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Childhood adversity is associated with poor mental and physical health outcomes across the life span. Alterations in the hypothalamic–pituitary–adrenal axis are considered a key mechanism underlying these associations, although findings have been mixed. These inconsistencies suggest that other aspects of stress processing may underlie variations in this these associations, and that differences in adversity type, sex, and age may be relevant. The current study investigated the relationship between childhood adversity, stress perception, and morning cortisol, and examined whether differences in adversity type (generalized vs. threat and deprivation), sex, and age had distinct effects on these associations. Salivary cortisol samples, daily hassle stress ratings, and retrospective measures of childhood adversity were collected from a large sample of youth at risk for serious mental illness including psychoses (n = 605, mean age = 19.3). Results indicated that childhood adversity was associated with increased stress perception, which subsequently predicted higher morning cortisol levels; however, these associations were specific to threat exposures in females. These findings highlight the role of stress perception in stress vulnerability following childhood adversity and highlight potential sex differences in the impact of threat exposures.
OBJECTIVES/SPECIFIC AIMS: Discrimination within the healthcare system and physician distrust have been associated with adverse clinical outcomes for people living with HIV; however, many studies do not link these variables to biological data. We hypothesize that perceived healthcare discrimination and physician distrust associates with higher longitudinal viremia among HIV-positive women. METHODS/STUDY POPULATION: A 2006 cross-sectional survey assessed healthcare-based discrimination and physician trust in 92 HIV-positive and 46 high-risk HIV-negative women from the Washington DC Women’s Interagency HIV Study (DC-WIHS). In addition, we identified HIV viral load trajectories and demographics from the HIV-positive women who contributed≥4 semi-annual visits from 1994 to 2015. Viral suppression was defined by assay detection limits (<80 to <20 copies/mL). Group-based probability trajectory analyses grouped women based on longitudinal viral load patterns, and identified 3 groups: sustained viremia (n=32) with low-viral suppression over time, intermittent viremia (n=27) with varying suppression over time, and non-viremia (n=33) with high-longitudinal viral suppression. Ordinal logistic regression models assessed trajectory group and discrimination variables, controlling for demographics, using stepwise selection with significance level of α=0.05. RESULTS/ANTICIPATED RESULTS: Most women were African American (60%), insured at the time of visit (89%) and nonsmokers (56%). While physician trust did not differ by HIV viral trajectory group, trust was lower among HIV-negative women compared with HIV-positive women (p=0.03). Over 1 in 5 HIV-positive women reported discrimination in the healthcare system based on HIV status (21.3%). Report of discrimination based on drug/alcohol use was higher among HIV-negative participants (19.2% vs. 6.5%, p=0.01). Among women with longitudinal sustained viremia, report of discrimination based on race ethnicity (29%, p=0.004) and sexual orientation (15.6%, p=0.008) were higher than within the nonviremic and intermittent trajectory groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Physician trust did not associate with increased longitudinal viral suppression among HIV-positive women in Washington, DC. Lack of physician trust among high-risk HIV-negative women could have implications for uptake of prevention methods. Reports of discrimination vary between HIV-positive and HIV-negative women in the Washington, DC area. The findings of healthcare system distrust among HIV-negative women has implications outside the realm of HIV, as this lack of trust may impact risk for other disease states among similar populations of women.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Accumulating behavioral and genetic research suggests that most forms of psychopathology share common genetic and neural vulnerabilities and are manifestations of a relatively few core underlying processes. These findings support the view that comorbidity mostly arises, not from true co-occurrence of distinct disorders, but from the behavioral expression of shared vulnerability processes across the life span. The purpose of this review is to examine the role of the prefrontal cortex (PFC) in the shared vulnerability mechanisms underlying the clinical phenomena of comorbidity from a transdiagnostic and ontogenic perspective. In adopting this perspective, we suggest complex transactions between neurobiologically rooted vulnerabilities inherent in PFC circuitry and environmental factors (e.g., parenting, peers, stress, and substance use) across development converge on three key PFC-mediated processes: executive functioning, emotion regulation, and reward processing. We propose that individual differences and impairments in these PFC-mediated functions provide intermediate mechanisms for transdiagnostic symptoms and underlie behavioral tendencies that evoke and interact with environmental risk factors to further potentiate vulnerability.
Anxiety often co-occurs with major depressive disorder (MDD). This preliminary study sought to ascertain the extent to which anxious depression drives group neurobiological differences between patients with MDD and healthy volunteers (HVs).
Magnetoencephalography beta-band frequency was used to compare differences in brain response during the N-back working memory task between 30 medication-free patients with treatment-resistant MDD (anxious depression=18; nonanxious depression=12) and 28 HVs.
Compared to HVs, patients with anxious depression had significantly reduced desynchronisation (less activation) in the left precuneus, right cuneus, and left insula extending into the inferior and middle frontal cortex during the 2-back condition compared with the 1-back condition of the N-back working memory task – indicating less activation of these neural networks in patients with anxious depression during the condition with the highest level of task demands. No other significant group differences were found during the working memory conditions.
This preliminary study suggests that a subset of patients – those with anxious depression – may be driving observed group differences between patients with MDD and HVs. Further neurobiological studies and replication experiments are necessary to determine the extent to which this subgroup has preferentially influenced our understanding of the underlying neurobiology of depression.
Psychotic disorders continue to be among the most disabling and scientifically challenging of all mental illnesses. Accumulating research findings suggest that the etiologic processes underlying the development of these disorders are more complex than had previously been assumed. At the same time, this complexity has revealed a wider range of potential options for preventive intervention, both psychosocial and biological. In part, these opportunities result from our increased understanding of the dynamic and multifaceted nature of the neurodevelopmental mechanisms involved in the disease process, as well as the evidence that many of these entail processes that are malleable. In this article, we review the burgeoning research literature on the prodrome to psychosis, based on studies of individuals who meet clinical high risk criteria. This literature has examined a range of factors, including cognitive, genetic, psychosocial, and neurobiological. We then turn to a discussion of some contemporary models of the etiology of psychosis that emphasize the prodromal period. These models encompass the origins of vulnerability in fetal development, as well as postnatal stress, the immune response, and neuromaturational processes in adolescent brain development that appear to go awry during the prodrome to psychosis. Then, informed by these neurodevelopmental models of etiology, we turn to the application of new research paradigms that will address critical issues in future investigations. It is expected that these studies will play a major role in setting the stage for clinical trials aimed at preventive intervention.
In most countries, male pigs are physically castrated soon after birth to reduce the risk of boar taint and to avoid behaviours such as fighting and mounting. However, entire male pigs are more feed efficient and deposit less fat than barrows. In addition, many animal welfare organizations are lobbying for a cessation of castration, with a likelihood that this could lead to inferior pork unless an alternative method is used to control boar taint. An alternative to physical castration is immunization against gonadotrophin releasing factor (GnRF) which allows producers to capitalize on the superior feed efficiency and carcass characteristics of boars without the risk of boar taint. From a physiological perspective, immunized pigs are entire males until shortly after the second dose, typically given 4 to 6 weeks before slaughter. Following full immunization, there is a temporary suppression of testicular function and a hormonal status that resembles that of a barrow. Nutrient requirements will be different in these two phases, before and after full immunization. Given that there have been few published studies comparing the lysine requirements of entire males and barrows in contemporary genotypes, it is useful to use gilt requirements as a benchmark. A series of meta-analyses comparing anti-GnRF immunized boars and physical castrates and use of nutritional models suggest that the lysine requirement of entire males before the second immunization is 5% higher than for gilts, from 25 to 50 kg BW, and by 8% from 50 to 95 kg. Given that the penalty in growth performance for having inadequate dietary lysine is greater in males than in gilts or barrows, it is important to ensure that lysine requirements are met to obtain the maximum benefits of entire male production during this phase. After the second immunization, the lysine requirement of immunized males decreases and may become more like that of barrows. In addition, a consistent effect of full immunization is a marked increase in voluntary feed intake from about 10 days after the second dose. Putting these together, the estimated lysine requirement, expressed in terms of diet composition, falls to 94% of the gilt level. Although general principles can be described now, further research is needed to fully define the lysine requirements of immunized boars. It is important that the temporal pattern of tissue deposition rates and feed intake be explored to be incorporated into models to predict nutrient requirements over the period of rapidly changing metabolism.
A cross-sectional survey of 210 healthcare workers at a pediatric teaching hospital was performed to assess knowledge of published guidelines for proper measurement and documentation of tuberculin skin test Results. We conclude that many healthcare workers have inadequate knowledge for optimal measurement and documentation of tuberculin skin test results.
Twenty-three chronic nonfluent aphasia patients with moderate or
severe word-finding impairments and 11 with profound word-finding
impairments received two novel picture-naming treatments. The intention
treatment initiated picture-naming trials with a complex left-hand
movement and was designed to enhance right frontal participation during
word retrieval. The attention treatment required patients to view visual
stimuli for picture-naming trials in their left hemispace and was designed
to enhance right posterior perisylvian participation during word
retrieval. Because the intention treatment addressed action mechanisms and
nonfluent aphasia reflects difficulty initiating or maintaining action
(i.e., language output), it was hypothesized that intention component of
the treatment would enhance re-acquisition of picture naming more than the
attention component. Patients with moderate and severe word-finding
impairment showed gains with both treatments but greater incremental
improvement from one treatment phase to the next with the intention than
the attention treatment. Thus, the hypothesis that intention component
would be a more active constituent than the attention component was
confirmed for these patients. Patients with profound word-finding
impairment showed some improvement with both treatments but no
differential effects for the intention treatment. Almost all patients who
showed treatment gains on either treatment also demonstrated
generalization from trained to untrained items. (JINS, 2007,
Background. Borderline personality disorder (BPD) is often co-morbid with major depression and may complicate its treatment. We were interested in differences in genetic and developmental risk factors between depressed patients with or without a co-morbid BPD.
Method. Out-patients with major depressive disorder were recruited for two treatment trials. Assessment of depressed patients included the assessment of personality disorders, developmental risk factors and DNA samples for genetic analyses.
Results. In each study there was a significant association between the 9-repeat allele of the dopamine transporter (DAT1) and BPD, with odds ratios (OR) >3 and p[les ]0·02. This association remained significant when developmental risk factors for BPD (childhood abuse and neglect and borderline temperament) were also included in the analyses. The OR was even larger in the depressed patients aged [ges ]35 years (OR 9·31, p=0·005).
Conclusion. This replicated association in depressed patients between the 9-repeat allele of DAT1 and BPD may provide clues to understanding the neurobiology of BPD. The finding that the association is larger in the older depressed patients, suggests that the 9-repeat allele may be associated with a poorer prognosis BPD, rather than a young adult limited variant of BPD.
In Volume 136, 407–426, you published a paper entitled ‘Responses of potato (Solanum tuberosum) to potassium fertilizers’ by M. F. Allison, J. H. Fowler and E. J. Allen. We consider that the authors' conclusions were not justified and they have mis-interpreted and criticized earlier published work. One of their criticisms is levelled at the use of exchangeable potassium (Kex – rapidly plant-available K) to categorize soils on the basis of the likely response of crops to an application of potassium (K) fertilizer. While Kex is not perfect, it is the best rapid method currently available (Johnston & Goulding 1990). To support their contention about Kex, the authors quote in Table 15 data from Rothamsted experiments done in the late 1950s and early 1960s. They state that despite the large amounts of K applied in fertilizers and manures the effect on Kex was relatively small. This comment fails to recognize that it is the K balance (K applied minus K removed) that must be related to Kex, not the K applied, and the inevitable transfer of part of the K balance from Kex to fixed K (less readily available K). Warren & Johnston (1962) showed that on these soil types as much as 60% of the K balance is rapidly transferred to fixed K.