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1. Over the past three decades changes in agricultural management have resulted in increased crop and grass production. This intensification has been accompanied by population declines among farmland bird species and a decline in farmland biodiversity. We have analysed trends in agricultural management in order to quantify the degree of intensification, and have considered how they match change in the farmland bird community. 2. Changes in agriculture through time (1962-95) were examined quantitatively for 31 variables representing crop areas, livestock numbers, fertilizer application, grass production and pesticide use. The majority were highly intercorrelated because factors facilitating intensification simultaneously affected many management activities. 3. Change in agriculture was measured using detrended correspondence analysis (DCA). The period 1970-88 saw most intensification, characterized by increases in the area of oilseed rape, autumn-sown cereals, and the use of pesticides and inorganic fertilizers. Spring-sown cereals, bare fallow and root crops declined. 4. Indices of relative population change between 1962 and 1996 were determined for 29 bird species using data from Common Birds Census (CBC) plots on farmland in England and Wales. Principal components analysis (PCA) described a gradient from species that had declined most to those that had increased. 5. The ordinations of agricultural change and bird population change were broadly matching but with a time lag in the response of birds. The most accurately measured agricultural variables for the period 1974-91 matched the changes in farmland birds more closely. 6. We conclude that large shifts in agricultural management are a plausible explanation for the declines in farmland bird populations. We propose a threshold model relating to critical amounts of high-quality habitat or food resources that may be relevant in explaining the lag in response of birds, and propose it should be taken into account in predicting the effects of future agri-environment schemes. Identifying individual factors responsible for bird declines is not possible without detailed experimental work because many components of intensification are interdependent. Birds may be responding to a suite of interacting factors rather individual aspects of farm management. Holistic conservation strategy that encourages general extensification of farming practices will be most likely to benefit farmland bird communities.

Dick Potts (2003) makes a valid point in that there are few historical data on the ploughing dates of stubble fields. It is hard to know, therefore, exactly what percentage survived through the winter to March. Potts also points out that this percentage is likely to vary regionally, with which we agree. We disagree most strongly, however, with his assertion that Government agri-environment schemes are not properly designed and that if they are to succeed in restoring lost biodiversity 'they should recapitulate the traditional cropping practice which produced it in the first place'. We also dispute the fact that overwintered stubbles were not a feature of farm management unless undersown.

Some of what Ms. Smith wrote was accurate: Binge drinking does take place at Alpha Delta (as it does in every fraternity at Dartmouth and probably every college campus in the country); the brothers of Alpha Delta do...

Particulate interactions are dominated by aspects such as surface topography, exposed chemical moieties, environmental conditions, and thermodynamic properties such as surface free energy (gamma). The absolute value and relative magnitude of surface energies of a drug and excipients within a formulation can significantly influence manufacture, processing, and use. This study utilizes and compares the potentially complementary analytical techniques of atomic force microscopy (AFM) and inverse gas chromatography (IGC) in the quantitative determination of the surface energy of drug (budesonide) particles (micronized and unmilled) relevant to inhaled delivery. In addition, the study investigates with AFM another important parameter in determining material interactions, the local mechanical properties of the drug. AFM was used to acquire force of adhesion (Fadh) and related work of adhesion (WA) and surface energy values between individual mironized drug particles and also model substrates (graphite and mica). In addition, AFM probes were used to interrogate the surface energy of unmilled drug particles. Measurement with AFM probes also yielded localized measurements of Young's modulus for the unmilled drug. IGC was also used to probe the surface characteristics of the bulk drug material. The average values for surface energies acquired from budesonide micronized particle interactions with graphite, mica, and drug particles of the same substance were found to range from 35 to 175, 5 to 40, and 10 to 32 mJ m(-2), respectively. The unmilled material displayed a range of values of 39-88 mJ m(-2) with an average of 60 mJ m(-2). The IGC result for the surface energy of the micronized material was 68.47 +/- 1.60 mJ m(-2). The variability in surface energy from AFM, a feature particularly apparent for the micronized material was attributed to two factors, intrinsic material variations within a single particle and assumptions present within the contact mechanics model used. Here we provide a detailed description of these factors to go some way to rationalize the results. The Young's modulus of the unmilled drug was determined to be approximately 10 GPa. The range of determined surface energies between the AFM measurement on graphite, mica, and the drug is proposed to reflect the different chemistries displayed by the drug at the single particle level. The maximum values of these ranges can be related to the sites most likely to be involved in adhesion. AFM and IGC yield surface energy estimates in approximate agreement, but clearly are interrogating surfaces in different fashions. This raises questions as to the nature of the measurement being made by these approaches and to the most appropriate time to use these methods in terms of a direct relation to formulation design, manufacture, and drug delivery. Finally, we demonstrate a novel method for assessing the Young's modulus of a drug from a single particle.

