Pure single photons from a trapped atom source

Single atoms or atom-like emitters are the purest source of on-demand single photons, they are intrinsically incapable of multi-photon emission. To demonstrate this degree of purity we have realized a tunable, on-demand source of single photons using a single ion trapped at the common focus of high numerical aperture lenses. Our trapped-ion source produces single-photon pulses at a rate of 200 kHz with g$^2(0) = (1.9 \pm 0.2) \times 10^{-3}$, without any background subtraction. The corresponding residual background is accounted for exclusively by detector dark counts. We further characterize the performance of our source by measuring the violation of a non-Gaussian state witness and show that its output corresponds to ideal attenuated single photons. Combined with current efforts to enhance collection efficiency from single emitters, our results suggest that single trapped ions are not only ideal stationary qubits for quantum information processing, but promising sources of light for scalable optical quantum networks.Comment: 7 pages plus one page supplementary materia

Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome.

The short rib polydactyly syndromes (SRPSs) are a heterogeneous group of autosomal recessive, perinatal lethal skeletal disorders characterized primarily by short, horizontal ribs, short limbs and polydactyly. Mutations in several genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases. Here we identify an additional SRPS gene and further unravel the functional basis for IFT. We perform whole-exome sequencing and identify mutations in a new disease-producing gene, cytoplasmic dynein-2 light intermediate chain 1, DYNC2LI1, segregating with disease in three families. Using primary fibroblasts, we show that DYNC2LI1 is essential for dynein-2 complex stability and that mutations in DYNC2LI1 result in variable length, including hyperelongated, cilia, Hedgehog pathway impairment and ciliary IFT accumulations. The findings in this study expand our understanding of SRPS locus heterogeneity and demonstrate the importance of DYNC2LI1 in dynein-2 complex stability, cilium function, Hedgehog regulation and skeletogenesis

Temporal Dynamics of Spontaneous Ca2+ Transients, ERBB4, vGLUT1, GAD1, Connexin, and Pannexin Genes in Early Stages of Human Stem Cell Neurodifferentiation

Spontaneous Ca2+ transients drive stem cell proliferation and neurodifferentiation. Deciphering the relationship between neuronal and glial human genes on one side and spontaneous Ca2+ activity on the other side is essential for our understanding of normal brain development, and for insights into the pathogenesis of neurodegenerative and neurodevelopmental disorders. In the present study, forebrain neurons were derived from human embryonic and induced pluripotent stem cells (hESC-H9 and iPSC-15; 22q11.2 deletion) over a period of 21 days in vitro (DIV). Every 1–2 days, multisite optical imaging technique was applied to detect populations of cells with spontaneous Ca2+ transients. The expression levels of 14 genes of interest were analyzed by quantitative polymerase chain reaction (qPCR) on the same biological samples where physiological recordings were performed. The genes analyzed include: the schizophrenia candidate gene ERBB4, connexin (Cx) genes Cx26, Cx36, Cx43, Cx45, Cx47, pannexin-1 (PNX1), neuronal markers PAX6, vGLUT1, GAD1, TUBB3, glial lineage markers BLBP, GFAP, and housekeeping gene ACTB. We found that Ca2+ signals decrease in amplitude, decrease in duration, and increase in frequency during the first 21 days of human neurodifferentiation. The expression levels of ERBB4, PAX6, GAD1, vGLUT1, BLBP, Cx36, Cx45, and PNX1 were found to be strongly positively correlated with the percentage of cells exhibiting spontaneous Ca2+ transients (“Active Cells”). While expression of BLBP, Cx45, ERBB4, GAD1, PAX6, PNX1, and vGLUT1 were correlated with short-duration and long-amplitude Ca2+ transients, Cx43, TUBB3, and Cx47 were better correlated with long-duration and short-amplitude transients. The expression dynamics of Cx26 was unrelated to any aspect of spontaneous Ca2+ activity. Four genes showed an exponential time course with a distinct onset on a given DIV. The onset of PNX1, ERBB4, and vGLUT1 occurred before, while the onset of Cx36 occurred after the first action potentials were detected in early differentiating human neurons

Promoting Functional Health in Midlife and Old Age: Long-Term Protective Effects of Control Beliefs, Social Support, and Physical Exercise

