Pharmacogenetics, Kinetics, and Dynamics for Personalized Medicine by DF Kisor, MD Kane, JN Talbot and JE Sprague

Pharmacogenomics is the study of genetic differences responsible for the variability in drug response among individual patients. Emerging from this new science is the development of diagnostic tools crucial for improving treatment strategies, as well as reducing drug side effects. As the importance of this science is being realized, the need for this discipline in pharmacy student training is becoming increasingly crucial to their professional development and training as healthcare professionals. As this discipline evolves, there is a clear need for tools that can enable lecturers to deliver this essential training; the current book review investigates aspects that are specific to the needs of the target audience and will explore the potential of ‘Pharmacogenetics, Kinetics, and Dynamics for Personalized Medicine’ in achieving this task

Linking agri-environment scheme habitat area, predation and the abundance of chick invertebrate prey to the nesting success of a declining farmland bird

1. Across Europe, farmland bird populations have continued to decline since the 1970s owing to the intensification of farming practices. Studies of such declines have tended to focus specifically on either the impacts of habitats (nesting and foraging), nest predators or prey availability on bird demographics. The study presented here provides new insights into the relative effects of each of these factors on Yellowhammer nest survival. The Yellowhammer was selected for this study as it is a UK red-listed bird species whose population is in decline across much of Europe.2. We use a long-term dataset of 147 nests, monitored between 1995 and 2007, to provide an insight into how Yellowhammer nest survival is influenced by nesting habitat (nest concealment and nest height), foraging habitats (habitat coverage within 100 m of nests), the removal of nest predators (Magpie Pica pica abundance as an inverse measure of avian predator removal through gamekeeping) and food availability (measured with a D-vac invertebrate suction sampler). 3. Our results indicated that Yellowhammer hatching success was negatively related to the coverage of spring agri-environment scheme habitats, a group which represents invertebrate-rich agri-environment habitats, but hatching success increased with nest height. Fledging success was positively related to the coverage of the seed-rich habitat Wild Bird Seed mixture. The farm-level abundance of Yellowhammer chick-food invertebrates declined over the study period. 4. Synthesis and application. Our results highlight the importance of simultaneously considering multiple agents that shape avian breeding success, i.e. their ability to produce offspring, to inform conservation management. Our key finding for land managers relates to the positive relationship between the proportion seed rich foraging habitat within the Yellowhammer’s average foraging range and Yellowhammer fledging success, which shows that a habitat intended primarily to provide winter food resources is also important to breeding birds. Chick food abundance in this habitat was, however, similar to broadleaf and cereal crops. We recommend that this habitat should be provided near to potential Yellowhammer nesting sites and adjacent to invertebrate-rich agri-environment scheme habitats such as beetle banks and conservation headlands to further boost invertebrate resources for a declining farmland bird

MicroRNA Quantitation During Dendritic Cell Endocytosis Using Imaging Flow Cytometry: Key Factors and Requirements

Background/Aims: MicroRNA (miRNA)-induced suppression of dendritic cells (DCs) has been implicated in many diseases. Therefore, accurate monitoring of miRNA endocytosis by DCs is important for understanding the role of miRNAs in many diseases. Recently, a method for measuring the co-localization of Argonaute 2 (AGO2)-associated miRNAs on laser-scanning confocal microscopy method was proposed to localize the miRNAs. But its definition was limited by the number of observed cells through its accuracy. Methods: In this study, a method based on imaging flow cytometry was developed to localize miR-590-5p with fluorescent probes in DCs. miR-590-5p proven to play an important role in tumor immunity. This method enabled the quantification, visualization and localization of the fluorescence intensity in 30,000 individual cells. Results: Using this method, the DCs with different endocytotic ability were distinguished. The behaviour of miR-590-5p during endocytosis under the stimulation of tumor antigen in DCs was observed, binding to its cognate target mRNA and degradation in DCs. Conclusion: This method based on imaging flow cytometry provide an additional method to study miRNA processing in DCs, which makes it a valuable addition to existing miRNA research techniques

Spot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership (Grant IP.2007.32011.011), US Agency for International Development, UK Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, National Institutes of Health, AIDS Clinical Trials Group. The study was also supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426). Bayer Healthcare for donated moxifloxacin and Sanofi donated rifampin.Background:  The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. Methods:  Patients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses. Results:  Data from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24–41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/μL (IQR 318–535). Pre-treatment spot samples had a higher yield of positive Ziehl–Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P < 0.001). There were no differences in time to positivity in pre-treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan–Meier analyses in either EMS or spot samples. Conclusions:  Our data do not support the hypothesis that EMS samples are superior to spot sputum samples in a clinical trial of patients with smear positive pulmonary TB. Observed small differences in mycobacterial burden are of uncertain significance and EMS samples do not detect post-treatment positives any sooner than spot samples.Publisher PDFPeer reviewe

Topological Defects and CMB anisotropies : Are the predictions reliable ?

We consider a network of topological defects which can partly decay into neutrinos, photons, baryons, or Cold Dark Matter. We find that the degree-scale amplitude of the cosmic microwave background (CMB) anisotropies as well as the shape of the matter power spectrum can be considerably modified when such a decay is taken into account. We conclude that present predictions concerning structure formation by defects might be unreliable.Comment: 14 pages, accepted for publication in PR

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation