Cutting errors in total knee replacement: Assessment by computer assisted surgery

The observed errors in the position of the implanted prosthesis can be due to a number of potential causes. One of these is the potential error during execution of the bone cuts. However, there is only minimal information on this in the current literature. The amount of cutting errors in 40 consecutive total knee replacements was reported. All the operations were done by the same surgeon. The amount of cutting error was measured by the use of computer navigation system. It was hypothesized that there was no difference in the amount of error between bone cut through the cutting slot (slotted cutting) and bone cut done on the surface of the cutting guide (open cutting). It was found that the average absolute cutting error was 1° in the coronal plane and 1.4° in the sagittal plane. Significantly more outlier (more than 3°) was observed in the errors in the sagittal plane (P = 0.014, chi square test). Open cutting resulted in less error in the sagittal plane of the tibial cut when compared with slotted cutting (P = 0.031, Mann-Whitney U Test). This was attributed by the use of a thicker saw blade with higher stiffness in the open cutting method. © 2008 Springer-Verlag.postprin

A gene signature of loss of oestrogen receptor (ER) function and oxidative stress links ER-positive breast tumours with an absent progesterone receptor and a poor prognosis

Prognostic gene signatures like the wound and hypoxia signature differ by assumptions of cellular growth. Although gene signatures show little overlap, they also track within the group of luminal breast tumours those with a high proliferation and poor prognosis. Oxidative stress is another assumption of cellular growth. It affects several pathological conditions through its influence on the regulation of protein kinases and signal transduction pathways. A comprehensive set of 62 core genes from cultured oestrogen- and oestrogen receptor-deprived epithelial breast cancer cells is responsive to three forms of oxidative stress. Evidence is presented that oxidative stress involves the development of an aggressive subset of primary oestrogen receptor-positive breast tumours

Positivity of relative canonical bundles and applications

Given a family $f:\mathcal X \to S$ of canonically polarized manifolds, the unique K\"ahler-Einstein metrics on the fibers induce a hermitian metric on the relative canonical bundle $\mathcal K_{\mathcal X/S}$. We use a global elliptic equation to show that this metric is strictly positive on $\mathcal X$, unless the family is infinitesimally trivial. For degenerating families we show that the curvature form on the total space can be extended as a (semi-)positive closed current. By fiber integration it follows that the generalized Weil-Petersson form on the base possesses an extension as a positive current. We prove an extension theorem for hermitian line bundles, whose curvature forms have this property. This theorem can be applied to a determinant line bundle associated to the relative canonical bundle on the total space. As an application the quasi-projectivity of the moduli space $\mathcal M_{\text{can}}$ of canonically polarized varieties follows. The direct images $R^{n-p}f_*\Omega^p_{\mathcal X/S}(\mathcal K_{\mathcal X/S}^{\otimes m})$, $m > 0$, carry natural hermitian metrics. We prove an explicit formula for the curvature tensor of these direct images. We apply it to the morphisms $S^p \mathcal T_S \to R^pf_*\Lambda^p\mathcal T_{\mathcal X/S}$ that are induced by the Kodaira-Spencer map and obtain a differential geometric proof for hyperbolicity properties of $\mathcal M_{\text{can}}$.Comment: Supercedes arXiv:0808.3259v4 and arXiv:1002.4858v2. To appear in Invent. mat

Kahler-Ricci flow on stable Fano manifolds

We study the Kahler-Ricci flow on Fano manifolds. We show that if the curvature is bounded along the flow and if the manifold is K-polystable and asymptotically Chow semistable, then the flow converges exponentially fast to a Kahler-Einstein metric.Comment: 19 page

Significance of Metastatic Lymph Node Ratio on Stimulated Thyroglobulin Levels in Papillary Thyroid Carcinoma after Prophylactic Unilateral Central Neck Dissection

