Determination of the 161Tb half-life.

There is significant interest in the use of terbium radioisotopes for applications in cancer therapy and diagnosis. Of these, 161Tb, as a medium energy beta-emitter, is being investigated as a potential alternative to 177Lu. The relatively high proportion of conversion electron and Auger electron emissions per decay make 161Tb an attractive targeted therapeutic. As a product of nuclear fission, 161Tb is also of importance to nuclear forensics. The standard uncertainty of the current evaluated half-life of 6.89(2) d contributes significantly to the standard uncertainty of any decay corrected activity determination made. Furthermore, the accuracy of this evaluated half-life has been called into question by measurements reported in 2020 at the Institute of Radiation Physics (IRA), Switzerland, who reported a half-life of 6.953(2) d. In the current work, the half-life of the 161Tb ground state decay has been measured at three independent laboratories located in the United Kingdom and the United States of America for a total of six determinations using three independent measurement techniques; gamma-ray spectrometry, ionisation chamber measurement and liquid scintillation counting. The half-life determined for 161Tb of 6.9637(29) d confirms the observed 1% relative increase observed by IRA, though the reported half-lives in this work and at IRA are significantly different (ζ-score = 3.1).

Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) drives migration and progression of T-cell acute lymphoblastic leukemia in vitro and in vivo.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer. There are no immunotherapies and few molecularly targeted therapeutics available for treatment of this malignancy. The identification and characterization of genes and pathways that drive T-ALL progression are critical for the development of new therapies for T-ALL. Here, we determined that the protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) plays a critical role in T-ALL initiation and progression by promoting leukemia cell migration. PRL-3 is highly expressed in patient T-ALL samples at both the mRNA and protein levels compared to normal lymphocytes. Knock-down of PRL-3 expression using short-hairpin RNA (shRNA) in human T-ALL cell lines significantly impeded T-ALL cell migration capacity in vitro and reduced their ability to engraft and proliferate in vivo in xenograft mouse models. Additionally, PRL-3 overexpression in a Myc-induced zebrafish T-ALL model significantly accelerated disease onset and shortened the time needed for cells to enter blood circulation. Reverse-phase protein array (RPPA) and gene set enrichment analysis (GSEA) revealed that the SRC signaling pathway is affected by PRL-3. Immunoblot analyses validated that manipulation of PRL-3 expression in T-ALL cells affected the SRC signaling pathway, which is directly involved in cell migration, although Src was not a direct substrate of PRL-3. More importantly, T-ALL cell growth and migration were inhibited by small molecule inhibition of PRL-3, suggesting that PRL-3 has potential as a therapeutic target in T-ALL. Taken together, our study identifies PRL-3 as an oncogenic driver in T-ALL both in vitro and in vivo and provides a strong rationale for targeted therapies that interfere with PRL-3 function.

Turkish teachers' self-efficacy to manage food allergy and anaphylaxis: A psychometric testing study

Introduction and objectives: Food allergy in school children ranges between 5.7 and 6.4% in Turkey. Studies emphasize the importance of improving school personnel's self-efficacy in managing food allergy and anaphylaxis. However, a brief and valid measurement tool for school personnel is not available in Turkey. The aim of this study was to determine the validity and reliability of the Turkish version of the School Personnel's Self-efficacy in Managing Food Allergy and Anaphylaxis (SPSMFAA-T) scale with teachers. Patients or materials and methods: This methodological study was conducted by 282 primary school teachers. Data were collected with a demographic characteristics form and SPSMFAA-T. The psychometric properties of the SPSMFAA-T were evaluated by content, discriminant, construct validity and internal consistency. Results: Cronbach's alpha for the scale was 0.91 and item-total correlations were between 0.50 and 0.82 (p < 0.001). The discriminant validity suggested that the scale successfully discriminated the teachers who had training on food allergy and anaphylaxis from the teachers who did not. The model fit indices of scale were determined to be the root mean square error of approximation (RMSEA) at 0.08, goodness of fit index (GFI) at 0.96, comparative fit index (CFI) at 0.99. Conclusions: The results supported that the SPSMFAA-T was a valid and reliable measurement tool to assess Turkish teachers’ self-efficacy levels to manage food allergy and anaphylaxis in school setting. The scale can be used in education programs to improve school personnel's skills to manage food allergy and anaphylaxis

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Turkish teachers' self-efficacy to manage food allergy and anaphylaxis: A psychometric testing study.

INTRODUCTION AND OBJECTIVES: Food allergy in school children ranges between 5.7 and 6.4% in Turkey. Studies emphasize the importance of improving school personnel's self-efficacy in managing food allergy and anaphylaxis. However, a brief and valid measurement tool for school personnel is not available in Turkey. The aim of this study was to determine the validity and reliability of the Turkish version of the School Personnel's Self-efficacy in Managing Food Allergy and Anaphylaxis (SPSMFAA-T) scale with teachers. PATIENTS OR MATERIALS AND METHODS: This methodological study was conducted by 282 primary school teachers. Data were collected with a demographic characteristics form and SPSMFAA-T. The psychometric properties of the SPSMFAA-T were evaluated by content, discriminant, construct validity and internal consistency. RESULTS: Cronbach's alpha for the scale was 0.91 and item-total correlations were between 0.50 and 0.82 (p<0.001). The discriminant validity suggested that the scale successfully discriminated the teachers who had training on food allergy and anaphylaxis from the teachers who did not. The model fit indices of scale were determined to be the root mean square error of approximation (RMSEA) at 0.08, goodness of fit index (GFI) at 0.96, comparative fit index (CFI) at 0.99. CONCLUSIONS: The results supported that the SPSMFAA-T was a valid and reliable measurement tool to assess Turkish teachers' self-efficacy levels to manage food allergy and anaphylaxis in school setting. The scale can be used in education programs to improve school personnel's skills to manage food allergy and anaphylaxis.

Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure.

BACKGROUND: Adult critically ill patients often suffer from acute circulatory failure and those with low cardiac output may be treated with inotropic agents. The aim of this Scandinavian Society of Anaesthesiology and Intensive Care Medicine guideline was to present patient-important treatment recommendations on this topic. METHODS: This guideline was developed according to GRADE. We assessed the following subpopulations of patients with shock: (1) shock in general, (2) septic shock, (3) cardiogenic shock, (4) hypovolemic shock, (5) shock after cardiac surgery, and (6) other types of shock, including vasodilatory shock. We assessed patient-important outcome measures, including mortality and serious adverse reactions. RESULTS: For all patients, we suggest against the routine use of any inotropic agent, including dobutamine, as compared to placebo/no treatment (very low quality of evidence). For patients with shock in general, and in those with septic and other types of shock, we suggest using dobutamine rather than levosimendan or epinephrine (very low quality of evidence). For patients with cardiogenic shock and in those with shock after cardiac surgery, we suggest using dobutamine rather than milrinone (very low quality of evidence). For the other clinical questions, we refrained from giving any recommendations or suggestions. CONCLUSIONS: We suggest against the routine use of any inotropic agent in adult patients with shock. If used, we suggest using dobutamine rather than other inotropic agents for the majority of patients, however, the quality of evidence was very low, implying high uncertainty on the balance between the benefits and harms of inotropic agents.

The impact of fatigue on the non-technical skills performance of critical care air ambulance clinicians.

BACKGROUND: The relationship between fatigue-related risk and impaired clinical performance is not entirely clear. Non-technical factors represent an important component of clinical performance and may be sensitive to the effects of fatigue. The hypothesis was that the sum score of overall non-technical performance is degraded by fatigue. METHODS: Nineteen physicians undertook two different simulated air ambulance missions, once when rested, and once when fatigued (randomised crossover design). Trained assessors blinded to participants' fatigue status performed detailed structured assessments based on expected behaviours in four non-technical skills domains: teamwork, situational awareness, task management, and decision making. Participants also provided self-ratings of their performance. The primary endpoint was the sum score of overall non-technical performance. RESULTS: The main finding, the overall non-technical skills performance rating of the clinicians, was better in rested than fatigued states (mean difference with 95% CI, 2.8 [2.2-3.4]). The findings remained consistent across individual non-technical skills domains; also when controlling for an order effect and examining the impact of a number of possible covariates. There was no difference in self-ratings of clinical performance between rested and fatigued states. CONCLUSION: Non-technical performance of critical care air transfer clinicians is degraded when they are fatigued. Fatigued clinicians may fail to recognise the degree to which their performance is compromised. These findings represent risk to clinical care quality and patient safety in the dynamic and isolated environment of air ambulance transfer.

