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Extrinsic and intrinsic factors may influence the activity budget of wild animals, resulting in a variation in the time spent in different activities among populations or individuals of the same species. In this study, we examined how extrinsic and intrinsic factors affect the behaviour of the alpine marmot (Marmota marmota), a hibernating social rodent inhabiting high-elevation prairies in the European Alps. We collected behavioural observations during scan sampling sessions on marked individuals at two study sites with different environmental characteristics. We used Bayesian hierarchical multinomial regression models to analyse the influence of both intrinsic (sex and age-dominance status) and extrinsic (environmental and climatic variables) factors on the above-ground activity budget. Marmots spent most of their time above ground foraging, and were more likely to forage when it was cloudy. Extrinsic factors such as the site, period of the season (June, July–August, and August–September), and time of the day were all related to the probability of engaging in vigilance behaviour, which reaches its peak in early morning and late afternoon and during July, the second period included in the study. Social behaviours, such as affiliative and agonistic behaviours, were associated mostly with sex and age-dominance status, and yearlings were the more affiliative individuals compared to other status. Overall, our results suggest that in alpine marmots, intrinsic factors mostly regulate agonistic and affiliative behaviours, while extrinsic factors, with the unexpected exception of temperature, affect the probabilities of engaging in all types of behavioural categories.

Zusammenfassung Hintergrund Immun-Checkpoint-Inhibitoren (ICI) sind seit wenigen Jahren in der Uroonkologie zugelassen. Real-world-Erfahrung zu Nutzen und Risiken bei neuartigen Nebenwirkungen liegt kaum vor. Material und Methoden In einer retrospektiven Analyse wurden an zwei Krankenhäusern in Deutschland von 2016–2021 Patienten erfasst, die aufgrund eines metastasierten Nierenzell- (NCC) oder Urothelkarzinoms (UCA) eine ICI-Therapie erhielten. Es wurde das radiologische Ansprechen, das progressionsfreie Überleben (PFS) sowie Nebenwirkungen, die zu einer Therapieunterbrechung führten, erhoben. Das onkologische Ansprechen wurde den Zulassungsstudien gegenübergestellt. Ergebnisse Bei 145 Patienten (111 Männer [77 %] und 34 Frauen [23 %]) wurden 1185 ICI-Zyklen appliziert. 64 (44,1 %) Patienten mit NCC und 81 (55,9 %) Patienten mit UCA erhielten eine ICI-Therapie. Von 141 Patienten mit Verlaufsbildgebung wurde ein objektives Ansprechen bei 21,3 % (n = 13) der Patienten mit NCC und 20,0 % (n = 16) mit UCA beobachtet (mediane Ansprechdauer 14,9 (3,0–51,3) Monate). Das PFS betrug bei Patienten mit NCC im Median 5,3 Monate und mit UCA 4,8 Monate. ICI-assoziierte Nebenwirkungen mit der Notwendigkeit einer Therapieunterbrechung wurden bei 17,2 % der NCC- und 20,9 % der UCA-Patienten beobachtet. Hierbei handelte es sich am häufigsten um renale (5,5 %: Nephritis) und gastrointestinale (4,8 %: Kolitis, Diarrhö) Nebenwirkungen. 22 (15,1 %) Patienten mussten deshalb hospitalisiert werden. Schlussfolgerung Diese Real-world-Erfahrung kann die patientenzentrierte Beratung in der Therapieentscheidung unterstützen. Weitere Studien zu prognostischen Faktoren sind notwendig. Therapieunterbrechungen sind häufig und das Nebenwirkungsspektrum erfordert eine interdisziplinäre Behandlung.

The objective of the study was to investigate the development of clinical outcomes of young people with early psychosis in a specialized inpatient treatment and assess the feasibility of such an intervention in an inpatient setting. The study was a prospective cohort study of patients with early psychosis treated at the specialized inpatient treatment “Fühinterventions-und Therapiezentrum, FRITZ” (early intervention and therapy center) in Berlin, Germany. The primary outcomes were attitudes towards psychiatric medication and patient satisfaction with treatment after 6 weeks. Secondary outcomes were clinical symptoms, functioning, remission, recovery, all-cause treatment discontinuation, and rehospitalisation at 6 and 12 months after inpatient treatment. We recruited 95 inpatients with early psychosis. Attitudes towards psychiatric medication (Δ6weeks = 3.00, d6weeks = 0.55; Δ6mo = 2.15, d6mo = 0.35; Δ12mo = 3.03, d12mo = 0.52) and patient satisfaction (Δ6weeks = 0.21, d6weeks = 0.40; Δ6mo = 0.32, d6mo = 0.43; Δ12mo = 0.13, d12mo = 0.17) changed with medium effect sizes at six weeks up to a 6- and 12-month follow-up. Clinical outcomes changed significantly with medium-to-large-effect sizes over 12 months CGIΔ12mo = 1.64, d12mo = −1.12; PANSS totalΔ12mo = 20.10, d12mo = −0.76; GAFΔ12mo = 19.58, d12mo = 1.25). The all-cause treatment discontinuation rate was 13.69% (n = 13) at a 6-month and 35.79% (n = 34) at a 12-month follow-up. The rehospitalization rate was 30.53% (n = 29) at a 6-month and 43.16% (n = 41) at a 12-month follow-up. Patients with specialized inpatient treatment for early psychosis showed improvements in attitude towards psychiatric medication, patient satisfaction, symptoms, and functioning for up to 12 months.Trial registration: DRKS00024351, 2021/02/11 retrospectively registered.

Background Although multiparametric magnetic resonance imaging (mpMRI) is recommended for primary risk stratification and follow-up in Active Surveillance (AS), it is not part of common AS inclusion criteria. The objective was to compare AS eligibility by systematic biopsy (SB) and combined MRI-targeted (MRI-TB) and SB within real-world data using current AS guidelines. Methods A retrospective multicenter study was conducted by a German prostate cancer (PCa) working group representing six tertiary referral centers and one outpatient practice. Men with PCa and at least one MRI-visible lesion according to Prostate Imaging Reporting and Data System (PI-RADS) v2 were included. Twenty different AS inclusion criteria of international guidelines were applied to calculate AS eligibility using either a SB or a combined MRI-TB and SB. Reasons for AS exclusion were assessed. Results Of 1941 patients with PCa, per guideline, 583–1112 patients with PCa in both MRI-TB and SB were available for analysis. Using SB, a median of 22.1% (range 6.4–72.4%) were eligible for AS. Using the combined approach, a median of 15% (range 1.7–68.3%) were eligible for AS. Addition of MRI-TB led to a 32.1% reduction of suitable patients. Besides Gleason Score upgrading, the maximum number of positive cores were the most frequent exclusion criterion. Variability in MRI and biopsy protocols potentially limit the results. Conclusions Only a moderate number of patients with PCa can be monitored by AS to defer active treatment using current guidelines for inclusion in a real-world setting. By an additional MRI-TB, this number is markedly reduced. These results underline the need for a contemporary adjustment of AS inclusion criteria.

Purpose Magnetic resonance imaging (MRI)/ultrasound-fusion prostate biopsy (FB) comprises multiple steps each of which can cause alterations in targeted biopsy (TB) accuracy leading to false-negative results. The aim was to assess the inter-operator variability of software-based fusion TB by targeting the same MRI-lesions by different urologists. Methods In this prospective study, 142 patients eligible for analysis underwent software-based FB. TB of all lesions (n = 172) were carried out by two different urologists per patient (n = 31 urologists). We analyzed the number of mismatches [overall prostate cancer (PCa), clinically significant PCa (csPCa) and non-significant PCa (nsPCa)] between both performed TB per patient. In addition we evaluated factors contributing to inter-operator variability by uni- and multivariable analyses. Results In 11.6% of all MRI-lesions (10.6% of all patients) there was a mismatch between TB1 and TB2 in terms of overall prostate cancer (PCa detection. Regarding csPCa, patient-based mismatch occurred in 14.8% (n = 21). Overall PCa and csPCa detection rate of TB1 and TB2 did not differ significantly on a per-patient and per-lesion level. Analyses revealed a smaller lesion size as predictive for mismatches (OR 9.19, 95% CI 2.02–41.83, p Conclusion Reproducibility and precision of targeting particularly small lesions is still limited although using software-based FB. Further improvements in image-fusion, segmentation, needle-guidance, and automatization are necessary.

