986 research outputs found
Persistent Chlamydophila pneumoniae infection in thoracic aortic aneurysm and aortic dissection?
Normal calcium-activated anion secretion in a mouse selectively lacking TMEM16A in intestinal epithelium
Calcium-activated anion secretion is expected to ameliorate cystic fibrosis, a genetic disease that carries an anion secretory defect in exocrine tissues. Human patients and animal models of the disease that present a mild intestinal phenotype have been postulated to bear a compensatory calcium-activated anion secretion in the intestine. TMEM16A is calcium-activated anion channel whose presence in the intestinal epithelium is contradictory. We aim to test the functional expression of TMEM16A using animal models with Cftr and/or Tmem16a intestinal silencing. Expression of TMEM16A was studied in a wild type and intestinal Tmem16a knockout mice by mRNA-seq, mass-spectrometry, q-PCR, Western blotting and immunolocalization. Calcium-activated anion secretion was recorded in the ileum and proximal colon of these animals including intestinal Cftr knockout and double mutants with dual Tmem16a and Cftr intestinal ablation. Mucus homeostasis was studied by immune-analysis of Mucin-2 (Muc2) and survival curves were recorded. Tmem16a transcript was found in intestine. Nevertheless, protein was barely detected in colon samples. Electrophysiological measurements demonstrated that the intestinal deletion of Tmem16a did not change calcium-activated anion secretion induced by carbachol or ATP in ileum and proximal colon. Muc2 architecture was not altered by Tmem16a silencing as was observed when Cftr was deleted from mouse intestine. Tmem16a silencing neither affected animal survival nor modified the lethality observed in the intestinal Cftr-null mouse. Our results demonstrate that TMEM16A function in the murine intestine is not related to electrogenic calcium-activated anion transport and does not affect mucus homeostasis and survival of animals
The transition to parenthood following a history of childhood maltreatment: a review of the literature on prospective and new parents' experiences
Background: Becoming a parent is viewed as one of the most important transitions in one’s life. However, a history of childhood maltreatment may affect the adjustment to parenthood. Objective: The objective of this review was to synthesize the current evidence base to further our understanding of prospective and new parents’ experiences in the transition to parenthood (pregnancy to 2 years post-birth), in the context of having a childhood maltreatment history. Method: A scoping review of the literature was conducted using the following online databases: PubMed, PsycINFO, PsycNET, and Published International Literature of Traumatic Stress. Results: The findings were synthesized into a four-component theoretical framework, which included mental health of the parent, physical changes, parental view of the child, and view of the self as a parent. A total of 69 papers, including 181,537 participants (of whom 30,482 mothers and 235 fathers had maltreatment histories), investigated the transition to parenthood. The majority of the studies showed that parents with a maltreatment history may suffer from a range of mental health problems during the transition to parenthood, experience more negative physical changes, and have more negative views of their child (or children). However, they reported both positive and negative experiences regarding their identity as a parent. Conclusions: The findings suggest that maltreatment is a risk factor for a more challenging transition to parenthood. Experiences of fathers with maltreatment histories merit more attention, as do those of parents in low- and middle-income countries. Future directions should include predictors of positive experiences and the development of early interventions to improve outcomes for this population
Biological invasions, ecological resilience and adaptive governance
In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience-based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services
Organizational Culture and Physician Satisfaction with Dimensions of Group Practice
To assess the extent to which the organizational culture of physician group practices is associated with individual physician satisfaction with the managerial and organizational capabilities of the groups. Study Design and Methods . Physician surveys from 1997 to 1998 assessing the culture of their medical groups and their satisfaction with six aspects of group practice. Organizational culture was conceptualized using the Competing Values framework, yielding four distinct cultural types. Physician-level data were aggregated to the group level to attain measures of organizational culture. Using hierarchical linear modeling, individual physician satisfaction with six dimensions of group practice was predicted using physician-level variables and group-level variables. Separate models for each of the four cultural types were estimated for each of the six satisfaction measures, yielding a total of 24 models. Sample Studied . Fifty-two medical groups affiliated with 12 integrated health systems from across the U.S., involving 1,593 physician respondents (38.3 percent response rate). Larger medical groups and multispecialty groups were over-represented compared with the U.S. as a whole. Principal Findings . Our models explain up to 31 percent of the variance in individual physician satisfaction with group practice, with individual organizational culture scales explaining up to 5 percent of the variance. Group-level predictors: group (i.e., participatory) culture was positively associated with satisfaction with staff and human