Addiction is a brain disease, and it doesn’t matter: prior choice in drug use blocks leniency in criminal punishment

Our aim was to explore how (neuro)scientific understanding of addiction as a brain-disease impacts criminal sentencing decisions in courts in England and Wales, where legal rules concerning intoxication, prior-fault and mental disease conflict, and sentencing guidelines lack clarity. We hypothesized that despite significant neuropsychiatric overlap of addiction and other brain-disorders, variables in relation to etiology would moderate magistrates’ sentencing decisions in cases involving addicted offenders. Using a questionnaire-based, quantitative design, and combining frequentist and Bayesian analysis approaches, we probed court magistrates’ sentencing decisions, and underlying rationale, for defendants presenting with brain damage resulting from a (fictional) disease, addiction to heroin, or more complex, mixed etiologies. When identical neuropsychiatric profiles resulted from disease, but not heroin addiction, prison sentences were significantly reduced. Study 1 (N=109) found the pivotal factor preventing addiction from mitigating sentences was perceived choice in its acquisition; removing choice from addiction increased the odds of sentence reduction (~20- fold) and attaching choice to disease aggravated or reversed earlier leniency. Study 2 (N=276) replicated these results and found that when heroin use led to disease or vice versa, magistrates found middle ground. These differences were independent of the age of first drug use. Finally, evidence of addiction was more likely to evoke punishment considerations by magistrates, rather than rehabilitation. Consistent with legal rules relating to intoxication but running counter to norms around mental-illness and choice, our results demonstrate the need for greater clarity in sentencing guidance on addiction specifically, and mental disorders more generally

On-board demux/demod

To make satellite channels cost competitive with optical cables, the use of small, inexpensive earth stations with reduced antenna size and high powered amplifier (HPA) power will be needed. This will necessitate the use of high e.i.r.p. and gain-to-noise temperature ratio (G/T) multibeam satellites. For a multibeam satellite, onboard switching is required in order to maintain the needed connectivity between beams. This switching function can be realized by either an receive frequency (RF) or a baseband unit. The baseband switching approach has the additional advantage of decoupling the up-link and down-link, thus enabling rate and format conversion as well as improving the link performance. A baseband switching satellite requires the demultiplexing and demodulation of the up-link carriers before they can be switched to their assigned down-link beams. Principles of operation, design and implementation issues of such an onboard demultiplexer/demodulator (bulk demodulator) that was recently built at COMSAT Labs. are discussed

Evaluation of milk yield losses associated with Salmonella antibodies in bulk-tank milk in bovine dairy herds

The effect of Salmonella on milk production is not well established in cattle. The objective of this study was to investigate whether introduction of Salmonella into dairy cattle herds was associated with reduced milk yield and the duration of any effect. Longitudinal data from 2005 through 2009 were used, with data from 12 months before until 18 months after the estimated date of infection. Twenty-eight case herds were selected based on an increase in the level of Salmonella specific antibodies in bulk-tank milk from < 10 corrected optic density percentage (ODC%) to ≥ 70 ODC% between two consecutive 3-monthly measurements in the Danish Salmonella surveillance program. All selected case herds were conventional Danish Holstein herds. Control herds (n = 40) were selected randomly from Danish Holstein herds with Salmonella antibody levels consistently < 10 ODC%. A date of herd infection was randomly allocated to the control herds. Hierarchical mixed effect models with the outcome test day energy corrected milk yield (ECM)/cow were used to investigate the daily milk yield before and after the estimated herd infection date for cows in parity 1, 2 and 3+. Control herds were used to evaluate whether the effects in the case herds could be reproduced in herds without Salmonella infection. Herd size, days in milk, somatic cell count, season, and year were included in the models. The key results were that first parity cow yield was reduced by a mean of 1.4 kg (95% CI: 0.5 to 2.3) ECM/cow per day from seven to 15 months after the estimated herd infection date, compared with first parity cows in the same herds in the 12 months before the estimated herd infection date. Yield for parity 3+ was reduced by a mean of 3.0 kg (95% CI: 1.3 to 4.8) ECM/cow per day from seven to 15 months after herd infection compared with parity 3+ cows in the 12 months before the estimated herd infection. There were minor differences in yield in second parity cows before and after herd infection, and no difference between cows in control herds before and after the simulated infection date. There was a significant drop in milk yield in affected herds and the reduction was detectable several months after the increase in bulk-tank milk Salmonella antibodies. It took more than a year for milk yield to return to pre- infection levels

Testing the performance of the ENRICHD Social Support Instrument in cardiac patients

