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Quantitative genetics is the study of continuously varying traits which make up the majority of biological attributes of evolutionary and commercial interest. This book provides a much-needed up-to-date, in-depth yet accessible text for the field. In lucid language, the author guides readers through the main concepts of population and quantitative genetics and their applications. It is written to be approachable to even those without a strong mathematical background, including applied examples, a glossary of key terms, and problems and solutions to support students in grasping important theoretical developments and their relevance to real-world biology. An engaging, must-have textbook for advanced undergraduate and postgraduate students. Given its applied focus, it also equips researchers in genetics, genomics, evolutionary biology, animal and plant breeding, and conservation genetics with the understanding and tools for genetic improvement, comprehension of the genetic basis of human diseases, and conservation of biological resources.
Previous studies have shown that a single nighttime dose of standard doxazosin, an alpha-adrenergic antagonist, reduces blood pressure (BP) throughout the 24 h. We investigated the administration-time-dependent effects of the new doxazosin gastrointestinal therapeutic system (GITS) formulation. We studied 91 subjects (49 men and 42 women), 56.7+/-11.2 (mean+/-SD) yrs of age with grade 1-2 essential hypertension; 39 patients had been previously untreated, and the remaining 52 had been treated with two antihypertensive medications with inadequate control of their hypertension. The subjects of the two groups, the monotherapy and polytherapy groups, respectively, were randomly assigned to receive the single daily dose of doxazosin GITS (4 mg/day) either upon awakening or at bedtime. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours just before and after 3 months of treatment. After 3 months of doxazosin GITS therapy upon awakening, there was a small and nonstatistically significant reduction in BP (1.8 and 3.2mm Hg in the 24 h mean of systolic and diastolic BP in monotherapy; 2.2 and 1.9mm Hg in polytherapy), mainly because of absence of any effect on nocturnal BP. The 24 h mean BP reduction was larger and statistically significant (6.9 and 5.9 mm for systolic and diastolic BP, respectively, in monotherapy; 5.3 and 4.5 mm Hg in polytherapy) when doxazosin GITS was scheduled at bedtime. This BP-lowering effect was similar during both the day and nighttime hours. Doxazosin GITS ingested daily on awakening failed to provide full 24h therapeutic coverage. Bedtime dosing with doxazosin GITS, however, significantly reduced BP throughout the 24h both when used as a monotherapy and when used in combination with other antihypertensive pharmacotherapy. Knowledge of the chronopharmacology of doxazosin GITS is key to optimizing the efficiency of its BP-lowering effect, and this must be taken into consideration when prescribing this medication to patients.
Replacing pressure-driven flow with electroosmotic flow in chromatography with packed capillary columns results in a new and powerful analytical technique, combining the advantages of high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE): capillary electrochromatography (CEC). In essence, it involves packing CE capillaries with HPLC stationary phases and applying a voltage across the packed capillary, which generates an electroosmotic flow (EOF) that transports solutes along the capillary toward the detector; on the way, both differential partitioning and electrophoretic migration of the solutes occur, resulting in their separation. This dual separation mechanism can afford unique selectivities. Also, the plug-flow profile of EOF reduces flow-related band broadening, so that separation efficiencies of several hundred thousand plates per meter are often obtained (i.e., one or two orders of magnitude greater than those of present conventional chromatographic systems). There is no back pressure when EOF occurs, so small particle sizes (1–3 μm) and/or long columns can be used. Generally, carrier electrolytes containing high levels (40–80%) of organic solvents such as methanol or acetonitrile are employed, making it useful for water-insoluble compounds, which can be difficult to analyse by CE. CEC can be faster than HPLC, and gradient-elution CEC is being developed as an alternative to gradient-elution liquid chromatography of polymers.
