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Objective We reviewed our institutional experience of radical prostatectomy with and without preoperative multiparametric magnetic resonance imaging (mpMRI) to assess the impact of preoperative prostate mpMRI on surgical outcomes of radical prostatectomy. Methods We identified patients at our institution who underwent radical prostatectomy for prostate cancer (PCa) between January 2012 and December 2017 (n = 1044). Using propensity scoring analysis, patients who underwent preoperative mpMRI (n = 285) were matched 1:1 to patients who did not receive preoperative mpMRI (n = 285). Multivariable regression analysis was performed to identify factors predictive of operative time, estimated blood loss (EBL), lymph node yield, rates of complications within 30 days, and positive surgical margin (PSM). Results There were no significant differences in operative time, EBL, PSM, lymph node yield, or complication rates between the two cohorts. Multivariable analysis demonstrated that preoperative mpMRI was not predictive of the measured perioperative outcomes. Significant comorbidity (Charlson Comorbidity Index ≥3) was the sole predictor of perioperative complications (P = 0.015). Increasing biopsy Gleason score predicted increased lymph node yield (P < 0.001). The probability of PSM was associated with increasing preoperative prostate-specific antigen (odds ratio 1.036, P = 0.009). Body mass index was a predictor of operative time (P = 0.016) and EBL (P = 0.001). Conclusions Although preoperative mpMRI has an important role in the diagnosis and staging of PCa, it does not impact perioperative radical prostatectomy outcomes. Our findings do not support the routine use of preoperative mpMRI for surgical planning in patients already diagnosed with clinically localized PCa.

Abstract Purpose Real‐world data about pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) are limited. We have aimed to highlight the role of PLD in daily practice focusing on older patients and patients with comorbidities with MBC. Methods We analyzed electronic records of all patients with advanced/metastatic breast cancer treated with single‐agent PLD at the University Hospital Basel between 2003 and 2021. Primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression‐free survival (PFS), and overall response rate (ORR). We performed univariate and multivariate analysis for clinical variables. Results 112 patients with MBC having received single‐agent PLD in any treatment line were analyzed, including 34 patient who were older than 70 years and 61 patients with relevant comorbidities. Median TTNC, OS, and PFS for treatment with PLD were 4.6, 11.9, and 4.4 months, respectively. ORR was 13.6%. Age >70 years predicted shorter OS (median 11.2 months) in multivariate analysis (hazard ratio [HR] 1.83, 95% CI 1.07–3.11, p = 0.026). Age and comorbidities did not significantly affect other endpoints. Unexpectedly, hypertension predicted longer TTNC (8.3 months, p = 0.04) in univariate analysis, maintained in multivariate analysis as a trend for both TTNC (HR 0.62, p = 0.07) and OS (HR 0.63, p = 0.1). Conclusion Age predicted shorter OS significantly but median OS was not relevantly shorter in older patients. PLD remains a treatment option in patients with comorbidities and older patients with MBC. However, our real‐world results of PLD appear underwhelming compared to relevant phase II trials through all age groups, pointing to an efficacy‐effectiveness gap, possibly due to sampling bias.

Abstract Background Canine heartworm disease (CHD) caused by Dirofilaria immitis remains a common preventable disease with increasing incidence in some parts of the USA. The treatment guidelines of the American Heartworm Society (AHS) currently recommend monthly macrocyclic lactone administration, 28 days of doxycycline given orally every 12 h and three injections of melarsomine dihydrochloride (1 injection on day 2 of treatment followed 30 days later by 2 injections 24 h apart). Minocycline has also been utilized when doxycycline is unavailable. The systemic effects of CHD, which particularly impact cardiac and renal function, have been described, with infected dogs often experiencing renal damage characterized by an increase in serum concentrations of renal biomarkers. Although the AHS treatment protocol for CHD has been shown to be safe and effective in most cases, the potential for complications remains. No study as of yet has evaluated changes in symmetric dimethylarginine (SDMA), a sensitive marker of renal function, during treatment for CHD. The purpose of the present study was to evaluate renal function in dogs by measuring serum creatinine and SDMA concentrations during the adulticide treatment period. Methods Serum creatinine and SDMA concentrations were measured in 27 client-owned dogs affected by CHD at the following time points: prior to starting doxycycline or minocycline therapy (baseline), during doxycycline or minocycline therapy (interim), at the time of the first dose of melarsomine (first dose), at the time of the second dose of melarsomine (second dose) and at the dog’s follow-up visit after treatment, occurring between 1 and 6 months after completion of therapy (post-treatment). Concentrations of creatinine and SDMA were compared between time points using a mixed effects linear model. Results Mean SDMA concentrations following the second dose of melarsomine were significantly lower (−1.80 ug/dL, t-test, df = 99.067, t = −2.694, P-Value = 0.00829) than baseline concentrations. There were no other statistically significant differences in the concentration of either biomarker between the baseline and the other time points in CHD dogs undergoing treatment. Conclusions The results suggest that the current AHS protocol may not have a substantial impact on renal function. Graphical Abstract