Background: Prognostic significance of metastatic central lymph node ratio (CLNR) in papillary thyroid carcinoma (PTC) remains unknown. Because postsurgical detectable stimulated thyroglobulin (DsTg) after radioiodine ablation may imply persistent or recurrent disease, we evaluated the association between CLNR and rate of DsTg in patients with PTC who underwent unilateral prophylactic central neck dissection. Methods: To be eligible for analysis, the prophylactic central neck dissection specimen had to contain ≥3 central lymph nodes (CLNs) with ≥1 harboring metastasis. Of 129 specimens, 51 (39.5%) were eligible. CLNR was calculated as follows: (number of metastatic CLNs/number of CLNs retrieved) × 100. They were categorized into group 1 (CLNR 66.67%) (n = 22). Postablation sTg level was measured 6 months after radioiodine ablation. A multivariate analysis was conducted to identify factors for postablation DsTg. Results: Young age, palpable neck swelling, large tumor size, advanced tumor, node, metastasis system (TNM) stage, and large number of metastatic CLNs were significantly associated with high CLNR (Ppublished_or_final_versionSpringer Open Choice, 21 Feb 201

Determining Peptide Partitioning Properties via Computer Simulation

The transfer of polypeptide segments into lipid bilayers to form transmembrane helices represents the crucial first step in cellular membrane protein folding and assembly. This process is driven by complex and poorly understood atomic interactions of peptides with the lipid bilayer environment. The lack of suitable experimental techniques that can resolve these processes both at atomic resolution and nanosecond timescales has spurred the development of computational techniques. In this review, we summarize the significant progress achieved in the last few years in elucidating the partitioning of peptides into lipid bilayer membranes using atomic detail molecular dynamics simulations. Indeed, partitioning simulations can now provide a wealth of structural and dynamic information. Furthermore, we show that peptide-induced bilayer distortions, insertion pathways, transfer free energies, and kinetic insertion barriers are now accurate enough to complement experiments. Further advances in simulation methods and force field parameter accuracy promise to turn molecular dynamics simulations into a powerful tool for investigating a wide range of membrane active peptide phenomena

Comparison of single versus fractionated dose of stereotactic radiotherapy for salvaging local failures of nasopharyngeal carcinoma: a matched-cohort analysis

BACKGROUND: Local failure is an important cause of morbidity and mortality in nasopharyngeal carcinoma (NPC). Although surgery or brachytherapy may be feasible in selected cases, most patients with local failure require external beam re-irradiation. Stereotactic radiation using single or multiple fractions have been employed in re-irradiation of NPC, but the optimal fractionation scheme and dose are not clear. METHODS: Records of 125 NPC patients who received salvage stereotactic radiation were reviewed. A matched-pair design was used to select patients with similar prognostic factors who received stereotactic re-irradiation using single fraction (SRS) or multiple fractions (SRM). Eighty-six patients were selected with equal number in SRS and SRM groups. All patients were individually matched for failure type (persistent or recurrent), rT stage (rT1-2 or rT3-4), and tumor volume (5-10 cc, or >10 cc). Median dose was 12.5 Gy in single fraction by SRS, and 34 Gy in 2-6 fractions by SRM. RESULTS: Local control rate was better in SRM group although overall survival rates were similar. One- and 3-year local failure-free rates were 70% and 51% in SRS group compared with 91% and 83% in SRM group (p = 0.003). One- and 3-year overall survival rates were 98% and 66% in SRS group compared with 78% and 61% in SRM group (p = 0.31). The differences in local control were mainly observed in recurrent or rT2-4 disease. Incidence of severe late complications was 33% in SRS group vs. 21% in SRM group, including brain necrosis (16% vs. 12%) and hemorrhage (5% vs. 2%). CONCLUSION: Our study showed that SRM was superior to SRS in salvaging local failures of NPC, especially in the treatment of recurrent and rT2-4 disease. In patient with local failure of NPC suitable for stereotactic re-irradiation, use of fractionated treatment is preferred.link_to_subscribed_fulltex