Deficits in striatal dopamine release in cannabis dependence.

Most drugs of abuse lead to a general blunting of dopamine release in the chronic phase of dependence, which contributes to poor outcome. To test whether cannabis dependence is associated with a similar dopaminergic deficit, we examined striatal and extrastriatal dopamine release in severely cannabis-dependent participants (CD), free of any comorbid conditions, including nicotine use. Eleven CD and 12 healthy controls (HC) completed two positron emission tomography scans with [11C]-(+)-PHNO, before and after oral administration of d-amphetamine. CD stayed inpatient for 5-7 days prior to the scans to standardize abstinence. Magnetic resonance spectroscopy (MRS) measures of glutamate in the striatum and hippocampus were obtained in the same subjects. Percent change in [11C]-(+)-PHNO-binding potential (ΔBPND) was compared between groups and correlations with MRS glutamate, subclinical psychopathological and neurocognitive parameters were examined. CD had significantly lower ΔBPND in the striatum (P=0.002, effect size (ES)=1.48), including the associative striatum (P=0.003, ES=1.39), sensorimotor striatum (P=0.003, ES=1.41) and the pallidus (P=0.012, ES=1.16). Lower dopamine release in the associative striatum correlated with inattention and negative symptoms in CD, and with poorer working memory and probabilistic category learning performance in both CD and HC. No relationships to MRS glutamate and amphetamine-induced subclinical positive symptoms were detected. In conclusion, this study provides evidence that severe cannabis dependence-without the confounds of any comorbidity-is associated with a deficit in striatal dopamine release. This deficit extends to other extrastriatal areas and predicts subclinical psychopathology.

Scandinavian SSAI clinical practice guideline on choice of first-line vasopressor for patients with acute circulatory failure.

BACKGROUND: Adult critically ill patients often suffer from acute circulatory failure, necessitating use of vasopressor therapy. The aim of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force for Acute Circulatory Failure was to present clinically relevant, evidence-based treatment recommendations on this topic. METHODS: This guideline was developed according to standards for trustworthy guidelines, including a systematic review of the literature and use of the GRADE methodology for assessment of the quality of evidence and for moving from evidence to recommendations. We assessed the following subpopulations of patients with acute circulatory failure: 1) shock in general, 2) septic shock, 3) cardiogenic shock, 4) hypovolemic shock and 5) other types of shock, including vasodilatory shock. We assessed patient-important outcome measures, including mortality, serious adverse reactions and quality-of-life. RESULTS: For patients with shock in general and those with septic shock, we recommend using norepinephrine rather than dopamine, and we suggest using norepinephrine rather than epinephrine, vasopressin analogues, and phenylephrine. For patients with cardiogenic shock and those with hypovolemic shock, we suggest using norepinephrine rather than dopamine, and we provide no recommendations/suggestions of norepinephrine vs. epinephrine, vasopressin analogues, and phenylephrine. For patients with other types of shock, including vasodilatory shock, we suggest using norepinephrine rather than dopamine, epinephrine, vasopressin analogues, and phenylephrine. CONCLUSIONS: We recommend using norepinephrine rather than other vasopressors as first-line treatment for the majority of adult critically ill patients with acute circulatory failure.

Scandinavian clinical practice guideline on choice of fluid in resuscitation of critically ill patients with acute circulatory failure

BACKGROUND: The task force on Acute Circulatory Failure of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine produced this guideline with recommendations concerning the use of crystalloid vs. colloid solutions in adult critically ill patients with acute circulatory failure. METHODS: Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to grade the quality of evidence and to determine the strengths of the recommendations. As efficacy and harm may vary in different subpopulations of patients with acute circulatory failure, we produced recommendations for general intensive care unit (ICU) patients and those with sepsis, trauma and burn injury. RESULTS: For general ICU patients and those with sepsis, we recommend using crystalloids for resuscitation rather than hydroxyethyl starch and we suggest using crystalloids rather than gelatin and albumin. For patients with trauma we recommend to use crystalloids for resuscitation rather than colloid solutions. For patients with burn injury we provide no recommendations as there are very limited data from randomised trials on fluid resuscitation in this patient population. CONCLUSIONS: We recommend using crystalloid solutions rather than colloid solutions for resuscitation in the majority of critically ill patients with acute circulatory failure.