Background: In early luminal breast cancer, the Oncotype DX® Recurrence Score (RS) prognostic and predictive value with regards to chemotherapy (CHT) application benefit has been broadly validated. In older patients its value has not been deeply addressed. This study aimed to evaluate the benefits of RS testing and to look at differences in treatment allocation for these patients when compared with younger ones. Methods: We included data from consecutive patients with early luminal HER2-negative breast cancer, treated between 2010 and 2022 at the University Hospital Basel and Cantonal Hospital Baselland, Switzerland. The older cohort included 63 (19%) patients aged ≥70, and the younger cohort 263 (81%) patients aged 4 cycles: 78% vs. 97%). Conclusion: Breast cancer patients aged ≥70 have higher clinical risk status, more co-morbidities, higher clinical stage (driven by larger tumor size), and more often RS ≥26. However, they receive fewer adjuvant RT and CHT than those aged

Androgen receptor can promote tumour progression in desmoplastic small round cell tumour (DSRCT), an aggressive paediatric malignancy that predominantly affects young males. Here, the authors show that DSRCT is an AR-driven malignancy and sensitive to androgen deprivation therapy

Abstract Background Overactive bladder is a heterogenous condition with poorly characterized clinical phenotypes. To discover potential patient subtypes in patients with overactive bladder (OAB), we used consensus clustering of their urinary symptoms and other non-urologic factors. Methods Clinical variables included in the k-means consensus clustering included OAB symptoms, urinary incontinence, anxiety, depression, psychological stress, somatic symptom burden, reported childhood traumatic exposure, and bladder pain. Results 48 OAB patients seeking care of their symptoms were included. k-means consensus clustering identified two clusters of OAB patients: a urinary cluster and a systemic cluster. The systemic cluster, which consisted of about half of the cohort (48%), was characterized by significantly higher psychosocial burden of anxiety (HADS-A, 9.5 vs. 3.7, p

Numerical modeling provides an opportunity to quantify the reaction of lakes to alterations in their environment, such as changes in climate or hydrological conditions. The one-dimensional hydrodynamic General Lake Model (GLM) is an open-source software and widely used within the limnological research community. Nevertheless, no interface to process the input data and run the model and no tools for an automatic parameter calibration yet exist. Hence, we developed glmGUI, a graphical user interface (GUI) including a toolbox for an autocalibration, parameter sensitivity analysis, and several plot options. The tool is provided as a package for the freely available scientific code language R. The model parameters can be analyzed and calibrated for the simulation output variables water temperature and lake level. The glmGUI package is tested for two sites (lake Ammersee, Germany, and lake Baratz, Italy), distinguishing size, mixing regime, hydrology of the catchment area (i.e., the number of inflows and their runoff seasonality), and climatic conditions. A robust simulation of water temperature for both lakes (Ammersee: RMSE =1.17 ∘C; Baratz: RMSE =1.30 ∘C) is achieved by a quick automatic calibration. The quality of a water temperature simulation can be assessed immediately by means of a difference plot provided by glmGUI, which displays the distribution of the spatial (vertical) and temporal deviations. The calibration of the lake-level simulations of lake Ammersee for multiple hydrological inputs including also unknown inflows yielded a satisfactory model fit (RMSE =0.20 m). This shows that GLM can also be used to estimate the water balance of lakes correctly. The tools provided by glmGUI enable a less time-consuming and simplified parameter optimization within the calibration process. Due to this, i.e., the free availability and the implementation in a GUI, the presented R package expands the application of GLM to a broader field of lake modeling research and even beyond limnological experts.

