In Vitro Evaluation of Non-Protein Adsorbing Breast Cancer Theranostics Based on 19F-Polymer Containing Nanoparticles

Eight fluorinated nanoparticles (NPs) are synthesized, loaded with doxorubicin (DOX), and evaluated as theranostic delivery platforms to breast cancer cells. The multifunctional NPs are formed by self-assembly of either linear or star-shaped amphiphilic block copolymers, with fluorinated segments incorporated in the hydrophilic corona of the carrier. The sizes of the NPs confirm that small circular NPs are formed. The release kinetics data of the particles reveals clear hydrophobic core dependence, with longer sustained release from particles with larger hydrophobic cores, suggesting that the DOX release from these carriers can be tailored. Viability assays and flow cytometry evaluation of the ratios of apoptosis/necrosis indicate that the materials are non-toxic to breast cancer cells before DOX loading; however, they are very efficient, similar to free DOX, at killing cancer cells after drug encapsulation. Both flow cytometry and confocal microscopy confirm the cellular uptake of NPs and DOX-NPs into breast cancer cells, and in vitro 19F-MRI measurement shows that the fluorinated NPs have strong imaging signals, qualifying them as a potential in vivo contrast agent for 19F-MRI

Does the transcription factor AP-2β have an impact on the genetic and early environmental influence on ethanol consumption?

Genes involved in alcoholism have consensus sites for the transcription factor activator protein (TFAP) 2β. In the present study, we investigated TFAP-2β protein levels in the ethanol-preferring alko, alcohol (AA) and the ethanol-avoiding alko, non-alcohol (ANA) rat lines. Furthermore, basal and ethanol-induced TFAP-2β levels were examined in Wistar rats exposed to different early postnatal environments that are known to affect later ethanol consumption. Taken together, we found differences in brainstem TFAP-2β protein between the AA and ANA rats

Neuronal RARβ signaling modulates PTEN activity directly in neurons and via exosome transfer in astrocytes to prevent glial scar formation and induce spinal cord regeneration

Failure of axonal regeneration in the central nervous system (CNS) is mainly attributed to a lack of intrinsic neuronal growth programs and an inhibitory environment from a glial scar. Phosphatase and tensin homolog (PTEN) is a major negative regulator of neuronal regeneration and, as such, inhibiting its activity has been considered a therapeutic target for spinal cord (SC) injuries (SCIs). Using a novel model of rat cervical avulsion, we show that treatment with a retinoic acid receptor β (RARβ) agonist results in locomotor and sensory recovery. Axonal regeneration from the severed roots into the SC could be seen by biotinylated dextran amine labeling. Light micrographs of the dorsal root entry zone show the peripheral nervous system (PNS)–CNS transition of regrown axons. RARβ agonist treatment also resulted in the absence of scar formation. Mechanism studies revealed that, in RARβ-agonist-treated neurons, PTEN activity is decreased by cytoplasmic phosphorylation and increased secretion in exosomes. These are taken up by astrocytes, resulting in hampered proliferation and causing them to arrange in a normal-appearing scaffold around the regenerating axons. Attribution of the glial modulation to neuronal PTEN in exosomes was demonstrated by the use of an exosome inhibitor in vivo and PTEN siRNA in vitro assays. The dual effect of RARβ signaling, both neuronal and neuronal–glial, results in axonal regeneration into the SC after dorsal root neurotmesis. Targeting this pathway may open new avenues for the treatment of SCIs. SIGNIFICANCE STATEMENT Spinal cord injuries (SCIs) often result in permanent damage in the adult due to the very limited capacity of axonal regeneration. Intrinsic neuronal programs and the formation of a glial scar are the main obstacles. Here, we identify a single target, neuronal retinoic acid receptor β (RARβ), which modulates these two aspects of the postinjury physiological response. Activation of RARβ in the neuron inactivates phosphatase and tensin homolog and induces its transfer into the astrocytes in small vesicles, where it prevents scar formation. This may open new therapeutic avenues for SCIs

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

Payment for performance (P4P): any future in Italy?

<p>Abstract</p> <p>Background</p> <p>Pay for Performance (P4P) programs, based on provision of financial incentives for service quality, have been widely adopted to enhance quality of care and to promote a more efficient use of health care resources whilst improving patient outcomes. In Italy, as in other countries, the growing concern over the quality of health services provided and the scarcity of resources would make P4P programs a useful means of improving their performance. The aim of this paper is to evaluate whether it is possible to implement P4P programs in the Lombardy Region, in Italy, based on the existing data set.</p> <p>Methods</p> <p>Thirteen quality measures were identified regarding four clinical conditions (acute myocardial infarction (AMI), heart failure (HF), ischemic stroke and hip and knee replacement) on the basis of an international literature review. Data was collected using the database of three institutions, which included hospital discharge records (Scheda di Dimissione ospedaliera-SDO-) and letters of discharge. The study population was identified using both the Principal ICD-9-CM diagnosis codes and the discharge date. A Statistical Analysis System (SAS) program was used for the text analysis.</p> <p>Results</p> <p>It was possible to calculate almost all the parameters pertaining to the three hospitals as all the data required was available with the exception of inpatient mortality in two hospitals and smoking cessation advice/counseling in one hospital.</p> <p>Conclusions</p> <p>On the ground of this analysis, we believe that it is possible to implement a P4P program in the Lombardy Region. However, for this program to be initiated, all necessary data must be available in electronic format and uniformly collected. Moreover, several other factors must be assessed: which clinical conditions should be included, the threshold for each quality parameter, the amount of financial incentives offered and how they will be provided.</p

Design choices made by target users for a pay-for-performance program in primary care: an action research approach

Contains fulltext : 110832.pdf (publisher's version ) (Open Access)BACKGROUND: International interest in pay-for-performance (P4P) initiatives to improve quality of health care is growing. Current programs vary in the methods of performance measurement, appraisal and reimbursement. One may assume that involvement of health care professionals in the goal setting and methods of quality measurement and subsequent payment schemes may enhance their commitment to and motivation for P4P programs and therefore the impact of these programs. We developed a P4P program in which the target users were involved in decisions about the P4P methods. METHODS: For the development of the P4P program a framework was used which distinguished three main components: performance measurement, appraisal and reimbursement. Based on this framework design choices were discussed in two panels of target users using an adapted Delphi procedure. The target users were 65 general practices and two health insurance companies in the South of the Netherlands. RESULTS: Performance measurement was linked to the Dutch accreditation program based on three domains (clinical care, practice management and patient experience). The general practice was chosen as unit of assessment. Relative standards were set at the 25th percentile of group performance. The incentive for clinical care was set twice as high as the one for practice management and patient experience. Quality scores were to be calculated separately for all three domains, and for both the quality level and the improvement of performance. The incentive for quality level was set thrice as high as the one for the improvement of performance. For reimbursement, quality scores were divided into seven levels. A practice with a quality score in the lowest group was not supposed to receive a bonus. The additional payment grew proportionally for each extra group. The bonus aimed at was on average 5% to 10% of the practice income. CONCLUSIONS: Designing a P4P program for primary care with involvement of the target users gave us an insight into their motives, which can help others who need to discuss similar programs. The resulting program is in line with target users' views and assessments of relevance and applicability. This may enhance their commitment to the program as was indicated by the growing number of voluntary participants after a successfully performed field test during the procedure. The elements of our framework can be very helpful for others who are developing or evaluating a P4P program

The Effect of Performance-Based Financial Incentives on Improving Patient Care Experiences: A Statewide Evaluation

Patient experience measures are central to many pay-for-performance (P4P) programs nationally, but the effect of performance-based financial incentives on improving patient care experiences has not been assessed. The study uses Clinician &amp; Group CAHPS data from commercially insured adult patients (n = 124,021) who had visits with 1,444 primary care physicians from 25 California medical groups between 2003 and 2006. Medical directors were interviewed to assess the magnitude and nature of financial incentives directed at individual physicians and the patient experience improvement activities adopted by groups. Multilevel regression models were used to assess the relationship between performance change on patient care experience measures and medical group characteristics, financial incentives, and performance improvement activities. Over the course of the study period, physicians improved performance on the physician-patient communication (0.62 point annual increase, p &lt; 0.001), care coordination (0.48 point annual increase, p &lt; 0.001), and office staff interaction (0.22 point annual increase, p = 0.02) measures. Physicians with lower baseline performance on patient experience measures experienced larger improvements (p &lt; 0.001). Greater emphasis on clinical quality and patient experience criteria in individual physician incentive formulas was associated with larger improvements on the care coordination (p &lt; 0.01) and office staff interaction (p &lt; 0.01) measures. By contrast, greater emphasis on productivity and efficiency criteria was associated with declines in performance on the physician communication (p &lt; 0.01) and office staff interaction (p &lt; 0.001) composites. In the context of statewide measurement, reporting, and performance-based financial incentives, patient care experiences significantly improved. In order to promote patient-centered care in pay for performance and public reporting programs, the mechanisms by which program features influence performance improvement should be clarified

Superimposing Dynamic Range

We present a simple and cost-efficient way of extending contrast, perceived tonal resolution, and the color space of static hardcopy images, beyond the capabilities of hardcopy devices or low-dynamic range displays alone. A calibrated projector-camera system is applied for automatic registration, scanning and superimposition of hardcopies. We explain how high-dynamic range content can be split for linear devices with different capabilities, how luminance quantization can be optimized with respect to the non-linear response of the human visual system as well as for the discrete nature of the applied modulation devices; and how inverse tone-mapping can be adapted in case only untreated hardcopies and softcopies (such as regular photographs) are available. We believe that our approach has the potential to complement hardcopy-based technologies, such as X-ray prints for filmless imaging, in domains that operate with high quality static image content, like radiology and other medical fields, or astronomy

The Impact of Hydrogen Bonding on Amide 1H Chemical Shift Anisotropy Studied by Cross-Correlated Relaxation and Liquid Crystal NMR Spectroscopy

Site-specific (1)H chemical shift anisotropy (CSA) tensors have been derived for the well-ordered backbone amide moieties in the B3 domain of protein G (GB3). Experimental input data include residual chemical shift anisotropy (RCSA), measured in six mutants that align differently relative to the static magnetic field when dissolved in a liquid crystalline Pf1 suspension, and cross-correlated relaxation rates between the (1)H(N) CSA tensor and either the (1)H-(15)N, the (1)H-(13)C&#39;, or the (1)H-(13)C(alpha) dipolar interactions. Analyses with the assumption that the (1)H(N) CSA tensor is symmetric with respect to the peptide plane (three-parameter fit) or without this premise (five-parameter fit) yield very similar results, confirming the robustness of the experimental input data, and that, to a good approximation, one of the principal components orients orthogonal to the peptide plane. (1)H(N) CSA tensors are found to deviate strongly from axial symmetry, with the most shielded tensor component roughly parallel to the N-H vector, and the least shielded component orthogonal to the peptide plane. DFT calculations on pairs of N-methyl acetamide and acetamide in H-bonded geometries taken from the GB3 X-ray structure correlate with experimental data and indicate that H-bonding effects dominate variations in the (1)H(N) CSA. Using experimentally derived (1)H(N) CSA tensors, the optimal relaxation interference effect needed for narrowest (1)H(N) TROSY line widths is found at similar to 1200 MHz

Health and life insurance as an alternative to malpractice tort law

<p>Abstract</p> <p>Background</p> <p>Tort law has legitimate social purposes of deterrence, punishment and compensation, but medical tort law does none of these well. Tort law could be counterproductive in medicine, encouraging costly defensive practices that harm some patients, restricting access to care in some settings and discouraging innovation.</p> <p>Discussion</p> <p>Patients might be better served by purchasing combined health and life insurance policies and waiving their right to pursue malpractice claims. The combined policy should encourage the insurer to profit by inexpensively delaying policyholders' deaths. A health and life insurer would attempt to minimize mortal risks to policyholders from any cause, including medical mistakes and could therefore pursue systematic quality improvement efforts. If policyholders trust the insurer to seek, develop and reward genuinely effective care; identify, deter and remediate poor care; and compensate survivors through the no-fault process of paying life insurance benefits, then tort law is largely redundant and the right to sue may be waived. If expensive defensive medicine can be avoided, that savings alone could pay for fairly large life insurance policies.</p> <p>Summary</p> <p>Insurers are maligned largely because of their logical response to incentives that are misaligned with the interests of patients and physicians in the United States. Patient, provider and insurer incentives could be realigned by combining health and life insurance, allowing the insurer to use its considerable information access and analytic power to improve patient care. This arrangement would address the social goals of malpractice torts, so that policyholders could rationally waive their right to sue.</p