Scandinavian clinical practice guideline on choice of fluid in resuscitation of critically ill patients with acute circulatory failure.

BACKGROUND: The task force on Acute Circulatory Failure of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine produced this guideline with recommendations concerning the use of crystalloid vs. colloid solutions in adult critically ill patients with acute circulatory failure. METHODS: Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to grade the quality of evidence and to determine the strengths of the recommendations. As efficacy and harm may vary in different subpopulations of patients with acute circulatory failure, we produced recommendations for general intensive care unit (ICU) patients and those with sepsis, trauma and burn injury. RESULTS: For general ICU patients and those with sepsis, we recommend using crystalloids for resuscitation rather than hydroxyethyl starch and we suggest using crystalloids rather than gelatin and albumin. For patients with trauma we recommend to use crystalloids for resuscitation rather than colloid solutions. For patients with burn injury we provide no recommendations as there are very limited data from randomised trials on fluid resuscitation in this patient population. CONCLUSIONS: We recommend using crystalloid solutions rather than colloid solutions for resuscitation in the majority of critically ill patients with acute circulatory failure.

Emotion regulation: quantitative meta-analysis of functional activation and deactivation.

Emotion regulation is hypothesized to be a multifaceted process by which individuals willfully modulate the intensity and direction of emotional response via prefrontally mediated inhibition of subcortical response-related regions of the brain. Here we employ activation likelihood estimation (ALE) meta-analysis of functional magnetic resonance imaging studies to (1) reveal a consistent network of structures active during emotion regulation, (2) identify the target regions inactivated by the willful regulation process, and (3) investigate the consistency of activated structures associated with downregulation and upregulation. Results reveal signal change in bilateral amygdala/parahippocampal gyrus that decreased in downregulated states and increased in upregulated states, while cortical regions including superior frontal gyrus, cingulate, and premotor areas exhibited enhanced activity across all regulation conditions. These results provide consistent evidence for the role of amygdala activity in experienced emotional intensity, where intentional dampening and exaggeration are clearly expressed. However, the execution of emotional upregulation and downregulation may involve distinct subsets of frontocortical structures.

Regional changes in cerebral blood flow oxygenation can indicate global changes in cerebral blood flow during coronary artery occlusion in juvenile pigs.

Near infrared spectroscopy (NIRS) is a widely employed method for assessment of regional cerebral oxygenation (RcStO2). RcStO2 values are expected to vary with changes in the relative amount of oxyhaemoglobin. The present experimental study aimed to assess the response of RcStO2 to controlled alterations of carotid blood flow (CQ). Landrace pigs were anesthetized followed by surgical preparation. Cyclic variations in cardiac output were accomplished by intermittently occluding the main stem of the left coronary artery. A flow measurement probe for assessing CQ was placed around the left carotid artery. One NIRS probe was placed on the left ipsilateral forehead to assess regional cerebral oximetry. Simultaneous registration of CQ and RcStO2 was conducted. There was a strong correlation for variation in CQ and RcStO2 signal values. Based on coherence analysis the fraction of power of the RcStO2 that was coherent with the CQ signal reached 0.84 ± 0.12 (P < 0.05) for frequencies lower than 0.1 Hz. The agreement of the sample-to-sample co-variation, as assessed by the Pearson correlation coefficient, was 0.83 ± 0.08 (P < 0.05). One explanatory component for variations in cerebral oxygenation verified by NIRS should be attributed to variations in the cerebral blood flow.

Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.

BACKGROUND: Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia. METHODS: Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 µg/kg bolus plus infusion 0.5 µg/kg/min (n = 7), levosimendan 24 µg/kg plus infusion 0.2 µg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery. RESULTS: During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable. CONCLUSIONS: These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium.