High count rate {\gamma}-ray spectroscopy with LaBr3:Ce scintillation detectors

The applicability of LaBr3:Ce detectors for high count rate {\gamma}-ray spectroscopy is investigated. A 3"x3" LaBr3:Ce detector is used in a test setup with radioactive sources to study the dependence of energy resolution and photo peak efficiency on the overall count rate in the detector. Digitized traces were recorded using a 500 MHz FADC and analysed with digital signal processing methods. In addition to standard techniques a pile-up correction method is applied to the data in order to further improve the high-rate capabilities and to reduce the losses in efficiency due to signal pile-up. It is shown, that {\gamma}-ray spectroscopy can be performed with high resolution at count rates even above 1 MHz and that the performance can be enhanced in the region between 500 kHz and 10 MHz by using pile-up correction techniques

Prospects for High Energy Resolution Gamma Ray Spectroscopy with Europium-Doped Strontium Iodide

Europium-doped strontium iodide scintillators offer a light yield exceeding 100,000 photons/MeV and excellent light yield proportionality, while at the same time, SrI{sub 2} is readily grown in single crystal form. Thus far, our collaboration has demonstrated an energy resolution with strontium iodide of 2.6% at 662 keV and 7.6% at 60 keV, and we have grown single crystals surpassing 30 cm{sup 3} in size (with lower resolution). Our analysis indicates that SrI{sub 2}(Eu) has the potential to offer 2% energy resolution at 662 keV with optimized material, optics, and read-out. In particular, improvements in feedstock purity may result in crystal structural and chemical homogeneity, leading to improved light yield uniformity throughout the crystal volume, and consequently, better energy resolution. Uniform, efficient light collection and detection, is also required to achieve the best energy resolution with a SrI{sub 2}(Eu) scintillator device

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. METHODS: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold is reported. RESULTS: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. CONCLUSIONS: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R 2) at the optimal p-value threshold is reported. Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R 2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R 2 = 8.18%, p = .0013), Belgium (R 2 = 6.83%, p = .016), and the Netherlands (R 2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R 2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R 2 = 4.42%, p = .0024) and unipolar MDE only (R 2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry

The impact of treatment resistance on outcome and course of electroconvulsive therapy in major depressive disorder

Introduction: Major depressive disorder (MDD) is a common psychiatric disorder. Despite several treatment options, a subgroup of patients will not respond to the commonly used antidepressant treatments and thus express treatment resistance (TRD). TRD can be quantified with the Dutch Measure for Treatment Resistance in Depression (DM-TRD). Electroconvulsive therapy (ECT) is an effective treatment for MDD, also in TRD. Yet, the position of ECT as “treatment-of-last-resort” may decrease the likelihood of beneficial outcome. Our aim was to investigate the association between treatment resistance and outcome and course of ECT. Methods: We performed a retrospective, multicenter cohort study with 440 patients of which data was retrieved from patient records as collected in the Dutch ECT Cohort database. Linear and logistic regression models were used to explore the association between level of treatment resistance and outcome of ECT. Median split was used to explore the differences between high and low level of TRD and course of treatment. Results: A higher DM-TRD score was associated with significantly smaller reduction of depression symptoms (R 2 = 0.160; β = −2.968; p < 0.001) and lower chance of response (OR = 0.821 [95 CI: 0.760–0.888]; β = −0.197; p < 0.001). Low level TRD patients underwent fewer ECT sessions (mean 13 ± 6 SD vs. 16 ± 7 SD; p < 0.001) and fewer switches from right unilateral tot bifrontotemporal electrode placement (29% vs. 40%; p = 0.032). Conclusion: Reserving ECT as “treatment-of-last-resort” in the treatment algorithm for MDD seems questionable, because in our study lower level of treatment resistance predicted more beneficial ECT-outcome. Moreover, providing ECT in less treatment resistant patients showed fewer needed ECT-sessions and less switches to BL electrode placement, which may decrease the risk for cognitive side-effects

