Isometry of medial collateral ligament reconstruction

The purpose of this study was to determine the femoral and tibial fixation sites that would result in the most isometric MCL reconstruction technique. Seven cadaveric knees were used in this study. A navigation system was utilized to determine graft isometry continuously from 0º to 90º. Five points on the medial side of the femur and four on the tibia were tested. A graft positioned in the center of the MCL femoral attachment (FC) and attached in the center of the superficial MCL attachment on the tibia led to the best isometry (2.7 ± 1.1 mm). Movement of the origin superiorly only 4 mm (FS) led to graft excursion of greater than 10 mm (P < 0.01). MCL reconstruction performed with the origin of the MCL within the femoral footprint and the insertion in tibial footprint of the superficial MCL results in the least graft excursion when the knee is cycled between 0º and 90º. Although the MCL often heals without surgical intervention, surgical reconstruction is occasionally in Grade III MCL and combined ligamentous injuries to the knee. This study demonstrates the optimal position of the MCL reconstruction to reproduce the kinematics of the native knee

Sequential analysis of global gene expression profiles in immature and in vitro matured bovine oocytes: potential molecular markers of oocyte maturation

Abstract Background Without intensive selection, the majority of bovine oocytes submitted to in vitro embryo production (IVP) fail to develop to the blastocyst stage. This is attributed partly to their maturation status and competences. Using the Affymetrix GeneChip Bovine Genome Array, global mRNA expression analysis of immature (GV) and in vitro matured (IVM) bovine oocytes was carried out to characterize the transcriptome of bovine oocytes and then use a variety of approaches to determine whether the observed transcriptional changes during IVM was real or an artifact of the techniques used during analysis. Results 8489 transcripts were detected across the two oocyte groups, of which ~25.0% (2117 transcripts) were differentially expressed (p < 0.001); corresponding to 589 over-expressed and 1528 under-expressed transcripts in the IVM oocytes compared to their immature counterparts. Over expression of transcripts by IVM oocytes is particularly interesting, therefore, a variety of approaches were employed to determine whether the observed transcriptional changes during IVM were real or an artifact of the techniques used during analysis, including the analysis of transcript abundance in oocytes in vitro matured in the presence of α-amanitin. Subsets of the differentially expressed genes were also validated by quantitative real-time PCR (qPCR) and the gene expression data was classified according to gene ontology and pathway enrichment. Numerous cell cycle linked (CDC2, CDK5, CDK8, HSPA2, MAPK14, TXNL4B), molecular transport (STX5, STX17, SEC22A, SEC22B), and differentiation (NACA) related genes were found to be among the several over-expressed transcripts in GV oocytes compared to the matured counterparts, while ANXA1, PLAU, STC1and LUM were among the over-expressed genes after oocyte maturation. Conclusion Using sequential experiments, we have shown and confirmed transcriptional changes during oocyte maturation. This dataset provides a unique reference resource for studies concerned with the molecular mechanisms controlling oocyte meiotic maturation in cattle, addresses the existing conflicting issue of transcription during meiotic maturation and contributes to the global goal of improving assisted reproductive technology

Evaluating the Influence of Epidemiological Parameters and Host Ecology on the Spread of Phocine Distemper Virus through Populations of Harbour Seals

Catriona Harris was supported by a grant from the UK Natural Environment Research Council. The funders had no role in study design, data collections and analysis, decision to publish, or preparation of the manuscript.Background: Outbreaks of phocine distemper virus (PDV) in Europe during 1988 and 2002 were responsible for the death of around 23,000 and 30,000 harbour seals, respectively. These epidemics, particularly the one in 2002, provided an unusual opportunity to estimate epidemic parameters for a wildlife disease. There were marked regional differences in the values of some parameters both within and between epidemics. Methodology and Principal Findings: We used an individual-based model of seal movement that allowed us to incorporate realistic representations of space, time and animal behaviour into a traditional epidemiological modelling framework. We explored the potential influence of a range of ecological (foraging trip duration, time of epidemic onset, population size) and epidemiological (length of infectious period, contact rate between infectious and susceptible individuals, case mortality) parameters on four readily-measurable epidemic characteristics (number of dead individuals, duration of epidemic, peak mortality date and prevalence) and on the probability that an epidemic would occur in a particular region. We analysed the outputs as if they were the results of a series of virtual experiments, using Generalised Linear Modelling. All six variables had a significant effect on the probability that an epidemic would be recognised as an unusual mortality event by human observers. Conclusions: Regional and temporal variation in contact rate was the most likely cause of the observed differences between the two epidemics. This variation could be a consequence of differences in the way individuals divide their time between land and sea at different times of the year.Publisher PDFPeer reviewe

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

hSAGEing: An Improved SAGE-Based Software for Identification of Human Tissue-Specific or Common Tumor Markers and Suppressors

