Cox's regression model for the analysis of survival data relies on the proportional hazards assumption. However, this assumption is often violated in practice and as a consequence the average relative risk may be under-or overestimated. Weighted estimation of Cox regression is a parsimonious alternative which supplies well interpretable average effects also in case of non-proportional hazards. We provide the R package coxphw implementing weighted Cox regression. By means of two biomedical examples appropriate analyses in the presence of non-proportional hazards are exemplified and advantages of weighted Cox regression are discussed. Moreover, using package coxphw, time-dependent effects can be conveniently estimated by including interactions of covariates with arbitrary functions of time.

Many collaborative filtering recommender systems collect and use users' explicitly entered preferences in the form of ratings for items. However, in many real world scenarios, this form of feedback can be difficult to obtain or unavailable (e.g., news portals). In this case recommendations must be built by leveraging more abundant implicit feedback data, which only indirectly signal users' preferences or opinions. A record in such datasets is a result of an action performed by a user on an item (e.g., the item was clicked or viewed). State-of-the-art implicit feedback recommender systems predict whether the user will act on a target item and interpret this prediction as a discovered preference for the item. These models are trained by observations of user actions of one single type. For instance, they predict that a user will watch a video using a dataset of observed video watch actions. In this paper we conjecture that multiple types of user actions may be jointly exploited to predict one target type of actions. We present a general prediction model (MMF - Multiple action types Matrix Factorization) that implements this conjecture and we illustrate some practical examples. The empirical evaluation of MMF, which was conducted on a large real world dataset, shows that using multiple actions is beneficial and it can outperform a state-of-the-art implicit feedback model that uses only the target action data.

In the logistic regression analysis of a small-sized, case-control study on Alzheimer's disease, some of the risk factors exhibited missing values, motivating the use of multiple imputation. Usually, Rubin's rules (RR) for combining point estimates and variances would then be used to estimate (symmetric) confidence intervals (CIs), on the assumption that the regression coefficients were distributed normally. Yet, rarely is this assumption tested, with or without transformation. In analyses of small, sparse, or nearly separated data sets, such symmetric CI may not be reliable. Thus, RR alternatives have been considered, for example, Bayesian sampling methods, but not yet those that combine profile likelihoods, particularly penalized profile likelihoods, which can remove first order biases and guarantee convergence of parameter estimation.To fill the gap, we consider the combination of penalized likelihood profiles (CLIP) by expressing them as posterior cumulative distribution functions (CDFs) obtained via a chi-squared approximation to the penalized likelihood ratio statistic. CDFs from multiple imputations can then easily be averaged into a combined CDF (c), allowing confidence limits for a parameter at level 1- to be identified as those * and ** that satisfy CDF (c)(*)=/2 and CDF (c)(**)=1-/2.We demonstrate that the CLIP method outperforms RR in analyzing both simulated data and data from our motivating example. CLIP can also be useful as a confirmatory tool, should it show that the simpler RR are adequate for extended analysis. We also compare the performance of CLIP to Bayesian sampling methods using Markov chain Monte Carlo. CLIP is available in the R package logistf. Copyright (c) 2013 John Wiley & Sons, Ltd.

Pharmacokinetic studies are commonly performed using the two-stage approach. The first stage involves estimation of pharmacokinetic parameters such as the area under the concentration versus time curve (AUC) for each analysis subject separately, and the second stage uses the individual parameter estimates for statistical inference. This two-stage approach is not applicable in sparse sampling situations where only one sample is available per analysis subject similar to that in non-clinical in vivo studies. In a serial sampling design, only one sample is taken from each analysis subject. A simulation study was carried out to assess coverage, power and type I error of seven methods to construct two-sided 90% confidence intervals for ratios of two AUCs assessed in a serial sampling design, which can be used to assess bioequivalence in this parameter.

Purpose. Due to the widespread use of Free Functional Muscle Transplant (FFMT) around the world to reanimate the paralysed face, it is important to be aware of ethnic differences in facial movements.Methods and material. Participants in this study were born in Taiwan (n = 24) and Austria (n = 24). Analyses were conducted applying the digitised three-dimensional video-analysis system. All 48 subjects have never undergone any treatments in the face nor did they have previous histories of craniofacial anomalies.Results. In general, Europeans were observed to have larger facial movements than Asians, from 0.4 mm (e.g. 5.7%) up to 3.9 mm (e.g. 30.3%), on average 1.3 mm +/- 0.82 SD (e.g. 20.6%). Particularly the eyebrow, nose and mouth regions show statistically significant larger excursions on average 1.4 mm (e.g. 19.9%), 1.3 mm (e.g. 34.6%) and 3.0 mm (e.g. 30.3%). One exception is in the eye region, where Asians have a larger excursion (1.4 mm, e.g. 15.8%) of the eyelids, due to the larger distances between the upper and lower eyelids in the rest position.Conclusion. Europeans have generally larger facial movements than Asians. Particularly the eyebrow, nose and mouth regions show statistically significant larger excursions; exception must be made to the eye region, where Asians have a larger excursion of the eyelids. This is the first step to gather essential information about the ethnical differences in facial movements, a factor that should be considered as FFMT is becoming more popular worldwide. (C) 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.

