The timing of maternal depressive symptoms and child cognitive development: a longitudinal study.

Background: Maternal depression is known to be associated with impairments in child cognitive development, although the effect of timing of exposure to maternal depression is unclear. Methods: Data collected for the Avon Longitudinal Study of Parents and Children, a longitudinal study beginning in pregnancy, included self-report measures of maternal depression the Edinburgh Postnatal Depression Scale, completed on 6 occasions up to 3 years of age, and IQ of the index child (WISC) measured at aged 8 years. We used these data to assign women to 8 groups according to whether depression occurred in the antenatal, postnatal, preschool period, any combination of these times, or not at all. We compared a model comprising all patterns of depression (saturated model) with models nested within this to test whether there is a relationship between depression and child cognitive development and, if so, whether there is a sensitive period. We then investigated the relationship with child IQ for each model, following adjustment for confounders. Results: Six thousand seven hundred and thirty-five of 13,615 children from singleton births (49.5%, of eligible core sample) attended a research clinic at 8 years and completed a WISC with a score ≥ 70. A total of 5,029 mothers of these children had completed mood assessments over the 3 time periods. In unadjusted analyses, all three sensitive period models were as good as the saturated model, as was an accumulation model. Of the sensitive period models, only that for antenatal exposure was a consistently better fit than the accumulation model. After multiple imputation for missing data (to n = 6,735), there was no effect of postnatal depression on child IQ independent of depression at other times [-0.19 IQ points, 95% confidence interval (CI) -1.5 to 1.1 points]. There was an effect of antenatal depression (-3.19 IQ points, 95% CI: -4.33 to -2.06) which attenuated following adjustment (-0.64 IQ points, 95% CI: -1.68 to 0.40). Conclusions: The postnatal period is not a sensitive one for the effect of maternal depression on child cognitive development. © 2011 The Authors. Journal of Child Psychology and Psychiatry

Comparison of Subjective Responses to Oral and Intravenous Alcohol Administration under Similar Systemic Exposures

Objective To test whether an individual's subjective responses to alcohol are similar when the breath alcohol concentration (BrAC) trajectory resulting from oral administration is matched by intravenous administration. Background Individuals perceive the effects of alcohol differently, and the variation is commonly used in research assessing the risk for developing an alcohol use disorder. Such research is supported by both oral and intravenous alcohol administration techniques, and any differences attributable to the route employed should be understood. Methods We conducted a 2‐session, within‐subject study in 44 young adult, healthy, non‐dependent drinkers (22 females and 22 males). In the first session, subjects ingested a dose of alcohol which was individually calculated, on the basis of total body water, to yield a peak BrAC near 80 mg/dl, and the resulting BrAC trajectory was recorded. A few days later, subjects received an intravenous alcohol infusion rate profile, pre‐computed to replicate each individual's oral alcohol BrAC trajectory. In both sessions, we assessed 4 subjective responses to alcohol: SEDATION, SIMULATION, INTOXICATION, and HIGH; at baseline and frequently for 4 hours. We compared the individuals’ baseline‐corrected responses at peak BrAC and at half‐peak BrAC on both the ascending and descending limbs. We also computed and compared Pearson‐product moment correlations of responses by route of administration, the Mellanby measure of acute adaptation to alcohol, and the area under the entire response curve for each subjective response. Results No significant differences in any measure could be attributed to the route of alcohol administration. Eleven of 12 response comparisons were significantly correlated across the routes of alcohol administration, with 9 surviving correction for multiple measures, as did the Mellanby effect and area under the response curve correlations. Conclusion The route of alcohol administration has a minimal effect on subjective responses to alcohol when an individual's BrAC exposure profiles are similar

Effects of 12-O-tetradecanoylphorbol-13-acetate on the incorporation of labelled precursors into RNA, DNA and protein in epidermis, dermis and subcutis from precancerous mouse skin with reference to enhanced tumorigenesis

The effects of a single application of 1.8 nmol 12-O-tetra-decanoylphorbol-13-acetate (TPA) on precursor incorporation into RNA, DNA and protein in the epidermis, dermis and subcutis from 3-methylcholanthrene (MCA) injected precancerous mouse skin were studied at various time points between 3 and 96 h. In the precancerous tissues, the rates of incorporation of [3H]uridine into RNA did not alter appreciably from those in the control tissues; while the rates of [3H]methylthymidine incorporation into DNA were elevated with peaks appearing between 6 and 12 h, at 24 h and at 72 h in epidermis, dermis and subcutis. The rate of incorporation of [14C] leucine into protein was markedly elevated in all the three tissues which showed 3-4 sharp peaks. The maximum stimulation ranged between 14 and 20 times that of the control. A single application of TPA to the precancerous mouse skin induced early stimulation of precursor incorporation into all the three macromolecules in epidermis, dermis and subcutis. The increased stimulation was maintained for 36- 72 h. The patterns of incorporation of [3H]methylthymidine into DNA gave rise to 2-3 peaks of elevated uptake in each tissue up to 36-48 h. A lowered rate of DNA synthesis between 48 and 60 h was followed by a peak at 72 h. In each group, epidermal mitotic activity correlated well with spurts of precursor incorporation into cellular DNA. The observations indicate that TPA recruits more cells into the DNA synthetic phase and accelerates selective growth of preneoplastic cells during tumor progression

Classifying the embedded young stellar population in Perseus and Taurus & the LOMASS database

Context. The classification of young stellar objects (YSOs) is typically done using the infrared spectral slope or bolometric temperature, but either can result in contamination of samples. More accurate methods to determine the evolutionary stage of YSOs will improve the reliability of statistics for the embedded YSO population and provide more robust stage lifetimes. Aims. We aim to separate the truly embedded YSOs from more evolved sources. Methods. Maps of HCO+ J=4-3 and C18O J=3-2 were observed with HARP on the James Clerk Maxwell Telescope (JCMT) for a sample of 56 candidate YSOs in Perseus and Taurus in order to characterize emission from high (column) density gas. These are supplemented with archival dust continuum maps observed with SCUBA on the JCMT and Herschel PACS to compare the morphology of the gas and dust in the protostellar envelopes. The spatial concentration of HCO+ J=4-3 and 850 micron dust emission are used to classify the embedded nature of YSOs. Results. Approximately 30% of Class 0+I sources in Perseus and Taurus are not Stage I, but are likely to be more evolved Stage II pre-main sequence (PMS) stars with disks. An additional 16% are confused sources with an uncertain evolutionary stage. Conclusions. Separating classifications by cloud reveals that a high percentage of the Class 0+I sources in the Perseus star forming region are truly embedded Stage I sources (71%), while the Taurus cloud hosts a majority of evolved PMS stars with disks (68%). The concentration factor method is useful to correct misidentified embedded YSOs, yielding higher accuracy for YSO population statistics and Stage timescales. Current estimates (0.54 Myr) may overpredict the Stage I lifetime on the order of 30%, resulting in timescales of 0.38 Myr for the embedded phase.Comment: 33 pages, 21 figures, 6 tables, Accepted to be published in A&

Parental depression and child outcomes--is marital conflict the missing link?

BACKGROUND: Both maternal and paternal depression during the perinatal period are associated with adverse effects on child outcomes. Attention has started to focus on the mechanisms mediating these relationships. Marital conflict may play a role in this context. METHODS: In a large cohort study, the Avon Longitudinal Study of Parents and Children (n = 14,541 pregnancies), we aimed to (i) investigate the relative influences of parental postnatal depression and marital conflict on child outcomes and to attempt to determine the pathway(s) of risk; (ii) investigate the impact of two types of antenatal stress (parental depression and marital conflict) on child outcomes; and (iii) determine the relative contributions of antenatal and postnatal risk. Parents completed the Edinburgh Postnatal Depression Scale and a marital conflict scale during the second trimester and at 8 months postnatally. Child outcomes were assessed at 42 months using the Rutter revised pre-school scales. RESULTS: Marital conflict partially mediated the relationship between postnatal depression in both mothers and fathers and child outcomes, and acted as an independent risk for adverse outcomes. Parental depression (maternal and paternal) and marital conflict in the antenatal period were both associated with adverse effects which persisted even when postnatal stresses were taken into account. CONCLUSIONS: These findings, if replicated, suggest that screening and intervention programmes targeted at parental depression and marital problems should be considered antenatally, as well as postnatally

Pharmacokinetics and Pharmacodynamics of Ethanol in Healthy Volunteers: Effects of Input-Rate and Degree of Ethanol Exposure on Subjective and Objective Measures of Impairment

The goal of this project was to investigate the effect of input-rate (oral and intravenous) and degree of exposure on the pharmacokinetics of ethanol and on subjective and objective measures of impairment, as well as on the development of acute tolerance to the effects of ethanol in young, healthy volunteers. The primary objective of this research was to test the following hypotheses: 1) the rate and degree of ethanol exposure (oral and intravenous) in normal healthy males and females affect the pharrnacokinetics (PK) and pharmacodynarnics (PD) of ethanol in a non-linear fashion; 2) the EEG changes after ethanol administration correlate with changes in psychometric performance and subject-rated impairment, as well as serum ethanol concentrations; and 3) acute tolerance develops to the subjective effects of ethanol which is not reflected in changes in electroencephalographic (EEG) activity or psychometric performance. This study was conducted in two parts. Part I was a five-way crossover pilot study in six healthy male volunteers to evaluate the effect of dose and dose-rate on the PK and PD of ethanol. This study evaluated changes in EEG activity, psychometric performance and subjective impairment to evaluate the relationship between these subjective and objective measures, and the relationship between these measures and serum ethanol concentrations. Part II was a 4-way crossover study in 16 healthy male and female subjects to study the PK-PD relationship for intravenous (IV) ethanol and acute tolerance development to the effects of ethanol. In this study, subjects were administered individualized intravenous ethanol infusions, to achieve a target concentration of 1000 mg/L after different durations of exposure. This study was designed to i:nvestigate the PK of ethanol, as well as to assess changes in EEG activity, psychometric performance and subjective impairment. This study evaluated the relationship between these measures, and the relationship between these measures and serum ethanol concentrations, as well as the development of acute tolerance to the effects of ethanol. Results from both studies showed that: 1) Ethanol, after oral and intravenous administration, follows capacity-limited pharmacokinetics. Intrinsic PK parameters, V max• Km and Vd were independent of dose and input-rate, but were associated with fairly high inter-individual variability. 2) Ethanol, after oral and intravenous administration, induced a transient slowing of the EEG and impairment in psychometric performance. The magnitude of the changes in these measures appeared to be dose-related as well as inputrate- related (observed in the IV study), however there was a fairly large degree of variability in response between individuals. 3) Ethanol, after oral and intravenous administration, induced transient subjective impairment, which was dose-related and input-rate-related, and correlated with serum ethanol concentrations across treatments. 4) A subset of subjects (2/6 males in the oral ethanol study, and 2/8 males and 4/8 female subjects in the IV study) were classified as non-responders based on their lack of subjective response to ethanol, despite serum ethanol concentrations, psychometric impairment and EEG changes that were consistent with the other subjects. 5) There was significant exposure-related acute tolerance development to the subjective effects of ethanol observed in both studies. This acute tolerance development could be characterized by a PK-PD model incorporating tolerance as a compensatory feedback mechanism to counter-regulate the direct subjective impairment effect of the drug. Acute tolerance was not observed for the psychometric impairment or changes in EEG activity, indicating that there was a temporal disparity be~een objective and subjective impairment following ethanol administration. 6) The EEG changes were not correlated with the psychometric or subjective impairment. 7) There was a significant gender difference observed in the Cmax and Vdss for ethanol, probably due to gender differences in body weight and body water content. There was also a significant gender difference observed in the magnitude of ethanol-induced subjective impairment, with females showing a lower degree of subjective impairment, despite achieving similar concentrations and demonstrating similar psychometric impairment and EEG changes. This gender difference may be partly confounded by the larger proportion of female non-responders compared to the male non-responders in the study

Evaluation of carcinogenic/co-carcinogenic activity of a common chewing product, pan masala, in mouse skin, stomach and esophagus

Pan masala, a dry powdered mixture of areca nut, catechu, lime, unspecified spices and flavoring agents, has gained widespread popularity as a chewing substitute in India. In this study, the carcinogenic and tumor-promoting potential of an ethanolic pan masala extract (EPME) was determined using skin of S/RVCri-ba mice and forestomach and esophagus of ICRC mice as the target tissues. Carcinogenic activity of pan masala was tested by painting the mouse skin for 40 weeks with EPME or by gavage feeding for 6 months. Following initiation with 9,10-dimethylbenz(a)anthracene (DMBA), carcinogenesis of mouse skin was promoted with different doses of EPME, while gastric- and esophageal-tumor-promoting activity was determined by administering EPME by gavage to animals initiated with diethylnitrosamine (DEN). The ability of EPME to effect progression of skin papilloma to carcinoma and cutaneous alterations after a single or multiple EPME treatment were also evaluated. EPME at 25 mg per dose promoted skin-papilloma formation between 30 and 40 weeks of treatment and enhanced the rate of conversion of papilloma to carcinoma. Induction of mild epidermal hyperplasia, dermal edema, increase in epidermal mitotic activity and the rate of epidermal and dermal DNA synthesis by EPME correlated well with its skin-tumor-promoting potential. In ICRC mice, EPME was inactive as a complete carcinogen, but effectively promoted the development of forestomach and esophageal papilloma and carcinoma in a concentration-dependent manner. The tumor incidence at 25 mg EPME per dose was comparable with that obtained in the 12-0-tetradecanoylphorbol-13 acetate(TPA)-treated group. The findings indicate that habitual pan-masala use may exert carcinogenic and co-carcinogenic influence

The acute psychobiological impact of the intensive care experience on relatives.

There is a growing awareness amongst critical care practitioners that the impact of intensive care medicine extends beyond the patient to include the psychological impact on close family members. Several studies have addressed the needs of relatives within the intensive care context but the psychobiological impact of the experience has largely been ignored. Such impact is important in respect to health and well-being of the relative, with potential to influence patient recovery. The current feasibility study aimed to examine the acute psychobiological impact of the intensive care experience on relatives. Using a mixed methods approach, quantitative and qualitative data were collected simultaneously. Six relatives of patients admitted to the intensive care unit (ICU) of a District General Hospital, were assessed within 48 h of admission. Qualitative data were provided from semi-structured interviews analysed using interpretative phenomenological analysis. Quantitative data were collected using a range of standardised self-report questionnaires measuring coping responses, emotion, trauma symptoms and social support, and through sampling of diurnal salivary cortisol as a biomarker of stress. Four themes were identified from interview: the ICU environment, emotional responses, family relationships and support. Questionnaires identified high levels of anxiety, depression and trauma symptoms; the most commonly utilised coping techniques were acceptance, seeking support through advice and information, and substance use. Social support emerged as a key factor with focused inner circle support relating to family and ICU staff. Depressed mood and avoidance were linked to greater mean cortisol levels across the day. Greater social network and coping via self-distraction were related to lower evening cortisol, indicating them as protective factors in the ICU context. The experience of ICU has a psychological and physiological impact on relatives, suggesting the importance of identifying cost-effective interventions with evaluations of health benefits to both relatives and patients

An investigation of home advantage in the Summer Paralympic Games

Purpose: There is a paucity of home advantage research set in the context of para-sport events. It is this gap in the knowledge that this paper addresses by investigating the prevalence and size of home advantage in the Summer Paralympic Games. Methods: Using a standardised measure of success, we compared the performances of nations when competing at home with their own performances away from home in the competition between 1960 and 2016. Both country level and individual sport level analysis was conducted for this time frame. A Wilcoxon signed rank test was used to determine whether there was a genuine difference in nations' performance under host and non-host conditions. Spearman's rank-order correlation was run to assess the relationship between nation quality and home advantage. Results: Strong evidence of a home advantage effect in the Summer Paralympic Games was found at country level (p 0.10). Conclusion: While our results confirm that home advantage is prevalent in the Summer Paralympic Games at an overall country level and within specific sports, they do not explain fully why such an effect does exist. Future studies should investigate the causes of home advantage in the competition and also draw comparisons with the Summer Olympic Games in order to explore any differences between para-sport events and able-bodied events