SAGE (serial analysis of gene expression) is a powerful method of analyzing gene expression for the entire transcriptome. There are currently many well-developed SAGE tools. However, the cross-comparison of different tissues is seldom addressed, thus limiting the identification of common- and tissue-specific tumor markers.To improve the SAGE mining methods, we propose a novel function for cross-tissue comparison of SAGE data by combining the mathematical set theory and logic with a unique “multi-pool method” that analyzes multiple pools of pair-wise case controls individually. When all the settings are in “inclusion”, the common SAGE tag sequences are mined. When one tissue type is in “inclusion” and the other types of tissues are not in “inclusion”, the selected tissue-specific SAGE tag sequences are generated. They are displayed in tags-per-million (TPM) and fold values, as well as visually displayed in four kinds of scales in a color gradient pattern. In the fold visualization display, the top scores of the SAGE tag sequences are provided, along with cluster plots. A user-defined matrix file is designed for cross-tissue comparison by selecting libraries from publically available databases or user-defined libraries

Spatial Variation in Foraging Behaviour of a Marine Top Predator (Phoca vitulina) Determined by a Large-Scale Satellite Tagging Program

The harbour seal (Phoca vitulina) is a widespread marine predator in Northern Hemisphere waters. British populations have been subject to rapid declines in recent years. Food supply or inter-specific competition may be implicated but basic ecological data are lacking and there are few studies of harbour seal foraging distribution and habits. In this study, satellite tagging conducted at the major seal haul outs around the British Isles showed both that seal movements were highly variable among individuals and that foraging strategy appears to be specialized within particular regions. We investigated whether these apparent differences could be explained by individual level factors: by modelling measures of trip duration and distance travelled as a function of size, sex and body condition. However, these were not found to be good predictors of foraging trip duration or distance, which instead was best predicted by tagging region, time of year and inter-trip duration. Therefore, we propose that local habitat conditions and the constraints they impose are the major determinants of foraging movements. Specifically the distance to profitable feeding grounds from suitable haul-out locations may dictate foraging strategy and behaviour. Accounting for proximity to productive foraging resources is likely to be an important component of understanding population processes. Despite more extensive offshore movements than expected, there was also marked fidelity to the local haul-out region with limited connectivity between study regions. These empirical observations of regional exchange at short time scales demonstrates the value of large scale electronic tagging programs for robust characterization of at-sea foraging behaviour at a wide spatial scale

Implementing glucose control in intensive care: a multicenter trial using statistical process control

Glucose control (GC) with insulin decreases morbidity and mortality of critically ill patients. In this study we investigated GC performance over time during implementation of GC strategies within three intensive care units (ICUs) and in routine clinical practice. All adult critically ill patients who stayed for >24 h between 1999 and 2007 were included. Effects of implementing local GC guidelines and guideline revisions on effectiveness/efficiency-related indicators, safety-related indicators, and protocol-related indicators were measured. Data of 17,111 patient admissions were evaluated, with 714,141 available blood glucose levels (BGL) measurements. Mean BGL, time to reach target, hyperglycemia index, sampling frequency, percentage of hyperglycemia events, and in-range measurements statistically changed after introducing GC in all ICUs. The introduction of simple rules on GC had the largest effect. Subsequent changes in the protocol had a smaller effect than the introduction of the protocol itself. As soon as the protocol was introduced, in all ICUs the percentage of hypoglycemia events increased. Various revisions were implemented to reduce hypoglycemia events, but levels never returned to those from pre-implementation. More intensive implementation strategies including the use of a decision support system resulted in better control of the process. There are various strategies to achieve GC in routine clinical practice but with variable success. All of them were associated with an increase in hypoglycemia events, but GC was never stopped. Instead, these events have been accepted and managed. Statistical process control is a useful tool for monitoring phenomena over time and captures within-institution change

Composite pheochromocytoma of the adrenal gland: a case series

Background: Composite pheochromocytoma is a rare pathological condition characterized by elements of both pheochromocytoma and neurogenic tumors. However, detailed clinical outcomes of this tumor have not been fully shown. From 2007 to 2013, we experienced three cases of adrenal composite pheochromocytoma. In this report, we investigate the clinicopathological features of these three cases of composite pheochromocytoma and compare them with previously reported cases. Case presentations: Cases 1 and 2 were a 29-year-old Japanese woman and a 59-year-old Japanese man, respectively. They underwent laparoscopic left adrenalectomy, and pathological examination revealed composite pheochromocytoma-ganglioneuroma. Case 3 was a 53-year-old Japanese man who had been receiving hemodialysis for 17 years. He underwent laparoscopic right adrenalectomy, and pathological examination revealed composite pheochromocytoma-ganglioneuroblastoma. Although the Ki67-positive rates varied from 1.0 to 6.2% among the three cases, no clinical recurrences occurred. Despite the relatively high rate of Ki67 positivity, complete tumor resection resulted in favorable clinical outcomes. Conclusion: We experienced three cases of adrenal composite pheochromocytoma. Although the clinical findings and treatment outcomes of composite pheochromocytoma were similar to those of ordinary pheochromocytoma, further studies of the biological behavior and genetic profiles of composite pheochromocytoma are necessary to achieve a better understanding of this tumor