A population-based study of visual impairment among pre-school children in Beijing: the Beijing study of visual impairment in children.

PURPOSE: To evaluate the prevalence and causes of visual impairment among Chinese children aged 3 to 6 years in Beijing. DESIGN: Population-based prevalence survey. METHODS: Presenting and pinhole visual acuity were tested using picture optotypes or, in children with pinhole vision < 6/18, a Snellen tumbling E chart. Comprehensive eye examinations and cycloplegic refraction were carried out for children with pinhole vision < 6/18 in the better-seeing eye. RESULTS: All examinations were completed on 17,699 children aged 3 to 6 years (95.3% of sample). Subjects with bilateral correctable low vision (presenting vision < 6/18 correctable to >or= 6/18) numbered 57 (0.322%; 95% confidence interval [CI], 0.237% to 0.403%), while 14 (0.079%; 95% CI, 0.038% to 0.120%) had bilateral uncorrectable low vision (best-corrected vision of < 6/18 and >or= 3/60), and 5 subjects (0.028%; 95% CI, 0.004% to 0.054%) were bilaterally blind (best-corrected acuity < 3/60). The etiology of 76 cases of visual impairment included: refractive error in 57 children (75%), hereditary factors (microphthalmos, congenital cataract, congenital motor nystagmus, albinism, and optic nerve disease) in 13 children (17.1 %), amblyopia in 3 children (3.95%), and cortical blindness in 1 child (1.3%). The cause of visual impairment could not be established in 2 (2.63%) children. The prevalence of visual impairment did not differ by gender, but correctable low vision was significantly (P < .0001) more common among urban as compared with rural children. CONCLUSION: The leading causes of visual impairment among Chinese preschool-aged children are refractive error and hereditary eye diseases. A higher prevalence of refractive error is already present among urban as compared with rural children in this preschool population.

Measurement of intraocular pressure with pressure phosphene tonometry in children.

PURPOSE: To study the accuracy and acceptability of intraocular pressure (IOP) measurement by the pressure phosphene tonometer, non-contact tonometer, and Goldmann tonometer in children. METHODS: Fifty children (5 to 14 years old) participated in this prospective comparative study. IOP was measured with the pressure phosphene tonometer, non-contact tonometer, and Goldmann tonometer by three different examiners who were masked to the results. The children were also asked to grade the degree of discomfort from 0 to 5 (0 = no discomfort; 5 = most discomfort). RESULTS: The mean IOPs measured by the Goldmann tonometer, pressure phosphene tonometer, and non-contact tonometer were 15.9 mm Hg (standard deviation [SD]: = 5.5 mm Hg; range: 10 to 36 mm Hg), 16.0 mm Hg (SD: 2.9 mm Hg; range: 12 to 25 mm Hg), and 15.7 mm Hg (SD = 5.1 mm Hg; range: 8 to 32 mm Hg), respectively (P = .722). The mean difference between pressure phosphene tonometer and Goldmann tonometer readings was 2.9 mm Hg and that between non-contact tonometer and Goldmann tonometer readings was 2.1 mm Hg. The 95% confidence interval of the mean difference between pressure phosphene tonometer and Goldmann tonometer readings was -1.07 and 1.19, and that between non-contact tonometer and Goldmann tonometer readings was -1.07 and 0.53. The mean discomfort ratings for the pressure phosphene tonometer, non-contact tonometer, and Goldmann tonometer were 0.6, 2.0, and 2.3, respectively (P < .001). CONCLUSION: Although the pressure phosphene tonometer was less accurate than the non-contact tonometer compared with Goldmann tonometer, it gave a reasonably close estimate and had a high specificity of raised IOP. In addition, measurement by the pressure phosphene tonometer is most acceptable to children. The pressure phosphene tonometer can be considered as an alternative method of IOP measurement in children.

Validating the accuracy of a model to predict the onset of myopia in children.

