Self-regulation of driving and its relationship to driving ability among older adults

Although it is known that older drivers limit their driving, it is not known whether this self-regulation is related to actual driving ability. A sample of 104 older drivers, aged between 60 and 92, completed a questionnaire about driving habits and attitudes. Ninety of these drivers also completed a structured on-road driving test. A measure of self-regulation was derived from drivers’ self-reported avoidance of difficult driving situations. The on-road driving test involved a standard assessment used to determine fitness to drive. Of the 90 participants who completed the driving assessment, 68 passed the test, eight passed but were recommended to have driving lessons and 14 failed. Driving test scores for the study were based on the number of errors committed in the driving tests, with weightings given according to the seriousness of the errors. The most commonly avoided difficult driving situations were parallel parking and driving at night in the rain, while the least avoided situation was driving alone. Poorer performance on the driving test was not strongly related to overall avoidance of difficult driving situations. Stronger relationships were found between driving ability and avoidance of specific difficult driving situations. These specific driving situations were the ones in which the drivers had low confidence and that the drivers were most able to avoid if they wished to. These results may reflect a tendency for those with poorer driving ability to lose confidence in their driving, and begin to avoid difficult driving situations. However, there are a number of situations that drivers find difficult to avoid.M.R.J. Baldock, J.L. Mathias, A.J. McLean, A. Bernd

The bradykinin BK2 receptor mediates angiotensin II receptor type 2 stimulated rat duodenal mucosal alkaline secretion

BACKGROUND: This study investigates bradykinin and nitric oxide as potential mediators of AT2-receptor-stimulated duodenal mucosal alkaline secretion. Duodenal mucosal alkaline secretion was measured in methohexital- and α-chloralose-anaesthetised rats by means of in situ pH-stat titration. Immunohistochemistry and Western blot were used to identify the BK2 receptors. RESULTS: The AT2 receptor agonist CGP42112A (0.1 μg kg(-1 )min(-1)) administered intravenously increased the duodenal mucosal alkaline secretion by ~50 %. This increase was sensitive to the selective BK2 receptor blocker HOE140 (100 ng/kg iv), but not to luminal administration of the NOS blocker L-NAME (0.3 mM). Mean arterial pressure did not differ between groups during the procedures. Immunohistochemistry showed a distinct staining of the crypt epithelium and a moderate staining of basal cytoplasm in villus enterocytes. CONCLUSION: The results suggest that the AT2-receptor-stimulated alkaline secretion is mediated via BK2 receptors located in the duodenal cryptal mucosal epithelium

Self-regulation of driving and older drivers' functional abilities

A sample of 90 adults aged between 60 and 91 completed a questionnaire about their driving behaviour, a battery of functional tests, and a structured on-road test. The section of the questionnaire featuring items about avoidance of difficult driving situations was used as an index of self-regulation of driving behaviour. The functional test battery consisted of mood, vision, physical functioning and neuropsychological tests. The on-road test used in the study was a standard assessment procedure developed by the Driver Assessment Rehabilitation Service to determine fitness to drive. Of the 90 participants in the study, 68 passed the driving test, 8 passed but were recommended to have lessons and 14 failed the test. Driving test scores for the study were based on the number of errors committed in the driving tests, with weightings given according to the seriousness of the errors. In order to identify risk factors for inadequate driver self-regulation, comparisons were made between the functional tests most strongly related to driving performance and the functional tests most strongly related to self-regulation. It was concluded that self-regulation of driving behaviour is inadequate among older drivers with poor contrast sensitivity, poor speed of information processing and poor visuospatial ability.M.R.J. Baldock, J.L. Mathias, A.J. McLean and A. Bernd

Differential nasal swab cytology represents a valuable tool for therapy monitoring but not prediction of therapy response in chronic rhinosinusitis with nasal polyps treated with Dupilumab

Introduction: Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common chronic disease with a high impact on patients’ quality of life. If conservative and surgical guideline treatment cannot sufficiently control disease burden, biologicals can be considered as a comparably new treatment option that has revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019. With the aim to select patients who benefit from this new treatment and to find a marker for therapy monitoring, we investigated the cellular composition of nasal mucous membranes and inflammatory cells of patients suffering from CRSwNP and undergoing Dupilumab therapy using non-invasive nasal swab cytology. Methods: Twenty CRSwNP patients with the indication for Dupilumab therapy have been included in this prospective clinical study. In total, five study visits were conducted with ambulatory nasal differential cytology using nasal swabs starting with the beginning of therapy and followed by visits every 3 months for 12 months. First, these cytology samples were stained with the May-GrunwaldGiemsa method (MGG) and the percentage of ciliated cells, mucinous cells, eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an immunocytochemical (ICC) ECP-staining was performed to detect eosinophil granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20 questionnaire, olfactometry, the total IgE concentration in peripheral blood as well as the eosinophil cell count in peripheral blood were recorded. The change of parameters was evaluated over one year and the correlation between clinical effectiveness and nasal differential cytology was analyzed. Results: In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant decrease of eosinophils was seen under Dupilumab treatment. When patients were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the percentage eosinophils in nasal swab catology in the first study visit, the Eo-highgroup showed a greater change of eosinophils over time (D17.82) compared to the Eo-low-group (D10.67) but, however, no better response to therapy. The polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral blood showed a significant decrease during the observation period (p<0.0001). Discussion: Nasal swab cytology as an easy-to-apply diagnostic method allows detection and quantification of the different cell populations within the nasal mucosa at a given time. The nasal differential cytology showed a significant decrease of eosinophils during Dupilumab therapy and can therefore be used as non-invasvive method for monitoring therapy success of this cost intensive therapy and potentially can allow an optimized individual therapy planning and management for CRSwNP patients. Since the validity of initial nasal swab eosinophil cell count as a predictive biomarker for therapy response was limited in our study, additional studies including larger number of participants will be necessary to further evaluate the potential benefits for clinical practice of this new diagnostic method