Previous studies have examined physical risk factors in relation to functional health, but less work has focused on the protective role of psychological and social factors. We examined the individual and joint protective contribution of control beliefs, social support and physical exercise to changes in functional health, beyond the influence of health status and physical risk factors in middle-aged and older adults. Given that functional health typically declines throughout adulthood, it is important to identify modifiable factors that can be implemented to maintain functioning, improve quality of life, and reduce disability.We conducted a national longitudinal study, Midlife in the United States (MIDUS), with assessments in 1995-1996 and 2004-2006, and 3,626 community-residing adults, aged 32 to 84, were included in the analyses. Functional health (Physical Functioning subscale of the SF-36) and protective factors were measured at both occasions. While controlling for socio-demographic, health status, and physical risk factors (large waist circumference, smoking, and alcohol or drug problems), a composite of the three protective variables (control beliefs, social support, and physical exercise) at Time 1 was significantly related to functional health change. The more of these factors at Time 1, the better the health maintenance over 10 years. Among middle-aged and older adults, declines in health were significantly reduced with an increased number of protective factors.Age-related declines in health were reduced among those with more protective factors up to a decade earlier in life. Modifiable psychological, social, and physical protective factors, individually and in the aggregate, are associated with maintenance of functional health, beyond the damaging effects of physical risk factors. The results are encouraging for the prospect of developing interventions to promote functional health and for reducing public health expenditures for physical disability in later life

Increasing Short-Stay Unplanned Hospital Admissions among Children in England; Time Trends Analysis '97-'06

BACKGROUND: Timely care by general practitioners in the community keeps children out of hospital and provides better continuity of care. Yet in the UK, access to primary care has diminished since 2004 when changes in general practitioners' contracts enabled them to 'opt out' of providing out-of-hours care and since then unplanned pediatric hospital admission rates have escalated, particularly through emergency departments. We hypothesised that any increase in isolated short stay admissions for childhood illness might reflect failure to manage these cases in the community over a 10 year period spanning these changes. METHODS AND FINDINGS: We conducted a population based time trends study of major causes of hospital admission in children 2 days. By 2006, 67.3% of all unplanned admissions were isolated short stays <2 days. The increases in admission rates were greater for common non-infectious than infectious causes of admissions. CONCLUSIONS: Short stay unplanned hospital admission rates in young children in England have increased substantially in recent years and are not accounted for by reductions in length of in-hospital stay. The majority are isolated short stay admissions for minor illness episodes that could be better managed by primary care in the community and may be evidence of a failure of primary care services

2020 Heart Failure Society of South Africa perspective on the 2016 European Society of Cardiology Chronic Heart Failure Guidelines

Heart failure with a reduced ejection fraction (HFrEF) is a condition frequently encountered by healthcare professionals and, in order to achieve the best outcomes for patients, needs to be managed optimally. This guideline document is based on the European Society of Cardiology Guidelines for the treatment of acute and chronic heart failure published in 2016, and summarises what is considered the best current management of patients with the condition. It provides information on the definition, diagnosis and epidemiology of HFrEF in the African context. The best evidence-based treatments for HFrEF are discussed, including established therapies (beta-blockers, ACE-i/ARBs, mineralocorticoid receptor antagonists (MRAs), diuretics) that form the cornerstone of heart failure management as well as therapies that have only recently entered clinical use (angiotensin receptor-neprilysin inhibitor (ARNI), sodium/glucose cotransporter-2 (SGLT2) inhibitors). Guidance is offered in terms of more invasive therapies (revascularisation, implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy (CRT) by implantation of a biventricular pacemaker with (CRT-D) or without (CRT-P) an ICD, left ventricular assist device (LVAD) use and heart transplantation) in order to ensure efficient use of these expensive treatment modalities in a resource-limited environment. Furthermore, additional therapies (digoxin, hydralazine and nitrates, ivabradine, iron supplementation) are discussed and advice is provided on general preventive strategies (vaccinations). Sections to discuss conditions that are particularly prevalent in sub-Saharan Africa (HIV-associated cardiomyopathy (CMO), peripartum CMO, rheumatic heart disease, atrial fibrillation) have been added to further improve clinical care for these commonly encountered disease processes. You are encouraged to read the complete 2016 ESC Heart Failure guideline: Ponikowski P, Voors AA, Anker SD, et al.; on behalf of the European Society of Cardiology. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016,37:2129-2200

Characterising the types of paediatric adverse events detected by the global trigger tool - CareTrack Kids

Introduction A common method of learning about adverse events (AEs) is by reviewing medical records using the global trigger tool (GTT). However, these studies generally report rates of harm. The aim of this study is to characterise paediatric AEs detected by the GTT using descriptive and qualitative approaches. Methods Medical records of children aged 0–15 were reviewed for presence of harm using the GTT. Records from 2012–2013 were sampled from hospital inpatients, emergency departments, general practice and specialist paediatric practices in three Australian states. Nurses undertook a review of each record and if an AE was suspected a doctor performed a verification review of a summary created by the nurse. A qualitative content analysis was undertaken on the summary of verified AEs. Results A total of 232 AEs were detected from 6,689 records reviewed. Over four-fifths of the AEs (193/232, 83%) resulted in minor harm to the patient. Nearly half (112/232, 48%) related to medication/intravenous (IV) fluids. Of these, 83% (93/112) were adverse drug reactions. Problems with medical devices/equipment were the next most frequent with nearly two-thirds (32/51, 63%) of these related to intravenous devices. Problems associated with clinical processes/procedures comprise one in six AEs (38/232, 16%), of which diagnostic problems (12/38, 32%) and procedural complications (11/38, 29%) were the most frequent. Conclusion Adverse drug reactions and issues with IVs are frequently identified AEs reflecting their common use in paediatrics. The qualitative approach taken in this study allowed AE types to be characterised, which is a prerequisite for developing and prioritising improvements in practice

How are falls and fear of falling associated with objectively measured physical activity in a cohort of community-dwelling older men?

BACKGROUND: Falls affect approximately one third of community-dwelling older adults each year and have serious health and social consequences. Fear of falling (FOF) (lack of confidence in maintaining balance during normal activities) affects many older adults, irrespective of whether they have actually experienced falls. Both falls and fear of falls may result in restrictions of physical activity, which in turn have health consequences. To date the relation between (i) falls and (ii) fear of falling with physical activity have not been investigated using objectively measured activity data which permits examination of different intensities of activity and sedentary behaviour. METHODS: Cross-sectional study of 1680 men aged 71-92 years recruited from primary care practices who were part of an on-going population-based cohort. Men reported falls history in previous 12 months, FOF, health status and demographic characteristics. Men wore a GT3x accelerometer over the hip for 7 days. RESULTS: Among the 12% of men who had recurrent falls, daily activity levels were lower than among non-fallers; 942 (95% CI 503, 1381) fewer steps/day, 12(95% CI 2, 22) minutes less in light activity, 10(95% CI 5, 15) minutes less in moderate to vigorous PA [MVPA] and 22(95% CI 9, 35) minutes more in sedentary behaviour. 16% (n = 254) of men reported FOF, of whom 52% (n = 133) had fallen in the past year. Physical activity deficits were even greater in the men who reported that they were fearful of falling than in men who had fallen. Men who were fearful of falling took 1766(95% CI 1391, 2142) fewer steps/day than men who were not fearful, and spent 27(95% CI 18, 36) minutes less in light PA, 18(95% CI 13, 22) minutes less in MVPA, and 45(95% CI 34, 56) minutes more in sedentary behaviour. The significant differences in activity levels between (i) fallers and non-fallers and (ii) men who were fearful of falling or not fearful, were mediated by similar variables; lower exercise self-efficacy, fewer excursions from home and more mobility difficulties. CONCLUSIONS: Falls and in particular fear of falling are important barriers to older people gaining health benefits of walking and MVPA. Future studies should assess the longitudinal associations between falls and physical activity

DNA methylation and mRNA expression of SYN III, a candidate gene for schizophrenia

<p>Abstract</p> <p>Background</p> <p>The synapsin III (<it>SYN III</it>) gene on chromosome 22q is a candidate gene for schizophrenia susceptibility due to its chromosome location, neurological function, expression patterns and functional polymorphisms.</p> <p>Methods</p> <p>This research has established the mRNA expression of <it>SYN III </it>in 22 adult human brain regions as well as the methylation specificity in the closest CpG island of this gene. The methylation specificity studied in 31 brain regions (from a single individual) was also assessed in 51 human blood samples (representing 20 people affected with schizophrenia and 31 normal controls) including a pair of monozygotic twin discordant for schizophrenia and 2 non-human primates.</p> <p>Results</p> <p>The results show that the cytosine methylation in this genomic region is 1) restricted to cytosines in CpG dinucleotides 2) similar in brain regions and blood and 3) appears conserved in primate evolution. Two cytosines (cytosine 8 and 20) localized as the CpG dinucleotide are partially methylated in all brain regions studied. The methylation of these sites in schizophrenia and control blood samples was variable. While cytosine 8 was partially methylated in all samples, the distribution of partial to complete methylation at the cytosine 20 was 22:9 in controls as compared to 18:2 in schizophrenia (p = 0.82). Also, there is no difference in methylation between the affected and unaffected member of a monozygotic twin pair.</p> <p>Conclusion</p> <p>The variation in <it>SYN III </it>methylation studied is 1) not related to schizophrenia in the population sample or a monozygotic twin pair discordant for schizophrenia and 2) not related to the mRNA level of <it>SYN IIIa </it>in different human brain regions.</p