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Concept: Multivariate statistics


To re-analyse bicycle overtaking data collected by Walker (2007) with a view to assess factors associated with close passing (<1 m), to adjust for other observed factors in a multivariable analysis, and to assess the extent to which the sample size in the original analysis may have contributed to spurious results.

Concepts: Multivariate statistics, Automobile, Bicycle helmet


The study of how long-term changes affect metacommunities is a relevant topic, that involves the evaluation of connections among biological assemblages across different spatio-temporal scales, in order to fully understand links between global changes and macroevolutionary patterns. We applied multivariate statistical analyses and diversity tests using a large data matrix of rodent fossil sites in order to analyse long-term faunal changes. Late Miocene rodent faunas from southwestern Europe were classified into metacommunities, presumably sharing ecological affinities, which followed temporal and environmental non-random assembly and disassembly patterns. Metacommunity dynamics of these faunas were driven by environmental changes associated with temperature variability, but there was also some influence from the aridity shifts described for this region during the late Miocene. Additionally, while variations in the structure of rodent assemblages were directly influenced by global climatic changes in the southern province, the northern sites showed a pattern of climatic influence mediated by diversity-dependent processes.

Concepts: Statistics, Mathematics, Ecology, Multivariate statistics, Climate change, Europe, Pattern, Miocene


Background The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. Methods We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. Results Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). Conclusions Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; number, NCT01064284 ; EudraCT number, 2009-011186-88 .).

Concepts: Regression analysis, Epidemiology, Multivariate statistics, Von Willebrand factor, Von Willebrand disease, Factor VIII


Rapid evaporative ionization mass spectrometry (REIMS) is an emerging technique that allows near-real-time characterization of human tissue in vivo by analysis of the aerosol (“smoke”) released during electrosurgical dissection. The coupling of REIMS technology with electrosurgery for tissue diagnostics is known as the intelligent knife (iKnife). This study aimed to validate the technique by applying it to the analysis of fresh human tissue samples ex vivo and to demonstrate the translation to real-time use in vivo in a surgical environment. A variety of tissue samples from 302 patients were analyzed in the laboratory, resulting in 1624 cancerous and 1309 noncancerous database entries. The technology was then transferred to the operating theater, where the device was coupled to existing electrosurgical equipment to collect data during a total of 81 resections. Mass spectrometric data were analyzed using multivariate statistical methods, including principal components analysis (PCA) and linear discriminant analysis (LDA), and a spectral identification algorithm using a similar approach was implemented. The REIMS approach differentiated accurately between distinct histological and histopathological tissue types, with malignant tissues yielding chemical characteristics specific to their histopathological subtypes. Tissue identification via intraoperative REIMS matched the postoperative histological diagnosis in 100% (all 81) of the cases studied. The mass spectra reflected lipidomic profiles that varied between distinct histological tumor types and also between primary and metastatic tumors. Thus, in addition to real-time diagnostic information, the spectra provided additional information on divergent tumor biochemistry that may have mechanistic importance in cancer.

Concepts: Cancer, Oncology, Mass spectrometry, Histology, Multivariate statistics, Principal component analysis, Tissue, Linear discriminant analysis


Saffron is one of the oldest and most expensive spices, which is often target of fraudulent activities. In this research, a new strategy of saffron authentication based on metabolic fingerprinting was developed. In the first phase, a solid liquid extraction procedure was optimized, the main aim was to isolate as maximal representation of small molecules contained in saffron as possible. In the second step, a detection method based on liquid chromatography coupled with high-resolution mass spectrometry was developed. Initially, principal component analysis (PCA) revealed clear differences between saffron cultivated and packaged in Spain, protected designation of origin (PDO), and saffron packaged in Spain of unknown origin, labeled Spanish saffron. Afterwards, orthogonal partial least square discriminant analysis (OPLS-DA) was favorably used to discriminate between Spanish saffron. The tentative identification of markers showed glycerophospholipids and their oxidized lipids were significant markers according to their origin.

Concepts: Protein, Mass spectrometry, Multivariate statistics, Principal component analysis, Biochemistry, Tandem mass spectrometry, Linear discriminant analysis, The Unscrambler


Background  Patient preferences for psoriasis treatments can impact treatment satisfaction and adherence and may therefore influence clinical outcome. Objective  To assess the impact of treatment experience (satisfaction with current treatment, number of prior visits, disease duration, number of preceding therapies and currently prescribed treatment modalities) on treatment preferences. Methods  A computer-based conjoint analysis experiment was conducted to analyse preferences of patients with moderate or severe psoriasis (n = 163) treated at a German University Medical Center for outcome (probability, magnitude and duration of benefit; probability, severity and reversibility of side effects) and process attributes (location, frequency, duration, delivery method, individual cost) of psoriasis treatments. Relative importance scores (RIS) were calculated for each attribute and compared using anova, post hoc test and multivariate regression analysis. Results  Participants with longer disease duration attached significantly greater importance to duration of benefit (β = 0.206, P = 0.018), whereas participants on oral therapy were more concerned about magnitude of benefit by trend (β = 0.218, P = 0.058). Participants receiving injectables not only set higher value to probability of benefit (RIS = 32.80 vs. 21.89, P = 0.025) but also to treatment location (RIS = 44.74 vs. 23.03, P = 0.011), delivery method (RIS = 43.75 vs. 19.29, P = 0.019), treatment frequency (RIS = 31.24 vs. 16.89, P = 0.005) and duration (RIS = 32.54 vs. 16.57, P = 0.003) when compared with others. Treatment satisfaction was significantly higher in participants on infusions or injections compared with those on phototherapy and mere topical therapy. Conclusions  Treatment preferences may change over time course and with treatment experience. Participants on injectables attach great importance to efficiency and convenience of therapies, and are highly satisfied with their treatment.

Concepts: Regression analysis, Statistics, Therapy, Multivariate statistics, Psoriasis, Injection, Attribute, Attached


Introduction The analysis of predictive factors of response may aid in predicting which patients with advanced renal cell carcinoma (RCC) would be good candidates for systemic treatments. Materials and methods The expression of several biomarkers was retrospectively analyzed using immunohistochemistry (IHC), as well as 2 analytical variables in 135 patients with advanced RCC treated with cytokines (CK) and/or new targeted drugs (NTD). Results 67 patients were treated solely with NTD and 68 with CK (23 also received NTD). Univariate analysis: HIF1α did not correlate significantly with response to these drugs. Overexpression of CAIX was associated with more responses (%) to NTD (64.7 vs. 21.1; p = 0.004) and CK (22.6 vs. 0; p = 0.038). PTEN demonstrated predictive value of response to sunitinib (70.8 vs. 34.1; p = 0.005). p21 was associated with a lower response to sunitinib (35.9 vs. 65.4; p = 0.025). Thrombocytosis was not significantly associated with response to NTD, although it was with CK (0 vs. 20; p = 0.017). Neutrophilia correlated with a lower response to NTD (29.6 vs. 57.5; p = 0.045), although not with CK. Multivariate analysis: Overexpression of CAIX was an independent predictor of significantly higher response to NTD and CK; OR = 8.773 (p < 0.001). Conclusions Our findings highlight the usefulness of CAIX in selecting patients with advanced RCC as candidates for systemic treatment. PTEN and p21 may be important in predicting response to sunitinib. Thrombocytosis and neutrophilia correlate well with response to CK and NTD, respectively.

Concepts: Scientific method, Multivariate statistics, Univariate, Renal cell carcinoma


It has been suggested that second to fourth digit ratio (digit ratio) may correlate with male reproductive system function or disorders. This hypothesis is based on finding that the Hox genes control finger development and differentiation of the genital bud during embryogenesis. Thus, we investigated the association between digit ratio and adult testicular volume. A total of 172 Korean men (aged 20-69 years) hospitalized for urological surgery were prospectively enrolled. Patients with conditions known to strongly influence testicular volume were excluded. Before determining testicular volume, the lengths of the second and fourth digits of the right hand were measured by a single investigator using a digital vernier calliper. Using orchidometry, the testes were measured by an experienced urologist who had no information about the patient’s digit ratio. To identify the independent predictive factors influencing testicular volume, univariate and multivariate analyses were performed using linear regression models. Age, height, serum testosterone and free testosterone level were not correlated with testicular volume. Digit ratio, along with weight, was significantly correlated with testicular volume (right testicular volume: r = -0.185, p = 0.015; left testicular volume: r = -0.193, p = 0.011; total testicular volume: r = -0.198, p = 0.009). Multivariate analysis using linear regression models showed that only digit ratio was the independent factor to predict all (right, left and total) testicular volumes (right testicular volume: β = -0.174, p = 0.023; left testicular volume: β = -0.181, p = 0.017; total testicular volume: β = -0.185, p = 0.014). Our findings demonstrated that digit ratio is negatively associated with adult testicular volume. This means that men with a higher digit ratio may be more likely to have smaller testis compared to those with a lower digit ratio.

