I See! Scotland: Tackling sectarianism and promoting community psychosocial health

We developed and tested through two studies a new intervention run as a course, I SEE! Scotland, to reduce and prevent Protestant-Catholic sectarianism in Scotland, a historic inter-group conflict expressed in forms ranging from polite to violent, within a wider population that includes those who feel untouched. Designed to reflect the social ecology of Scotland and engage individuals regardless of sectarian involvement, the intervention aimed to increase cognitive complexity, measured as integrative complexity, through participatory theatre and experiential methods. We hypothesised that the confluence of experiential learning to support multiple forms of self, other, and systems awareness with narrative framing would increase integrative complexity management capacities. Tested with a diverse sample of 104 participants (secondary school staff; achieving, disruptive or vulnerable students; young adults returning to education; other professionals; prisoners; recovering drug addicts; unemployed), study one pre-post comparisons showed significant integrative complexity gains that cohered with second end of intervention integrative complexity measures, replicating results from other integrative complexity interventions despite differences in samples, conflicts, and context. Study two with twenty-eight of the one hundred and four participants showed significant pre post increases in resilience. These results predict peaceful outcomes to intergroup conflict, tackling sectarianism and promoting community psychosocial health. We note future research plans

Determinants of wellbeing in university students: The role of residential status, stress, loneliness, resilience, and sense of coherence

Maintaining wellbeing in university students is a government priority, but robust evidence has been lacking. Higher wellbeing is associated with better mental and physical health, higher self-esteem, self-efficacy, and effective coping strategies. This study aimed to identify, through an online survey in 2018, key determinants of wellbeing amongst a sample of 574 (65.5% female) students across all levels of study at a university in the UK. Most respondents (526 (91.8%)) reported feeling unusually stressed or overwhelmed at university. Residential students reported higher loneliness and number of stressors than commuter students, and postgraduate students reported higher wellbeing, resilience, and sense of coherence, and lower perceived stress and loneliness. Hierarchical regression analyses showed that 71.8% of the variance in wellbeing was predicted by a model containing demographics (age/gender, level of study, number of stressors), psychosocial variables, and perceived stress, with perceived stress, sense of coherence, loneliness, and resilience the strongest predictors. The findings suggest that interventions designed to improve resilience and sense of coherence, and reduce loneliness and perceived stress are likely to be effective in enhancing wellbeing in a student populatio

Photovoltaic restoration of sight with high visual acuity

Patients with retinal degeneration lose sight due to the gradual demise of photoreceptors. Electrical stimulation of surviving retinal neurons provides an alternative route for the delivery of visual information. We demonstrate that subretinal implants with 70-μm-wide photovoltaic pixels provide highly localized stimulation of retinal neurons in rats. The electrical receptive fields recorded in retinal ganglion cells were similar in size to the natural visual receptive fields. Similarly to normal vision, the retinal response to prosthetic stimulation exhibited flicker fusion at high frequencies, adaptation to static images and nonlinear spatial summation. In rats with retinal degeneration, these photovoltaic arrays elicited retinal responses with a spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in healthy rats. The ease of implantation of these wireless and modular arrays, combined with their high resolution, opens the door to the functional restoration of sight in patients blinded by retinal degeneration

Empirical Distributions of F-ST from Large-Scale Human Polymorphism Data

Studies of the apportionment of human genetic variation have long established that most human variation is within population groups and that the additional variation between population groups is small but greatest when comparing different continental populations. These studies often used Wright’s FST that apportions the standardized variance in allele frequencies within and between population groups. Because local adaptations increase population differentiation, high-FST may be found at closely linked loci under selection and used to identify genes undergoing directional or heterotic selection. We re-examined these processes using HapMap data. We analyzed 3 million SNPs on 602 samples from eight worldwide populations and a consensus subset of 1 million SNPs found in all populations. We identified four major features of the data: First, a hierarchically FST analysis showed that only a paucity (12%) of the total genetic variation is distributed between continental populations and even a lesser genetic variation (1%) is found between intra-continental populations. Second, the global FST distribution closely follows an exponential distribution. Third, although the overall FST distribution is similarly shaped (inverse J), FST distributions varies markedly by allele frequency when divided into non-overlapping groups by allele frequency range. Because the mean allele frequency is a crude indicator of allele age, these distributions mark the time-dependent change in genetic differentiation. Finally, the change in mean-FST of these groups is linear in allele frequency. These results suggest that investigating the extremes of the FST distribution for each allele frequency group is more efficient for detecting selection. Consequently, we demonstrate that such extreme SNPs are more clustered along the chromosomes than expected from linkage disequilibrium for each allele frequency group. These genomic regions are therefore likely candidates for natural selection

Genomic analysis of 6,000-year-old cultivated grain illuminates the domestication history of barley

The cereal grass barley was domesticated about 10,000 years ago in the Fertile Crescent and became a founder crop of Neolithic agriculture. Here, we report genome sequences of five 6,000-year-old barley grains excavated at a cave in the Judean Desert close to the Dead Sea. Comparison to whole exome sequence data from a diversity panel of present-day barley accessions revealed the close affinity of ancient samples to extant landraces from the Southern Levant and Egypt, consistent with a proposed origin of domesticated barley in the Upper Jordan Valley. Our findings suggest that barley landraces grown in present-day Israel in the past six millennia have not experienced a major lineage turnover although there is evidence for gene flow between cultivated and sympatric wild populations. We show the utility of ancient genomes from desiccated archaeobotanical remains in informing research into the origin, early domestication and subsequent migration of crop species

Temporal evolution of electrographic seizures in newborn infants with hypoxic-ischaemic encephalopathy requiring therapeutic hypothermia: a secondary analysis of the ANSeR studies

Background: Despite extensive research on neonatal hypoxic-ischaemic encephalopathy, detailed information about electrographic seizures during active cooling and rewarming of therapeutic hypothermia is sparse. We aimed to describe temporal evolution of seizures and determine whether there is a correlation of seizure evolution with 2-year outcome. / Methods: This secondary analysis included newborn infants recruited from eight European tertiary neonatal intensive care units for two multicentre studies (a randomised controlled trial [NCT02431780] and an observational study [NCT02160171]). Infants were born at 36+0 weeks of gestation with moderate or severe hypoxic-ischaemic encephalopathy and underwent therapeutic hypothermia with prolonged conventional video-electroencephalography (EEG) monitoring for 10 h or longer from the start of rewarming. Seizure burden characteristics were calculated based on electrographic seizures annotations: hourly seizure burden (minutes of seizures within an hour) and total seizure burden (minutes of seizures within the entire recording). We categorised infants into those with electrographic seizures during active cooling only, those with electrographic seizures during cooling and rewarming, and those without seizures. Neurodevelopmental outcomes were determined using the Bayley's Scales of Infant and Toddler Development, Third Edition (BSID-III), the Griffiths Mental Development Scales (GMDS), or neurological assessment. An abnormal outcome was defined as death or neurodisability at 2 years. Neurodisability was defined as a composite score of 85 or less on any subscales for BSID-III, a total score of 87 or less for GMDS, or a diagnosis of cerebral palsy (dyskinetic cerebral palsy, spastic quadriplegia, or mixed motor impairment) or epilepsy. / Findings: Of 263 infants recruited between Jan 1, 2011, and Feb 7, 2017, we included 129 infants: 65 had electrographic seizures (43 during active cooling only and 22 during and after active cooling) and 64 had no seizures. Compared with infants with seizures during active cooling only, those with seizures during and after active cooling had a longer seizure period (median 12 h [IQR 3–28] vs 68 h [35–86], p<0·0001), more seizures (median 12 [IQR 5–36] vs 94 [24–134], p<0·0001), and higher total seizure burden (median 69 min [IQR 22–104] vs 167 min [54–275], p=0·0033). Hourly seizure burden peaked at about 20–24 h in both groups, and infants with seizures during and after active cooling had a secondary peak at 85 h of age. When combined, worse EEG background (major abnormalities and inactive background) at 12 h and 24 h were associated with the seizure group: compared with infants with a better EEG background (normal, mild, or moderate abnormalities), infants with a worse EEG background were more likely to have seizures after cooling at 12 h (13 [54%] of 24 vs four [14%] of 28; odds ratio 7·09 [95% CI 1·88–26·77], p=0·0039) and 24 h (14 [56%] of 25 vs seven [18%] of 38; 5·64 [1·81–17·60], p=0·0029). There was a significant relationship between EEG grade at 12 h (four categories) and seizure group (p=0·020). High total seizure burden was associated with increased odds of an abnormal outcome at 2 years of age (odds ratio 1·007 [95% CI 1·000–1·014], p=0·046), with a medium negative correlation between total seizure burden and BSID-III cognitive score (rS=–0·477, p=0·014, n=26). / Interpretation: Overall, half of infants with hypoxic-ischaemic encephalopathy had electrographic seizures and a third of those infants had seizures beyond active cooling, with worse outcomes. These results raise the importance of prolonged EEG monitoring of newborn infants with hypoxic-ischaemic encephalopathy not only during active cooling but throughout the rewarming phase and even longer when seizures are detected. / Funding: Wellcome Trust, Science Foundation Ireland, and the Irish Health Research Board

Neonatal Seizure Management – Is the Timing of Treatment Critical?

OBJECTIVE: To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden; secondary aim was to describe overall seizure management in a large neonatal cohort. STUDY DESIGN: Newborns (36-44 weeks' gestation) requiring electroencephalographic (EEG) monitoring recruited to two multicentre European studies were included. Infants who received anti-seizure medication exclusively after electrographic seizure onset, were grouped based on time to treatment of the first seizure: ASM within 1-hour, ASM between 1-2 hours and ASM after 2-hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures and ASM dose over 24-hours following seizure onset. RESULTS: Out of 472 newborns recruited, 154(32.6%) infants had confirmed electrographic seizures. Sixty-nine infants were exclusively treated after onset of electrographic seizures: 21 infants received ASM within 1 hour, 15 infants between 1-2 hours and 33 infants after 2 hours of seizure onset. Significantly lower seizure burden and less seizures were noted in infants treated with ASM within 1 hour from seizure onset (p value=0.029 and 0.035, respectively). Overall, 258/472(54.7%) infants received ASM throughout the study period, of which 40 infants without electrographic seizures had treatment during EEG monitoring and 11 infants with electrographic seizures had no treatment. CONCLUSION: Treatment of neonatal seizures may be time-critical, but more research is required to confirm this. We also need to improve neonatal seizure diagnosis and treatment

Next-generation transcriptome sequencing of the premenopausal breast epithelium using specimens from a normal human breast tissue bank

IntroductionOur efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established. The KTB is, to our knowledge, the only biorepository in the world prospectively established to collect normal, healthy breast tissue from volunteer donors. As a first initiative toward a molecular understanding of the biology and developmental genetics of the normal mammary gland, the effect of the menstrual cycle and hormonal contraceptives on DNA expression in the normal breast epithelium was examined.MethodsUsing normal breast tissue from 20 premenopausal donors to KTB, the changes in the mRNA of the normal breast epithelium as a function of phase of the menstrual cycle and hormonal contraception were assayed using next-generation whole transcriptome sequencing (RNA-Seq).ResultsIn total, 255 genes representing 1.4% of all genes were deemed to have statistically significant differential expression between the two phases of the menstrual cycle. The overwhelming majority (221; 87%) of the genes have higher expression during the luteal phase. These data provide important insights into the processes occurring during each phase of the menstrual cycle. There was only a single gene significantly differentially expressed when comparing the epithelium of women using hormonal contraception to those in the luteal phase.ConclusionsWe have taken advantage of a unique research resource, the KTB, to complete the first-ever next-generation transcriptome sequencing of the epithelial compartment of 20 normal human breast specimens. This work has produced a comprehensive catalog of the differences in the expression of protein-coding genes as a function of the phase of the menstrual cycle. These data constitute the beginning of a reference data set of the normal mammary gland, which can be consulted for comparison with data developed from malignant specimens, or to mine the effects of the hormonal flux that occurs during the menstrual cycle

Development of a cDNA microarray for the measurement of gene expression in the sheep scab mite Psoroptes ovis

Background: Sheep scab is caused by the ectoparasitic mite Psoroptes ovis which initiates a profound cutaneous inflammatory response, leading to the development of the skin lesions which are characteristic of the disease. Existing control strategies rely upon injectable endectocides and acaricidal dips but concerns over residues, eco-toxicity and the development of acaricide resistance limit the sustainability of this approach. In order to identify alternative means of disease control, a deeper understanding of both the parasite and its interaction with the host are required. Methods: Herein we describe the development and utilisation of an annotated P. ovis cDNA microarray containing 3,456 elements for the measurement of gene expression in this economically important ectoparasite. The array consists of 981 P. ovis EST sequences printed in triplicate along with 513 control elements. Array performance was validated through the analysis of gene expression differences between fed and starved P. ovis mites. Results: Sequences represented on the array include homologues of major house dust mite allergens and tick salivary proteins, along with factors potentially involved in mite reproduction and xenobiotic metabolism. In order to validate the performance of this unique resource under biological conditions we used the array to analyse gene expression differences between fed and starved P. ovis mites. These analyses identified a number of house dust mite allergen homologues up-regulated in fed mites and P. ovis transcripts involved in stress responses, autophagy and chemosensory perception up-regulated in starved mites. Conclusion: The P. ovis cDNA microarray described here has been shown to be both robust and reproducible and will enable future studies to analyse gene expression in this important ectoparasite