Are cost advantages from a modern Indian hospital transferable to the United States?

BACKGROUND: Multiple modern Indian hospitals operate at very low cost while meeting US-equivalent quality accreditation standards. Though US hospitals face intensifying pressure to lower their cost, including proposals to extend Medicare payment rates to all admissions, the transferability of Indian hospitals' cost advantages to US peers remains unclear. METHODS: Using time-driven activity-based costing methods, we estimate the average cost of personnel and space for an elective coronary artery bypass graft (CABG) surgery at two American hospitals and one Indian hospital (NH). All three hospitals are Joint Commission accredited and have reputations for use of modern performance management methods. Our case study applies several analytic steps to distinguish transferable from non-transferable sources of NH's cost savings. RESULTS: After removing non-transferable sources of efficiency, NH's residual cost advantage primarily rests on shifting tasks to less-credentialed and/or less-experienced personnel who are supervised by highly-skilled personnel when perceived risk of complications is low. NH's high annual CABG volume facilitates such supervised work "downshifting." The study is subject to limitations inherent in case studies, does not account for the younger age of NH's patients, or capture savings attributable to NH's negligible frequency of re-admission or post-acute care facility placement. CONCLUSIONS: Most transferable bases for a modern Indian hospital's cost advantage would require more flexible American states' hospital and health professional licensing regulations, greater family participation in inpatient care, and stronger support by hospital executives and clinicians for substantially lowering the cost of care via regionalization of complex surgeries and weekend use of costly operating rooms.

Number and location of drainage catheter side holes: in vitro evaluation.

AIM: To evaluate the influence of number and location of catheter shaft side holes regarding drainage efficiency in an in vitro model. MATERIALS AND METHODS: Three different drainage catheter models were constructed: open-ended model with no side holes (one catheter), unilateral side hole model (six catheters with one to six unilateral side holes), and bilateral side hole model (six catheters with one to six bilateral side holes). Catheters were inserted into a drainage output-measuring device with a constant-pressure reservoir of water. The volume of water evacuated by each of the catheters at 10-second intervals was measured. A total of five trials were performed for each catheter. Data were analysed using one-way analysis of variance. RESULTS: The open-ended catheter had a mean drainage volume comparable to the unilateral model catheters with three, four, and five side holes. Unilateral model catheters had significant drainage volume increases up to three side holes; unilateral model catheters with more than three side holes had no significant improvement in drainage volume. All bilateral model catheters had significantly higher mean drainage volumes than their unilateral counterparts. There was no significant difference between the mean drainage volume with one, two, or three pairs of bilateral side holes. Further, there was no drainage improvement by adding additional bilateral side holes. CONCLUSION: The present in vitro study suggests that beyond a critical side hole number threshold, adding more distal side holes does not improve catheter drainage efficiency. These results may be used to enhance catheter design towards improving their drainage efficiency.

Report into a discordant result at D16S539 between SGM Plus® and PowerPlex® ESI 16 kits in a criminal case sample and implications for the UK National DNA Database upgrade.

Upon re-testing of a DNA extract as part of a defence examination, a discordant result was observed at D16S539. Further STR testing and DNA sequencing of the sample identified the cause as a primer binding site mutation which was shown to be a previously unreported SNP. The testing results obtained in this case are considered in light of the current ongoing Multiplex Upgrade Project in the UK and the likely increase in discordant results that may be observed once different next generation kits are introduced.

The cognitive profile of essential tremor on the Repeatable Battery for the Assessment of Neuropsychological Status.

