Modeling Exposure-Lag-Response Associations with Penalized Piece-wise Exponential Models

We present a novel approach for the flexible modeling of exposure-lag-response associations, i.e., time-to-event data where multiple past exposures are cumulatively associated with the hazard after a certain temporal delay. Our method is based on piece-wise exponential models and allows estimation of a wide variety of effects, including potentially smooth and time-varying effects as well as cumulative effects with leads and lags, taking advantage of the advanced inference methods that have recently been developed for generalized additive mixed models

Katatones Dilemma unter Kombinationsbehandlung mit Lithium und Risperidon

OBJECTIVE: The case of a schizoaffective patient suffering from a malignant catatonic syndrome following combined lithium-risperidone therapy is explored. METHOD: A case report and relevant deliberations regarding pathophysiology of the catatonic dilemma are discussed. CONCLUSIONS: There are two critical transitions in the development of a malignant catatonic syndrome. Dopaminergic system and psychopharmacological factors are supposed to play a key role. However, other neurotransmitter systems and the individual predisposition must be considered

Modeling Exposure-Lag-Response Associations with Penalized Piece-wise Exponential Models

We present a novel approach for the flexible modeling of exposure-lag-response associations, i.e., time-to-event data where multiple past exposures are cumulatively associated with the hazard after a certain temporal delay. Our method is based on piece-wise exponential models and allows estimation of a wide variety of effects, including potentially smooth and time-varying effects as well as cumulative effects with leads and lags, taking advantage of the advanced inference methods that have recently been developed for generalized additive mixed models

Modeling Exposure-Lag-Response Associations with Penalized Piece-wise Exponential Models

We present a novel approach for the flexible modeling of exposure-lag-response associations, i.e., time-to-event data where multiple past exposures are cumulatively associated with the hazard after a certain temporal delay. Our method is based on piece-wise exponential models and allows estimation of a wide variety of effects, including potentially smooth and time-varying effects as well as cumulative effects with leads and lags, taking advantage of the advanced inference methods that have recently been developed for generalized additive mixed models

Acute and long-term survival in chronically critically ill surgical patients: a retrospective observational study

Introduction Various cohort studies have shown that acute ( short-term) mortality rates in unselected critically ill patients may have improved during the past 15 years. Whether these benefits also affect acute and long-term prognosis in chronically critically ill patients is unclear, as are determinants relevant to prognosis. Methods We conducted a retrospective analysis of data collected from March 1993 to February 2005. A cohort of 390 consecutive surgical patients requiring intensive care therapy for more than 28 days was analyzed. Results The intensive care unit ( ICU) survival rate was 53.6%. Survival rates at one, three and five years were 61.8%, 44.7% and 37.0% among ICU survivors. After adjustment for relevant covariates, acute and long-term survival rates did not differ significantly between 1993 to 1999 and 1999 to 2005 intervals. Acute prognosis was determined by disease severity during ICU stay and by primary diagnosis. However, only the latter was independently associated with long-term prognosis. Advanced age was an independent prognostic determinant of poor short-term and long-term survival. Conclusion Acute and long-term prognosis in chronically critically ill surgical patients has remained unchanged throughout the past 12 years. After successful surgical intervention and intensive care, long-term outcome is reasonably good and is mainly determined by age and underlying disease

Protein intake and outcome of critically ill patients: analysis of a large international database using piece-wise exponential additive mixed models

BACKGROUND Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use. METHODS Using a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: 1.2~g/kg per day) during the first 11~days after ICU admission (acute phase). Time-varying cause-specific hazard ratios (HR) were calculated from piece-wise exponential additive mixed models. We used the estimated model to compare five different hypothetical protein diets (an exclusively low protein diet, a standard protein diet administered early (day 1 to 4) or late (day 5 to 11) after ICU admission, and an early or late high protein diet). RESULTS Of 21,100 critically ill patients in the database, 16,489 fulfilled inclusion criteria for the analysis. By day 60, 11,360 (68.9%) patients had been discharged from hospital, 4,192 patients (25.4%) had died in hospital, and 937 patients (5.7%) were still hospitalized. Median daily low protein intake was 0.49~g/kg IQR 0.27-0.66, standard intake 0.99~g/kg IQR 0.89- 1.09, and high intake 1.41~g/kg IQR 1.29-1.60. In comparison with an exclusively low protein diet, a late standard protein diet was associated with a lower hazard of in-hospital death: minimum 0.75 (95{\%} CI 0.64, 0.87), and a higher hazard of live hospital discharge: maximum HR 1.98 (95{\%} CI 1.72, 2.28). Results on hospital discharge, however, were qualitatively changed by a sensitivity analysis. There was no evidence that an early standard or a high protein intake during the acute phase was associated with a further improvement of outcome. CONCLUSIONS Provision of a standard protein intake during the late acute phase may improve outcome compared to an exclusively low protein diet. In unselected critically ill patients, clinical outcome may not be improved by a high protein intake during the acute phase. Study registration ID number ISRCTN17829198

External forcing of earthquake swarms at Alpine regions: example from a seismic meteorological network at Mt. Hochstaufen SE-Bavaria

