From presence to consciousness through virtual reality

Immersive virtual environments can break the deep, everyday connection between where our senses tell us we are and where we are actually located and whom we are with. The concept of 'presence' refers to the phenomenon of behaving and feeling as if we are in the virtual world created by computer displays. In this article, we argue that presence is worthy of study by neuroscientists, and that it might aid the study of perception and consciousness

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

Implications of a Modified Higgs to Diphoton Decay Width

Motivated by recent results from Higgs searches at the Large Hadron Collider, we consider possibilities to enhance the diphoton decay width of the Higgs boson over the Standard Model expectation, without modifying either its production rate or the partial widths in the WW and ZZ channels. Studying effects of new charged scalars, fermions and vector bosons, we find that significant variations in the diphoton width may be possible if the new particles have light masses of the order of a few hundred GeV and sizeable couplings to the Higgs boson. Such couplings could arise naturally if there is large mass mixing between two charged particles that is induced by the Higgs vacuum expectation value. In addition, there is generically also a shift in the Z + Gamma partial width, which in the case of new vector bosons tends to be of similar magnitude as the shift in the diphoton partial width, but smaller in other cases. Therefore simultaneous measurements in these two channels could reveal properties of new charged particles at the electroweak scale.Comment: 29 pages, 8 figures; v2: updated references and minor improvements in presentations; v3: sign of the scalar contribution to Z+Gamma amplitudes fixed. Related figures update

A rainfall model for drought risk analysis in south-east UK

Drought risk assessment ideally requires long-term rainfall records especially where inter-annual droughts are of potential concern, and spatially consistent estimates of rainfall to support regional and inter-regional scale assessments. This paper addresses these challenges by developing a spatially consistent stochastic model of monthly rainfall for south-east UK. Conditioned on 50 gauged sites, the model infills the historic record from 1855-2011 in both space and time, and extends the record by synthesising droughts which are consistent with the observed rainfall statistics. The long record length allows more insight into the variability of rainfall and potentially a stronger basis for risk assessment than is generally possible. It is shown that, although localised biases exist in both space and time, the model results are generally consistent with the observed record including for a range of inter-annual droughts and spatial statistics. Simulations show that some of the most severe inter-annual droughts on the record may recur, despite a trend towards generally wetter winters

Middleborns disadvantaged? testing birth-order effects on fitness in pre-industrial finns

Parental investment is a limited resource for which offspring compete in order to increase their own survival and reproductive success. However, parents might be selected to influence the outcome of sibling competition through differential investment. While evidence for this is widespread in egg-laying species, whether or not this may also be the case in viviparous species is more difficult to determine. We use pre-industrial Finns as our model system and an equal investment model as our null hypothesis, which predicts that (all else being equal) middleborns should be disadvantaged through competition. We found no overall evidence to suggest that middleborns in a family are disadvantaged in terms of their survival, age at first reproduction or lifetime reproductive success. However, when considering birth-order only among same-sexed siblings, first-, middle-and lastborn sons significantly differed in the number of offspring they were able to rear to adulthood, although there was no similar effect among females. Middleborn sons appeared to produce significantly less offspring than first-or lastborn sons, but they did not significantly differ from lastborn sons in the number of offspring reared to adulthood. Our results thus show that taking sex differences into account is important when modelling birth-order effects. We found clear evidence of firstborn sons being advantaged over other sons in the family, and over firstborn daughters. Therefore, our results suggest that parents invest differentially in their offspring in order to both preferentially favour particular offspring or reduce offspring inequalities arising from sibling competition

Culture Adaptation Alters Transcriptional Hierarchies among Single Human Embryonic Stem Cells Reflecting Altered Patterns of Differentiation

We have used single cell transcriptome analysis to re-examine the substates of early passage, karyotypically Normal, and late passage, karyotypically Abnormal (‘Culture Adapted’) human embryonic stem cells characterized by differential expression of the cell surface marker antigen, SSEA3. The results confirmed that culture adaptation is associated with alterations to the dynamics of the SSEA3(+) and SSEA3(-) substates of these cells, with SSEA3(-) Adapted cells remaining within the stem cell compartment whereas the SSEA3(-) Normal cells appear to have differentiated. However, the single cell data reveal that these substates are characterized by further heterogeneity that changes on culture adaptation. Notably the Adapted population includes cells with a transcriptome substate suggestive of a shift to a more naïve-like phenotype in contrast to the cells of the Normal population. Further, a subset of the Normal SSEA3(+) cells expresses genes typical of endoderm differentiation, despite also expressing the undifferentiated stem cell genes, POU5F1 (OCT4) and NANOG, whereas such apparently lineage-primed cells are absent from the Adapted population. These results suggest that the selective growth advantage gained by genetically variant, culture adapted human embryonic stem cells may derive in part from a changed substate structure that influences their propensity for differentiation