Objective: Essential tremor (ET), while defined by progressive motor symptoms, is increasingly associated with cognitive impairments (e.g. attention, memory, and executive functions). This study characterizes the cognitive profile of individuals with ET on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a commonly-used neuropsychological screening measure. Method: Seventy-seven individuals (mean age: 70.6, 34% female) diagnosed with ET and being considered for surgical/procedural intervention were recruited from a Movement Disorders Clinic. All participants completed the RBANS, Grooved Pegboard Test (GPB), and Fahn, Tolosa, Marin Tremor Scale (FTMTS) in the clinical evaluation of their tremor. Results: One-sample t-tests found Immediate Memory, Language, Attention, and Total Scale Index scores to be significantly lower than the expected population mean (p < .05). List Learning, Semantic Fluency, Coding, and List Recall subtests were significantly lower and Picture Naming was significantly higher than the expected population mean (p < .05). GPB scores were correlated with the Attention Index as well as List Learning and Coding subtests. FTMTS Severity was correlated with the Coding subtest and FTMTS Disability was correlated with the Figure Recall subtest. Conclusions: Results support prior literature indicating cognitive weaknesses in those with ET. Individuals with ET had poorer global cognitive abilities, with specific decrements in Immediate Memory, Attention, and Language. Notably, the Attention Index and Coding subtest were most affected by motor functioning. Cognitive screening measures, like the RBANS, can efficiently identify strengths and weaknesses in individuals with ET seeking surgical/procedural interventions.

Using cross-correlation for automated stitching of two-dimensional multi-tile electron backscatter diffraction data.

A method for automatically aligning consecutive data sets of large, two-dimensional multi-tile electron backscatter diffraction (EBSD) scans with high accuracy was developed. The method involved first locating grain and phase boundaries within search regions containing overlapping data in adjacent scan tiles, and subsequently using cross-correlation algorithms to determine the relative position of the individual scan tiles which maximizes the fraction of overlapping boundaries. Savitzky-Golay filtering in two dimensions was used to estimate the background, which was then subtracted from the cross-correlation to enhance the peak signal in samples with a high density of interfaces. The technique was demonstrated on data sets with a range of interface densities. The equations were implemented as enhancements to a recently published open source code for stitching of multi-tile EBSD data sets.

AnyStitch: a tool for combining electron backscatter diffraction data sets.

Recent advances in electron backscatter diffraction equipment and software have permitted increased data acquisition rates on the order of hundreds of points per second with additional increases in the foreseeable future likely. This increase in speed allows users to collect data from statistically significant areas of samples by combining beam-control scans and automated stage movements. To facilitate data analysis, however, the individual tiles must be combined, or stitched, into a single data set. In this paper, we describe a matlab(®) (The Mathworks, Inc., Natick, MA, USA) program to facilitate stitching of electron backscatter diffraction data. The method offers users a wide range of controls for tile placement including independent overlaps for horizontal and vertical tiles and also includes a parameter to account for systematic stage positioning errors or improperly calibrated scan rotation. The code can stitch data collected on either square or hexagonal grids and contains a function to reduce the resolution of square grid data if the resulting file is too large (or has too many grains) to be opened by the analysis software. The software was primarily written to work with TSL(®) OIM™ data sets and includes a function to quickly read compressed *.osc files into a variable in the matlab(®) workspace as opposed to using slower, text-reading functions. The output file is in *.ang format and can be opened directly by TSL(®) OIM™ Analysis software. A set of functions to facilitate stitching of text-based *.ctf files produced by Oxford Instruments HKL systems are also included. Finally, the code can also be used to combine *.tif images to produce a montage. The source code, a graphical user interface and a compiled version of the software was made available in the online version of this paper.

Evaluation of a custom QIAseq targeted DNA panel with 164 ancestry informative markers sequenced with the Illumina MiSeq.