In the last few years, it has been shown that above-average rainfall and the following diffusion of excess water into subsurface structures is able to trigger earthquake swarms in the uppermost brittle portion of the Earth's crust. However, there is still an ongoing debate on whether the crust already needs to be in a critical-to-failure state or whether it is sufficient that water is transported rapidly within channels and veins of karst or similar geological formations to the underlying, earthquake-generating layers. Also unknown is the role of other forcing mechanisms, possible co-variables and probably necessary tectonic loading in the triggering process of earthquakes. Because of these problems, we do not use an explicit physical model but instead analyze the meteorological and geophysical data via sophisticated statistical models. ewline We are interested in the influence of a more complete set of possible forcing parameters, including the influence of synthetic earth tides, on the occurrence of earthquake swarms. In this context, regression models are the adequate tool, since the calculation of simple correlations can be confounded by the other variables. Since our outcome variable (the number of quakes) is a count, we use Poisson regression models that include the plausible assumption of a Poisson distribution for the counts. For this study, we use nearly continuous recordings of a seismic and meteorological network in the years 2002–2008 at Mt. Hochstaufen in SE-Bavaria. Our non-linear regression model reveals correlations between external forces and the triggering of earthquakes. In addition to the still dominant influence of rainfall, theoretical estimated tidal tilt show some weak influence on the swarm generation. However, the influence of the modeled trend functions shows that rain is by far not the most important forcing mechanism present in the data

How do rehomed laboratory beagles behave in everyday situations? Results from an observational test and a survey of new owners

When laboratory dogs are rehomed into private households, they experience an extreme change in their life situation. They leave their familiar, limited environment in the research facility and encounter a multitude of animate and inanimate stimuli in their new home. Although literature reports have described the experiences with rehoming as being mostly positive, scientific observations of the dogs in everyday situations have not been done. Hence, we conducted an observational test with 74 laboratory beagles 6 weeks after adoption in their new homes. This test included standardized tasks and elements;the dogs were observed during specific interactions with their new owners and during a walk. Furthermore, the owners of these 74 and of 71 additional dogs participated in standardized phone interviews 1 and 12 weeks after adoption, during which they answered questions about the dogs' behavior in everyday situations. In the observational test, the dogs behaved mostly friendly towards humans and dogs, were tolerant during manipulations by the owner and were relaxed during the walk, even in traffic. Eighty percent (of n = 71) of the dogs walked well behaved on the leash without pulling. According to the interviews, the majority of the dogs showed desired, friendly and relaxed behavior, and the survey results reflected the bonding between dog and owner. The analysis of a possible influence of various factors (age, sex, origin, etc.) using mixed regression models confirmed the results from two previous behavior tests and interviews. Specifically, dogs that had been bred in the research facility scored significantly better than dogs that the research facility had purchased from commercial laboratory dog breeders (p = 0.0113). The results of this study demonstrate a successful adaptation of the rehomed beagles to their new life situation

Mindfulness in informal caregivers of palliative patients.

OBJECTIVES: Mindfulness is a concept of growing impact on psychotherapy and has been shown to be effective for stress reduction and to improve psychological well-being. Existential Behavioural Therapy (EBT) was developed to support relatives of palliative care (PC) patients to cope with their situation during caregiving and bereavement. Mindfulness training was a core element of the intervention. We investigated the relationship between mindfulness, mental distress, and psychological well-being in informal caregivers, and evaluated if the effects of the intervention were mediated by mindfulness. METHODS: Relatives of PC inpatients took part in a randomized-controlled EBT trial and completed the Cognitive and Affective Mindfulness Scale-Revised, items from the Five Facets of Mindfulness as well as the Brief Symptom Inventory, the Satisfaction with Life Scale, the WHOQOL-BREF, a numerical rating scale on quality of life (range 0-10), and the Schedule for Meaning in Life Evaluation at pre- and post-intervention, and a 3- and 12-months follow-up. RESULTS: One-hundred-and-thirty carers were included, most of them (71.6%) recently being bereaved at the beginning of the intervention. High correlations between mindfulness and mental distress (r = -0.51, p < 0.001) as well as life satisfaction (r = 0.52, p < 0.001) were found. Mindfulness was a significant predictor of improvement in psychological distress, meaning in life and quality of life three months after the intervention. The EBT effects were partly mediated by mindfulness. SIGNIFICANCE OF RESULTS: Mindfulness seems to be a promising concept in supporting informal caregivers of PC patients. Further research is needed to identify the required format and intensity of mindfulness practice necessary for improvement

High-dimensional quantum dynamics of adsorption and desorption of H2_2 at Cu(111)

We performed high-dimensional quantum dynamical calculations of the dissociative adsorption and associative desorption of hydrogen on Cu(111). The potential energy surface (PES) is obtained from density functional theory calculations. Two regimes of dynamics are found, at low energies sticking is determined by the minimum energy barrier, at high energies by the distribution of barrier heights. Experimental results are well-reproduced qualitatively, but some quantitative discrepancies are identified as well.Comment: 4 two column pages, revtex, 4 figures, to appear in Phys. Rev. Let