Neuropsychopharmacology of appetite in healthy volunteers

This thesis aimed to develop an Experimental Medicine Model for the assessment of the potential efficacy and psychiatric safety of novel anti-obesity drugs. Chapter 1 provides a general introduction. In Chapter 2, a Universal Eating Monitor (UEM) detected the satiety enhancing effects of an appetite suppressant drug (meta-chlorophenylpiperazine – mCPP) and the P1vital® Oxford Emotional Test Battery (ETB) suggested an absence of psychiatric side-effects. In Chapter 3, UEM measures of eating behaviour were similar whether or not the participants were aware of the UEM. Chapter 4 presents two studies providing evidence that 1) repeated use of the ETB is feasible and 2) performance on the ETB is not affected by satiety. In Chapter 5, functional magnetic resonance imaging (fMRI) was used to identify a profile of natural satiety. In Chapter 6, mCPP reduced brain activity to high calorie food images. It also reduced consumption of a palatable cookie snack but not a pasta meal. Analysis of individual differences to the drug showed that brain activity predicted anorectic response. Chapter 7 concludes that the Experimental Medicine Model may be valuable for the development of efficacious and safe appetite suppressant drugs, providing data to inform go/no go decisions in early phase clinical trials

Epeoloides pilosulus (Cresson) Rediscovered in Michigan, with Notes on the Distribution and Status of its Macropis hosts.

Epeoloides pilosulus (Cresson 1878) is one of the rarest bees in North America with only a handful of records since 1960. The last collection in Michigan was made in 1944. Epeoloides pilosulus is a brood parasite of Macropis bees, which until recently had not been collected in Michigan for several decades. Bee surveys in Midland County, Michigan have led to the rediscovery of E. pilosulus in this state – the first record in 74 years. Michigan becomes the fourth state where E. pilosulus has been rediscovered after Connecticut in 2006, New York in 2014 and Maine in 2016, and the sixth region in North America after Nova Scotia in 2002 and Alberta in 2010. State-wide bee surveys have also shown that the principal host, Macropis nuda (Provancher 1882), remains widespread in Michigan, and that Macropis patellata Patton 1880 is newly recorded for the state

Experimental measurements of the permeability of fibrous carbon at high temperature

A series of experiments was performed to obtain permeability data on FiberForm(R), a commercial carbon preform used for manufacturing thermal protection systems. A porous sample was placed in a quartz flow-tube heated by an isothermal furnace. The setup was instrumented to measure mass flow through and pressure drop across the sample. The intrinsic permeability and the Klinkenberg correction, which accounts for rarefied effects, were computed from the experimental data. The role of the gas temperature and pressure on the effective permeability is shown, and it is demonstrated that with proper data reduction, the intrinsic permeability is strictly a function of the micro-structure of the material. A function for the effective permeability of FiberForm, dependent on temperature, pressure, pore geometry, and type of gas is proposed. The intrinsic permeability was evaluated at $K_0 = 5.57 \times 10^{-11}$ m$^2$, with a Klinkenberg parameter of $8c/d_p = 2.51 \times 10^5$ m$^{-1}$ and a reference porosity of $\phi^\dagger = 0.87$

Ampk regulates IgD expression but not energy stress with B cell activation.

Ampk is an energy gatekeeper that responds to decreases in ATP by inhibiting energy-consuming anabolic processes and promoting energy-generating catabolic processes. Recently, we showed that Lkb1, an understudied kinase in B lymphocytes and a major upstream kinase for Ampk, had critical and unexpected roles in activating naïve B cells and in germinal center formation. Therefore, we examined whether Lkb1 activities during B cell activation depend on Ampk and report surprising Ampk activation with in vitro B cell stimulation in the absence of energy stress, coupled to rapid biomass accumulation. Despite Ampk activation and a controlling role for Lkb1 in B cell activation, Ampk knockout did not significantly affect B cell activation, differentiation, nutrient dynamics, gene expression, or humoral immune responses. Instead, Ampk loss specifically repressed the transcriptional expression of IgD and its regulator, Zfp318. Results also reveal that early activation of Ampk by phenformin treatment impairs germinal center formation but does not significantly alter antibody responses. Combined, the data show an unexpectedly specific role for Ampk in the regulation of IgD expression during B cell activation

The rise of a middle class in East and Southern Africa: Implications for food system transformation

We examine the implications of the rise of a middle class in East and Southern Africa for food consumption patterns and the food system. A unique classification of food items shows that highly processed food has one-third of the purchased food market, with comparable shares in rural and urban areas (31 per cent vs 35 per cent), and among the vulnerable and upper middle classes (33 per cent vs 41 per cent). By linking FAOSTAT import data to consumption bundles, we show that the net import share falls with income in urban areas. Implications for food system change to 2040 are discussed