Concepts: Regression analysis, Linear regression, Multivariate statistics, Testosterone, Testicle, Sertoli cell, Puberty, French Revolution


PURPOSE: To describe the long-term cancer control and morbidity of high intensity focused ultrasound (HIFU) with neoadjuvant transurethral resection of the prostate (TURP), the risk of metastatic induction by TURP and the evolution of HIFU application and technology over time. PATIENTS AND METHODS: Prospective Harlaching HIFU database was searched for patients with primary localized PCa (T1-2, N0, M0, PSAi <50 ng/ml) and follow-up > 15 months; those with previous long-term ADT, locally advanced PCa, or any PSA-influencing therapy were excluded. All patients were treated completely by Ablatherm® HIFU device. Evaluation was performed in aggregate and by stratification according to cohort group, risk group (D'Amico criteria), PSA Nadir, and Gleason score. Phoenix definition was used for biochemical failure. Statistical analysis was performed using the Kaplan-Meier method, univariate and multivariate analysis employing a Cox model. RESULTS: Of 704 study patients, 78.5% had intermediate- or high-risk disease. Mean follow-up was 5.3 (1.3-14) years. Cancer-specific survival was 99%, metastasis-free survival 95%, and 10-year salvage treatment-free rates were 98% in low-risk, 72% in intermediate-risk, and 68% in high-risk patients. PSA Nadir and Gleason score predicted biochemical failure, side effects showed to be moderate. HIFU retreatment rate was 15% since 2005. CONCLUSIONS: Long-term follow-up with HIFU therapy showed a high overall rate of cancer-specific survival and an exceptionally high rate of freedom from salvage therapy requirement in low-risk patients. Advances in HIFU technology and clinical practice and the use of neoadjuvant TURP allow complete treatment of any sized prostate without induction of metastasis.

Concepts: Cancer, Metastasis, Prostate cancer, Urology, Multivariate statistics, Prostate, Prostatic stent, Transurethral resection of the prostate


Object Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that often arise from major peripheral nerves. Approximately half of MPNSTs arise in patients with neurofibromatosis Type 1 (NF1) who, in comparison with patients without NF1, present at younger ages and with larger tumors that are commonly associated with extensive plexiform neurofibromas. These tumors therefore pose a particularly difficult treatment challenge because of the morbidity often associated with attempted gross-total resection (GTR). Here, the authors aim to examine what role the extent of resection and other covariates play in the long-term survival of patients with NF1 in the setting of MPNST. Methods The authors retrospectively reviewed the records of 23 adult patients with NF1 who underwent surgery for MPNSTs at their institution between 1991 and 2008. The primary end points of the study were mortality, local recurrence, and metastasis. Kaplan-Meier survival curves were evaluated for all patients. Differences for each of the primary end points were evaluated based on cause-specific covariates, which included tiered tumor size, tumor location, grade, resection margin status, postoperative weakness, and use of chemotherapy and radiation therapy. Multivariate analysis was performed using Cox proportional hazards models. Results Gross-total resection (p = 0.01) and surgical margin status (p = 0.034) had a statistically important role in prolonging overall survival in patients with NF1 by univariate analysis. When tumor size, location, grade, postoperative weakness, and radiation therapy were also taken into account using multivariate analysis, GTR continued to be a significant prognostic factor (p = 0.035). Conclusions These findings suggest that GTR offers significant long-term benefit on survival in patients with NF1. Benefit on survival occurred independently of all other covariates, suggesting that complete resection should be the principal goal of treatment in this patient population.

Concepts: Cancer, Oncology, Survival analysis, Action potential, Multivariate statistics, Malignant peripheral nerve sheath tumor, Nerve sheath tumor, Peripheral nervous system