Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial

This is the final version. Available from BMC via the DOI in this record. Data availability: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Code for the TCM model is available here: https://github.com/alexandershaw4/LTP_code.Background Microdosing psychedelics is a phenomenon with claimed cognitive benefts that are relatively untested clinically. Pre-clinically, psychedelics have demonstrated enhancing efects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This study used a visual long-term potentiation (LTP) EEG paradigm to test the efects of microdosed lysergic acid diethylamide (LSD) on neural plasticity, both acutely while on the drug and cumulatively after microdosing every third day for six weeks. Healthy adult males (n=80) completed the visual LTP paradigm at baseline, 2.5 h following a dose of 10 µg of LSD or inactive placebo, and 6 weeks later after taking 14 repeated microdoses. Visually induced LTP was used as indirect index of neural plasticity. Surface level event-related potential (ERPs) based analyses are presented alongside dynamic causal modelling of the source localised data using a generative thalamocortical model (TCM) of visual cortex to elucidate underlying synaptic circuitry. Results Event-related potential (ERP) analyses of N1b and P2 components did not show evidence of changes in visually induced LTP by LSD either acutely or after 6 weeks of regular dosing. However modelling the complete timecourse of the ERP with the TCM demonstrated changes in laminar connectivity in primary visual cortex. This primarily included changes to self-gain and inhibitory input parameters acutely. Layer 2/3 to layer 5 excitatory connectivity was also diferent between LSD and placebo groups. After regular dosing only excitatory input from layer 2/3 into layer 5 and inhibitory input into layer 4 were diferent between groups. Conclusions Without modulation of the ERPs it is difcult to relate the fndings to other studies visually inducing LTP. It also indicates the classic peak analysis may not be sensitive enough to demonstrate evidence for changes in LTP plasticity in humans at such low doses. The TCM provides a more sensitive approach to assessing changes to plasticity as diferences in plasticity mediated laminar connectivity were found between the LSD and placebo groups.Health Research Council of New ZealandMindBio Therapeutics Ltd

Comparative Field Evaluation of Combinations of Long-Lasting Insecticide Treated Nets and Indoor Residual Spraying, Relative to Either Method Alone, for Malaria Prevention in an Area where the main Vector is Anopheles Arabiensis.

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In contrast, adding intact bednets onto IRS enhances protection by preventing mosquito blood-feeding (even if the nets are non-insecticidal) and by slightly increasing mosquito mortality (in case of LLINs). The primary mode of action of intact LLINs against An. arabiensis is clearly bite prevention rather than insecticidal activity. Therefore, where resources are limited, priority should be to ensure that everyone at risk consistently uses LLINs and that the nets are regularly replaced before being excessively torn. Measures that maximize bite prevention (e.g. proper net sizes to effectively cover sleeping spaces, stronger net fibres that resist tears and burns and net use practices that preserve net longevity), should be emphasized

Perspective from a Younger Generation -- The Astro-Spectroscopy of Gisbert Winnewisser

Gisbert Winnewisser's astronomical career was practically coextensive with the whole development of molecular radio astronomy. Here I would like to pick out a few of his many contributions, which I, personally, find particularly interesting and put them in the context of newer results.Comment: 14 pages. (Co)authored by members of the MPIfR (Sub)millimeter Astronomy Group. To appear in the Proceedings of the 4th Cologne-Bonn-Zermatt-Symposium "The Dense Interstellar Medium in Galaxies" eds. S. Pfalzner, C. Kramer, C. Straubmeier, & A. Heithausen (Springer: Berlin

Assessing newborn body composition using principal components analysis: differences in the determinants of fat and skeletal size

BACKGROUND: Birth weight is a composite of skeletal size and soft tissue. These components are likely to have different growth patterns. The aim of this paper is to investigate the association between established determinants of birth weight and these separate components. METHODS: Weight, length, crown-rump, knee-heel, head circumference, arm circumference, and skinfold thicknesses were measured at birth in 699 healthy, term, UK babies recruited as part of the Exeter Family Study of Childhood Health. Corresponding measurements were taken on both parents. Principal components analysis with varimax rotation was used to reduce these measurements to two independent components each for mother, father and baby: one highly correlated with measures of fat, the other with skeletal size. RESULTS: Gestational age was significantly related to skeletal size, in both boys and girls (r = 0.41 and 0.52), but not fat. Skeletal size at birth was also associated with parental skeletal size (maternal: r = 0.24 (boys), r = 0.39 (girls) ; paternal: r = 0.16 (boys), r = 0.25 (girls)), and maternal smoking (0.4 SD reduction in boys, 0.6 SD reduction in girls). Fat was associated with parity (first borns smaller by 0.45 SD in boys; 0.31 SD in girls), maternal glucose (r = 0.18 (boys); r = 0.27 (girls)) and maternal fat (r = 0.16 (boys); r = 0.36 (girls)). CONCLUSION: Principal components analysis with varimax rotation provides a useful method for reducing birth weight to two more meaningful components: skeletal size and fat. These components have different associations with known determinants of birth weight, suggesting fat and skeletal size may have different regulatory mechanisms, which would be important to consider when studying the associations of birth weight with later adult disease

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Use of a food frequency questionnaire in American Indian and Caucasian pregnant women: a validation study

BACKGROUND: Food frequency questionnaires (FFQs) have been validated in pregnant women, but few studies have focused specifically on low-income women and minorities. The purpose of this study was to examine the validity of the Harvard Service FFQ (HSFFQ) among low-income American Indian and Caucasian pregnant women. METHODS: The 100-item HSFFQ was administered three times to a sample of pregnant women, and two sets of 24-hour recalls (six total) were collected at approximately 12 and 28 weeks of gestation. The sample included a total of 283 pregnant women who completed Phase 1 of the study and 246 women who completed Phase 2 of the study. Deattenuated Pearson correlation coefficients were used to compare intakes of 24 nutrients estimated from the second and third FFQ to average intakes estimated from the week-12 and week-28 sets of diet recalls. RESULTS: Deattenuated correlations ranged from 0.09 (polyunsaturated fat) to 0.67 (calcium) for Phase 1 and from 0.27 (sucrose) to 0.63 (total fat) for Phase 2. Average deattenuated correlations for the two phases were 0.48 and 0.47, similar to those reported among other groups of pregnant women. CONCLUSION: The HSFFQ is a simple self-administered questionnaire that is useful in classifying low-income American Indian and Caucasian women according to relative dietary intake during pregnancy. Its use as a research tool in this population may provide important information about associations of nutrient intakes with pregnancy outcomes and may help to identify groups of women who would benefit most from nutritional interventions

Time-resolved crystallography using the Hadamard transform

YesWe describe a method for performing time-resolved X-ray crystallographic experiments based on the Hadamard transform, in which time resolution is defined by the underlying periodicity of the probe pulse sequence, and signal/noise is greatly improved over that for the fastest pump-probe experiments depending on a single pulse. This approach should be applicable on standard synchrotron beamlines and will enable high-resolution measurements of protein and small-molecule structural dynamics. It is also applicable to other time-resolved measurements where a probe can be encoded, such as pump-probe spectroscopy.Wellcome Trust 4-year PhD program “The Molecular Basis of Biological Mechanisms” 089312/Z/09/Z. This work was also supported by the EPSRC Award “Dynamic Structural Science at the Research Complex at Harwell” EP/I01974X/1 and by BBSRC Award BB/H001905/1

Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells

Invariant natural killer T cells (iNKT cells) are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled gene expression in iNKT cells during ontogeny and in peripheral subsets as part of the Immunological Genome Project. High-resolution comparative transcriptional analyses defined developmental and subset-specific programs of gene expression by iNKT cells. In addition, we found that iNKT cells shared an extensive transcriptional program with NK cells, similar in magnitude to that shared with major histocompatibility complex (MHC)-restricted T cells. Notably, the program shared by NK cells and iNKT cells also operated constitutively in γδ T cells and in adaptive T cells after activation. Together our findings highlight a core effector program regulated distinctly in innate and adaptive lymphocytes

"Half plate of rice to a male casual sexual partner, full plate belongs to the husband": Findings from a qualitative study on sexual behaviour in relation to HIV and AIDS in northern Tanzania

A thorough understanding of the contexts of sexual behaviour of the people who are vulnerable to HIV infection is an important component in the battle against AIDS epidemic. We conducted a qualitative study to investigate perceptions, attitudes and practices of sexually active people in three districts of northern Tanzania with the view of collecting data to inform the formulation of appropriate complementary interventions against HIV and AIDS in the study communities. We conducted 96 semi-structured interviews and 48 focus group discussions with sexually active participants (18-60 years of age) who were selected purposively in two fishing and one non-fishing communities. The study revealed a number of socio-economic and cultural factors which act as structural drivers of HIV epidemic. Mobility and migration were mentioned to be associated with the risk of HIV acquisition and transmission. Sexual promiscuous behaviour was common in all study communities. Chomolea, (a quick transactional sex) was reported to exist in fishing communities, whereas extramarital sex in the bush was reported in non-fishing community which was predominantly Christian and polygamous. Traditional practices such as Kusomboka (death cleansing through unprotected sex) was reported to exist. Other risky sexual behaviour and traditional practices together with their socio-economic and cultural contexts are presented in details and discussed. Knowledge of condom was low as some people mistook them for balloons to play with and as decorations for their living rooms. Acute scarcity of condoms in some remote areas such as vizingani (fishing islands) push some people to make their own condoms locally known as kondomu za pepsi using polythene bags. HIV prevention efforts can succeed by addressing sexual behaviour and its socio-economic and cultural contexts. More innovative, interdisciplinary and productive structural approaches to HIV prevention need to be developed in close collaboration with affected communities and be closely related to policy-making and implementation; to go beyond the limited success of traditional behavioural and biomedical interventions to particularly address the underlying social and structural drivers of HIV risk and vulnerability in the study communities