Introduction of new methods requires meticulous evaluation before they can be applied to forensic genetic case work. Here, a custom QIAseq Targeted DNA panel with 164 ancestry informative markers was assessed using the MiSeq sequencing platform. Concordance, sensitivity, and the capability for analysis of mixtures were tested. The assay gave reproducible and nearly concordant results with an input of 10 and 2 ng DNA. Lower DNA input led to an increase in both locus and allele drop-outs, and a higher variation in heterozygote balance. Locus or allele drop-outs in the samples with less than 2 ng DNA input were not necessarily associated with the overall performance of a locus. Thus, the QIAseq assay will be difficult to implement in a forensic genetic setting where the sample material is often scarce and of poor quality. With equal or near equal mixture ratios, the mixture DNA profiles were easily identified by an increased number of imbalanced heterozygotes. For more skewed mixture ratios, the mixture DNA profiles were identified by an increased noise level. Lastly, individuals from Great Britain and the Middle East were investigated. The Middle Eastern individuals showed a greater affinity with South European populations compared to North European populations.

Perturbation of the T lymphocyte lineage in transgenic mice expressing a constitutive repressor of nuclear factor (NF)-kappaB.

Members of the nuclear factor (NF)-kappaB/Rel family transcription factors are induced during thymic selection and in mature T lymphocytes after ligation of the T cell antigen receptor (TCR). Despite these findings, disruption of individual NF-kappaB/Rel genes has revealed no intrinsic defect in the development of mature T cells, perhaps reflecting functional redundancy. To circumvent this possibility, the T cell lineage was targeted to express a trans-dominant form of IkappaBalpha that constitutively represses the activity of multiple NF-kappaB/Rel proteins. Transgenic cells expressing this inhibitor exhibit a significant proliferative defect, which is not reversed by the addition of exogenous interleukin-2. Moreover, mitogenic stimulation of splenocytes leads to increased apoptosis of transgenic T cells as compared with controls. In addition to deregulated T cell growth and survival, transgene expression impairs the development of normal T cell populations as evidenced by diminished numbers of TCRhi CD8 single-positive thymocytes. This defect was significantly amplified in the periphery and was accompanied by a decrease in CD4(+) T cells. Taken together, these in vivo findings indicate that the NF-kappaB/Rel signaling pathway contains compensatory components that are essential for the establishment of normal T cell subsets.

Bruton's tyrosine kinase is required for activation of IkappaB kinase and nuclear factor kappaB in response to B cell receptor engagement.

Mutations in the gene encoding Bruton's tyrosine kinase (btk) cause the B cell deficiency diseases X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. In vivo and in vitro studies indicate that the BTK protein is essential for B cell survival, cell cycle progression, and proliferation in response to B cell antigen receptor (BCR) stimulation. BCR stimulation leads to the activation of transcription factor nuclear factor (NF)-kappaB, which in turn regulates genes controlling B cell growth. We now demonstrate that a null mutation in btk known to cause the xid phenotype prevents BCR-induced activation of NF-kappaB. This defect can be rescued by reconstitution with wild-type BTK. This mutation also interferes with BCR-directed activation of IkappaB kinase (IKK), which normally targets the NF-kappaB inhibitor IkappaBalpha for degradation. Taken together, these findings indicate that BTK couples IKK and NF-kappaB to the BCR. Interference with this coupling mechanism may contribute to the B cell deficiencies observed in XLA and xid.

Human keratinocytes contain mRNA indistinguishable from monocyte interleukin 1 alpha and beta mRNA. Keratinocyte epidermal cell-derived thymocyte-activating factor is identical to interleukin 1.

Keratinocytes produce an IL-1 like factor termed epidermal cell-derived thymocyte-activating factor (ETAF). In this study, we show that ETAF and IL-1 are identical by the following criteria: Both normal and malignant human keratinocytes contain mRNAs identical to monocytic IL-1 alpha and IL-1 beta mRNA, as determined by an S1 nuclease protection assay; and IL-1 activity in medium conditioned by these cells can be neutralized by antibodies specific for human IL-1. The IL-1 alpha and IL-1 beta mRNAs can be identified in cultured human keratinocytes in the absence of identifiable stimulation; this basal level of mRNA can be further induced to accumulate with certain defined stimuli. Cultured normal human keratinocytes (HFKs) contain 2-4 times more IL-1 alpha than IL-1 beta mRNA; in contrast, human peripheral blood monocytes contain 10-20 times more IL-1 beta than IL-1 alpha mRNA. The IL-1 activity released by these HFK can be neutralized by an antibody that neutralizes both alpha and beta IL-1, but not by an antibody that neutralizes only IL-1 beta. While human monocytes produce a large excess of IL-1 beta after appropriate stimulation, these data suggest that IL-1 alpha is a major (and may be the predominant) form of IL-1 produced by human keratinocytes.

A Comparison of Forensic Age Prediction Models Using Data From Four DNA Methylation Technologies.

Individual age estimation can be applied to criminal, legal, and anthropological investigations. DNA methylation has been established as the biomarker of choice for age prediction, since it was observed that specific CpG positions in the genome show systematic changes during an individual's lifetime, with progressive increases or decreases in methylation levels. Subsequently, several forensic age prediction models have been reported, providing average age prediction error ranges of ±3-4 years, using a broad spectrum of technologies and underlying statistical analyses. DNA methylation assessment is not categorical but quantitative. Therefore, the detection platform used plays a pivotal role, since quantitative and semi-quantitative technologies could potentially result in differences in detected DNA methylation levels. In the present study, we analyzed as a shared sample pool, 84 blood-based DNA controls ranging from 18 to 99 years old using four different technologies: EpiTYPER®, pyrosequencing, MiSeq, and SNaPshotTM. The DNA methylation levels detected for CpG sites from ELOVL2, FHL2, and MIR29B2 with each system were compared. A restricted three CpG-site age prediction model was rebuilt for each system, as well as for a combination of technologies, based on previous training datasets, and age predictions were calculated accordingly for all the samples detected with the previous technologies. While the DNA methylation patterns and subsequent age predictions from EpiTYPER®, pyrosequencing, and MiSeq systems are largely comparable for the CpG sites studied, SNaPshotTM gives bigger differences reflected in higher predictive errors. However, these differences can be reduced by applying a z-score data transformation.

Body fluid identification and assignment to donors using a targeted mRNA massively parallel sequencing approach - results of a second EUROFORGEN / EDNAP collaborative exercise.

In a previous EUROFORGEN/EDNAP collaborative exercise, we tested two assays for targeted mRNA massively parallel sequencing for the identification of body fluids/tissues, optimized for the Illumina MiSeq/FGx and the Ion Torrent PGM/S5 platforms, respectively. The task of the second EUROFORGEN/EDNAP collaborative exercise was to analyze dried body fluid stains with two different multiplexes, the former Illumina 33plex mRNA panel for body fluid/tissue identification and a 35plex cSNP panel for assignment of body fluids/tissues to donors that was introduced in a proof-of-concept study recently. The coding region SNPs (cSNPs) are located within the body fluid specific mRNA transcripts and represent a direct link between the body fluid and the donor. We predicted the origin of the stains using a partial least squares discriminant analysis (PLS-DA) model, where most of the single source samples were correctly predicted. The mixed body fluid stains showed poorer results, however, at least one component was predicted correctly in most stains. The cSNP data demonstrated that coding region SNPs can give valuable information on linking body fluids/tissues with donors in mixed body fluid stains. However, due to the unfavorable performance of some cSNPs, the interpretation remains challenging. As a consequence, additional markers are needed to increase the discrimination power in each body fluid/tissue category.

NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway.

The eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) participates in many parts of the genetic program mediating T lymphocyte activation and growth. Nuclear expression of NF-kappa B occurs after its induced dissociation from its cytoplasmic inhibitor I kappa B alpha. Phorbol ester and tumor necrosis factor-alpha induction of nuclear NF-kappa B is associated with both the degradation of performed I kappa B alpha and the activation of I kappa B alpha gene expression. Transfection studies indicate that the I kappa B alpha gene is specifically induced by the 65-kilodalton transactivating subunit of NF-kappa B. Association of the newly synthesized I kappa B alpha with p65 restores intracellular inhibition of NF-kappa B DNA binding activity and prolongs the survival of this labile inhibitor. Together, these results show that NF-kappa B controls the expression of I kappa B alpha by means of an inducible autoregulatory pathway.