BACKGROUND: In patients suffering from gallbladder cancer (GBC), procedure-related tumor dissemination during laparoscopy is reported. The aim of this study was to investigate if laparoscopy reduces the overall survival of patients compared to primarily open-operated patients. METHODS: In 29 patients with GBC, laparoscopic surgery was performed. In a matched-pair analysis with conventionally operated patients the impact of several prognostic factors on overall survival was investigated by uni- and multivariate tests retrospectively. RESULTS: Laparoscopic surgery did not impair patient survival either after resection (n = 11, P = 0.751) or after palliative operation (n = 2) compared to conventional surgery. Patients who underwent conversion to open resection (n = 6) did not experience different survival when compared with primary open-resected individuals (P = 0.263). Patients with laparoscopic palliative procedures (n = 2) survived 4.4 and 5.7 months; and matched patients, 2.4 and 3.6 months. In 10 patients conversion to open palliative procedure was performed and no better survival was calculated (P = 0.165). Multivariate analyses showed that T stage and tumor-free resection margins were the strongest predictors of survival. CONCLUSIONS: Our results seem to support the conclusion that laparoscopy does not reduce patient survival in gallbladder carcinoma when compared to open surgery.

Objective: In order to achieve an accurate intraoperative ECG detection, a new technique in detecting the trigger-signal was developed. In contrast to the traditional three-lead ECG-configuration, the left leg electrode was connected to a transient epicardial pacemaker electrode on the left-ventricular surface. Background Data: The Holmium:YAG-Laser for Transmyocardial Laser Revascularization (TMLR) is R-wave-triggered, providing the release of energy only during the refractory period of the heart cycle. However, an exact ECG-triggering during mobilization of the apex and/or posterior wall is difficult to achieve by using conventional ECG-configuration, therefore increasing the risk for mistriggering and induction of arrhythmias during TMLR. Materials and Methods: Two groups of patients, all undergoing stand alone TMLR-procedures via left minithoracotomy, were compared. Ten patients were operated with the conventional ECG configuration (group 1) and ten patients with the modified epicardial ECG configuration (group 2). Results: In patients of group 1, as a result of a loss of the trigger signal or due to the triggering of artifacts, the incidence of correctly triggered QRS-complexes was 56 % of all documented QRS-complexes. In contrast, an excellent triggering was observed in 98 % (p < 0.001) in group 2, resulting in a reduction of laser operative time by 35 % (p < 0.001) and a decrease in the incidence of intraoperative ventricular fibrillation (0 vs. 3). Conclusion: In conclusion, this new ECG configuration is a simple but effective method in achieving an excellent ECG signal during all stages of TMLR. As a consequence, a reduction in operative time and incidence of ventricular fibrillation can be achieved.

In case-based studies, controls are retrospectively assigned to patients in order to permit a statistical evaluation of the study results through a comparison of the main outcome measures for the patient and retrieved control groups. Inappropriate selection of the controls by using false retrieval parameters or a false algorithm might lead to an incorrect data analysis and a false interpretation of the results. The main hypothesis of the presented study was that, if the matching baseline parameters were at least nearly perfectly selected, then the outcomes of the matched pairs should be similar, or no significant differences in study outcome should be observed between the patients and the matched controls. In the present study, the case-based domain was created from 1566 patients who had undergone intracoronary stent implantation. Uni- and multivariate logistic regression analysis determined nine significant predictors (matching variables) for the occurrence of major adverse cardiac events. An additional 425 consecutive patients undergoing intracoronary stent implantation were then matched with all the potential controls from the database by calculating the individual distance between the patient and the matched control on the basis of the elaborated retrieval algorithm. To test the matching hypothesis, different distance measurements, and an altered outcome and retrieval process were examined. With "flexible" distance measurements, the mean distance between the patients and the first matched controls was 1.31. The major adverse cardiac events were compared in the patient and matched control groups. The best sensitivity and specificity values of the matching system could be achieved in matched pairs with the distance < or =3.00 (95.1% of all patients). On the further stepwise exclusion of the matched pairs exhibiting a distance greater than 2 and 1, then the number of "matchable" controls and the specificity of our matching concept decreased considerably. When the short- or mid-term outcome was compared by using the long-term follow-up matching parameters, no correlation could be found between the treated subjects and controls, indicating that for the other study, main measures of other appropriate parameters must be selected, and demonstrating the importance of the outcome-oriented selection of the retrieval parameters. Furthermore, the outcome measures of the patients and randomly (non-systematically) selected controls did not correlate, revealing the impossibility of drawing correct study conclusions from a non-matched, randomly assigned pairs. In conclusion, the sensitivity and specificity of the matching program, and the study conclusions depend on the appropriately predefined matching parameters and retrieval algorithm.