The clinical phenotypes of maternal and paternal uniparental disomy of chromosome 14 (UPD14) are attributed to dysregulation of imprinted genes. A large candidate locus exists within 14q32, under the regulation of a paternally methylated intergenic differentially methylated region (IG-DMR). We present a patient with clinical features of maternal UPD14, including growth retardation, hypotonia, scoliosis, small hands and feet, and advanced puberty, who had loss of methylation of the IG-DMR with no evidence of maternal UPD14. This case provides support for the hypothesis that the maternal UPD14 phenotype is due to aberrant gene expression within the imprinted domain at 14q32.

Chromosome microdeletions or duplications are detected in 10–20% of patients with mental impairment and normal karyotypes. A few cases have been reported of mental impairment with microdeletions comprising tumor suppressor genes. By array-CGH we detected 4 mentally impaired individuals carrying de novo microdeletions sharing an overlapping segment of ∼180 kb in 17p13.1. This segment encompasses 18 genes, including 3 involved in cancer, namely KCTD11/REN, DLG4/PSD95, and GPS2. Furthermore, in 2 of the patients, the deletions also included TP53, the most frequently inactivated gene in human cancers. The 3 tumor suppressor genes KCTD11, DLG4, and GPS2, in addition to the GABARAP gene, have a known or suspected function in neuronal development and are candidates for causing mental impairment in our patients. Among our 4 patients with deletions in 17p13.1, 3 were part of a Brazilian cohort of 300 mentally retarded individuals, suggesting that this segment may be particularly prone to rearrangements and appears to be an important cause (∼1%) of mental retardation. Further, the constitutive deletion of tumor suppressor genes in these patients, particularly TP53, probably confers a significantly increased lifetime risk for cancer and warrants careful oncological surveillance of these patients. Constitutional chromosome deletions containing tumor suppressor genes in patients with mental impairment or congenital abnormalities may represent an important mechanism linking abnormal phenotypes with increased risks of cancer.

To develop a rapid and reliable method for predicting the pattern of aerosol particle deposition within the human lungs, using artificial neural networks (ANNs). Experimental data from the literature were used to train multi-layer perceptron (MLP) networks to allow for prediction of regional and total aerosol particle deposition patterns in human lungs. These data covered particle sizes in the range 0.05-15 microm and three different breathing patterns (ranging from \"quiet\" breathing to breathing \"under physical work conditions\"). Three different MLPs were trained, to provide separate predictions of aerosol particle deposition in the laryngeal, bronchial, and alveolar regions. The total deposition fraction for a given set of breathing conditions was computed simply as the sum of the outputs produced from the corresponding regional deposition MLPs. The ANNs developed are shown to give highly accurate predictions for both regional and total aerosol deposition patterns for all particle sizes and breathing conditions (with errors typically less than 0.04%). We conclude that the current set of ANNs can be used to give good predictions of particle deposition from polydisperse pharmaceutical aerosols generated from breath-actuated dry powder inhalers, nebulizers, and metered dose inhalers with spacers.