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies

There is strong evidence in literature supporting the benefit of monitoring plasma concentrations of β-lactam antibiotics in the critically ill to ensure appropriateness of dosing. The objective of this work was to develop a method for the simultaneous determination of total concentrations piperacillin, benzylpenicillin, flucloxacillin, meropenem, ertapenem, cephazolin and ceftazidime in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 0.1% formic acid and subsequent dilution of supernatant with 0.1% formic acid in water. Chromatographic separation was achieved on a reversed phase column (C18, 2.6. μm, 2.1. ×. 50. mm) via gradient elution using water and acetonitrile, each containing 0.1% formic acid, as mobile phase. Tandem mass spectrometry (MSMS) analysis was performed, after electrospray ionization in the positive mode, with multiple reaction monitoring (MRM). The method is accurate with the inter-day and intra-day accuracies of quality control samples (QCs) ranging from 95 to 107% and 95 to 108%, respectively. It is also precise with intra-day and inter-day coefficient of variations ranging from 4 to 12% and 5 to 14%, respectively. The lower limit of quantification was 0.1. μg/mL for each antibiotic except flucloxacillin (0.25. μg/mL). Recovery was greater than 96% for all analytes except for ertapenem (78%). Coefficients of variation for the matrix effect were less than 10% over the six batches of plasma. Analytes were stable over three freeze-thaw cycles, and for reasonable hours on the bench top as well as post-preparation. This novel liquid chromatography tandem mass spectrometry method proved accurate, precise and applicable for therapeutic drug monitoring and pharmacokinetic studies of the selected β-lactam antibiotics

Auxin and tryptophan homeostasis are facilitated by the ISS1/VAS1 aromatic aminotransferase in arabidopsis

Indole-3-acetic acid (IAA) plays a critical role in regulating numerous aspects of plant growth and development. While there is much genetic support for tryptophan-dependent (Trp-D) IAA synthesis pathways, there is little genetic evidence for tryptophan-independent (Trp-I) IAA synthesis pathways. Using Arabidopsis, we identified two mutant alleles of ISS1 ( I: ndole S: evere S: ensitive) that display indole-dependent IAA overproduction phenotypes including leaf epinasty and adventitious rooting. Stable isotope labeling showed that iss1, but not WT, uses primarily Trp-I IAA synthesis when grown on indole-supplemented medium. In contrast, both iss1 and WT use primarily Trp-D IAA synthesis when grown on unsupplemented medium. iss1 seedlings produce 8-fold higher levels of IAA when grown on indole and surprisingly have a 174-fold increase in Trp. These findings indicate that the iss1 mutant's increase in Trp-I IAA synthesis is due to a loss of Trp catabolism. ISS1 was identified as At1g80360, a predicted aromatic aminotransferase, and in vitro and in vivo analysis confirmed this activity. At1g80360 was previously shown to primarily carry out the conversion of indole-3-pyruvic acid to Trp as an IAA homeostatic mechanism in young seedlings. Our results suggest that in addition to this activity, in more mature plants ISS1 has a role in Trp catabolism and possibly in the metabolism of other aromatic amino acids. We postulate that this loss of Trp catabolism impacts the use of Trp-D and/or Trp-I IAA synthesis pathways.T32 AR059033 - NIAMS NIH HH

Mass casualty events: what to do as the dust settles?

Care during mass casualty events (MCE) has improved during the last 15 years. Military and civilian collaboration has led to partnerships which augment the response to MCE. Much has been written about strategies to deliver care during an MCE, but there is little about how to transition back to normal operations after an event. A panel discussion entitled The Day(s) After: Lessons Learned from Trauma Team Management in the Aftermath of an Unexpected Mass Casualty Event at the 76th Annual American Association for the Surgery of Trauma meeting on September 13, 2017 brought together a cadre of military and civilian surgeons with experience in MCEs. The events described were the First Battle of Mogadishu (1993), the Second Battle of Fallujah (2004), the Bagram Detention Center Rocket Attack (2014), the Boston Marathon Bombing (2013), the Asiana Flight 214 Plane Crash (2013), the Baltimore Riots (2015), and the Orlando Pulse Night Club Shooting (2016). This article focuses on the lessons learned from military and civilian surgeons in the days after MCEs

Deep Optical Photometry of Six Fields in the Andromeda Galaxy

Using the Advanced Camera for Surveys on the Hubble Space Telescope, we have obtained deep optical images reaching well below the oldest main sequence turnoff in six fields of the Andromeda Galaxy. The fields fall at four positions on the southeast minor axis, one position in the giant stellar stream, and one position on the northeast major axis. These data were obtained as part of three large observing programs designed to probe the star formation history of the stellar population in various structures of the galaxy. In this paper, we present the images, catalogs, and artificial star tests for these observing programs as a supplement to the analyses published previously. These high-level science products are also archived at the Multimission Archive at the Space Telescope Science Institute.Comment: Accepted for publication in The Astrophysical Journal Supplement Series. 6 pages, latex. The full set of high-level science products can be found at http://archive.stsci.edu/prepds/andromeda