Purpose: To create a simple model using clinical variables for predicting lipid-poor angiomyolipoma (AML) in patients with small renal masses presumed to be renal cell carcinoma (RCC) from preoperative imaging. Materials and Methods: A series of patients undergoing partial nephrectomy (PN) for renal masses ≤4 cm was identified using a prospectively maintained database. Patients were excluded if standard preoperative imaging was not consistent with RCC. Chi square and Mann-Whitney U analyses were used to evaluate differences in characteristics between patients with AML and other types of pathology. A logistic regression model was constructed for multivariable analysis of predictors of lipid-poor AML. Results: A total of 730 patients were identified that underwent PN for renal masses ≤4 cm between 2007–2015, including 35 with lipid-poor AML and 620 with RCC. In multivariable analysis, the following features predicted AML: female sex (odds ratio, 6.89; 95% confidence interval, 2.35–20.92; p

Microorganisms are well adapted to their habitat but are partially sensitive to toxic metabolites or abiotic compounds secreted by other organisms or chemically formed under the respective environmental conditions. Thermoacidophiles are challenged by pyroglutamate, a lactam that is spontaneously formed by cyclization of glutamate under aerobic thermoacidophilic conditions. It is known that growth of the thermoacidophilic crenarchaeon Saccharolobus solfataricus (formerly Sulfolobus solfataricus) is completely inhibited by pyroglutamate. In the present study, we investigated the effect of pyroglutamate on the growth of S. solfataricus and the closely related crenarchaeon Sulfolobus acidocaldarius. In contrast to S. solfataricus, S. acidocaldarius was successfully cultivated with pyroglutamate as a sole carbon source. Bioinformatical analyses showed that both members of the Sulfolobaceae have at least one candidate for a 5-oxoprolinase, which catalyses the ATP-dependent conversion of pyroglutamate to glutamate. In S. solfataricus, we observed the intracellular accumulation of pyroglutamate and crude cell extract assays showed a less effective degradation of pyroglutamate. Apparently, S. acidocaldarius seems to be less versatile regarding carbohydrates and prefers peptidolytic growth compared to S. solfataricus. Concludingly, S. acidocaldarius exhibits a more efficient utilization of pyroglutamate and is not inhibited by this compound, making it a better candidate for applications with glutamate-containing media at high temperatures.

Purpose: The goal of this study was to compare the rate of systemic inflammatory response syndrome (SIRS) in high-risk patients undergoing percutaneous nephrolithotomy (PCNL) between patients who received 7, 2, or 0 days of preoperative antibiotics. Materials and Methods: We retrospectively reviewed a series of consecutive PCNLs performed at our institution. Patients with infected preoperative urine cultures were excluded. High-risk patients were defined as those with a history of previous urinary tract infection (UTI), hydronephrosis, or stone size ≥2 cm. Patients were treated with 7, 2, or 0 days of preoperative antibiotic prophylaxis prior to PCNL. All patients received a single preoperative dose of antibiotics within 60 minutes of the start of surgery. Fisher exact test was used to compare the rate of SIRS by preoperative antibiotic length. Results: Of the 292 patients identified, 138 (47.3%) had sterile urine and met high-risk criteria, of which 27 (19.6%), 39 (28.3%), and 72 (52.2%) received 7, 2, and 0 days of preoperative antibiotics, respectively. The 3 groups were similar in age, sex, and duration of surgery (p>0.05). There was no difference in the rate of SIRS between the groups, with 1 of 27 (3.7%), 2 of 39 (5.1%) and 3 of 72 patients (4.2%) meeting criteria in the 7, 2, and 0 days antibiotic groups (p=~1). Conclusions: Extended preoperative antibiotic prophylaxis was not found to reduce the risk of SIRS after PCNL in our institutional experience of high-risk patients. For these patients, a single preoperative dose of antibiotics is sufficient.

In this contribution the complexity of the vertical vegetation structure, based on dense airborne laser scanning (ALS) point cloud data (25 echoes/m2 ), is analyzed to calculate vegetation roughness for hydraulic applications. Using the original 3D ALS point cloud, three levels of abstractions are derived (cells, voxels and connections) to analyze ALS data based on a 1×1 m2 raster over the whole data set. A voxel structure is used to count the echoes in predefined detrended height levels within each cell. In general, it is assumed that the number of voxels containing echoes is an indicator for elevated objects and consequently for increased roughness. Neighboring voxels containing at least one data point are merged together to connections. An additional height threshold is applied to connect vertical neighboring voxels with a certain distance in between. Thus, the connections indicate continuous vegetation structures. The height of the surface near or lowest connection is an indicator for hydrodynamic roughness coefficients. For cells, voxels and connections the laser echoes are counted within the structure and various statistical measures are calculated. Based on these derived statistical parameters a rule-based classification is developed by applying a decision tree to assess vegetation types. Roughness coefficient values such as Manning's n are estimated, which are used as input for 2D hydrodynamic-numerical modeling. The estimated Manning’s values from the ALS point cloud are compared with a traditional Manning's map. Finally, the effect of these two different Manning's n maps as input on the 2D hydraulics are quantified by calculating a height difference model of the inundated depth maps. The results show the large potential of using the entire vertical vegetation structure for hydraulic roughness estimation.

Globally, the year 2003 is associated with one of the largest atmospheric CO2 rises on record. In the same year, Europe experienced an anomalously strong flux of CO2 from the land to the atmosphere associated with an exceptionally dry and hot summer in Western and Central Europe. In this study we analyze the magnitude of this carbon flux anomaly and key driving ecosystem processes using simulations of seven terrestrial ecosystem models of different complexity and types (process-oriented and diagnostic). We address the following questions: (1) how large were deviations in the net European carbon flux in 2003 relative to a short-term baseline (1998–2002) and to longer-term variations in annual fluxes (1980 to 2005), (2) which European regions exhibited the largest changes in carbon fluxes during the growing season 2003, and (3) which ecosystem processes controlled the carbon balance anomaly . In most models the prominence of 2003 anomaly in carbon fluxes declined with lengthening of the reference period from one year to 16 years. The 2003 anomaly for annual net carbon fluxes ranged between 0.35 and –0.63 Pg C for a reference period of one year and between 0.17 and –0.37 Pg C for a reference period of 16 years for the whole Europe. In Western and Central Europe, the anomaly in simulated net ecosystem productivity (NEP) over the growing season in 2003 was outside the 1σ variance bound of the carbon flux anomalies for 1980–2005 in all models. The estimated anomaly in net carbon flux ranged between –42 and –158 Tg C for Western Europe and between 24 and –129 Tg C for Central Europe depending on the model used. All models responded to a dipole pattern of the climate anomaly in 2003. In Western and Central Europe NEP was reduced due to heat and drought. In contrast, lower than normal temperatures and higher air humidity decreased NEP over Northeastern Europe. While models agree on the sign of changes in simulated NEP and gross primary productivity in 2003 over Western and Central Europe, models diverge in the estimates of anomalies in ecosystem respiration. Except for two process models which simulate respiration increase, most models simulated a decrease in ecosystem respiration in 2003. The diagnostic models showed a weaker decrease in ecosystem respiration than the process-oriented models. Based on the multi-model simulations we estimated the total carbon flux anomaly over the 2003 growing season in Europe to range between –0.02 and –0.27 Pg C relative to the net carbon flux in 1998–2002.

Three terrestrial biosphere models (LPJ, Orchidee, Biome-BGC) were evaluated with respect to their ability to simulate large-scale climate related trends in gross primary production (GPP) across European forests. Simulated GPP and leaf area index (LAI) were compared with GPP estimates based on flux separated eddy covariance measurements of net ecosystem exchange and LAI measurements along a temperature gradient ranging from the boreal to the Mediterranean region. The three models capture qualitatively the pattern suggested by the site data: an increase in GPP from boreal to temperate and a subsequent decline from temperate to Mediterranean climates. The models consistently predict higher GPP for boreal and lower GPP for Mediterranean forests. Based on a decomposition of GPP into absorbed photosynthetic active radiation (APAR) and radiation use efficiency (RUE), the overestimation of GPP for the boreal coniferous forests appears to be primarily related to too high simulated LAI - and thus light absorption (APAR) – rather than too high radiation use efficiency. We cannot attribute the tendency of the models to underestimate GPP in the water limited region to model structural deficiencies with confidence. A likely dry bias of the input meteorological data in southern Europe may create this pattern. On average, the models compare similarly well to the site GPP data (RMSE of ~30% or 420 gC/m2/yr) but differences are apparent for different ecosystem types. In terms of absolute values, we find the agreement between site based GPP estimates and simulations acceptable when we consider uncertainties about the accuracy in model drivers, a potential representation bias of the eddy covariance sites, and uncertainties related to the method of deriving GPP from eddy covariance measurements data. Continental to global data-model comparison studies should be fostered in the future since they are necessary to identify consistent model bias along environmental gradients.

Thin film solar cells based on monocrystalline Si films are transferred to a glass superstrate. Chemical vapor deposition serves to epitaxially deposit Si on quasi-monocrystalline Si films obtained from thermal crystallization of a double layer porous Si film on a Si wafer. A separation layer that forms during this crystallization process allows one to separate the epitaxial layer on top of the quasi-monocrystalline film from the starting Si wafer. We presently achieve an independently confirmed solar cell conversion efficiency of 9:26%. Ray tracing studies in combination with electrical device simulation indicate an efficiency potential of around 17% using simple device processing and moderate assumptions on minority carrier lifetime and surface recombination.

