Community health center efficiency: The role of grant revenue in health center efficiency

Abstract: Objective: To test the relationship between external environments, organizational characteristics, and technical efficiency in federally qualified health centers (FQHCs). We tested the relationship between grant revenue and technical efficiency in FQHCs. Principal Findings: Increased grant revenues did not increase the probability that a health center would be on the efficiency frontier. However, increased grant revenues had a negative association with technical efficiency for health centers that were not fully efficient. Data Conclusion: If all health centers were operating efficiently, anywhere from 39 to 45 million patient encounters could have been delivered instead of the actual total of 29 million in 2007. Policy makers should consider tying grant revenues to performance indicators, and future work is needed to understand the mechanisms through which diseconomies of scale are present in FQHCs

Understanding acute metabolic decompensation in propionic and methylmalonic acidemias: A deep metabolic phenotyping approach

Background: Pathophysiology of life-threatening acute metabolic decompensations (AMD) in propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) is insufficiently understood. Here, we study the metabolomes of PA and MMA patients over time, to improve insight in which biochemical processes are at play during AMD. Methods: Longitudinal data from clinical chemistry analyses and metabolic assays over the life-course of 11 PA and 13 MMA patients were studied retrospectively. Direct-infusion high-resolution mass spectrometry was performed on 234 and 154 remnant dried blood spot and plasma samples of PA and MMA patients, respectively. In addition, a systematic literature search was performed on reported biomarkers. All results were integrated in an assessment of biochemical processes at play during AMD. Results: We confirmed many of the metabolite alterations reported in literature, including increases of plasma valine and isoleucine during AMD in PA patients. We revealed that plasma leucine and phenylalanine, and urinary pyruvic acid were increased during AMD in PA patients. 3-hydroxyisovaleric acid correlated positively with plasma ammonia. We found that known diagnostic biomarkers were not significantly further increased, while intermediates of the branched-chain amino acid (BCAA) degradation pathway were significantly increased during AMD. Conclusions: We revealed that during AMD in PA and MMA, BCAA and BCAA intermediates accumulate, while known diagnostic biomarkers remain essentially unaltered. This implies that these acidic BCAA intermediates are responsible for metabolic acidosis. Based on this, we suggest to measure plasma 3-hydroxyisovaleric acid and urinary ketones or 3-hydroxybutyric acid for the biochemical follow-up of a patient's metabolic stability

Bilateral posterior lamellar corneal transplant surgery in an infant of 17 weeks old: Surgical challenges and the added value of intraoperative optical coherence tomography

This study aimed to describe the surgical challenges, management, and value of intraoperative optical coherence tomography in a case of a bilateral Descemet Stripping Automated Endothelial Keratoplasty corneal transplantation at 17 weeks of age for the treatment of severe posterior polymorphous corneal dystrophy resulting from a de novo mutation of the OVOL2-gene

Structure-based prediction of anti-infective drug concentrations in the human lung epithelial lining fluid

Pharmacolog

On the importance of the heterogeneity assumption in the characterization of reservoir geomechanical properties

The geomechanical analysis of a highly compartmentalized reservoir is performed to simulate the seafloor subsidence due to gas production. The available observations over the hydrocarbon reservoir consist of bathymetric surveys carried out before and at the end of a 10-yr production life. The main goal is the calibration of the reservoir compressibility cM, that is, the main geomechanical parameter controlling the surface response. Two conceptual models are considered: in one (i) cM varies only with the depth and the vertical effective stress (heterogeneity due to lithostratigraphic variability); in another (ii) cM varies also in the horizontal plane, that is, it is spatially distributed within the reservoir stratigraphic units. The latter hypothesis accounts for a possible partitioning of the reservoir due to the presence of sealing faults and thrusts that suggests the idea of a block heterogeneous system with the number of reservoir blocks equal to the number of uncertain parameters. The method applied here relies on an ensemble-based data assimilation (DA) algorithm (i.e. the ensemble smoother, ES), which incorporates the information from the bathymetric measurements into the geomechanical model response to infer and reduce the uncertainty of the parameter cM. The outcome from conceptual model (i) indicates that DA is effective in reducing the cM uncertainty. However, the maximum settlement still remains underestimated, while the areal extent of the subsidence bowl is overestimated. We demonstrate that the selection of the heterogeneous conceptual model (ii) allows to reproduce much better the observations thus removing a clear bias of the model structure. DA allows significantly reducing the cM uncertainty in the five blocks (out of the seven) characterized by large volume and large pressure decline. Conversely, the assimilation of land displacements only partially constrains the prior cM uncertainty in the reservoir blocks marginally contributing to the cumulative seafloor subsidence, that is, blocks with low pressure

Increase in circulating Foxp3+CD4+CD25high regulatory T cells in nasopharyngeal carcinoma patients

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus-associated disease with high prevalence in Southern Chinese. Using multiparametric flow cytometry, we identified significant expansions of circulating naïve and memory CD4+CD25high T cells in 56 NPC patients compared with healthy age- and sex-matched controls. These were regulatory T cells (Treg), as they overexpressed Foxp3 and GITR, and demonstrated enhanced suppressive activities against autologous CD4+CD25− T-cell proliferation in functional studies on five patients. Abundant intraepithelial infiltrations of Treg with very high levels of Foxp3 expression and absence of CCR7 expression were also detected in five primary tumours. Our current study is the first to demonstrate an expansion of functional Treg in the circulation of NPC patients and the presence of infiltrating Treg in the tumour microenvironment. As Treg may play an important role in suppressing antitumour immunity, our findings provide critical insights for clinical management of NPC

A review of the use of blood and blood products in HIV-infected patients

Despite numerous publications on the appropriate use of blood and blood products, few specifically consider the role of transfusion in the management of HIV. This review is a synthesis of conditions encountered in the management of HIV-infected patients where the transfusion of blood or blood products may be indicated. A consistent message emerging from the review is that the principles of transfusion medicine do not differ between HIV-negative and -positive patients. The aim of the review is to provide clinicians witha practical and succinct overview of the haematological abnormalities and clinical circumstances most commonly encountered in the HIV setting, while focusing on the rational and appropriate use of blood and blood products forHIV patients. Important ethical considerations in dealing with both the collection and transfusion blood and blood products in the HIV era have also been addressed

The potential and limitations of intrahepatic cholangiocyte organoids to study inborn errors of metabolism

Inborn errors of metabolism (IEMs) comprise a diverse group of individually rare monogenic disorders that affect metabolic pathways. Mutations lead to enzymatic deficiency or dysfunction, which results in intermediate metabolite accumulation or deficit leading to disease phenotypes. Currently, treatment options for many IEMs are insufficient. Rarity of individual IEMs hampers therapy development and phenotypic and genetic heterogeneity suggest beneficial effects of personalized approaches. Recently, cultures of patient-own liver-derived intrahepatic cholangiocyte organoids (ICOs) have been established. Since most metabolic genes are expressed in the liver, patient-derived ICOs represent exciting possibilities for in vitro modeling and personalized drug testing for IEMs. However, the exact application range of ICOs remains unclear. To address this, we examined which metabolic pathways can be studied with ICOs and what the potential and limitations of patient-derived ICOs are to model metabolic functions. We present functional assays in patient ICOs with defects in branched-chain amino acid metabolism (methylmalonic acidemia), copper metabolism (Wilson disease), and transporter defects (cystic fibrosis). We discuss the broad range of functional assays that can be applied to ICOs, but also address the limitations of these patient-specific cell models. In doing so, we aim to guide the selection of the appropriate cell model for studies of a specific disease or metabolic process

DC-electric-field-induced and low-frequency electromodulation second-harmonic generation spectroscopy of Si(001)-SiO2_2 interfaces

The mechanism of DC-Electric-Field-Induced Second-Harmonic (EFISH) generation at weakly nonlinear buried Si(001)-SiO$_2$ interfaces is studied experimentally in planar Si(001)-SiO$_2$-Cr MOS structures by optical second-harmonic generation (SHG) spectroscopy with a tunable Ti:sapphire femtosecond laser. The spectral dependence of the EFISH contribution near the direct two-photon $E_1$ transition of silicon is extracted. A systematic phenomenological model of the EFISH phenomenon, including a detailed description of the space charge region (SCR) at the semiconductor-dielectric interface in accumulation, depletion, and inversion regimes, has been developed. The influence of surface quantization effects, interface states, charge traps in the oxide layer, doping concentration and oxide thickness on nonlocal screening of the DC-electric field and on breaking of inversion symmetry in the SCR is considered. The model describes EFISH generation in the SCR using a Green function formalism which takes into account all retardation and absorption effects of the fundamental and second harmonic (SH) waves, optical interference between field-dependent and field-independent contributions to the SH field and multiple reflection interference in the SiO$_2$ layer. Good agreement between the phenomenological model and our recent and new EFISH spectroscopic results is demonstrated. Finally, low-frequency electromodulated EFISH is demonstrated as a useful differential spectroscopic technique for studies of the Si-SiO$_2$ interface in silicon-based MOS structures.Comment: 31 pages, 14 figures, 1 table, figures are also available at http://kali.ilc.msu.su/articles/50/efish.ht

Automatic quantification of lymphocyte vacuolization in peripheral blood smears of patients with Batten's disease (CLN3 disease)

Quantifying lymphocyte vacuolization in peripheral blood smears (PBSs) serves as a measure for disease severity in CLN3 disease—a lysosomal storage disorder of childhood-onset. However, thus far quantification methods are based on labor-intensive manual assessment of PBSs. As machine learning techniques like convolutional neural networks (CNNs) have been deployed quite successfully in detecting pathological features in PBSs, we explored whether these techniques could be utilized to automate quantification of lymphocyte vacuolization. Here, we present and validate a deep learning pipeline that automates quantification of lymphocyte vacuolization. By using two CNNs in succession, trained for cytoplasm-segmentation and vacuolization-detection, respectively, we obtained an excellent correlation with manual quantification of lymphocyte vacuolization (r = 0.98, n = 40). These results show that CNNs can be utilized to automate the otherwise cumbersome task of manually quantifying lymphocyte vacuolization, thereby aiding prompt clinical decisions in relation to CLN3 disease, and potentially beyond