Can Playing the Computer Game “Tetris” Reduce the Build-Up of Flashbacks for Trauma? A Proposal from Cognitive Science

Background: Flashbacks are the hallmark symptom of Posttraumatic Stress Disorder (PTSD). Although we have successful treatments for full-blown PTSD, early interventions are lacking. We propose the utility of developing a ‘cognitive vaccine ’ to prevent PTSD flashback development following exposure to trauma. Our theory is based on two key findings: 1) Cognitive science suggests that the brain has selective resources with limited capacity; 2) The neurobiology of memory suggests a 6-hr window to disrupt memory consolidation. The rationale for a ‘cognitive vaccine ’ approach is as follows: Trauma flashbacks are sensory-perceptual, visuospatial mental images. Visuospatial cognitive tasks selectively compete for resources required to generate mental images. Thus, a visuospatial computer game (e.g. ‘‘Tetris’’) will interfere with flashbacks. Visuospatial tasks post-trauma, performed within the time window for memory consolidation, will reduce subsequent flashbacks. We predicted that playing ‘‘Tetris’ ’ half an hour after viewing trauma would reduce flashback frequency over 1-week. Methodology/Principal Findings: The Trauma Film paradigm was used as a well-established experimental analog for Posttraumatic Stress. All participants viewed a traumatic film consisting of scenes of real injury and death followed by a 30-min structured break. Participants were then randomly allocated to either a no-task or visuospatial (‘‘Tetris’’) condition which they undertook for 10-min. Flashbacks were monitored for 1-week. Results indicated that compared to the no-tas

Tablet versus paper marking in assessment : feedback matters

University of Aberdeen Medical Education Summer Teaching Bursary.Peer reviewedPublisher PD

The Wide Brown Dwarf Binary Oph 1622-2405 and Discovery of A Wide, Low Mass Binary in Ophiuchus (Oph 1623-2402): A New Class of Young Evaporating Wide Binaries?

We imaged five objects near the star forming clouds of Ophiuchus with the Keck Laser Guide Star AO system. We resolved Allers et al. (2006)'s #11 (Oph 16222-2405) and #16 (Oph 16233-2402) into binary systems. The #11 object is resolved into a 243 AU binary, the widest known for a very low mass (VLM) binary. The binary nature of #11 was discovered first by Allers (2005) and independently here during which we obtained the first spatially resolved R~2000 near-infrared (J & K) spectra, mid-IR photometry, and orbital motion estimates. We estimate for 11A and 11B gravities (log(g)>3.75), ages (5+/-2 Myr), luminosities (log(L/Lsun)=-2.77+/-0.10 and -2.96+/-0.10), and temperatures (Teff=2375+/-175 and 2175+/-175 K). We find self-consistent DUSTY evolutionary model (Chabrier et al. 2000) masses of 17+4-5 MJup and 14+6-5 MJup, for 11A and 11B respectively. Our masses are higher than those previously reported (13-15 MJup and 7-8 MJup) by Jayawardhana & Ivanov (2006b). Hence, we find the system is unlikely a ``planetary mass binary'', (in agreement with Luhman et al. 2007) but it has the second lowest mass and lowest binding energy of any known binary. Oph #11 and Oph #16 belong to a newly recognized population of wide (>100 AU), young (<10 Myr), roughly equal mass, VLM stellar and brown dwarf binaries. We deduce that ~6+/-3% of young (<10 Myr) VLM objects are in such wide systems. However, only 0.3+/-0.1% of old field VLM objects are found in such wide systems. Thus, young, wide, VLM binary populations may be evaporating, due to stellar encounters in their natal clusters, leading to a field population depleted in wide VLM systems.Comment: Accepted version V2. Now 13 pages longer (45 total) due to a new discussion of the stability of the wide brown dwarf binary population, new summary Figure 17 now included, Astrophysical Journal 2007 in pres

A submillimetre survey of the kinematics of the Perseus molecular cloud: I. data

We present submillimetre observations of the J = 3-2 rotational transition of 12CO, 13CO and C18O across over 600 sq arcmin of the Perseus molecular cloud, undertaken with HARP, a new array spectrograph on the James Clerk Maxwell Telescope. The data encompass four regions of the cloud, containing the largest clusters of dust continuum condensations: NGC 1333, IC348, L1448 and L1455. A new procedure to remove striping artefacts from the raw HARP data is introduced. We compare the maps to those of the dust continuum emission mapped with SCUBA (Hatchell et al. 2005) and the positions of starless and protostellar cores (Hatchell et al. 2007a). No straightforward correlation is found between the masses of each region derived from the HARP CO and SCUBA data, underlining the care that must be exercised when comparing masses of the same object derived from different tracers. From the 13CO/C18O line ratio the relative abundance of the two species ([13CO]/[C18O] ~ 7) and their opacities (typically tau is 0.02-0.22 and 0.15-1.52 for the C18O and 13CO gas respectively) are calculated. C18O is optically thin nearly everywhere, increasing in opacity towards star-forming cores but not beyond tau(C18O)~0.9. Assuming the 12CO gas is optically thick we compute its excitation temperature (around 8-30 K), which has little correlation with estimates of the dust temperature.Comment: 20 pages, 15 figures, accepted for publication by MNRA

The properties of SCUBA cores in the Perseus molecular cloud: the bias of clump-finding algorithms

We present a new analysis of the properties of star-forming cores in the Perseus molecular cloud, identified in SCUBA 850 micron data. Our goal is to determine which core properties can be robustly identified and which depend on the extraction technique. Four regions in the cloud are examined: NGC1333, IC348/HH211, L1448 and L1455. We identify clumps of dust emission using two popular automated algorithms, CLFIND and GAUSSCLUMPS, finding 85 and 122 clumps in total respectively. Some trends are true for both populations: clumps become increasingly elongated over time and are consistent with constant surface brightness objects, with an average brightness ~4 to 10 times larger than the surrounding molecular cloud; the clump mass distribution (CMD) resembles the stellar intial mass function, with a slope alpha = -2.0+/-0.1 for CLFIND and alpha = -3.15+/-0.08 for GAUSSCLUMPS, which straddle the Salpeter value. The mass at which the slope shallows (similar for both algorithms at M~6 Msun) implies a star-forming efficiency of between 10 and 20 per cent. Other trends reported elsewhere depend on the clump-finding technique: we find protostellar clumps are both smaller (for GAUSSCLUMPS) and larger (for CLFIND) than their starless counterparts; the functional form, best-fitting to the CMD, is different for the two algorithms. The GAUSSCLUMPS CMD is best-fitted with a log-normal distribution, whereas a broken power law is best for CLFIND; the reported lack of massive starless cores in previous studies can be seen in the CLFIND but not the GAUSSCLUMPS data. Our approach highlights similarities and differences between the clump populations, illustrating the caution that must be exercised when comparing results from different studies and interpreting the properties of continuum cores.Comment: 19 pages, 17 figures, accepted for publication by MNRA

A submillimetre survey of the kinematics of the Perseus molecular cloud - III. Clump kinematics

We explore the kinematics of continuum clumps in the Perseus molecular cloud, derived from C18O J=3-2 data. Two populations are examined, identified using the automated algorithms CLFIND and GAUSSCLUMPS on existing SCUBA data. The clumps have supersonic linewidths with distributions which suggest the C18O line probes a lower-density 'envelope' rather than a dense inner core. Similar linewidth distributions for protostellar and starless clumps implies protostars do not have a significant impact on their immediate environment. The proximity to an active young stellar cluster seems to affect the linewidths: those in NGC1333 are greater than elsewhere. In IC348 the proximity to the old IR cluster has little influence, with the linewidths being the smallest of all. A virial analysis suggests that the clumps are bound and close to equipartition. In particular, the starless clumps occupy the same parameter space as the protostars, suggesting they are true stellar precursors and will go on to form stars. We also search for ordered C18O velocity gradients across the face of each core, usually interpreted as rotation. We note a correlation between the directions of the identified gradients and outflows across protostars, indicating we may not have a purely rotational signature. The fitted gradients are larger than found in previous work, probably as a result of the higher resolution of our data and/or outflow contamination. These gradients, if interpreted solely in terms of rotation, suggest that rotation is not dynamically significant. Furthermore, derived specific angular momenta are smaller than observed in previous studies, centred around j~0.001 km/s pc, which indicates we have identified lower levels of rotation, or that the C18O J=3-2 line probes conditions significantly denser and/or colder than n~10^5 per cc and T~10 K.Comment: 20 pages, 20 figures, accepted for publication by MNRAS. Supplementary, on-line only material available from http://www.mrao.cam.ac.uk/~eic22/Papers/CR10b_suppmaterial.pd