Synthesis of trace element bearing single crystals of Chlor-Apatite (Ca5(PO4)3Cl) using the flux growth method

We present a new strategy on how to synthesize trace-element bearing (REE, Sr) chlorapatites Ca5(PO4)3Cl using the flux growth method. Synthetic apatites were up to several mm long, light blue in colour. The apatites were characterized using XRD, electron microprobe and laser ablation ICP-MS (LA-ICPMS) techniques and contained several hundred μg/g La, Ce, Pr, Sm, Gd and Lu and about 1700 μg/g Sr. The analyses indicate that apatites were homogenous (within the uncertainties) for major and trace elements

68Ga-Radiolabeling and Pharmacological Characterization of a Kit-Based Formulation of the Gastrin-Releasing Peptide Receptor (GRP-R) Antagonist RM2 for Convenient Preparation of [68Ga]Ga-RM2

Background: [68Ga]Ga-RM2 is a potent Gastrin-Releasing Peptide-receptor (GRP-R) antagonist for imaging prostate cancer and breast cancer, currently under clinical evaluation in several specialized centers around the world. Targeted radionuclide therapy of GRP-R-expressing tumors is also being investigated. We here report the characteristics of a kit-based formulation of RM2 that should ease the development of GRP-R imaging and make it available to more institutions and patients. Methods: Stability of the investigated kits over one year was determined using LC/MS/MS and UV-HPLC. Direct 68Ga-radiolabeling was optimized with respect to buffer (pH), temperature, reaction time and shaking time. Conventionally prepared [68Ga]Ga-RM2 using an automated synthesizer was used as a comparator. Finally, the [68Ga]Ga-RM2 product was assessed with regards to hydrophilicity, affinity, internalization, membrane bound fraction, calcium mobilization assay and efflux, which is a valuable addition to the in vivo literature. Results: The kit-based formulation, kept between 2 °C and 8 °C, was stable for over one year. Using acetate buffer pH 3.0 in 2.5–5.1 mL total volume, heating at 100 °C during 10 min and cooling down for 5 min, the [68Ga]Ga-RM2 produced by kit complies with the requirements of the European Pharmacopoeia. Compared with the module production route, the [68Ga]Ga-RM2 produced by kit was faster, displayed higher yields, higher volumetric activity and was devoid of ethanol. In in vitro evaluations, the [68Ga]Ga-RM2 displayed sub-nanomolar affinity (Kd = 0.25 ± 0.19 nM), receptor specific and time dependent membrane-bound fraction of 42.0 ± 5.1% at 60 min and GRP-R mediated internalization of 24.4 ± 4.3% at 30 min. The [natGa]Ga-RM2 was ineffective in stimulating intracellular calcium mobilization. Finally, the efflux of the internalized activity was 64.3 ± 6.5% at 5 min. Conclusion: The kit-based formulation of RM2 is suitable to disseminate GRP-R imaging and therapy to distant hospitals without complex radiochemistry equipment

Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity

The cell's endogenous antioxidant system is vital to maintenance of redox homeostasis. Despite its central role in normal and pathophysiology, no non-invasive tools exist to measure this system in patients. The cystine/glutamate antiporter system xc- maintains the balance between intracellular reactive oxygen species and antioxidant production through the provision of cystine, a key precursor in glutathione biosynthesis. Here we show that tumor cell retention of a system xc--specific positron emission tomography radiotracer, (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG), decreases in proportion to levels of oxidative stress following treatment with a range of redox-active compounds. The decrease in [18F]FSPG retention correlated with a depletion of intracellular cystine resulting from increased de novo glutathione biosynthesis, shown through [U-13C6, U-15N2]cystine isotopic tracing. In vivo, treatment with the chemotherapeutic doxorubicin decreased [18F]FSPG tumor uptake in a mouse model of ovarian cancer, coinciding with markers of oxidative stress but preceding tumor shrinkage and decreased glucose utilization. Having already been used in pilot clinical trials, [18F]FSPG PET could be rapidly translated to the clinic as an early redox indicator of tumor response to treatment

Value of Ga-68-labeled bombesin antagonist (RM2) in the detection of primary prostate cancer comparing with [F-18]fluoromethylcholine PET-CT and multiparametric MRI-a phase I/II study

