Improving the usefulness of molecular similarity-based chemical prioritization strategies.

Quantitative molecular similarity analysis (QMSA) is a seemingly useful tool for estimating environmental properties for the hundreds of emerging contaminants that have not yet been fully evaluated. Moreover, calibrated QMSA models are also useful for prioritizing research among currently unmeasured chemicals of interest. Previous work has demonstrated that prioritization based on molecular 'representativeness', as parameterized using summed Euclidean distances in n dimensions corresponding to n molecular descriptors, improves the prediction accuracy of QMSA models compared to random selection of compounds to be measured. In this study, we use two datasets of environmental parameters (i.e. in vitro oestrogenicity and sorption distribution coefficient Kd ) to demonstrate that maximizing representativeness alone cannot deliver optimal improvement in prediction accuracy if many of the chemicals that have already been measured are themselves highly representative. Thus, proper QMSA-based prioritization among unmeasured chemicals constitutes a balance between maximizing representativeness and minimizing redundancy. It is demonstrated that redundancy considerations are especially critical for highly heterogeneous datasets, and some discussion about achieving a proper balance between the two prioritization criteria is presented.

[Circadian rhythm of serum levo-carnitine: parameters]. / Ritmo circadiano della levo-carnitina sierica: parametri ritmometrici per programmare una eventuale cronoterapia.

OBJECTIVE: The present study investigates the circadian rhythm (CR) of levo-carnitine (L-c) in systemic venous blood, in order to detect rhythmometric parameters that can be used for programming an eventual chronoterapy with such a molecule. MATERIALS AND METHODS: The L-c CR was investigated in 10 clinically healthy subjects (5 M; 5 F; mean age: 26.02 +/- 1.11 yrs), who were diurnally active and nocturnally resting. Blood samples were taken at 06:00; 08:00; 12:00; 18:00; 20:00; 24:00, not juxtaposed to breakfast, lunch and dinner. The serum concentrations of L-c were assayed via a spectrophotometric method. RESULTS: A nychtohemeral variability in circulating levels of L-c was observed, with a peak in the afternoon. Such a intradiem variability was validated to have the properties of a significant CR (MESOR = 33.37 mumol/l with a SEM of 1.19 mumol/l; amplitude = 6.31 mumol/l with 95%CL ranging from 3.58 mumol/l to 9.69 mumol/l; acrophase at 15:52 h:min with 95%CL ranging from 13:28 h:min to 17:00 h:min). CONCLUSIONS: It is important to remark that the validation of a CR for the systemic serum levels of L-c was obtained in diurnally-active/nocturnally resting subjects. Such validated rhythmometric properties are parameters that can be used for programming an eventual chronotherapy, considering that the molecule L-c is used for treating its various types of primary and secondary deficiency.

Anxiety, depression, hunger and body composition: III. Their relationships in obese patients.

The present paper explores the relationships between anxiety, depression, hunger sensation and body composition in obese patients (OP). The aim is to detect whether or not there are abnormalities in these relationships in OP as compared to clinically healthy subjects (CHS). The study was performed on 22 CHS (2 M, 20 W; mean age = 24 +/- 2 years; mean body mass index = 21 +/- 2 kg/m2) and 48 OP (4 M, 44 W; mean age = 40 +/- 17 years; mean body mass index = 32 +/- 7 kg/m2). Anxiety and depression were found to be correlated, negatively, with the relative lean body mass, and, positively, with the fat body mass in OP but not in CHS. These findings corroborate the idea that anxiety and depression can reach an abnormal expression when obesity shows its worst loss in lean body mass and its highest expansion in adipocyte mass. As hunger sensation was found not to correlate with either anxiety or depression in OP, the opinion is expressed that the impairment of anxio-depressive integrity is a corollary of obesity rather than a primary affective disorder leading to obesity via an enhanced food intake.

Daily hunger sensation and body compartments: II. Their relationships in obese patients.

Hunger sensation (HS) is a signal whose levels change during the 24-h day. The daily mean level of HS was correlated with the human body compartments, as investigated by bioelectrical impedance analysis, to detect the relationship between the orectic perception and both the free fat mass (FFM) and the fat body mass (FBM) in 22 clinically healthy subjects (CHS) (2 M, 20 W, BMI: 18.5-24.0 kg/m2) and 48 obese patients (OP) (4 M, 44 W, BMI: 25.2-54.7 kg/m2). In CHS, the daily mean level of HS correlated positively with the FFM and negatively with the FBM. These correlations were not present in OP. This lack of relationships between HS and the body compartments where energy is maximally consumed (i.e., the FFM) and maximally stored (i.e., the FBM) indicates that the orectic response to energy expenditure and the orectic inhibition to fat accumulation are feedback mechanisms which are impaired in obesity.

Evaluation of welfare reform. A framework for addressing the urgent and the important.

Assessing the effects of changes still emerging under welfare reform and its overarching policy of devolution presents a challenge to evaluators. Given such features as time limits and benefits caps that vary widely across states and communities, it is necessary not only to attend to urgent issues of immediate relevance for individuals on public assistance but also to focus on important long-term analyses of this complex intergovernmental set of policies. The authors present a conceptual framework based on evaluation utilization and illustrate it with research questions under the rubric of welfare reform. The approach crosses three types of utilization--conceptual, instrumental, and political--with two utilization settings--policy adoption and program implementation. Evaluation strategies are linked to the utilization framework and illustrated with examples from studies of welfare reform. In the aggregate, evaluation studies represent a reasonable range of urgent and important issues across most utilization types and settings.