Distribution and associations of vision-related quality of life and functional vision of children with visual impairment.

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly used in paediatric ophthalmology. However, little is known about the distribution of PROM scores among children and young people with visual impairment. AIM: To investigate the distributions and predictors of scores on the VQoL_CYP (measuring vision-related quality of life) and FVQ_CYP (measuring functional vision). METHODS: Children and young people aged 8-18 years, with visual impairment/blindness (logarithm of the minimum angle of resolution (LogMAR) worse than 0.48 in the better eye, and/or eligible visual field restriction) completed the VQoL_CYP and FVQ_CYP at home or Great Ormond Street Hospital, London, UK. Associations between VQoL_CYP and FVQ_CYP scores and sociodemographic and clinical factors were analysed using multiple linear regression models. RESULTS: Among 93 participants, VQoL_CYP scores ranged from 36.6 to 78.2 (mean=57.9, SD=8.1). FVQ_CYP scores ranged from 23.5 to 70.3 (mean=48.3, SD=10.1). Only 0.4% of the variation in VQoL_CYP scores was explained, with no associations with the variables of interest. By contrast, 21.6% of the variation in FVQ_CYP scores was explained, with a gradient of worse acuity (p<0.001) and female gender (p=0.04) associated with worse self-rated functional vision. Age, ethnicity, time of onset and stability/progression of visual impairment were not associated. DISCUSSION: Self-rated vision-related quality of life and functional vision are not readily predicted from sociodemographic or clinical characteristics that ophthalmologists measure/record. Routine use of PROMs in clinical practice can offer important insights. Use in research can provide valuable measures of effectiveness of interventions. The reference values provided will aid interpretation in both settings

Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation.

Human liver contains an Eomes(hi) population of NK cells that is not present in the blood. In this study, we show that these cells are characterized by a molecular signature that mediates their retention in the liver. By examining liver transplants where donors and recipients are HLA mismatched, we distinguish between donor liver-derived and recipient-derived leukocytes to show that Eomes(lo) NK cells circulate freely whereas Eomes(hi) NK cells are unable to leave the liver. Furthermore, Eomes(hi) NK cells are retained in the liver for up to 13 y. Therefore, Eomes(hi) NK cells are long-lived liver-resident cells. We go on to show that Eomes(hi) NK cells can be recruited from the circulation during adult life and that circulating Eomes(lo) NK cells are able to upregulate Eomes and molecules mediating liver retention under cytokine conditions similar to those in the liver. This suggests that circulating NK cells are a precursor of their liver-resident counterparts

Differences in Self-Rated Versus Parent Proxy–Rated Vision-Related Quality of Life and Functional Vision of Visually Impaired Children

PURPOSE: To investigate disagreement between children's self-reported vision-related quality of life (VQoL) and functional vision (FV), and their parents' proxy-reports. DESIGN: Cross-sectional study. METHODS: 152 children aged 7-18 years with visual impairment (VI) (defined by the World Health Organization), and their parents, were recruited from 22 National Health Service (NHS) Ophthalmology Departments in the United Kingdom. Age-appropriate versions of 2 vision-specific instruments capturing VQoL and FV, were administered to children alongside modified versions for completion by parents on behalf of their child (i.e. parent proxy-report). Disagreement between self- and parent proxy-report was examined using the Bland-Altman (BA) method, and a threshold of disagreement based on 0.5 standard deviation. Disagreement was analysed according to participants' age, gender and clinical characteristics, using logistic regression analyses. RESULTS: Children rated themselves as having better outcomes than their parents did, although parents both under- and over-estimated their child's VQoL (mean score difference = 7.7). With each year of increasing age, there was a 1.18 (1.04 - 1.35) higher odds of children self-rating their VQoL better than their parents (p = 0.013). Although parents consistently under-estimated their child's FV (mean score difference = -4.7), no characteristics were significantly associated with differences in disagreement. CONCLUSIONS: Disagreement between child self-report on the impact of VI, and their parents' proxy-reports varies by age. This implies that self-report from children must remain the gold standard. Where self-reporting is not possible, parent proxy-reports may provide useful insights, but must be interpreted with caution

A patient-reported outcome measure of functional vision for children and young people aged 8 to 18 years with visual impairment

