Differential Changes in QTc Duration during In-Hospital Haloperidol Use

Aims: To evaluate changes in QT duration during low-dose haloperidol use, and determine associations between clinical variables and potentially dangerous QT prolongation. Methods: In a retrospective cohort study in a tertiary university teaching hospital in The Netherlands, all 1788 patients receiving haloperidol between 2005 and 2007 were studied; ninety-seven were suitable for final analysis. Rate-corrected QT duration (QTc) was measured before, during and after haloperidol use. Clinical variables before haloperidol use and at the time of each ECG recording were retrieved from hospital charts. Mixed model analysis was used to estimate changes in QT duration. Risk factors for potentially dangerous QT prolongation were estimated by logistic regression analysis. Results: Patients with normal before-haloperidol QTc duration (male <= 430 ms, female <= 450 ms) had a significant increase in QTc duration of 23 ms during haloperidol use; twenty-three percent of patients rose to abnormal levels (male >= 450 ms, female >= 470 ms). In contrast, a significant decrease occurred in patients with borderline (male 430-450 ms, female 450-470 ms) or abnormal before-haloperidol QTc duration (15 ms and 46 ms, respectively); twenty-three percent of patients in the borderline group, and only 9% of patients in the abnormal group obtained abnormal levels. Potentially dangerous QTc prolongation was independently associated with surgery before haloperidol use (OR(adj) 34.9, p = 0.009) and before-haloperidol QTc duration (OR(adj) 0.94, p = 0.004). Conclusion: QTc duration during haloperidol use changes differentially, increasing in patients with normal before-haloperidol QTc duration, but decreasing in patients with prolonged before-haloperidol QTc duration. Shorter before-haloperidol QTc duration and surgery before haloperidol use predict potentially dangerous QTc prolongatio

Beyond in-phase and anti-phase coordination in a model of joint action

In 1985, Haken, Kelso and Bunz proposed a system of coupled nonlinear oscillators as a model of rhythmic movement patterns in human bimanual coordination. Since then, the Haken–Kelso–Bunz (HKB) model has become a modelling paradigm applied extensively in all areas of movement science, including interpersonal motor coordination. However, all previous studies have followed a line of analysis based on slowly varying amplitudes and rotating wave approximations. These approximations lead to a reduced system, consisting of a single differential equation representing the evolution of the relative phase of the two coupled oscillators: the HKB model of the relative phase. Here we take a different approach and systematically investigate the behaviour of the HKB model in the full four-dimensional state space and for general coupling strengths. We perform detailed numerical bifurcation analyses and reveal that the HKB model supports previously unreported dynamical regimes as well as bistability between a variety of coordination patterns. Furthermore, we identify the stability boundaries of distinct coordination regimes in the model and discuss the applicability of our findings to interpersonal coordination and other joint action tasks

Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation

Poorly organized tumour vasculature often results in areas of limited nutrient supply and hypoxia. Despite our understanding of solid tumour responses to hypoxia, how nutrient deprivation regionally affects tumour growth and therapeutic response is poorly understood. Here, we show that the core region of solid tumours displayed glutamine deficiency compared with other amino acids. Low glutamine in tumour core regions led to dramatic histone hypermethylation due to decreased α-ketoglutarate levels, a key cofactor for the Jumonji-domain-containing histone demethylases. Using patient-derived ^(V600E)BRAF melanoma cells, we found that low-glutamine-induced histone hypermethylation resulted in cancer cell dedifferentiation and resistance to BRAF inhibitor treatment, which was largely mediated by methylation on H3K27, as knockdown of the H3K27-specific demethylase KDM6B and the methyltransferase EZH2 respectively reproduced and attenuated the low-glutamine effects in vitro and in vivo. Thus, intratumoral regional variation in the nutritional microenvironment contributes to tumour heterogeneity and therapeutic response

Ecological effects of water-level fluctuations in lakes: An urgent issue

These articles show the large variety of issues that involve WLF in lakes. When attempting to summarise the manuscripts for the current article, we found how many lacunae still exist and how necessary it is to intensify research in this interesting and important field of ecology