Interactions between Predation and Resources Shape Zooplankton Population Dynamics

Identifying the relative importance of predation and resources in population dynamics has a long tradition in ecology, while interactions between them have been studied less intensively. In order to disentangle the effects of predation by juvenile fish, algal resource availability and their interactive effects on zooplankton population dynamics, we conducted an enclosure experiment where zooplankton were exposed to a gradient of predation of roach (Rutilus rutilus) at different algal concentrations. We show that zooplankton populations collapse under high predation pressure irrespective of resource availability, confirming that juvenile fish are able to severely reduce zooplankton prey when occurring in high densities. At lower predation pressure, however, the effect of predation depended on algal resource availability since high algal resource supply buffered against predation. Hence, we suggest that interactions between mass-hatching of fish, and the strong fluctuations in algal resources in spring have the potential to regulate zooplankton population dynamics. In a broader perspective, increasing spring temperatures due to global warming will most likely affect the timing of these processes and have consequences for the spring and summer zooplankton dynamics

Azacitidine and Durvalumab in First-line Treatment of Elderly Patients With Acute Myeloid Leukemia.

Evidence suggests that combining immunotherapy with hypomethylating agents may enhance antitumor activity. This phase 2 study investigated the activity and safety of durvalumab, a programmed death ligand 1 (PD-L1) inhibitor, combined with azacitidine for patients aged ≥65 years with acute myeloid leukemia (AML), including analyses to identify biomarkers of treatment response. Patients were randomized to first-line therapy with azacitidine 75 mg/m2 on days 1-7 with (Arm A, n= 64) or without (Arm B, n=65) durvalumab 1500 mg on day 1 every 4 weeks. Overall response rate (complete response [CR] + CR with incomplete blood recovery [CRi]) was similar in both arms (Arm A, 31.3%; Arm B, 35.4%), as were overall survival (A, 13.0 months; B, 14.4 months) and duration of response (A, 24.6 weeks; B, 51.7 weeks; P=0.0765). No new safety signals emerged with combination treatment. The most frequently reported treatment-emergent adverse events were constipation (Arm A, 57.8%; Arm B, 53.2%) and thrombocytopenia (A, 42.2%; B, 45.2%). DNA methylation, mutational status, and PD-L1 expression were not associated with response to treatment. In this study, first-line combination therapy with durvalumab and azacitidine in older patients with AML was feasible, but did not improve clinical efficacy compared with azacitidine alone. ClinicalTrials.gov: NCT02775903

A multicenter retrospective study of charcot-marie-tooth disease type 4B (CMT4B) associated with mutations in myotubularin-related proteins (MTMRs).

OBJECTIVE: Charcot-Marie-Tooth (CMT) disease 4B1 and 4B2 (CMT4B1/B2) are characterized by recessive inheritance, early onset, severe course, slowed nerve conduction, and myelin outfoldings. CMT4B3 shows a more heterogeneous phenotype. All are associated with myotubularin-related protein (MTMR) mutations. We conducted a multicenter, retrospective study to better characterize CMT4B. METHODS: We collected clinical and genetic data from CMT4B subjects in 18 centers using a predefined minimal data set including Medical Research Council (MRC) scores of nine muscle pairs and CMT Neuropathy Score. RESULTS: There were 50 patients, 21 of whom never reported before, carrying 44 mutations, of which 21 were novel and six representing novel disease associations of known rare variants. CMT4B1 patients had significantly more-severe disease than CMT4B2, with earlier onset, more-frequent motor milestones delay, wheelchair use, and respiratory involvement as well as worse MRC scores and motor CMT Examination Score components despite younger age at examination. Vocal cord involvement was common in both subtypes, whereas glaucoma occurred in CMT4B2 only. Nerve conduction velocities were similarly slowed in both subtypes. Regression analyses showed that disease severity is significantly associated with age in CMT4B1. Slopes are steeper for CMT4B1, indicating faster disease progression. Almost none of the mutations in the MTMR2 and MTMR13 genes, responsible for CMT4B1 and B2, respectively, influence the correlation between disease severity and age, in agreement with the hypothesis of a complete loss of function of MTMR2/13 proteins for such mutations. INTERPRETATION: This is the largest CMT4B series ever reported, demonstrating that CMT4B1 is significantly more severe than CMT4B2, and allowing an estimate of prognosis. ANN NEUROL 2019

SAFETY OF INTRAVENOUS HIGH-DOSE DIPYRIDAMOLE ECHOCARDIOGRAPHY

Clinical data on 10,451 high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole-echocardiography tests (DET) performed in 9,122 patients were prospectively collected from 33 echocardiographic laboratories, each contributing >100 tests. All patients were studied for documented or suspected coronary artery disease (1,117 early [<18 days] after acute myocardial infarction and 293 had unstable angina). Significant side effects including major adverse reactions and minor but limiting side effects occurred in 113 patients (1.2%). Major adverse reactions occurred in 7 cases (0.07%). In 6 of these cases, adverse reactions were associated with echocardiographically assessed ischemia and included 1 prolonged cardiac asystole (complicated by acute myocardial infarction and coma, with death after 23 days), 1 short-lasting cardiac asystole, 2 myocardial infarctions, 1 pulmonary edema and 1 sustained ventricular tachycardia. In all 6 cases, the cardiologist-echocardiographer performing the study had a limited experience (<100 tests) with DET, and at off-line reading in 5 cases, the obvious echo-positivity preceded the onset of complications by 1 to 5 minutes. The only ischemia-independent major side effect was a short-lasting cardiac asystole that was reversed by aminophylline and atropine. Significant side effects associated with echocardiographically assessed ischemia occurred in 89 additional cases (21 with and 68 without concomitant echocardiographically assessed myocardial ischemia). The most frequent of these side effects was hypotension or bradycardia, or both, which occurred in 40 patients with negative and 6 with positive DET. In all cases, side effects promptly subsided after aminophylline. In 1,857 cases, the high dose was not given for echo-positivity before the eighth minute. In 60 cases, the full high dose was not given despite the echocardiographic negativity for limiting side effect, yielding an overall feasibility of high-dose DET of 99%. Aminophylline was routinely administered also at the end of negative tests. Noticeable side effects occurred in 17 cases. In 13 patients (7 with negative and 6 with positive DET) transient ST-segment elevation occurred 1 to 4 minutes after the onset of aminophylline infusion, accompanied by regional dyssynergy. All 13 patients had variant angina. Thus, high-dose DET is reasonably safe and well-tolerated, even early after acute myocardial infarction and in patients with unstable angina, when selectively used in patients in whom the lower dose did not induce either echocardiographic signs of ischemia or limiting side effects