Purpose: To develop age-appropriate extensions of a patient-reported outcome measure for capturing the functional impact of visual impairment on daily activities of children and young people aged 8 up to 18 years. Design: Questionnaire development and validation study. Setting: Pediatric Ophthalmology departments at Great Ormond Street Hospital and Moorfields Eye Hospital, and, in the final study phase, 20 further UK hospitals. Participants: Children and young people (aged 6-19 years) with visual impairment (acuity of the logarithm of the minimum angle of resolution (LogMAR) worse than 0.50 in the better eye) due to any cause but without significant non-ophthalmic impairments. Methods: We used our prototype FVQ_CYP for 10-15 year olds as the foundation. Twenty-nine semi-structured interviews confirmed relevance of existing, and identified new, age-specific items. Twenty-eight cognitive interviews captured information regarding comprehensibility and format. The FVQ_Child (8-12 years) and FVQ_Young Person (13-18 years), were evaluated with a national sample of 113 children and 96 young people using Rasch analysis. Results: Issues emerging from interviews with children and young people were largely congruent with those elicited originally with 10-15 year olds. The 28-item FVQ_Child and 38-item FVQ_Young Person versions have goodness-of-fit statistics within the interval 0.5, 1.5 and person separation values of 5.87 and 6.09 respectively. Twenty-four overlapping ‘core’ items enabled their calibration on the same measurement scale. Correlations with acuity (r = 0.47) demonstrated construct validity. Conclusions: The FVQ_C and FVQ_Young Person are robust age-appropriate versions of the FVQ_CYP which can be used cross-sectionally or sequentially/longitudinally across the age-range of 8-18 years in clinical practice and research

The fate of steroid estrogens: Partitioning during wastewater treatment and onto river sediments

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media B.V.The partitioning of steroid estrogens in wastewater treatment and receiving waters is likely to influence their discharge to, and persistence in, the environment. This study investigated the partitioning behaviour of steroid estrogens in both laboratory and field studies. Partitioning onto activated sludge from laboratory-scale Husmann units was rapid with equilibrium achieved after 1 h. Sorption isotherms and Kd values decreased in the order 17α-ethinyl estradiol > 17α-estradiol > estrone > estriol without a sorption limit being achieved (1/n >1). Samples from a wastewater treatment works indicated no accumulation of steroid estrogens in solids from primary or secondary biological treatment, however, a range of steroid estrogens were identified in sediment samples from the River Thames. This would indicate that partitioning in the environment may play a role in the long-term fate of estrogens, with an indication that they will be recalcitrant in anaerobic conditions.EPSR

Early star-forming galaxies and the reionization of the Universe

Star forming galaxies represent a valuable tracer of cosmic history. Recent observational progress with Hubble Space Telescope has led to the discovery and study of the earliest-known galaxies corresponding to a period when the Universe was only ~800 million years old. Intense ultraviolet radiation from these early galaxies probably induced a major event in cosmic history: the reionization of intergalactic hydrogen. New techniques are being developed to understand the properties of these most distant galaxies and determine their influence on the evolution of the universe.Comment: Review article appearing in Nature. This posting reflects a submitted version of the review formatted by the authors, in accordance with Nature publication policies. For the official, published version of the review, please see http://www.nature.com/nature/archive/index.htm

Human embryonic stem cells from aneuploid blastocysts identified by pre-implantation genetic screening

Human embryonic stem cells are derived from the inner cell mass of pre-implantation embryos. The cells have unlimited proliferation potential and capacity to differentiate into the cells of the three germ layers. Human embryonic stem cells are used to study human embryogenesis and disease modeling and may in the future serve as cells for cell therapy and drug screening. Human embryonic stem cells are usually isolated from surplus normal frozen embryos and were suggested to be isolated from diseased embryos detected by pre-implantation genetic diagnosis. Here we report the isolation of 12 human embryonic stem cell lines and their thorough characterization. The lines were derived from embryos detected to have aneuploidy by pre-implantation genetic screening. Karyotype analysis of these cell lines showed that they are euploid, having 46 chromosomes. Our interpretation is that the euploid cells originated from mosaic embryos, and in vitro selection favored the euploid cells. The undifferentiated cells exhibited long-term proliferation and expressed markers typical for embryonic stem cells such as OCT4, NANOG, and TRA-1-60. The cells manifested pluripotent differentiation both in vivo and in vitro. To further characterize the different lines, we have analyzed their ethnic origin and the family relatedness among them. The above results led us to conclude that the aneuploid mosaic embryos that are destined to be discarded can serve as source for normal euploid human embryonic stem cell lines. These lines represent various ethnic groups; more lines are needed to represent all populations