DNA damage is a constant event in every cell caused by exogenous factors such as ultraviolet and ionizing radiation (UVR/IR) and intercalating drugs, or endogenous metabolic and replicative stress. Proteins of the DNA damage response (DDR) network sense DNA lesions and induce cell cycle arrest, DNA repair, and apoptosis. Genetic defects of DDR or DNA repair proteins can be associated with immunodeficiency, bone marrow failure syndromes, and cancer susceptibility. Although various diagnostic tools are available to evaluate DNA damage, their quality to identify DNA repair deficiencies differs enormously and depends on affected pathways. In this study, we investigated the DDR biomarkers γH2AX (Ser139), p-ATM (Ser1981), and p-CHK2 (Thr68) using flow cytometry on peripheral blood cells obtained from patients with combined immunodeficiencies due to non-homologous end-joining (NHEJ) defects and ataxia telangiectasia (AT) in response to low-dose IR. Significantly reduced induction of all three markers was observed in AT patients compared to controls. However, delayed downregulation of γH2AX was found in patients with NHEJ defects. In contrast to previous reports of DDR in cellular models, these biomarkers were not sensitive enough to identify ARTEMIS deficiency with sufficient reliability. In summary, DDR biomarkers are suitable for diagnosing NHEJ defects and AT, which can be useful in neonates with abnormal TREC levels (T cell receptor excision circles) identified by newborn screening. We conclude that DDR biomarkers have benefits and some limitations depending on the underlying DNA repair deficiency., publishedVersion

Die multiparametrische Magnetresonanztomographie (mpMRT) der Prostata ist als entscheidender Bestandteil in der Fruherkennung und Ausbreitungsdiagnostik des primaren Prostatakarzinoms etabliert. Bildgestutzte Biopsieverfahren, wie die MRT-Ultraschall-Fusionsbiopsie, erlauben nicht nur die zielgerichtete Probengewinnung aus Indexlasionen zur Diagnosesicherung, sondern verbessern die Detektion klinisch signifikanter Prostatakarzinome. Minimal-invasive Therapieformen des lokalisierten Prostatakarzinoms erganzen das Behandlungsspektrum insbesondere fur Patienten mit niedrigem und mittlerem Risiko. Fur Patienten mit niedrigem bis mittlerem Risiko konnten die MRT-gestutzten, minimal-invasiven Therapieformen in Zukunft eine lokale Tumorkontrolle, verbesserte funktionelle Ergebnisse und die Moglichkeit einer spateren Therapieeskalation vereinen. Weitere Studienergebnisse in Bezug auf multimodale Ansatze sowie den Einsatz kunstlicher Intelligenz (KI) mittels Machine-Learning- und Deep-Learning-Algorithmen konnen zukunftig dabei helfen, das volle Potenzial fokaler Therapieansatze im Sinne der personalisierten Medizin auszuschopfen. Fur die einzelnen MRT-gestutzten minimal-invasiven Therapieverfahren ist der Abschluss laufender randomisierter Studien im Vergleich zur etablierten Ganzdrusentherapie erforderlich, bevor minimal-invasive Therapieformen Einzug in die klinischen Leitlinien finden. Dieser Ubersichtartikel beschaftigt sich mit minimal-invasiven Therapieverfahren des Prostatakarzinoms und der zentralen Rolle der mpMRT der Prostata in Therapieplanung und -durchfuhrung unter besonderer Berucksichtigung der Herausforderungen im klinischen Alltag.

Die Bestimmung des prostataspezifischen Antigens (PSA) ist die Basis der Fruherkennung des Prostatakarzinoms als haufigste Tumorentitat des Mannes in Deutschland und Europa. Grose Screeningstudien zeigen, dass hierdurch die Inzidenz lokal fortgeschrittener und metastasierter Stadien reduziert werden kann. Auch ein Effekt auf die krebsspezifische Mortalitat konnte belegt werden. Da mit einer fruhzeitigen Erkennung klinisch signifikanter Karzinome aber auch eine Uberdiagnostik und Ubertherapie nicht-signifikanter Karzinome mit nachfolgenden therapieassoziierten Nebenwirkungen einhergehen kann, muss die moderne Fruherkennung individualisiert und risikoadaptiert erfolgen. Trotz der Ablehnung eines Baseline-PSA-Werts als GKV-Leistung (Gesetzliche Krankenversicherung) durch den Gemeinsamen Bundesausschuss 2020 stellt dieser einen elementaren Baustein dieses Fruherkennungskonzepts dar und sollte durch die verfugbaren validierten Instrumente zur optimierten Erkennung signifikanter Karzinome erganzt werden.

Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the sixth leading cause of cancer death worldwide with increasing numbers globally. Therefore, differentiated diagnostic imaging and risk-adapted therapeutic approaches are warranted. Multiparametric magnetic resonance imaging (mpMRI) of the prostate supports the diagnosis of PCa and is currently the leading imaging modality for PCa detection, characterization, local staging and image-based therapy planning. Due to the combination of different MRI sequences including functional MRI methods such as diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI), mpMRI enables a high sensitivity and specificity for the detection of PCa. The rising demand for individualized treatment strategies requires methods to ensure reproducibility, completeness, and quality of prostate MRI report data. The PI-RADS (Prostate Imaging Reporting and Data System) 2.1 classification represents the classification system that is internationally recommended for MRI-based evaluation of clinically significant prostate cancer. PI-RADS facilitates clinical decision-making by providing clear reporting parameters based on clinical evidence and expert consensus. Combined with software-based solutions, structured radiology reports form the backbone to integrate results from radiomics analyses or AI-applications into radiological reports and vice versa. This review provides an overview of imaging methods for PCa detection and local staging while placing special emphasis on mpMRI of the prostate. Furthermore, the article highlights the benefits of software-based structured PCa reporting solutions implementing PI-RADS 2.1 for the integration of structured data into decision support systems, thereby paving the way for workflow automation in radiology.

The Clavien-Dindo Classification (CDC) lacks a combined score of multiple complications in one patient. The comprehensive complication index (CCI) circumvents this problem making it a valuable instrument to optimize quality control. We aimed to introduce and validate CCI in the treatment of urolithiasis. 60 day postoperative complications of 327 consecutive patients undergoing percutaneous nephrolitholapaxy (PNL) and ureterorenoscopy (URS) between 2017 and 2019 were retrospectively assessed and graded according to CDC. CCI was calculated for each patient. Overall morbidity scores of CCI and CDC were compared. Correlation analyses between the two scores and length of hospital stay (LOS) were performed. A multivariate analysis was performed to identify predictive factors for complications. Sample size calculation for an imaginary clinical trial was compared between CCI and CDC. A significant difference in overall morbidity between CCI and CDC was revealed for PNL (p 0.001) and URS (p = 0.001). There was no statistically significant difference in comparing correlations between cumulative CCI and LOS versus non-cumulative CDC and LOS for both cohorts. Operating time 90 min, maximum stone size, positive preoperative urine culture and PNL type (p 0.001) were predictive factors for postoperative complications in PNL, while urine culture (p = 0.02) was for URS. Sample size calculation based on CCI resulted in a significant reduction of required patients for PNL (- 48%) and URS (- 84%) compared to CDC. CCI could successfully be validated in endourological stone treatment with the advantage of assessing complications in their entirety compared to CDC. CCI can significantly reduce the required sample size in future clinical trials.