BACKGROUND: There is accumulating evidence that autoimmune components, such as autoantibodies and autoantibody depositions, play a role in the pathogenesis of neurodegenerative diseases like Alzheimeŕs disease or Multiple Sclerosis. Due to alterations of autoantibody patterns in sera and aqueous humor, an autoimmune component is also assumed in the pathogenesis of glaucoma, a common reason for irreversible blindness worldwide. So far there has been no convincing evidence that autoantibodies are accumulated in the retina of glaucoma patients and that the local immune homeostasis might be affected. METHODS AND RESULTS: Six human glaucomatous donor eyes and nine samples from donors with no recorded ocular disease were included. Antibody microarrays were used to examine the patterns of pro-inflammatory proteins and complement proteins. Analysis of TNF-α and interleukin levels revealed a slight up-regulation exclusively in the glaucomatous group, while complement protein levels were not altered. IgG autoantibody accumulations and/or cellular components were determined by immunohistology (n = 4 per group). A significantly reduced number of retinal ganglion cells was found in the glaucomatous group (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p = 0.0007). Cell loss was accompanied by strong retinal IgG autoantibody accumulations, which were at least twice as high as in healthy subjects (healthy: 5.0±0.5 IgG deposits/100 cells, glaucoma: 9.4±1.9 IgG deposits/100 cells; p = 0.004). CD27(+) cells and CD27(+)/IgG(+) plasma cells were observed in all glaucomatous subjects, but not in controls. CONCLUSION: This work provides serious evidence for the occurrence of IgG antibody deposition and plasma cells in human glaucomatous retina. Moreover, the results suggest that these IgG deposits occurred in a pro-inflammatory environment which seems to be maintained locally by immune-competent cells like microglia. Thereby, glaucoma features an immunological involvement comparable to other neurodegenerative diseases, but also shows a multifactorial pathomechanism, which diverges and might be linked to the specific nature of both eye and retina.

ABSTRACT Objectives To further elucidate which patients with metastatic renal cell carcinoma (mRCC) may benefit from cytoreductive nephrectomy (CN) before targeted therapy (TT), and to assess the overall survival of patients undergoing CN and TT versus TT alone. Materials and Methods We identified 88 patients who underwent CN at our institution prior to planned TT and 35 patients who received TT without undergoing CN. Preoperative risk factors described in the literature were assessed in our patient population (serum albumin, liver metastasis, symptomatic metastasis, clinical ≥T3 disease, retroperitoneal and supradiaphragmatic lymphadenopathy). Patients were stratified by number of pretreatment risk factors and overall survival (OS) was compared. Results TT patients had significantly more risk factors compared to CN patients (3.06 vs. 2.11, p

Objective: The donation of livers by living donors entails complex processes, both surgically and psychosocially, potentially involving risks in both domains. Thorough psychosocial evaluation is necessary to minimize those risks, yet little has been written about the donor assessment process. This article describes one such process, utilized by a transplant program in upstate New York. Method: Donor candidates undergo multiple psychosocial interviews early in the overall transplant evaluation process. Evaluators subsequently meet as a group, along with an independent ethicist, to determine psychosocial candidacy prior to final medical/surgical clearance. Results: Between 2003 and 2007, 416 donor candidates initiated and/or underwent full evaluation, resulting in a 17.5% surgery and 55.5% exclusion rate among those individuals. Of those ruled out, 20.8% were for (medical or psychosocial) reasons associated with the recipient, and 8.7% were for donor-related psychosocial issues. Conclusion: Given the primacy of psychosocial and ethical issues in living liver donor candidate evaluation, the multiple interview process, followed by team discussion and overseen by an ethicist removed from other transplant program functions, has advantages as a donor assessment model. [ABSTRACT FROM AUTHOR]

The Rutherford scattering experiment plays a central role in working out atomic models in physics and chemistry. Nevertheless, the experiment is rarely performed at school or in introductory physics courses at university. Therefore, we realized this experiment as a remotely controlled laboratory (RCL), i.e. the experiment is set up in reality and can be operated by a computer via the Internet. We present results of measurements and supplementary didactical material. In addition, we make suggestions on how to use the RCL in class and we describe the added value of performing this experiment as an RCL. [ABSTRACT FROM AUTHOR]