COVID-19 In Children Across Three Asian Cosmopolitan Regions

As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p < 0.001, respectively) and had more imported cases (87.5% vs. 16.5% vs. 0%, p < 0.001, respectively). The imported cases were also older (13.4 vs. 7.6 years, p < 0.001). More cases in HKSAR were asymptomatic compared to Korea and Wuhan (45.5% vs. 22.0% vs. 20.9%, p < 0.001, respectively), and significantly more patients from Wuhan developed fever (40.6% vs. 29.7% vs. 21.6%, p=0.003, respectively). There were significantly less imported cases than domestic cases developing fever after adjusting for age and region of origin (p = 0.046). 5.4% to 10.8% of patients reported anosmia and ageusia. None developed pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS). In general, adolescents were more likely to be asymptomatic and less likely to develop fever, but required longer hospital stays. In conclusion, majority patients in this pediatric Asian cohort had a mild disease. None developed PIMS-TS. Their clinical characteristics were influenced by travel history and age

Computational Analysis of Whole-Genome Differential Allelic Expression Data in Human

Allelic imbalance (AI) is a phenomenon where the two alleles of a given gene are expressed at different levels in a given cell, either because of epigenetic inactivation of one of the two alleles, or because of genetic variation in regulatory regions. Recently, Bing et al. have described the use of genotyping arrays to assay AI at a high resolution (∼750,000 SNPs across the autosomes). In this paper, we investigate computational approaches to analyze this data and identify genomic regions with AI in an unbiased and robust statistical manner. We propose two families of approaches: (i) a statistical approach based on z-score computations, and (ii) a family of machine learning approaches based on Hidden Markov Models. Each method is evaluated using previously published experimental data sets as well as with permutation testing. When applied to whole genome data from 53 HapMap samples, our approaches reveal that allelic imbalance is widespread (most expressed genes show evidence of AI in at least one of our 53 samples) and that most AI regions in a given individual are also found in at least a few other individuals. While many AI regions identified in the genome correspond to known protein-coding transcripts, others overlap with recently discovered long non-coding RNAs. We also observe that genomic regions with AI not only include complete transcripts with consistent differential expression levels, but also more complex patterns of allelic expression such as alternative promoters and alternative 3′ end. The approaches developed not only shed light on the incidence and mechanisms of allelic expression, but will also help towards mapping the genetic causes of allelic expression and identify cases where this variation may be linked to diseases

Excision Repair Cross-Complementation Group 1 (ERCC1) Status and Lung Cancer Outcomes: A Meta-Analysis of Published Studies and Recommendations

Despite discrepant results on clinical utility, several trials are already prospectively randomizing non-small cell lung cancer (NSCLC) patients by ERCC1 status. We aimed to characterize the prognostic and predictive effect of ERCC1 by systematic review and meta-analysis.Eligible studies assessed survival and/or chemotherapy response in NSCLC or SCLC by ERCC1 status. Effect measures of interest were hazard ratio (HR) for survival or relative risk (RR) for chemotherapy response. Random-effects meta-analyses were used to account for between-study heterogeneity, with unadjusted/adjusted effect estimates considered separately.23 eligible studies provided survival results in 2,726 patients. Substantial heterogeneity was observed in all meta-analyses (I(2) always >30%), partly due to variability in thresholds defining 'low' and 'high' ERCC1. Meta-analysis of unadjusted estimates showed high ERCC1 was associated with significantly worse overall survival in platinum-treated NSCLC (average unadjusted HR = 1.61, 95%CI:1.23-2.1, p = 0.014), but not in NSCLC untreated with chemotherapy (average unadjusted HR = 0.82, 95%CI:0.51-1.31). Meta-analysis of adjusted estimates was limited by variable choice of adjustment factors and potential publication bias (Egger's p<0.0001). There was evidence that high ERCC1 was associated with reduced response to platinum (average RR = 0.80; 95%CI:0.64-0.99). SCLC data were inadequate to draw firm conclusions.Current evidence suggests high ERCC1 may adversely influence survival and response in platinum-treated NSCLC patients, but not in non-platinum treated, although definitive evidence of a predictive influence is lacking. International consensus is urgently required to provide consistent, validated ERCC1 assessment methodology. ERCC1 assessment for treatment selection should currently be restricted to, and evaluated within, clinical trials