrity of the fornix. Therefore, we investigated the fornix of 45 school-aged children with 22q11.2DS and 38 matched typically developing children. Probabilistic diffusion tensor imaging tractography was used to reconstruct the body of the fornix in each child[U+05F3]s brain native space. Compared with (...) children, significantly lower fractional anisotropy and higher radial diffusivity was observed bilaterally in the body of the fornix in children with 22q11.2DS. Irregularities were especially prominent in the posterior aspect of the fornix where it emerges from the hippocampus. Smaller volumes of the hippocampal formations were also found in the 22q11.2DS group. The reduced hippocampal volumes were correlated with lower fornix FA and higher fornix RD in the right hemisphere. Our findings provide neuroanatomical evidence of disrupted hippocampal connectivity in children with 22q11.2DS, which may help to further understand the biological basis of spatial impairments, affective regulation, and other factors related to the ultra-high risk for schizophrenia in this population. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

BABAR, the detector for the SLAC PEP-II asymmetric e+e- B Factory operating at the γ resonance, was designed to allow comprehensive studies of CP-violation in B-meson decays. Charged particle tracks are measured in a multi-layer silicon vertex tracker surrounded by a cylindrical wire drift chamber. Electromagnetic showers from electrons and photons are detected in an array of CsI crystals located just inside the solenoidal coil of a superconducting magnet. Muons and neutral hadrons are identified by arrays of resistive plate chambers (...) inserted into gaps in the steel flux return of the magnet. Charged hadrons are identified by dE/dx measurements in the tracking detectors and by a ring-imaging Cherenkov detector surrounding the drift chamber. The trigger, data acquisition and data-monitoring systems, VME- and network-based, are controlled by custom-designed online software. Details of the layout and performance of the detector components and their associated electronics and software are presented. © 2002 Elsevier Science B.V. All rights reserved. (shrink)

OBJECTIVE: To evaluate the association of nicotinic acetylcholine receptor single nucleotide polymorphism with 7-day point prevalence abstinence in randomized clinical trials of smoking cessation therapies in individuals grouped by pharmacotherapy randomization to inform the development of personalized smoking cessation therapy. MATERIALS AND METHODS: We quantified association of four SNPs at three nAChRs with abstinence in eight randomized clinical trials. Participants were 2633 outpatient treatment-seeking, self-identified European ancestry individuals smoking at least 10 cigarettes/day, recruited through advertisement, prescribed pharmacotherapy, and provided with (...) behavioral therapy. Interventions included nicotine replacement therapy, bupropion, varenicline, placebo, or combined NRT and bupropion, and five modes of group and individual behavioral therapy. Outcome measures tested in multivariate logistic regression were end of treatment and 6 month abstinence, with demographic, behavioral, and genetic covariates. RESULTS: 'Risk' alleles previously associated with smoking heaviness were significantly associated with reduced abstinence in the PLA pharmacotherapy group at 6MO [for rs588765, odds ratio 0.41 ], and at end of treatment and at 6MO [for rs1051730, 0.42 and 0.31 ], and with increased abstinence in the NRT PG at 6MO [for rs588765, 2.07 and for rs1051730, 2.54 ]. We observed significant heterogeneity in rs1051730 effects between PGs. CONCLUSION: chr15q25.1 nAChR SNP risk alleles for smoking heaviness significantly increase relapse with PLA treatment and significantly increase abstinence with NRT. These SNP-PG associations require replication in independent samples for validation, and testing in larger sample sizes to evaluate whether similar effects occur in other PGs. © 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins. (shrink)

© 2017 The Author. Published by S. Karger AG, Basel.Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer, first-line treatment is (...) modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide. RECIST v.1.1 tumor progression on both RRx-001 and cisplatin/etoposide was accompanied by central necrosis in several of the enlarged lymph nodes and hepatic metastases, which may have been evidence of pseudoprogression, accounting for her ongoing longer-than-expected survival, since the necrotic tissue may have primed the activity of the PD-1 inhibitor. The lack of response to RRx-001 is hypothesized to have correlated with sparse tumor macrophage infiltration, seen on pre- and post-treatment biopsies, since the mechanism of action of RRx-001 relates to stimulation of tumor-associated macrophages. (shrink)

Exaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α 9β 1on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermine N 1-acetyltransferase in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking (...) integrin α 9β 1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α 9β 1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α 9β 1 or treated with integrin α 9β 1-blocking antibodies. Enhancement of SSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α 9β 1. Therefore, integrin α 9β 1 appears to serve as a brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for asthma. (shrink)

This book provides practical and research-based chapters that offer greater clarity about the particular kinds of teacher reflection that matter and avoids talking about teacher reflection generically, which implies that all kinds of reflection are of equal value.

High-spin states have been studied in Pr-135(59), populated through the Cd-116(Na-23,4n) reaction at 115 MeV, using the Gammasphere gamma-ray spectrometer. The negative-parity yrast band has been significantly extended to spin similar to 45 (h) over bar and excitation energy 21.5 MeV, showing evidence for several rotational alignments. The positive-parity yrast band of Ce-135(58), populated through the p4n channel of this reaction, was also populated to spin similar to 38 (h) over bar and excitation energy 18 MeV. Cranking calculations indicate that (...) these nuclei are soft with respect to the triaxiality parameter gamma and that several competing nuclear shapes occur at high spin. (shrink)