Radio Emission from Ultra-Cool Dwarfs

The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed that these objects can generate and dissipate powerful magnetic fields. Radio observations provide unparalleled insight into UCD magnetism: detections extend to brown dwarfs with temperatures <1000 K, where no other observational probes are effective. The data reveal that UCDs can generate strong (kG) fields, sometimes with a stable dipolar structure; that they can produce and retain nonthermal plasmas with electron acceleration extending to MeV energies; and that they can drive auroral current systems resulting in significant atmospheric energy deposition and powerful, coherent radio bursts. Still to be understood are the underlying dynamo processes, the precise means by which particles are accelerated around these objects, the observed diversity of magnetic phenomenologies, and how all of these factors change as the mass of the central object approaches that of Jupiter. The answers to these questions are doubly important because UCDs are both potential exoplanet hosts, as in the TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.Comment: 19 pages; submitted chapter to the Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag

An approach to heroin use disorder intervention within the South African context: A content analysis study

<p>Abstract</p> <p>Background</p> <p>The field of heroin use disorder intervention has been in transition in South Africa since the outbreak of the heroin epidemic. Yet despite growing evidence of an association between heroin users' use of supplementary intervention services and intervention outcomes, heroin use disorder intervention programmes in South Africa generally fail to meet international research-based intervention standards.</p> <p>Methods</p> <p>Semi-structured interviews with ten heroin use disorder specialists were conducted and the interviews were subjected to content analysis.</p> <p>Results and Discussion</p> <p>In terms of theory and practice, findings of the study suggest that the field of heroin use disorder intervention in South Africa remains fragmented and transitional. Specifically, limited strategic public health care polices that address the syndromes' complexities have been implemented within the South Africa context.</p> <p>Conclusions</p> <p>Although many interventions and procedures have begun to be integrated routinely into heroin use disorder clinical practice within the South African context, comorbidity factors, such as psychiatric illness and HIV/AIDS, need to be more cogently addressed. Pragmatic and evidence-based public health care policies designed to reduce the harmful consequences associated with heroin use still needs to be implemented in the South African context.</p

Trafficking Defect and Proteasomal Degradation Contribute to the Phenotype of a Novel KCNH2 Long QT Syndrome Mutation

The Kv11.1 (hERG) K+ channel plays a fundamental role in cardiac repolarization. Missense mutations in KCNH2, the gene encoding Kv11.1, cause long QT syndrome (LQTS) and frequently cause channel trafficking-deficiencies. This study characterized the properties of a novel KCNH2 mutation discovered in a LQT2 patient resuscitated from a ventricular fibrillation arrest. Proband genotyping was performed by SSCP and DNA sequencing. The electrophysiological and biochemical properties of the mutant channel were investigated after expression in HEK293 cells. The proband manifested a QTc of 554 ms prior to electrolyte normalization. Mutation analysis revealed an autosomal dominant frameshift mutation at proline 1086 (P1086fs+32X; 3256InsG). Co-immunoprecipitation demonstrated that wild-type Kv11.1 and mutant channels coassemble. Western blot showed that the mutation did not produce mature complex-glycosylated Kv11.1 channels and coexpression resulted in reduced channel maturation. Electrophysiological recordings revealed mutant channel peak currents to be similar to untransfected cells. Co-expression of channels in a 1∶1 ratio demonstrated dominant negative suppression of peak Kv11.1 currents. Immunocytochemistry confirmed that mutant channels were not present at the plasma membrane. Mutant channel trafficking rescue was attempted by incubation at reduced temperature or with the pharmacological agents E-4031. These treatments did not significantly increase peak mutant currents or induce the formation of mature complex-glycosylated channels. The proteasomal inhibitor lactacystin increased the protein levels of the mutant channels demonstrating proteasomal degradation, but failed to induce mutant Kv11.1 protein trafficking. Our study demonstrates a novel dominant-negative Kv11.1 mutation, which results in degraded non-functional channels leading to a LQT2 phenotype