Objectives The bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [Ga-68]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [F-18]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI).Methods This phase I/II study was conducted in 30 biopsy-positive PCa subjects. The patients were stratified into high (10 patients), intermediate (10 patients), and low risk (10 patients) for extraglandular metastases as defined by National Comprehensive Cancer Network (NCCN) criteria (NCCN Clinical Practice Guidelines in Oncology, 2016). The prostate gland was classified in 12 anatomic segments for data analysis of the imaging modalities as well as histopathologic findings. The segment with the highest radiotracer uptake was defined as the "index lesion." All cases were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate- and high-risk patients. Intraprostatic and pelvic nodal [Ga-68]Ga-RM2 and [F-18]FCH PET-CT findings were correlated with mpMRI and histopathologic results.Results Of the 312 analyzed regions, 120 regions (4 to 8 lesions per patient) showed abnormal findings in the prostate gland. In a region-based analysis, overall sensitivity and specificity of [Ga-68]Ga-RM2 PET-CT in the detection of primary tumor were 74% and 90%, respectively, while it was 60% and 80% for [F-18]FCH PET-CT and 72% and 89% for mpMRI. Although the overall sensitivity of [Ga-68]Ga-RM2 PET-CT was higher compared to that of [F-18]FCH PET-CT and mpMRI, the statistical analysis showed only significant difference between [Ga-68]Ga-RM2 PET-CT and [F-18]FCH PET-CT in the intermediate-risk group (p = 0.01) and [Ga-68]Ga-RM2 PET-CT and mpMRT in the high-risk group (p = 0.03). In the lesion-based analysis, there was no significant difference between SUVmax of [Ga-68]Ga-RM2 and [F-18]FCH PET-CT in the intraprostatic malignant lesions ([Ga-68]Ga-RM2: mean SUVmax: 5.98 +/- 4.13, median: 4.75; [F-18]FCH: mean SUVmax: 6.08 +/- 2.74, median: 5.5; p = 0.13).Conclusions [Ga-68]Ga-RM2 showed promising PET tracer for the detection of intraprostatic PCa in a cohort of patients with different risk stratifications. However, significant differences were only found between [Ga-68]Ga-RM2 PET-CT and [F-18]FCH PET-CT in the intermediate-risk group and [Ga-68]Ga-RM2 PET-CT and mpMRT in the high-risk group. In addition, GRP-R-based imaging seems to play a complementary role to choline-based imaging for full characterization of PCa extent and biopsy guidance in low- and intermediate-metastatic-risk PCa patients and has the potential to discriminate them from those at higher risks.</p

The Electron Capture in 163^{163} Ho Experiment - a Short Update

The definition of the absolute neutrino mass scale is one of the main goals of the Particle Physics today. The study of the end-point regions of the β- and electron capture (EC) spectrum offers a possibility to determine the effective electron (anti-)neutrino mass in a completely model independent way, as it only relies on the energy and momentum conservation. The ECHo (Electron Capture in 163Ho) experiment has been designed in the attempt to measure the effective mass of the electron neutrino by performing high statistics and high energy resolution measurements of the 163 Ho electron capture spectrum. To achieve this goal, large arrays of low temperature metallic magnetic calorimeters (MMCs) implanted with with 163Ho are used. Here we report on the structure and the status of the experiment

Comparative efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for early onset chronic depression: design and rationale of a multisite randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Effective treatment strategies for chronic depression are urgently needed since it is not only a common and particularly disabling disorder, but is also considered treatment resistant by most clinicians. There are only a few studies on chronic depression indicating that traditional psycho- and pharmacological interventions are not as effective as in acute, episodic depression. Current medications are no more effective than those introduced 50 years ago whereas the only psychotherapy developed specifically for the subgroup of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), faired well in one large trial. However, CBASP has never been directly compared to a non-specific control treatment.</p> <p>Methods/Design</p> <p>The present article describes the study protocol of a multisite parallel-group randomized controlled trial in Germany. The purpose of the study is to estimate the efficacy of CBASP compared to supportive psychotherapy in 268 non-medicated early-onset chronically depressed outpatients. The intervention includes 20 weeks of acute treatment with 24 individual sessions followed by 28 weeks of continuation treatment with another 8 sessions. Depressive symptoms are evaluated 20 weeks after randomisation by means of the 24-item Hamilton Rating Scale of Depression (HRSD). Secondary endpoints are depressive symptoms after 12 and 48 weeks, and remission after 12, 20, and 48 weeks. Primary outcome will be analysed using analysis of covariance (ANCOVA) controlled for pre-treatment scores and site. Analyses of continuous secondary variables will be performed using linear mixed models. For remission rates, chi-squared tests and logistic regression will be applied.</p> <p>Discussion</p> <p>The study evaluates the comparative effects of a disorder-specific psychotherapy and a well designed non-specific psychological approach in the acute and continuation treatment phase in a large sample of early-onset chronically depressed patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00970437">NCT00970437</a>).</p