BACKGROUND: Previous investigations suggest an important role of social support in the outcomes of patients treated for ischemic heart disease. The ENRICHD Social Support Instrument (ESSI) is a 7-item self-report survey that assesses social support. Validity and reliability of the ESSI, however, has not been formally tested in patients undergoing percutaneous coronary intervention (PCI). METHODS: The ESSI, along with the Short Form-36 (SF-36), was sequentially administered to a cohort of 271 patients undergoing PCI. The test-retest reliability was examined with an intra-class correlation coefficient by comparing scores among 174 patients who completed both instruments 5 and 6 months after their procedure. Internal reliability was assessed using Cronbach's alpha at the time of patients' baseline procedure. The concurrent validity of the ESSI was assessed by comparing scores between depressed (MHI-5 score < 44) vs. non-depressed patients. The correlation between the ESSI and the SF-36 Social Functioning sub-scale, an accepted measure of social functioning, was also examined. RESULTS: Test-retest reliability showed no significant differences in mean scores among ESSI questionnaires administered 1 month apart (27.8+/-1.4 vs 27.8+/-1.5, p = 0.98). The intra-class correlation coefficient was 0.94 and Cronbach's alpha was 0.88. Mean ESSI scores were significantly lower among depressed vs. non-depressed patients (24.6+/-1.7 vs 27+/-1.4, p < 0.018) and a positive albeit modest correlation with social functioning was seen (r = 0.19, p = 0.002). CONCLUSION: The ESSI appears to be a valid and reliable measure of social support in patients undergoing treatment for coronary artery disease. It may prove to be a valuable method of controlling for patient variability in outcomes studies where the outcomes are related to patients' social support

C/EBPα and C/EBPβ Are Required for Sebocyte Differentiation and Stratified Squamous Differentiation in Adult Mouse Skin

C/EBPα and C/EBPβ are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPα and C/EBPβ in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPα or C/EBPβ alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPα and C/EBPβ in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPα and C/EBPβ in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3) and melanocortin 5 receptor (MC5R), two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPα and C/EBPβ are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal

Associations between Maternal Cadmium Exposure with Risk of Preterm Birth and Low Birth Weight: Effect of Mediterranean Diet Adherence on Affected Prenatal Outcomes

Prenatal cadmium exposure at non-occupational levels has been associated with poor birth outcomes. The intake of essential metals, such as iron and selenium, may mitigate cadmium exposure effects. However, at high levels, these metals can be toxic. The role of dietary patterns rich in these metals is less studied. We used a linear and logistic regression in a cohort of 185 mother–infant pairs to assess if a Mediterranean diet pattern during pregnancy modified the associations between prenatal cadmium exposure and (1) birth weight and (2) preterm birth. We found that increased cadmium exposure during pregnancy was associated with lower birth weight (β = −210.4; 95% CI: −332.0, −88.8; p = 0.008) and preterm birth (OR = 0.11; 95% CI: 0.01, 0.72; p = 0.04); however, these associations were comparable in offspring born to women reporting high adherence to a Mediterranean diet (β = −274.95; 95% CI: −701.17, 151.26; p = 0.20) and those with low adherence (β = −64.76; 95% CI: −359.90, 230.37; p = 0.66). While the small sample size limits inference, our findings suggest that adherence to a Mediterranean dietary pattern may not mitigate cadmium exposure effects. Given the multiple organs targeted by cadmium and its slow excretion rate, larger studies are required to clarify these findings

Grouping of UVCB substances with dose-response transcriptomics data from human cell-based assays

The application of in vitro biological assays as new approach methodologies (NAMs) to support grouping of UVCB (unknown or variable composition, complex reaction products, and biological materials) substances has recently been demonstrated. In addition to cell-based phenotyping as NAMs, in vitro transcriptomic profiling is used to gain deeper mechanistic understanding of biological responses to chemicals and to support grouping and read-across. However, the value of gene expression profiling for characterizing complex substances like UVCBs has not been explored. Using 141 petroleum substance extracts, we performed dose-response transcriptomic profiling in human induced pluripotent stem cell (iPSC)-derived hepatocytes, cardiomyocytes, neurons, and endothelial cells, as well as cell lines MCF7 and A375. The goal was to determine whether transcriptomic data can be used to group these UVCBs and to further characterize the molecular basis for in vitro biological responses. We found distinct transcriptional responses for petroleum substances by manufacturing class. Pathway enrichment informed interpretation of effects of substances and UVCB petroleum-class. Transcriptional activity was strongly correlated with concentration of polycyclic aromatic compounds (PAC), especially in iPSC-derived hepatocytes. Supervised analysis using transcriptomics, alone or in combination with bioactivity data collected on these same substances/cells, suggest that transcriptomics data provide useful mechanistic information, but only modest additional value for grouping. Overall, these results further demonstrate the value of NAMs for grouping of UVCBs, identify informative cell lines, and provide data that could be used for justifying selection of substances for further testing that may be required for registration