PURPOSE: To assess the sensitivity and specificity of models predicting myopia onset among ethnically Chinese children. METHODS: Visual acuity, height, weight, biometry (A-scan, keratometry), and refractive error were assessed at baseline and 3 years later using the same equipment and protocol in primary schools in Xiamen (China) and Singapore. A regression model predicting the onset of myopia < -0.75 diopters (D) after 3 years in either eye among Xiamen children was validated with Singapore data. RESULTS: Baseline data were collected from 236 Xiamen children (mean age, 7.82 ± 0.63 years) and from 1979 predominantly Chinese children in Singapore (7.83 ± 0.84 years). Singapore children were significantly taller and heavier, and had more myopia (31.4% vs. 6.36% < -0.75 D in either eye, P < 0.001) and longer mean axial length. Three-year follow-up was available for 80.0% of Xiamen children and 83.1% in Singapore. For Xiamen, the area under the receiver-operator curve (AUC) in a model including ocular biometry, height, weight, and presenting visual acuity was 0.974 (95% confidence interval [CI], 0.945-0.997). In Singapore, the same model achieved sensitivity, specificity, and positive predictive value of 0.844, 0.650, and 0.669, with an AUC of 0.815 (95% CI, 0.791-0.839). CONCLUSIONS: Accuracy in predicting myopia onset based on simple measurements may be sufficient to make targeted early intervention practical in settings such as Singapore with high myopia prevalence. Models based on cohorts with a greater prevalence of high myopia than that in Xiamen could be used to assess accuracy of models predicting more severe forms of myopia.

School-based approaches to the correction of refractive error in children.

The World Health Organization estimates that 13 million children aged 5-15 years worldwide are visually impaired from uncorrected refractive error. School vision screening programs can identify and treat or refer children with refractive error. We concentrate on the findings of various screening studies and attempt to identify key factors in the success and sustainability of such programs in the developing world. We reviewed original and review articles describing children's vision and refractive error screening programs published in English and listed in PubMed, Medline OVID, Google Scholar, and Oxford University Electronic Resources databases. Data were abstracted on study objective, design, setting, participants, and outcomes, including accuracy of screening, quality of refractive services, barriers to uptake, impact on quality of life, and cost-effectiveness of programs. Inadequately corrected refractive error is an important global cause of visual impairment in childhood. School-based vision screening carried out by teachers and other ancillary personnel may be an effective means of detecting affected children and improving their visual function with spectacles. The need for services and potential impact of school-based programs varies widely between areas, depending on prevalence of refractive error and competing conditions and rates of school attendance. Barriers to acceptance of services include the cost and quality of available refractive care and mistaken beliefs that glasses will harm children's eyes. Further research is needed in areas such as the cost-effectiveness of different screening approaches and impact of education to promote acceptance of spectacle-wear. School vision programs should be integrated into comprehensive efforts to promote healthy children and their families.

Night-to-night variation of pulse oximetry in children with sleep-disordered breathing

BACKGROUND: Sleep-disordered breathing is a common and serious feature of many paediatric conditions and is particularly a problem in children with Down syndrome. Overnight pulse oximetry is recommended as an initial screening test, but it is unclear how overnight oximetry results should be interpreted and how many nights should be recorded.

METHODS: This retrospective observational study evaluated night-to-night variation using statistical measures of repeatability for 214 children referred to a paediatric respiratory clinic, who required overnight oximetry measurements. This included 30 children with Down syndrome. We measured length of adequate trace, basal SpO2, number of desaturations (>4% SpO2 drop for >10 s) per hour ('adjusted index') and time with SpO2<90%. We classified oximetry traces into normal or abnormal based on physiology.

RESULTS: 132 out of 214 (62%) children had three technically adequate nights' oximetry, including 13 out of 30 (43%) children with Down syndrome. Intraclass correlation coefficient for adjusted index was 0.54 (95% CI 0.20 to 0.81) among children with Down syndrome and 0.88 (95% CI 0.84 to 0.91) for children with other diagnoses. Negative predictor value of a negative first night predicting two subsequent negative nights was 0.2 in children with Down syndrome and 0.55 in children with other diagnoses.