Pragmatic trials of pain therapies

Pragmatic randomised clinical trials aim to directly inform clinical or health policy decision-making. Here, we systematically review methods and design of pragmatic trials of pain therapies to examine methods, identify common challenges, and areas for improvement. Seven databases were searched for pragmatic randomised controlled clinical trials which assessed pain treatment in a clinical population of adults reporting pain. All screening steps and data extractions were performed twice. Data were synthesised descriptively and correlation analyses between pre-specified trial features and PRECIS-2 (PRagmatic – Explanatory Continuum Indicator Summary 2) ratings and attrition were performed. Protocol registration: PROSPERO-ID CRD42020178954. Of 57 included trials, only 21% assessed pharmacological interventions, the remainder physical, surgical, psychological or self-management pain therapies. Three-quarters of the trials were comparative effectiveness designs, often conducted in multiple centres (median: 5; Q1/3: 1, 9.25) and with a median sample size of 234 patients at randomization (Q1/3: 135.5; 363.5). Although most trials recruited chronic pain patients, reporting of pain duration was poor and not well described. Reporting was comprehensive for most general items, while often deficient for specific pragmatic aspects. Average ratings for pragmatism were highest for treatment adherence flexibility and clinical relevance of outcome measures. They were lowest for patient recruitment methods and extent of follow-up measurements and appointments. Current practice in pragmatic trials of pain treatments can be improved in areas such as patient recruitment and reporting of methods, analysis and interpretation of data. These improvements will facilitate translatability to other real-world settings – the purpose of pragmatic trials

UK meteotsunamis: a revision and update on events and their frequency

A tsunami is a series of waves caused by the displacement of water. The displacement may result from ‘bottom‐up’ seabed movement, such as caused by earthquakes, landslides and volcanic eruptions or ‘top‐down’ movement, from pressure perturbations in the atmosphere. These ‘top‐down’ events are termed meteotsunamis. Meteotsunamis frequently occur in the Mediterranean, the Baltic Sea, the east coast and Great Lakes of North America, and Japan, so they are not exclusive to the United Kingdom. The most recent meteotsunami near the UK coast was in May 2017, when waves around 2m in elevation, generated by a storm passing over the UK, struck the coast of the Netherlands. Historical documents covering the past 150 years describe many meteotsunamis from United Kingdom (UK) coastal waters (Haslett et al ., 2009; Haslett and Bryant, 2009; Tappin et al ., 2013; Vilibić et al ., 2015; O'Brien et al ., 2018). Some of these events have resulted in fatalities, involving beach users who were struck by unexpected sea waves. Meteotsunamis commonly strike the coasts of the UK, damaging harbours, boats and very rarely, causing fatalities. In the UK, they were usually detected by analysis after the event, unless witnessed first‐hand. This post‐event analysis is particularly necessary in the UK because the data provided by the tide gauge system, operated by the Environment Agency, only records at 15‐min intervals, not in real time as in the rest of Europe. The periods of meteotsunamis are in the range of minutes to tens of minutes (Pattiaratchi and Wijeratne, 2015). A frequency of tens of minutes is similar to a typical frequency expected from a meteotsunami that would have an amplified response from harbour or bay resonance (Tappin et al ., 2013). Therefore, those occurring in UK waters are not often recorded with the present tide gauge settings and as a consequence, cannot be analysed effectively

Therapeutic monoclonal antibodies for Ebola virus infection derived from vaccinated humans

We describe therapeutic monoclonal antibodies isolated from human volunteers vaccinated with recombinant adenovirus expressing Ebola virus glycoprotein (EBOV GP) and boosted with modified vaccinia virus Ankara. Among 82 antibodies isolated from peripheral blood B cells, almost half neutralized GP pseudotyped influenza virus. The antibody response was diverse in gene usage and epitope recognition. Although close to germline in sequence, neutralizing antibodies with binding affinities in the nano- to pico-molar range, similar to “affinity matured” antibodies from convalescent donors, were found. They recognized the mucin-like domain, glycan cap, receptor binding region, and the base of the glycoprotein. A cross-reactive cocktail of four antibodies, targeting the latter three non-overlapping epitopes, given on day 3 of EBOV infection, completely protected guinea pigs. This study highlights the value of experimental vaccine trials as a rich source of therapeutic human monoclonal antibodies