Computer-assisted glucose control in critically ill patients

Objective: Intensive insulin therapy is associated with the risk of hypoglycemia and increased costs of material and personnel. We therefore evaluated the safety and efficiency of a computer-assisted glucose control protocol in a large population of critically ill patients. Design and setting: Observational cohort study in three intensive care units (32 beds) in a 1,300-bed university teaching hospital. Patients: All 2,800 patients admitted to the surgical, neurosurgical, and cardiothoracic units; the study period started at each ICU after implementation of Glucose Regulation for Intensive Care Patients (GRIP), a freely available computer-assisted glucose control protocol. Measurements and results: We analysed compliance in relation to recommended insulin pump rates and glucose measurement frequency. Patients were on GRIP-ordered pump rates 97% of time. Median measurement time was 5 min late (IQR 20 min early to 34 min late). Hypoglycemia was uncommon (7% of patients for mild hypoglycemia, <3.5 mmol/l; 0.86% for severe hypoglycemia, <2.2 mmol/l). Our predefined target range (4.0 - 7.5 mmol/l) was reached after a median of 5.6h (IQR 0.2 - 11.8) and maintained for 89% (70 - 100%) of the remaining stay at the ICU. The number of measurements needed was 5.9 (4.8 - 7.3) per patient per day. In-hospital mortality was 10.1%. Conclusions: Our computer-assisted glucose control protocol provides safe and efficient glucose regulation in routine intensive care practice. A low rate of hypoglycemic episodes was achieved with a considerably lower number of glucose measurements than used in most other schemes

The additional value of TGFβ1 and IL-7 to predict the course of prostate cancer progression

Background: Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGFβ1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer

Action 3:30R: Process evaluation of a cluster randomised feasibility study of a revised teaching assistant-led extracurricular physical activity intervention for 8 to 10 year olds

Background: Numerous interventions to increase children's physical activity levels are published, yet, few studies report indicators of external validity. Process evaluations are critical for assessing intervention implementation, sustainability and effectiveness. A mixed-methods process evaluation, using the RE-AIM framework, was conducted to evaluate the internal and external validity of Action 3:30R, a revised teaching assistant-led after-school intervention which aimed to increase physical activity in children aged 8-10 years and was underpinned by Self-determination Theory (SDT). Methods: Data were collected and reported in line with the five components of RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance). Quantitative measures included logbooks, registers and self-reported teaching-efficacy, autonomy support, child enjoyment and perceived exertion questionnaires. Questionnaire data were collected at three points throughout the 15-week intervention. Observations by trained researchers were also conducted to assess fidelity to the intervention manual and its underpinning theory. Post-intervention focus groups with pupils and interviews with teaching assistants (TAs), school staff and external stakeholders explored the implementation and potential sustainability of Action 3:30R from stakeholders' perspectives. Results: Action 3:30R appealed to a broad range of pupils, including girls and less-active pupils. The Action 3:30R TA training was implemented as intended and was perceived as valuable professional development. Releasing staff for training was a barrier in two of the six intervention schools, which were unable to deliver the intervention as a result. Pupils enjoyed the intervention, and the Action 3:30R core principles underpinned by SDT were implemented with high fidelity, as was the intervention itself. Scheduling conflicts with other clubs and lack of parental support were perceived as the main barriers to recruitment and attendance. Lack of space and season were cited as the main barriers affecting the quality of delivery. The study shows evidence of maintenance, as one intervention school decided to continue Action 3:30R beyond the study. Funding and continued TA training were suggested as factors which may affect the maintenance of Action 3:30R. Conclusions: Action 3:30R is an enjoyable, autonomy-supportive after-school programme, which engages a range of pupils and offers TAs valuable training. RE-AIM provided helpful structure and is recommended for intervention evaluations. Trial registration: ISRCTN34001941. Prospectively registered 01/12/2016