CONCLUSIONS: There is substantial night-to-night variation in overnight oximetry readings among children in all clinical groups undergoing overnight oximetry. This is a more pronounced problem in children with Down syndrome. Increasing the number of attempted nights' recording from one to three provides useful additional clinical information.

Abstract B64: The role of JAK1/2-STAT3 as acute resistance mechanism to MEK inhibition in BRAF mutant colorectal cancer.

Background: Oncogenic mutations in BRAF occur in 8% of patients with advanced colorectal cancer (CRC) and have been shown to correlate with poor prognosis. In contrast to BRAF mutant (MT) melanoma, where the BRAF inhibitor PLX4032 has shown significant increases in response rates and overall survival compared to standard Dacarbazine treatment, only minor responses to PLX4032 treatment have been reported in BRAFMT CRC. Clear understanding of the vulnerabilities of BRAFMT CRC is important, and identification of druggable targets uniquely required by BRAFMT CRC tumors has the potential to fill a gap in the therapeutic armamentarium of advanced CRC. The aim of this study was to identify novel resistance mechanisms to MAPK inhibition in BRAFMT CRC.

Methods: Paired BRAFMT/WT RKO and VACO432 CRC cell line models and non-isogenic BRAFMT LIM2405, WiDR and COLO205 CRC cells were used. Changes in protein expression/activity were assessed by Western Blotting. Interaction between MEK1/2 and JAK1/2 inhibition was assessed using the MTT cell viability assays and flow cytometry. Apoptosis was measured using Western blotting for PARP, cleaved caspase 3/8 and caspase 8, 3/7 activity assays.

Results: Treatment with MEK1/2 inhibitors AZD6244, GSK1120212, UO126 and PD98059 resulted in acute increases in STAT3 activity in the BRAFMT RKO and VACO432 cells but not in their BRAFWT clones and this was associated with increases in JAK2 activity. Inhibition of JAK/STAT3 activation using gene specific siRNA or small molecule inhibitors TG101348 or AZD1480, abrogated this survival response and resulted in significant increases in cell death when combined with MEK1/2 inhibitors AZD6244 or GSK1120212 in BRAFMT CRC cells. In addition, combination of MEK1/2 and JAK/STAT3 inhibition resulted in strong synergy with CI values between 0.3 and 0.7 in BRAFMT CRC cells.

Conclusions: We have identified JAK/STAT3 activation as an important escape mechanism for BRAFMT CRC following MEK1/2 inhibition. These data provide a strong rationale for further investigation of combination of MEK1/2 and JAK/STAT3 inhibition in BRAFMT in vivo models.

ThermoSpots to detect hypothermia in children with severe acute malnutrition

INTRODUCTION: Hypothermia is a risk factor for increased mortality in children with severe acute malnutrition (SAM). Yet frequent temperature measurement remains unfeasible in under-resourced units in developing countries. ThermoSpot is a continuous temperature monitoring sticker designed originally for neonates. When applied to skin, its liquid crystals are designed to turn black with hypothermia and remain green with normothermia.

AIMS: To (i) estimate the diagnostic accuracy of ThermoSpots for detecting WHO-defined hypothermia (core temperature <35.5°C or peripheral temperature <35.0°C) in children with SAM and (ii) determine their acceptability amongst mothers.

METHODS: Children with SAM in a malnutrition unit in Malawi were enrolled during March-July 2010. The sensitivity and specificity of ThermoSpots were calculated by comparing the device colour against 'gold standard' rectal temperatures taken on admission and follow up peripheral temperatures taken until discharge. Guardians completed a questionnaire to assess acceptability.