resources, technological sophistication, and price competition. Hierarchical (i.e., bureaucratic) culture was negatively associated with satisfaction with managerial decision making, practice level competitiveness, price competition, and financial capabilities. Rational (i.e., task-oriented) culture was negatively associated with satisfaction with staff and human resources, and price competition. Developmental (i.e., risk-taking) culture was not significantly associated with any of the satisfaction measures. In some of the models, being a single-specialty group (compared with a primary care group) and a group having a higher percent of male physicians were positively associated with satisfaction with financial capabilities. Physician-level predictors: individual physicians' ratings of organizational culture were significantly related to many of the satisfaction measures. In general, older physicians were more satisfied than younger physicians with many of the satisfaction measures. Male physicians were less satisfied with data capabilities. Primary care physicians (versus specialists) were less satisfied with price competition. Conclusion . Some dimensions of physician organizational culture are significantly associated with various aspects of individual physician satisfaction with group practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/1/j.1475-6773.2006.00648.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/2/HESR+648+Appendix+A.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/3/HESR+648+Appendix+C.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/4/HESR+648+Appendix+B.pd
Thermodynamic theory of epitaxial ferroelectric thin films with dense domain structures
A Landau-Ginsburg-Devonshire-type nonlinear phenomenological theory is
presented, which enables the thermodynamic description of dense laminar
polydomain states in epitaxial ferroelectric thin films. The theory explicitly
takes into account the mechanical substrate effect on the polarizations and
lattice strains in dissimilar elastic domains (twins). Numerical calculations
are performed for PbTiO3 and BaTiO3 films grown on (001)-oriented cubic
substrates. The "misfit strain-temperature" phase diagrams are developed for
these films, showing stability ranges of various possible polydomain and
single-domain states. Three types of polarization instabilities are revealed
for polydomain epitaxial ferroelectric films, which may lead to the formation
of new polydomain states forbidden in bulk crystals. The total dielectric and
piezoelectric small-signal responses of polydomain films are calculated,
resulting from both the volume and domain-wall contributions. For BaTiO3 films,
strong dielectric anomalies are predicted at room temperature near special
values of the misfit strain.Comment: 19 pages, 8 figure
Overcoming Public Resistance to Carbon Taxes
Carbon taxes represent a cost-effective way to steer the economy toward a greener future. In the real world, their application has however been limited. In this paper, we address one of the main obstacles to carbon taxes: public opposition. We identify drivers of and barriers to public support, and, under the form of stylized facts, provide general lessons on the acceptability of carbon taxes. We derive our lessons from a growing literature, as well as from a combination of policy “failures” and “successes.” Based on our stylized facts, we formulate a set of suggestions concerning the design of carbon taxes. We consider the use of trial periods, tax escalators, environmental earmarking, lump-sum transfers, tax rebates, and advanced communication strategies, among others. This paper contributes to the policy debate about carbon taxes, hopefully leading to more success stories and fewer policy failures
Prediction of higher mortality reduction for the UK Breast Screening Frequency Trial: A model-based approach on screening intervals
Background: The optimal interval between two consecutive mammograms is uncertain. The UK Frequency Trial did not show a significant difference in breast cancer mortality between screening every year (study group) and screening every 3 years (control group). In this study, the trial is simulated in order to gain insight into the results of the trial and to predict the effect of different screening intervals on breast cancer mortality. Methods: UK incidence, life tables and information from the trial were used in the microsimulation model MISCAN-Fadia to simulate the trial and predict the number of breast ca
Low-lying level structure of Cu and its implications on the rp process
The low-lying energy levels of proton-rich Cu have been extracted
using in-beam -ray spectroscopy with the state-of-the-art -ray
tracking array GRETINA in conjunction with the S800 spectrograph at the
National Superconducting Cyclotron Laboratory at Michigan State University.
Excited states in Cu serve as resonances in the
Ni(p,)Cu reaction, which is a part of the rp-process in
type I x-ray bursts. To resolve existing ambiguities in the reaction Q-value, a
more localized IMME mass fit is used resulting in ~keV. We derive
the first experimentally-constrained thermonuclear reaction rate for
Ni(p,)Cu. We find that, with this new rate, the
rp-process may bypass the Ni waiting point via the Ni(p,)
reaction for typical x-ray burst conditions with a branching of up to
40. We also identify additional nuclear physics uncertainties that
need to be addressed before drawing final conclusions about the rp-process
reaction flow in the Ni region.Comment: 8 pages, accepted for Phys. Rev.
Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases
The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy
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