Purpose Focal therapies (FTs) are investigated within prospective studies on selected patients treated for localized prostate cancer (PCa). Benefits are preservation of genitourinary function and reduced complications, but follow-up is elaborate and is associated with uncertainty as cancer-free survival appears to be lower compared to standard radical treatments. The aim of this study was to analyse patient-reported acceptance of FT and evaluate factors associated with treatment decision regret. Methods 52 patients who received focal high-intensity focused ultrasound for low- to intermediate-risk PCa between 2014 and 2019 within two prospective trials were eligible for a survey regarding PCa-related treatment regret and quality-of-life (Clark’s scale) and the following potential predictors: sociodemographic variables, Charlson Comorbidity Index, subjective aging (AARC-10 SF), and general health-related quality-of-life (SF-12). Cancer persistence/recurrence (multiparametric MRI and fusion biopsy after 12 months) and functional outcomes (EPIC-26 UI/UIO/S) data were also included in this study. Results The overall survey response rate was 92.3% (48/52 patients). Median follow-up was 38 months (interquartile range = 25–50 months). In total, ten patients (20.8%) reported treatment decision regret. In univariable analyses, a clinically meaningful increase in urinary incontinence showed a significant association (OR 4.43; 95% CI 0.99–20.53; p = 0.049) with regret. Cancer recurrence (OR 12.31; 95% CI 1.78–159.26; p = 0.023) and general health worry as a domain of Clark’s scale (OR 1.07; 95% CI 1.03–1.14; p Conclusion Acceptance of FT is comparable to standard treatments. Extensive follow-up including regular PSA testing does not cause additional regret but careful patient selection and information before FT is crucial.

Zusammenfassung Hintergrund und Ziel der Arbeit Der Jahreskongress der Deutschen Gesellschaft für Urologie (DGU) spiegelt die urologische Forschungslandschaft im deutschsprachigen Raum wider. Ziel war es, durch die longitudinale Analyse der Kongressabstracts und hervorgehenden Vollpublikationen Trends aufzudecken. Material und Methoden Es erfolgte die systematische Analyse der Kongressabstracts des Jahreskongresses 2016 auf Inhalt, Studiendesign, Kooperationen, hervorgehenden Vollpublikationen sowie der veröffentlichenden Journalen. Hiernach erfolgte der Vergleich mit den Kongressen 2002 und 2009. Statistische Berechnungen erfolgten per χ2-, Mann-Whitney-U-, Cochran-Armitage- und Kruskal-Wallis-Test. Ergebnisse Auf den Kongressen 2002, 2009 und 2016 wurden 1073 Abstracts präsentiert. Abstracts zu Prostataerkrankungen (24,2 %, 29,7 %, 34,0 %; p = 0,0043), onkologische Abstracts (50,6 %, 57,9 %, 61,7 %; p = 0,003), multizentrische Studien (18,3 %, 28,6 %, 34,3 %; p p p = 0,009) und prospektive Arbeiten (62,1 %, 42,0 %, 36,0 %; p p p p = 0,15). Schlussfolgerung Die nationale und internationale Vernetzung der urologischen Forschungsgemeinschaft nimmt zu, prospektive Studien werden weniger präsentiert. Die Rate aus DGU-Abstracts hervorgehender Vollpublikationen zeigt sich über die drei Kongresse auf hohem Niveau. Die Veröffentlichungsrate in Open-access-Journalen ist bisher gering.

Fatty acid-binding protein 5 (FABP5), a transport protein for lipophilic molecules, has been proposed as protein marker in prostate cancer (PCa). The role of FABP5 gene expression is merely unknown. In two cohorts of PCa patients who underwent radical prostatectomy (n = 40 and n = 57) and one cohort of patients treated with palliative transurethral resection of the prostate (pTUR-P; n = 50) FABP5 mRNA expression was analyzed with qRT-PCR. Expression was correlated with clinical parameters. BPH tissue samples served as control. To independently validate findings on FABP5 expression, three microarray and sequencing datasets were reanalyzed (MSKCC 2010 n = 216; TCGA 2015 n = 333; mCRPC, Nature Medicine 2016 n = 114). FABP5 expression was correlated with ERG-fusion status, TCGA subtypes, cancer driver mutations and the expression of druggable downstream pathway components. FABP5 was overexpressed in PCa compared to BPH in the cohorts analyzed by qRT-PCR (radical prostatectomy p = 0.003, p = 0.010; pTUR-P p = 0.002). FABP5 expression was independent of T stage, Gleason Score, nodal status and PSA level. FABP5 overexpression was associated with the absence of TMPRSS2:ERG fusion (p

The aim of this study was to assess the impact of experience on the outcome of image fusion-guided prostate biopsies performed by urologists working at a high-volume medical center. The first 210 consecutive fusion biopsies were analyzed following installation of the software-based biopsy platform Artemis™ (Eigen, USA). The impact of training was measured in terms of changes in prostate cancer detection rates and biopsy duration over time. We sought to identify a threshold of experience for urologists, which predicts higher detection rates of targeted biopsies. The influence of various factors on prostate cancer detection rates was evaluated using bi- and multivariate analysis. Twenty-two urologists (n = 9 senior urologists, n = 13 urological residents) performed targeted biopsies followed by systematic 12-core biopsies. Overall, targeted biopsies yielded a positive result in 39.6% of 260 suspicious MRI lesions. A subgroup analysis of the six urologists who performed more than ten biopsies was then conducted, and their level of experience (i.e., performance of more than eight biopsies) was found to be associated with higher detection rates than those with less experience (49.0% and 23.0%, respectively; p

Background Data from interventional studies suggest that a peritoneal flap after pelvic lymph node dissection (LND) during laparoscopic, robotic-assisted radical prostatectomy (RARP) may reduce the rate of symptomatic lymphoceles in transperitoneal approach. However, most of these studies are not conducted in a randomized controlled fashion, thus limiting their scientific value. A recent prospective, randomized, controlled trial (RCT) did not show superiority of a peritoneal flap while further trials are lacking. Therefore, the aim of the presented RCT will be to show that creating a peritoneal flap decreases the rate of symptomatic lymphoceles compared to the current standard procedure without creation of a flap. Methods/design PELYCAN is a parallel-group, patient- and assessor-blinded, phase III, adaptive randomized controlled superiority trial. Men with histologically confirmed prostate cancer who undergo transperitoneal RARP with pelvic LND will be randomly assigned in a 1:1 ratio to two groups—either with creating a peritoneal flap (PELYCAN) or without creating a peritoneal flap (control). Sample size calculation yielded a sample size of 300 with a planned interim analysis after 120 patients, which will be performed by an independent statistician. This provides a possibility for early stopping or sample size recalculation. Patients will be stratified for contributing factors for the development of postoperative lymphoceles. The primary outcome measure will be the rate of symptomatic lymphoceles in both groups within 6 months postoperatively. Patients and assessors will be blinded for the intervention until the end of the follow-up period of 6 months. The surgeon will be informed about the randomization result after performance of vesicourethral anastomosis. Secondary outcome measures include asymptomatic lymphoceles at the time of discharge and within 6 months of follow-up, postoperative complications, mortality, re-admission rate, and quality of life assessed by the EORTC QLQ-C30 questionnaire. Discussion The PELYCAN study is designed to assess whether the application of a peritoneal flap during RARP reduces the rate of symptomatic lymphoceles, as compared with the standard operation technique. In case of superiority of the intervention, this peritoneal flap may be suggested as a new standard of care. Trial registration German Clinical Trials Register DRKS00016794. Registered on 14 May 2019.

Fish stocking is a serious threat to originally fishless mountain lakes. We used non-chemical eradication methods (i.e. gillnetting and electrofishing) in four high mountain lakes in the Gran Paradiso National Park (Western Italian Alps) to eradicate alien brook trout Salvelinus fontinalis. Data of amphibians, macroinvertebrates, zooplankton, chlorophyll-a, nutrient concentrations, and water transparency were used as indicators of the recovery process. All treated lakes were returned to their original fishless condition in spite of their different sizes and habitat complexity, without permanent negative side-effects for native species. Several ecological indicators showed that many impacts of introduced fish can be reversed over a short time period following eradication. The present study adds to a still growing body of specialized literature on the recovery of habitats after the eradication of alien species and provides further evidence that physical eradication methods are effective and can be part of a more general strategy for the conservation of high mountain lake biota.

Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) imaging for the localization of prostate cancer is increasingly available in Germany. The advances and limitations in different disease stages are reviewed. As the clinical relevance of oligometastatic disease in primary cancer detected by PSMA PET-CT imaging is not yet completely understood, it should only be used in clinical trials. In recurrent prostate cancer after therapy with curative intent, PSMA PET-CT shows encouraging potential for the planning of salvage therapy. In metastatic castration-resistant prostate cancer evidence for its use is not available.

Ziel der fokalen Therapie (FT) des Prostatakarzinoms (PC) ist eine Teilbehandlung der Prostata unter Schonung der angrenzenden Strukturen. Dadurch sollen typische Nebenwirkungen radikaler Therapieoptionen bei gleichzeitiger Tumorkontrolle minimiert werden. Zahlreiche etablierte und neue Technologien kommen dazu zum Einsatz. Ergebnisse zahlreicher Fallserien belegen ein geringes Nebenwirkungsspektrum bei guten funktionellen Ergebnissen. Onkologische Langzeitergebnisse liegen bislang nicht vor.

To evaluate the accuracy of a T2-weighted (T2w) - and a parallel transmit zoomed b = 2000 s/mm2 (b2000) - diffusion-weighted imaging sequence among three readers with different degrees of experience for prostate cancer (Pca) detection.Ninety-three patients with suspected Pca were enrolled. For b2000 a two-dimensional spatially-selective RF pulse using an echo-planar transmit trajectory was applied, and the field of view (FOV) was reduced to one-third. All three readers (Reader A: 7, B 4 and C1 years of experience in prostate MRI) independently evaluated b2000 with regard to the presence of suspicious lesions that displayed increased signal. The results were compared to histopathology obtained by real-time MR/ultrasound fusion and systematic biopsy.In 62 patients Pca was confirmed. One significant Pca (Gleason score (GS) 7b) was missed by Reader C. Overall, sensitivity/specificity/positive predictive value/negative predictive value were 90/71/86/79% for Reader A, 87/84/92/76% for Reader B and 85/74/87/72% for Reader C, respectively. Detection rates for significant Pca (GS7a) were 100/100/94% for Readers A/B/C, respectively. Inter-reader agreement was generally good (Kappa A/B: 0.8; A/C: 0.82; B/C: 0.74).B2000 in combination with a T2w could be useful to detect clinically significant Pca.• Significant prostate cancer using zoomed ultra-high b-value DWI was detected. • Diagnostic performance among readers with different degrees of experience was good. • mp- MRI of the prostate using a comprehensive non-contrast protocol is clinically feasible.

This study was conducted in order to review randomized controlled trial (RCT) data published January 2016–March 2019 on long-acting injectable antipsychotics (LAIs) for schizophrenia. Thirty-one RCTs (primary studies = 7; post hoc analyses = 24; n = 4738) compared LAIs vs. placebo (studies = 11, n = 1875), LAIs vs. oral antipsychotics (OAPs) (studies = 7, n = 658), and LAI vs. LAI (studies = 13, n = 2205). LAIs included two new formulations, aripiprazole lauroxil nanocrystal dispersion and subcutaneously injectable risperidone Perseris, as well as aripiprazole lauroxil, aripiprazole once-monthly, paliperidone once-monthly, paliperidone 3-monthly, and risperidone-LAI. Regarding prevention of relapse and hospitalization, LAIs consistently outperformed placebo, being partly superior to OAPs, without relevant LAI–LAI differences. LAIs were comparable to OAPs regarding all-cause discontinuation, functioning, quality of life, and tolerability, being associated with higher patient satisfaction and service engagement. Recent meta-analyses yielded mixed results, but never favoring OAPs over LAIs. In RCTs, LAIs are superior to placebo, but only in some aspects, superior to OAPs. Comparative effectiveness of LAIs vs. OAPs requires further study, ideally in generalizable/real-world samples.

Avoiding hyperthermia entails considerable metabolic costs for endotherms. Such costs increase in warm conditions, when endotherms may trade food intake for cooler areas to avoid heat stress and maximize their energy balance. The need to reduce heat stress may involve the adoption of tactics affecting space use and foraging behaviour, which are important to understand and predict the effects of climate change and inform conservation. We used resource selection models to examine the behavioural response to heat stress in the Alpine ibex (Capra ibex), a cold-adapted endotherm particularly prone to overheating. Ibex avoided heat stress by selecting the space based on the maximum daily temperature rather than moving hourly to ‘surf the heat wave’, which minimised movement costs but prevented optimal foraging. By integrating these findings with new climate forecasts, we predict that rising temperatures will force mountain ungulates to move upward and overcrowd thermal refugia with reduced carrying capacity. Our approach helps in identifying priority areas for the conservation of mountain species.

Es existieren zahlreiche Systeme zur MRT/TRUS-fusionierten Biopsie der Prostata. Insgesamt liegt ausreichend Literatur zur Fusionsbiopsie vor, die einen Vorteil bei der Tumordetektion und der Diagnosequalitat gegenuber der Randombiopsie belegt. Der Nutzen der Systeme im Rahmen der fokalen Therapie des Prostatakarzinoms (PC) ist unklar. Ziel war die kritische Prufung der vorhandenen Fusionssysteme fur die Planung und Verlaufskontrolle einer fokalen Therapie des PC. Es erfolgte eine systematische Literaturrecherche zu den erhaltlichen Fusionssystemen fur den Zeitraum 2013–5/2016. Durch den Arbeitskreis „Fokale und Mikrotherapie“ wurde ein Kriterienkatalog zu technischen Details, der Eignung in speziellen Situationen und der Eignung im Rahmen der fokalen Therapie des PC erstellt. Acht Fusionssysteme wurden betrachtet (Artemis™, BioJet, BiopSee®, iSR’obot™ Mona Lisa, Hitachi HI-RVS, UroNav und Urostation®). Unterschiede zwischen den Systemen bestehen u. a. in der Art der Biopsie (transrektal, perineal, beides moglich), im Fusionsmodus (starr bzw. elastisch), in der Navigationsart (bildbasiert, elektromagnetisch bzw. mechanisch) sowie im Platzbedarf. Fusionssysteme werden im Rahmen der fokalen Therapie des PC von verschiedenen Konsensusgruppen empfohlen. Wunschenswerte Eigenschaften sind neben dem „needle tracking“ die Ubertragbarkeit des Biopsiedatensatzes in ein Behandlungsgerat (Artemis™, BiopSee® und Urostation®: jeweils mit Focal One®, BiopSee®, Hitachi HI-RVS: jeweils mit Nanoknife®, BioJet und BiopSee®: Kryoablation, Brachytherapie). Studien zur Planung einer fokalen Therapie liegen nur fur vereinzelte Systeme vor und fehlen fur die Verlaufskontrolle nach fokaler Therapie.

We use the output of twenty-seven Global Climate Models participating in the Coupled Model Intercomparison Project phase 5 (CMIP5) to investigate the temperature changes and their dependence on the elevation in the Tibetan Plateau, Himalaya and Karakoram mountains and in the surrounding areas in historical model simulations and in future projections. The aim of this study is to explore if and to what extent the CMIP5 models show elevation-dependent warming (EDW) in this part of the globe and to investigate what are the driving factors at play and their relative importance. Our results indicate that the models show enhanced rates of warming at higher elevations in the Tibetan Plateau-Himalayan region in the twentieth century, and this phenomenon is projected to strengthen by the end of the twenty-first century under a high-emission scenario. We find a nonlinear relationship between the warming rates and the elevation, for both the minimum and the maximum temperature: regions with temperatures below the freezing level of water show more warming than the regions with temperatures above, likely suggesting a key role of mechanisms involving water phase changes, the presence/absence of snow and the snow-albedo feedback. We consider the main variables simulated by the CMIP5 models whose change may be related to temperature changes at higher elevations. We find that changes in surface albedo, atmospheric humidity and downward longwave radiation are relevant factors for EDW in the Tibetan Plateau-Himalayas, with surface albedo being the leading driver.