RESULTS: Hypothermia was uncommon amongst the 162 children enrolled. ThermoSpot successfully detected the one rectal temperature and two peripheral temperatures recorded that met the WHO definition of hypothermia. Overall, 3/846 (0.35%) temperature measurements were in the WHO-defined hypothermia range. Interpreting the brown transition colour (between black and green) as hypothermia improved sensitivities. For milder hypothermia definitions, sensitivities declined (<35.4°C, 50.0%; <35.9°C, 39.2%). Specificity was consistently above 94%. From questionnaires, 40/43 (93%) mothers reported they were 90-100% happy with the device overall. Free-text answers revealed themes of "Skin Rashes", "User-satisfaction" and "Empowerment".

CONCLUSION: Although hypothermia was uncommon in this study, ThermoSpots successfully detected these episodes in malnourished children and were acceptable to mothers. Research in settings where hypothermia is common is needed to determine performance with certainty. Instructing users to act when the device's transition colour appears could improve accuracy. If reliable, ThermoSpots may offer simple, acceptable and continuous temperature measurement for high-burden areas and reduce the workload of over-stretched staff.

c-Met inhibition in a HOXA9/Meis1 model of CN-AML

BACKGROUND: Hematopoiesis is a paradigm for developmental processes, hierarchically organized, with stem cells at its origin. Hematopoietic stem cells (HSCs) replenish progenitor and precursor cells of multiple lineages, which normally differentiate into short-lived mature circulating cells. Hematopoiesis has provided insight into the molecular basis of tissue homeostasis and malignancy. Malignant hematopoiesis, in particular acute myeloid leukemia (AML), results from impaired development or differentiation of HSCs and progenitors. Co-overexpression of HOX and TALE genes, particularly the HOXA cluster and MEIS1, is associated with AML. Clinically relevant models of AML are required to advance drug development for an aging patient cohort.

RESULTS: Molecular analysis identified altered gene, microRNA, and protein expression in HOXA9/Meis1 leukemic bone marrow compared to normal controls. A candidate drug screen identified the c-Met inhibitor SU11274 for further analysis. Altered cell cycle status, apoptosis, differentiation, and impaired colony formation were shown for SU11274 in AML cell lines and primary leukemic bone marrow.

CONCLUSIONS: The clonal HOXA9/Meis1 AML model is amenable to drug screening analysis. The data presented indicate that human AML cells respond in a similar manner to the HOXA9/Meis1 cells, indicating pre-clinical relevance of the mouse model.

Child-focused psychosocial interventions for anger and aggression in children under 12 years of age (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows:

To evaluate the effectiveness of child-focused psychosocial interventions for anger and aggression in children under 12 years of age.

Cross-readings and ecoliteracy in children's pop-up books

The purpose of this text is to analyse two recently been published pop-up books aimed at children, by Anouck Boisrobert e Louis Rigaud, Popville (2009) and Dans la forêt du paresseux [Wake up, Sloth!, En el bosque del perezoso] (first published in 2009 and 2012, accompanied with texts by Joy Sorman and Sophie Strady, respectively). These books were published originally in France by Hélium Editions, but they can now be found in several western countries and in many languages (Catalan, French, Dutch, English, German, Italian, Portuguese and Spanish, at least). The objective is to analyse their verbal text and their visual aspects produced by a sophisticated paper engineered to question how they achieve what seems to be one of their goals, the promotion of the readers' ecoliteracy (Orr, 1992) by his involvement in the reading process. This issue seems to be one of the main trends on children's literature in western societies nowadays, transcending the traditional and almost omnipresent role of scenario that nature plays in many children's narratives.

Robotics and Development of Intellectual Abilities in Children

It is necessary to transform the educative experiences into the classrooms so that they favor the development of intellectual abilities of children and teenagers. We must take advantage of the new opportunities that offer information technologies to organize learning environments which they favor those experiences. We considered that to arm and to program robots, of the type of LEGO Mind Storms or the so called “crickets”, developed by M. Resnik from MIT, like means so that they children them and young people live experiences that favor the development of their intellectual abilities, is a powerful alternative to the traditional educative systems. They are these three tasks those that require a reflective work from pedagogy and epistemology urgently. Robotics could become in the proper instrument for the development of intelligence because it works like a mirror for the intellectual processes of each individual, its abilities like epistemologist and, therefore, is useful to favor those processes in the classroom.