The well-known poor prognosis of proximal bile duct cancer is due to its unfortunate anatomical location and its late diagnosis. Successful tumor resection, which is considered to be optimal treatment, depends on many factors. Eighty-eight patients suffering from proximal bile duct cancer underwent surgical exploration at our institution between 1977 and 1998. In 37 patients the tumor was resectable; in the remaining 51 patients exploratory laparotomy or a palliative operation was performed. The median survival after tumor resection was 18.6 months, but median survival after a palliative procedure or an exploratory laparotomy was only 3.4 months (p < 0.001). A curative R0 resection was possible in 11 patients, an R1 resection was performed in 22 patients, and 4 patients had an R2 resection. The median survival rate after R0 resection was 83.6 months, 12.3 months after R1 resection, and 2.7 months after R2 resection (p < 0.001). Survival after resection in patients with negative lymph nodes (n = 30) was significantly longer than in those with positive lymph nodes (n = 7) (p = 0.022). Grade of tumor sclerosis tended to have an influence on resectability rate (p = 0.076). The pattern of tumor growth was without statistical influence. Multivariate analysis revealed resection (p < 0.001) as the only significant prognostic marker for patient survival. Radical resection is the only therapy that provides a chance for long-term survival, with sclerosis of the cancer tending to have an influence on univariate analysis.

When analyzing clinical data with binary outcomes, the parameter estimates and consequently the odds ratio estimates of a logistic model sometimes do not converge to finite values. This phenomenon is due to special conditions in a data set and known as 'separation'. Statistical software packages for logistic regression using the maximum likelihood method cannot appropriately deal with this problem. A new procedure to solve the problem has been proposed by Heinze and Schemper (Stat. Med. 21 (2002) pp. 2409-3419). It has been shown that unlike the standard maximum likelihood method, this method always leads to finite parameter estimates. We developed a SAS macro and an SPLUS library to make this method available from within one of these widely used statistical software packages. Our programs are also capable of performing interval estimation based on profile penalized log likelihood (PPL) and of plotting the PPL function as was suggested by Heinze and Schemper (Stat. Med. 21 (2002) pp. 2409-3419).

The aim of this study was to determine the mean distances of facial movements in 24 healthy individuals aged between 22 and 70 years, using the digitised three-dimensional video-analysis system developed by Frey et al. The subjects were divided into three groups of eight. The first group consisted of individuals aged between 20 and 30 years (mean±s.d.=25.0±2.33 years). Subjects in the second group were aged between 40 and 50 years (mean±s.d.=46.8±2.53 years), and the third group consisted of subjects aged between 60 and 70 years (mean±s.d.=63.6±3.07 years). In all groups the sexes were equally represented. No subject had had treatment to the face, nor did they have paralysis, scars or diseases of the skin. Males showed larger movements of the face than females, on average by 1.40±0.73 mm (15.08%). Subjects aged between 60 and 70 years demonstrated the largest movements of the face. The evaluation of facial movements in 24 healthy volunteers showed that sex and age affect facial dynamics. Thus study generated three-dimensional standard values for healthy facial movements.

OBJECTIVES:The goal of this study was to evaluate the dose-dependency of morphometric changes in the coronary arterial wall after radioactive stenting. BACKGROUND:Radioactive stents have been found to reduce intrastent intimal hyperplasia (IIH) but lead to a characteristic type of restenosis occurring predominantly at the stent edges. METHODS:Fifteen patients underwent intravascular ultrasound (IVUS) examination after implantation of a P-32 radioactive stent and at the six-month follow-up. The post-stent IVUS measurements on seven predefined locations of each lesion were subjected to a computer algorithm for the development of dose-volume histograms (DVH). Thus, we derived the radiation doses delivered to at least 10% and 90% of the adventitia (DV10, DV90). The IIH and vascular remodeling at follow-up were correlated with the doses in each segment. RESULTS:The IIH was most pronounced at the stent edges and lowest in the stent-body, whereas we detected a significant expansive remodeling within the stent body. The delivered doses correlated with a decreased IIH (r = 0.52, p < 0.001 for DV10 and r = 0.62, p < 0.001 for DV90) and with expansive remodeling (r = 0.48, p = 0.009 for DV10 and r = 0.50, p = 0.006 for DV90). A DV10 >90 Gy or a DV90 >15 Gy reduced IIH and induced expansive remodeling. Plaque growth was not reduced by radioactive stents. CONCLUSIONS:The DVH analysis reveals a dose-dependent increase of external elastic lamina area behind radioactive stents, whereas plaque growth is not reduced but inverted into an outward direction from the stent. A DV10 >90 Gy or a DV90 >15 Gy results in a beneficial long-term outcome after radioactive stenting.