Kappa B-specific DNA binding proteins: role in the regulation of human interleukin-2 gene expression.

Transcriptional activation of the human interleukin-2 (IL-2) gene, like induction of the IL-2 receptor alpha (IL-2R alpha) gene and the type 1 human immunodeficiency virus (HIV-1), is shown to be modulated by a kappa B-like enhancer element. Mutation of a kappa B core sequence identified in the IL-2 promoter (-206 to -195) partially inhibits both mitogen- and HTLV-I Tax-mediated activation of this transcription unit and blocks the specific binding of two inducible cellular factors. These kappa B-specific proteins (80 to 90 and 50 to 55 kilodaltons) similarly interact with the functional kappa B enhancer present in the IL-2R alpha promoter. These data suggest that these kappa B-specific proteins have a role in the coordinate regulation of this growth factor-growth factor receptor gene system that controls T cell proliferation.

HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene.

Jurkat T cell lines constitutively expressing Tax, the 40-kilodalton transactivator protein of human T lymphotropic virus type I (HTLV-I), were used to investigate the mechanism by which this viral product deregulates the expression of the interleukin-2 receptor alpha gene (IL-2R alpha, Tac). Transfection of deleted forms of the IL-2R alpha promoter and in vitro DNA-binding studies revealed that a 12-base pair promoter segment, which has homology with the binding site for NF-kappa B, was required for Tax-induced activation of the IL-2R alpha promoter in vivo. An 18-base pair oligonucleotide containing this kappa B-like regulatory element proved sufficient to confer Tax inducibility upon a heterologous promoter. DNA affinity precipitation assays showed that Tax, like mitogenic stimuli, induced the expression of the 86-kilodalton cellular protein HIVEN86A, which specifically binds to the IL-2R alpha kappa B element in vitro. Furthermore, DNA/protein cross-linking studies revealed that several polypeptides interact with this sequence motif. Thus, the deregulation of IL-2R alpha gene expression encountered in HTLV-I leukemias appears to involve Tax activation of one or more cellular proteins that are normally induced by mitogens and that directly contribute to transcriptional activation of this receptor gene.

Development and validation of the EUROFORGEN NAME (North African and Middle Eastern) ancestry panel.

Inference of biogeographic origin is an important factor in clinical, population and forensic genetics. The information provided by AIMs (Ancestry Informative Markers) can allow the differentiation of major continental population groups, and several AIM panels have been developed for this purpose. However, from these major population groups, Eurasia covers a wide area between two continents that is difficult to differentiate genetically. These populations display a gradual genetic cline from West Europe to South Asia in terms of allele frequency distribution. Although differences have been reported between Europe and South Asia, Middle East populations continue to be a target of further investigations due to the lack of genetic variability, therefore hampering their genetic differentiation from neighboring populations. In the present study, a custom-built ancestry panel was developed to analyze North African and Middle Eastern populations, designated the 'NAME' panel. The NAME panel contains 111 SNPs that have patterns of allele frequency differentiation that can distinguish individuals originating in North Africa and the Middle East when combined with a previous set of 126 Global AIM-SNPs.

Diagnosis of fall risk in Parkinson disease: an analysis of individual and collective clinical balance test interpretation.