Repeat-measures longitudinal study evaluating behavioural and gastrointestinal symptoms in children with autism before, during and after visceral osteopathic technique (VOT)

Summary: This study investigated the influence of visceral osteopathic technique (VOT) on the behaviour and gastrointestinal (GI) symptoms of children with autism using a validated questionnaire to measure outcome. Methods: The 49 recruited autistic children suffered GI symptoms and impaired social interaction and communication, but were otherwise healthy. Thirty minute VOT sessions were applied to the abdomens of the children over a 6 week period whilst their GI and behavioural parameters were recorded. Outcomes were measured using a modified Autism Research Institute Secretin Outcomes Survey Form, the ‘S.O.S Form’. Four questionnaires were completed by parents before treatment (control period), four completed during treatment (treatment period) and one completed six weeks after the last treatment (post treatment period). Subjects acted as their own controls. Results: Results from repeat ANOVA demonstrated a positive, overall significant, symptomatic improvement (p < 0.05) in ‘social behaviour and communication’ and ‘digestive signs’ subscales of the questionnaire comparing before and after VOT. Significant improvement in vomiting (p = 0.00029), poor appetite (p = 0.039) and eye contact (p = 0.035) was also demonstrated after VOT application. Discussion and conclusion: The experimental hypothesis has been supported indicating a positive effect of VOT on some of the measured GI symptoms and behavioural patterns in this group of children with autism. This data indicates that the application of VOT may be of benefit to children with autism and GI disturbance.

Cerebral Sinovenous Thrombosis in Children: Clinical Presentation and Extension, Localization and Recanalization of Thrombosis

Many important questions regarding pathophysiology and treatment of cerebral sinovenous thrombosis need clarification and may depend on further knowledge on the etiology, site, extension and recanalization of the thrombosis. We studied these variables in a cohort of children and adolescents from seven Portuguese Centers. We conclude from our results that the deep venous system and the superior longitudinal sinus are less frequently affected with thrombosis but have a greater potential for serious neurologic disease and for major sequelae. Non-recanalization, at least in the long term, is not an adverse prognostic factor. Extensive propagation of the thrombus from the initial site of origin seems to be common. The early identification of risk factors and their treatment coupled with an aggressive attitude towards diagnosis and treatment for thrombosis involving the deep venous system would be warranted.

Mutilations Due to Medical Disorders in Children

Soft-tissue and bone necrosis, although rare in childhood, occasionally occur in the course of infectious diseases, either viral or bacterial, and seem to be the result of hypoperfusion on a background of disseminated intravascular coagulation. Treatment consists in correction of septic shock and control of necrosis. Necrosis, once started, shows extraordinarily rapid evolution, leading to soft-tissue and bone destruction and resulting in anatomic, functional, psychological, and social handicaps. Ten mutilated children were treated from January 1986 to January 1999 in Hospital de Dona Estefaˆ nia, Lisbon, Portugal. One was recovering from hemolytic-uremic syndrome with a severe combined immunodeficiency, another malnourished, anemic child had malaria, and three had chicken pox (in one case complicated by meningococcal septicemia). There were three cases of meningococcal and two of pyocyanic septicemia (one in a burned child and one in a patient with infectious mononucleosis). The lower limbs (knee,leg, foot) were involved in five cases, the face (ear, nose, lip) in four, the perineum in three, the pelvis (inguinal region, iliac crest) in two, the axilla in one, and the upper limb (radius, hand) in two. Primary prevention is based on early recognition of risk factors and timely correction. Secondary prevention consists of immediate etiologic and thrombolytic treatment to restrict the area of necrosis. Tertiary prevention relies on adequate rehabilitation with physiotherapy and secondary operations to obtain the best possible functional and esthetic result.