The disappearing January blip and other state employment mysteries

Employment (Economic theory) ; Statistics

Parasite co-infection: an ecological, molecular and experimental perspective.

Laboratory studies of pathogens aim to limit complexity in order to disentangle the important parameters contributing to an infection. However, pathogens rarely exist in isolation, and hosts may sustain co-infections with multiple disease agents. These interact with each other and with the host immune system dynamically, with disease outcomes affected by the composition of the community of infecting pathogens, their order of colonization, competition for niches and nutrients, and immune modulation. While pathogen-immune interactions have been detailed elsewhere, here we examine the use of ecological and experimental studies of trypanosome and malaria infections to discuss the interactions between pathogens in mammal hosts and arthropod vectors, including recently developed laboratory models for co-infection. The implications of pathogen co-infection for disease therapy are also discussed

African trypanosomes

Abstract African trypanosomes cause human African trypanosomiasis and animal African trypanosomiasis. They are transmitted by tsetse flies in sub-Saharan Africa. Although most famous for their mechanisms of immune evasion by antigenic variation, there have been recent important studies that illuminate important aspects of the biology of these parasites both in their mammalian host and during passage through their tsetse fly vector. This Primer overviews current research themes focused on these parasites and discusses how these biological insights and the development of new technologies to interrogate gene function are being used in the search for new approaches to control the parasite. The new insights into the biology of trypanosomes in their host and vector highlight that we are in a ‘golden age’ of discovery for these fascinating parasites

Dosimetric implications of the potential radionuclidic impurities in 153Sm-DOTMP

https://openworks.mdanderson.org/articleip/1000/thumbnail.jp

Uncomplicated obesity is associated with abnormal aortic function assessed by cardiovascular magnetic resonance

AIMS: Obese subjects with insulin resistance and hypertension have abnormal aortic elastic function, which may predispose them to the development of left ventricular dysfunction. We hypothesised that obesity, uncomplicated by other cardiovascular risk factors, is independently associated with aortic function. METHODS AND RESULTS: We used magnetic resonance imaging to measure aortic compliance, distensibility and stiffness index in 27 obese subjects (BMI 33 kg/m2) without insulin resistance and with normal cholesterol and blood pressure, and 12 controls (BMI 23 kg/m2). Obesity was associated with reduced aortic compliance (0.9 +/- 0.1 vs. 1.5 +/- 0.2 mm2/mmHg in controls, p < 0.02) and distensibility (3.3 +/- 0.01 vs. 5.6 +/- 0.01 mmHg-1 x 10-3, p < 0.02), as well as higher stiffness index (3.4 +/- 0.3 vs. 2.1 +/- 0.1, p < 0.02). Body mass index and fat mass were negatively correlated with aortic function. Leptin was higher in obesity (8.9 +/- 0.6 vs. 4.7 +/- 0.6 ng/ml, p < 0.001) and also correlated with aortic measures. In multiple regression models, fat mass, leptin and body mass index were independent predictors of aortic function. CONCLUSION: Aortic elastic function is abnormal in obese subjects without other cardiovascular risk factors. These findings highlight the independent importance of obesity in the development of cardiovascular disease

A preclinical investigation of the saturation and dosimetry of 153Sm-DOTMP as a bone-seeking radiopharmaceutical

Simón J, Frank RK, Crump DK, Erwin WD, Ueno NT, Wendt RE. A preclinical investigation of the saturation and dosimetry of 153Sm-DOTMP as a bone-seeking radiopharmaceutical. Nuclear Medicine and Biology. 2012/08/01/ 2012;39(6):770-776. doi:https://doi.org/10.1016/j.nucmedbio.2011.12.015https://openworks.mdanderson.org/mdacc_imgphys_pubs/1006/thumbnail.jp

Chemical-free lysis and fractionation of cells by use of surface acoustic waves for sensitive protein assays

We exploit the mechanical action of surface acoustic waves (SAW) to differentially lyse human cancer cells in a chemical-free manner. The extent to which cells were disrupted is reported for a range of SAW parameters, and we show that the presence of 10 μm polystyrene beads is required to fully rupture cells and their nuclei. We show that SAW is capable of subcellular fractionation through the chemical-free isolation of nuclei from whole cells. The concentration of protein was assessed in lysates with a sensitive microfluidic antibody capture (MAC) chip. An antibody-based sandwich assay in a microfluidic microarray format was used to detect unlabeled human tumor suppressor protein p53 in crude lysates, without any purification step, with single-molecule resolution. The results are digital, enabling sensitive quantification of proteins with a dynamic range >4 orders of magnitude. For the conditions used, the efficiency of SAW-induced mechanical lysis was determined to be 12.9% ± 0.7% of that for conventional detergent-based lysis in yielding detectable protein. A range of possible loss mechanisms that could lead to the drop in protein yield are discussed. Our results show that the methods described here are amenable to an integrated point-of-care device for the assessment of tumor protein expression in fine needle aspirate biopsies

Pharmacokinetic properties of remimazolam in subjects with hepatic or renal impairment

BACKGROUND: Remimazolam is a new benzodiazepine for procedural sedation and general anaesthesia. The aim of this study was to characterise its pharmacokinetic properties and safety in renally and hepatically impaired subjects. METHODS: Two separate trials were conducted in patients with hepatic (n=11) or renal impairment (n=11) compared with matched healthy subjects (n=9 and n=12, respectively). The hepatic impairment trial was an open-label adaptive 'Reduced Design' trial, using a single bolus of remimazolam 0.1 mg kg-1 i.v., whereas the renal impairment trial was an open-label trial of a single bolus dose of remimazolam 1.5 mg i.v. Remimazolam plasma concentrations over time were analysed by population pharmacokinetic modelling. RESULTS: Remimazolam pharmacokinetic properties were adequately described by a three-compartment, recirculatory model. Exposure in subjects with severe hepatic impairment was 38.1% higher (i.e. clearance was 38.1% lower) compared with healthy volunteers. This increase caused a slightly delayed recovery (8.0 min for healthy, 12.1 min for moderate, and 16.7 min for severe hepatic impairment). With renal impairment, plasma clearance was comparable with that measured in healthy subjects. Simulations of Cmax after a bolus dose of 10 mg showed no relevant impact of hepatic or renal impairment. The overall incidence of adverse events was low, and all adverse events were mild. CONCLUSIONS: As Cmax after a remimazolam bolus i.v. was not affected by hepatic or renal impairment, no dose adjustments are required. No unexpected adverse events related to remimazolam were seen in subjects with renal or hepatic impairment. CLINICAL TRIAL REGISTRATION: Hepatic impairment trial: ClinicalTrials.gov, NCT01790607 (https://clinicaltrials.gov/ct2/show/NCT01790607). Renal impairment trial: EudraCT Number: 2014-004575-23