BACKGROUND AND PURPOSE: Parkinson disease (PD) results in an increased frequency of falls relative to the frequency in neurologically healthy people. The purpose of this study was to compare the accuracy of PD fall risk diagnosis based on one test with that based on the collective interpretation of multiple tests. PARTICIPANTS: Seventy people with PD (mean age=73.91 years) participated in this study. METHOD: Clinical balance tests were conducted during the initial examinations of people with PD. Validity indices were calculated for individual tests and compared with validity indices calculated for a combination of multiple tests. RESULTS: Thirty-six participants reported a fall history. Analysis of individual tests revealed broad variations in validity indices, whereas the collective interpretation of multiple tests improved sensitivity and negative likelihood ratios. DISCUSSION AND CONCLUSION: Collective interpretation of clinical balance tests resulted in fewer false-negative results and more substantial adjustments to the posttest probability of being a "faller" than the interpretation of one test alone. These results should be confirmed in a prospective examination of fall risk in PD.

Predictive coding in the visual cortex: a functional interpretation of some extra-classical receptive-field effects.

We describe a model of visual processing in which feedback connections from a higher- to a lower-order visual cortical area carry predictions of lower-level neural activities, whereas the feedforward connections carry the residual errors between the predictions and the actual lower-level activities. When exposed to natural images, a hierarchical network of model neurons implementing such a model developed simple-cell-like receptive fields. A subset of neurons responsible for carrying the residual errors showed endstopping and other extra-classical receptive-field effects. These results suggest that rather than being exclusively feedforward phenomena, nonclassical surround effects in the visual cortex may also result from cortico-cortical feedback as a consequence of the visual system using an efficient hierarchical strategy for encoding natural images.

In vitro evaluation of percutaneous drainage catheters: Flow related to connections and liquid characteristics.

PURPOSE: To evaluate the effect of catheter connections on drainage catheters' flow rate. MATERIALS AND METHOD: The in vitro model used commercially available catheters (8.5-F, 10.2-F, 12-F, and 14-F), connections - Luer-lok (2.33mm inner diameter), and stopcocks (1.33mm, 2.00mm, and 2.67mm inner diameters), water, ultrasound gel, textured vegetable protein (TVP) 2-mm particles, and collection bags. Plain water, viscous fluid (30% ultrasound gel solution in water), or water/viscous fluid with TVP were placed in collection bags and drained by gravity through each of the catheters and each connection. The flow rate was measured, recorded, and compared for each catheter and each connection as well as to the control flow rate of the catheters without connections. Ten one-minute trials were performed, and the mean flow rates were analyzed using Student t-test and Pearson correlation coefficient. RESULTS: Flow rate was significantly decreased in the 12-F and 14-F catheters with all stopcock and Luer-Lok connections with both water and viscous fluids. There was no significant reduction in flow for the 8.5-F and 10.2-F catheters with the 2.00-mm, 2.33-mm, and 2.67-mm connections; flow rate was significantly decreased in the 8.5-F and 10.2-F catheters with the 1.33-mm connection. A majority of trials with particulate fluid became occluded, and no consistent pattern between connections could be made. CONCLUSION: This in vitro study suggests that stopcock and Luer-Lok connections limit catheter flow rate when their inner diameter is less than that of the drainage catheter.

Gizzard Helminths in Female Northern Pintails ( Anas acuta) Wintering Along the Texas Coast.

Gizzard helminths were examined in 100 (50 adult, 50 juvenile) female northern pintails ( Anas acuta). Sixty-three individual helminths, representing 5 species ( Amidostomum acutum, Echinuria uncinata, Epomidiostomum uncinatum, Streptocara crassicauda, and Gastrotaenia cygni) were found. Twenty-seven northern pintails were infected with 1-3 helminth species and averaged 1.4 species. Overall, A. acutum and G. cygni were the most prevalent and abundant species (20%, n = 31 and 10%, n = 25, respectively), followed by S. crassicauda (5%, n = 5), E. uncinata (1%, n = 1), and E. uncinatum (1%, n = 1). Intensity of infection for A. acutum, E. uncinata, E. uncinatum, S. crassicauda, and G. cygni was 1.6 ± 0.3 [SE], 1.0 ± 0, 1.0 ± 0, 1.0 ± 0, and 2.5 ± 0.6, respectively. Our findings represent new information about gizzard helminth infections in northern pintails wintering along the Texas coast.