Determinants of successful clinical networks : The conceptual framework and study protocol

Background Clinical networks are increasingly being viewed as an important strategy for increasing evidence-based practice and improving models of care, but success is variable and characteristics of networks with high impact are uncertain. This study takes advantage of the variability in the functioning and outcomes of networks supported by the Australian New South Wales (NSW) Agency for Clinical Innovation's non-mandatory model of clinical networks to investigate the factors that contribute to the success of clinical networks. Methods/Design The objective of this retrospective study is to examine the association between external support, organisational and program factors, and indicators of success among 19 clinical networks over a three-year period (2006-2008). The outcomes (health impact, system impact, programs implemented, engagement, user perception, and financial leverage) and explanatory factors will be collected using a web-based survey, interviews, and record review. An independent expert panel will provide judgements about the impact or extent of each network's initiatives on health and system impacts. The ratings of the expert panel will be the outcome used in multivariable analyses. Following the rating of network success, a qualitative study will be conducted to provide a more in-depth examination of the most successful networks. Discussion This is the first study to combine quantitative and qualitative methods to examine the factors that contribute to the success of clinical networks and, more generally, is the largest study of clinical networks undertaken. The adaptation of expert panel methods to rate the impacts of networks is the methodological innovation of this study. The proposed project will identify the conditions that should be established or encouraged by agencies developing clinical networks and will be of immediate use in forming strategies and programs to maximise the effectiveness of such networks

Human Nasal Challenge with Streptococcus pneumoniae Is Immunising in the Absence of Carriage

Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans

Germ band retraction as a landmark in glucose metabolism during Aedes aegypti embryogenesis

<p>Abstract</p> <p>Background</p> <p>The mosquito <it>A. aegypti </it>is vector of dengue and other viruses. New methods of vector control are needed and can be achieved by a better understanding of the life cycle of this insect. Embryogenesis is a part of <it>A. aegypty </it>life cycle that is poorly understood. In insects in general and in mosquitoes in particular energetic metabolism is well studied during oogenesis, when the oocyte exhibits fast growth, accumulating carbohydrates, lipids and proteins that will meet the regulatory and metabolic needs of the developing embryo. On the other hand, events related with energetic metabolism during <it>A. aegypti </it>embryogenesis are unknown.</p> <p>Results</p> <p>Glucose metabolism was investigated throughout <it>Aedes aegypti </it>(Diptera) embryonic development. Both cellular blastoderm formation (CBf, 5 h after egg laying - HAE) and germ band retraction (GBr, 24 HAE) may be considered landmarks regarding glucose 6-phosphate (G6P) destination. We observed high levels of glucose 6-phosphate dehydrogenase (G6PDH) activity at the very beginning of embryogenesis, which nevertheless decreased up to 5 HAE. This activity is correlated with the need for nucleotide precursors generated by the pentose phosphate pathway (PPP), of which G6PDH is the key enzyme. We suggest the synchronism of egg metabolism with carbohydrate distribution based on the decreasing levels of phosphoenolpyruvate carboxykinase (PEPCK) activity and on the elevation observed in protein content up to 24 HAE. Concomitantly, increasing levels of hexokinase (HK) and pyruvate kinase (PK) activity were observed, and PEPCK reached a peak around 48 HAE. Glycogen synthase kinase (GSK3) activity was also monitored and shown to be inversely correlated with glycogen distribution during embryogenesis.</p> <p>Conclusions</p> <p>The results herein support the hypothesis that glucose metabolic fate changes according to developmental embryonic stages. Germ band retraction is a moment that was characterized as a landmark in glucose metabolism during <it>Aedes aegypti </it>embryogenesis. Furthermore, the results also suggest a role for GSK3 in glycogen balance/distribution during morphological modifications.</p

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication