The late effects of haematopoietic stem cell transplants in paediatric patients: a 25 year review.

CONTEXT: A rare, large single centre study covering all long-term health outcomes of paediatric allogeneic HSCT survivors, to provide comprehensive local data, and identify gaps and future directions for improved care. OBJECTIVE: To document endocrine sequelae and other late effects of all HSCT recipients. DESIGN: Retrospective review. SETTING: Royal Children's Hospital Melbourne. PATIENTS: 384 children and adolescents received HSCT. 228 formed the study cohort; 212 were alive at commencement of data accrual. INTERVENTION: None. MAIN OUTCOME MEASURES: Incidence of endocrinopathies; fertility, growth, bone and metabolic status; subsequent malignant neoplasms (SMNs). RESULTS: Gonadotoxicity was more common in females (p<0.001). Total body irradiation (TBI) conditioning was more toxic than chemotherapy alone. All females receiving TBI or higher cyclophosphamide equivalent doses (CED) developed premature ovarian insufficiency (POI) . In males, impaired spermatogenesis +/- testicular endocrine dysfunction was associated with increasing testicular radiation exposure. Preservation of gonadal function was associated with younger age at HSCT. Of sexually active females, 22% reported spontaneous pregnancies. Short stature was common, with growth hormone axis disruption in 30% of these. Of patients exposed to thyroid radiation 51% developed nodules, 30% malignant. Metabolic disturbances included hypertension, dyslipidemias, with both excess and underweight reported. Fragility fractures occurred in 6%; avascular necrosis in 6%. 13% developed SMNs, risk continuing to rise throughout follow-up. CONCLUSIONS: We confirm gonadal dysfunction, multiple endocrine and metabolic abnormalities, thyroid cancer and SMNs, as common sequelae of HSCT, and identify gaps in management - particularly the need for informed fertility counselling and pretreatment fertility preservation, evaluation and management of bone health, and underline need for early lifestyle modification, long-term surveillance, and prospective planned studies aimed at reducing complication risk.

Unsupervised machine learning models reveal predictive clinical markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

Background: Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested the use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision-making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care. Methods: We collected retrospective data from patients seen at Ohio State University, University of Mississippi, Barretos Cancer Hospital (Brazil), and FLENI (Argentina) who were managed for glioblastoma-amounting to 581 patient records documented using REDCap. Patients were evaluated using an unsupervised machine learning approach comprised of dimensionality reduction and eigenvector analysis to visualize the inter-relationship of collected clinical features. Results: We discovered that the serum white blood cell (WBC) count of a patient during baseline planning for treatment was predictive of overall survival with an over 6-month median survival difference between the upper and lower quartiles of WBC count. By utilizing an objective PD-L1 immunohistochemistry quantification algorithm, we were further able to identify an increase in PD-L1 expression in glioblastoma patients with high serum WBC counts. Conclusions: These findings suggest that in a subset of glioblastoma patients the incorporation of WBC count and PD-L1 expression in the brain tumor biopsy as simple biomarkers predicting glioblastoma patient survival. Moreover, machine learning models allow the distillation of complex clinical data sets to uncover novel and meaningful clinical relationships.

Characterization and Diversification of AraC/XylS Family Regulators Guided by Transposon Sequencing.

In this study, we explored the development of engineered inducible systems. Publicly available data from previous transposon sequencing assays were used to identify regulators of metabolism in Pseudomonas putida KT2440. For AraC family regulators (AFRs) represented in these data, we posited AFR/promoter/inducer groupings. Twelve promoters were characterized for a response to their proposed inducers in P. putida, and the resultant data were used to create and test nine two-plasmid sensor systems in Escherichia coli. Several of these were further developed into a palette of single-plasmid inducible systems. From these experiments, we observed an unreported inducer response from a previously characterized AFR, demonstrated that the addition of a P. putida transporter improved the sensor dynamics of an AFR in E. coli, and identified an uncharacterized AFR with a novel potential inducer specificity. Finally, targeted mutations in an AFR, informed by structural predictions, enabled the further diversification of these inducible plasmids.

Management and Outcomes of Pediatric Craniopharyngioma: A 15-Year Experience in Singapore.

BACKGROUND: Craniopharyngiomas arise from the Rathke pouch and account for 1.2%-18.4% of pediatric primary brain tumors. Despite relatively good survival outcomes, patients face long-term morbidity from recurrences, visual impairment, and endocrinopathies, which reduce quality of life. We examined the management of pediatric craniopharyngiomas, their recurrences, and subsequent neuroendocrine sequelae in a tertiary center in South-East Asia. METHODS: A retrospective cohort of 12 paediatric patients (aged ≤18 years) with histologically confirmed diagnosis of craniopharyngioma treated from January 2002 to June 2017 was conducted. Data collected included demographics, clinical presentation, imaging data, treatment details, postoperative sequelae, and outcomes on mortality and recurrence. Survival analysis was conducted using Cox-proportional hazards model. RESULTS: The median follow-up time was 6.60 years (1.9-11.5 years). The mean age was 7.6 years (standard deviation 4.8) and 7 patients (58.3%) were male. The most common presenting symptoms were raised intracranial pressure (7, 58.3%), visual deficits (6, 50.0%), and preoperative endocrine abnormalities (2, 16.7%). Five patients underwent gross total resection (41.7%), and 7 underwent subtotal resection (58.3%). Overall survival was 75.0% (9 patients), and recurrence was 58.0% (7 patients). Median time-to-recurrence was 5.87 months (0.23-33.7, interquartile range 15.8), and median progression-free survival was 4.16 years (0.18-10.1, interquartile range 5.29). CONCLUSIONS: Long-term management of pediatric craniopharyngioma remains difficult, with multiple recurrences and long-term neuroendocrine sequelae impairing quality of life for patients. Further research into management of recurrences and neuroendocrine sequelae, as well as novel therapies to improve outcomes in these patients, may be warranted.

Review of Rat (Rattus norvegicus), Mouse (Mus musculus), Guinea pig (Cavia porcellus), and Rabbit (Oryctolagus cuniculus) Indicators for Welfare Assessment.

The monitoring and assessment of animals is important for their health and welfare. The appropriate selection of multiple, validated, and feasible welfare assessment indicators is required to effectively identify compromises or improvements to animal welfare. Animal welfare indicators can be animal or resource based. Indicators can be collated to form assessment tools (e.g., grimace scales) or animal welfare assessment models (e.g., 5 Domains) and frameworks (e.g., 5 Freedoms). The literature contains a wide variety of indicators, with both types needed for effective animal welfare assessment; however, there is yet to be an ideal constellation of indicators for animal-based welfare assessment in small mammals such as guinea pigs (Cavia Porcellus), mice (Mus musculus), rabbits (Oryctolagus cuniculus), and rats (Rattus norvegicus). A systematic review of grey and peer-reviewed literature was performed to determine the types of animal-based welfare indicators available to identify and assess animal health and welfare in these small mammals maintained across a wide variety of conditions. The available indicators were categorised and scored against a selection of criteria, including potential ease of use and costs. This review and analysis aim to provide the basis for further research into animal welfare indicators for these species. Future applications of this work may include improvements to animal welfare assessments or schemes, guiding better management, and implementing future strategies to enable better animal welfare.

Unsupervised machine learning models reveal predictive markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

Purpose: Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care. Methods: We collected retrospective data from patients seen at Ohio State University, University of Mississippi, Barretos Cancer Hospital (Brazil), and FLENI (Argentina) who were managed for glioblastoma-amounting to nearly 600 patient records documented using REDCap. Patients were evaluated using an unsupervised machine learning approach comprised of dimensionality reduction and eigenvector analysis to visualize the inter-relationship of collected clinical features. Results: We discovered that white blood cell count of a patient during baseline planning for treatment was predictive of overall survival with an over 6-month median survival difference between the upper and lower quartiles of white blood cell count. By utilizing an objective PDL-1 immunohistochemistry quantification algorithm, we were further able to identify an increase in PDL-1 expression in glioblastoma patients with high white blood cell counts. Conclusion: These findings suggest that in a subset of glioblastoma patients the incorporation of white blood cell count and PDL-1 expression in the brain tumor biopsy as simple biomarkers predicting glioblastoma patient survival. Moreover, use of machine learning models allows us to visualize complex clinical datasets to uncover novel clinical relationships.

The pGinger Family of Expression Plasmids.

The pGinger suite of expression plasmids comprises 43 plasmids that will enable precise constitutive and inducible gene expression in a wide range of Gram-negative bacterial species. Constitutive vectors are composed of 16 synthetic constitutive promoters upstream of red fluorescent protein (RFP), with a broad-host-range BBR1 origin and a kanamycin resistance marker. The family also has seven inducible systems (Jungle Express, Psal/NahR, Pm/XylS, Prha/RhaS, LacO1/LacI, LacUV5/LacI, and Ptet/TetR) controlling RFP expression on BBR1/kanamycin plasmid backbones. For four of these inducible systems (Jungle Express, Psal/NahR, LacO1/LacI, and Ptet/TetR), we created variants that utilize the RK2 origin and spectinomycin or gentamicin selection. Relevant RFP expression and growth data have been collected in the model bacterium Escherichia coli as well as Pseudomonas putida. All pGinger vectors are available via the Joint BioEnergy Institute (JBEI) Public Registry. IMPORTANCE Metabolic engineering and synthetic biology are predicated on the precise control of gene expression. As synthetic biology expands beyond model organisms, more tools will be required that function robustly in a wide range of bacterial hosts. The pGinger family of plasmids constitutes 43 plasmids that will enable both constitutive and inducible gene expression in a wide range of nonmodel Proteobacteria.

Quality of life and psychosocial outcomes among children with metabolically healthy and unhealthy obesity.

BACKGROUND: Obesity and obesity-related morbidities are associated with poor psychosocial adjustment and health-related quality of life (HRQoL). This study aims to examine HRQoL and psychosocial outcomes in children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and the effects of familial health on these outcomes. METHODS: Four hundred and six children with BMI for age ≥ 97th percentile were classified as having MHO and MUO based on the absence or presence of metabolic abnormalities. HRQoL and psychosocial outcomes were assessed using validated questionnaires such as PedsQL and DASS-21. RESULTS: There were no significant differences in HRQoL and psychosocial outcomes between children with MHO and children with MUO. Children with MUO and prior knowledge of existing metabolic conditions reported significantly lower total HRQoL (71.18 ± 17.42 vs. 75.34 ± 15.33), and higher depression (12.16 ± 11.80 vs. 8.95 ± 8.52) and stress (12.11 ± 8.21 vs. 10.04 ± 7.92) compared to children with MHO. Children with MUO who had fathers with metabolically unhealthy phenotype reported significantly lower total HRQoL (72.41 ± 15.67 vs. 76.82 ± 14.91) compared to children with MUO who had fathers with metabolically healthy phenotype. CONCLUSION: Prior knowledge of existing metabolic abnormalities was associated with poorer HRQoL and mental health in children with obesity. Paternal metabolic health status influenced HRQoL in children with MUO. IMPACT: First study that compared health-related quality of life (HRQoL) and psychosocial outcomes between children with metabolically healthy obesity (MHO) and children with metabolically unhealthy obesity (MUO). No significant differences in HRQoL and psychosocial outcomes between children with metabolically healthy obesity (MHO) and children with metabolically unhealthy obesity (MUO). Children with MUO who had prior knowledge of existing metabolic conditions reported lower HRQoL, higher depression and stress compared to children with MHO. Paternal metabolic health status was found to influence HRQoL in children with MUO. Mental health support intervention with paternal involvement should be provided for children with MUO.

Comparing pre-operative versus post-operative single and multi-fraction stereotactic radiotherapy for patients with resectable brain metastases.

Background: The standard treatment for patients with large brain metastases and limited intracranial disease is surgical resection and post-operative stereotactic radiosurgery (SRS). However, post-operative SRS still has elevated rates of local failure (LF) and is complicated by radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated therapy may improve local control through delivering a higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) will have less toxicity compared to patients who receive post-operative SRS or FSRT. Methods: A multi-institutional analysis was conducted and included patients who had surgical resection and stereotactic radiation therapy to treat at least one brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined as patients with one of the following adverse events: 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results: 279 patients were eligible for analysis. The median follow-up time was 9 months. 87 % of patients received fractionated treatment. 29 % of patients received pre-operative treatment. The composite endpoint incidences for post-operative SRS (n = 10), post-operative FSRT (n = 189), pre-operative SRS (n = 27), and pre-operative FSRT (n = 53) were 0 %, 17 %, 15 %, and 7.5 %, respectively. Conclusions: In our study, the composite endpoint of 7.5% for pre-operative FSRT compares favorably to our post-operative FSRT rate of 17%. Pre-operative FSRT was observed to have low rates of LF, MD, and RN. Prospective validation is needed.

A De Novo Mosaic PHEX Variant Causing Sporadic X-Linked Hypophosphatemic Rickets in a 2-Year-Old Girl.

Pathogenic variants in the PHEX gene are causative of X-linked hypophosphatemic rickets (XLH). We present a case of a 2-year-old girl with hypophosphatemic rickets with genu varum and short stature without any family history of XLH. Next generation sequencing of the PHEX gene identified a splice donor variant, NM_000444.6:c.1173 + 5G > A in intron 10. This variant had a mosaic pattern with only 22% of the sequence reads showing the variant allele and was not present in the girl's parents, both of whom had a normal phenotype. This is a sporadic case of a de novo mosaic splice-site variant in the PHEX gene.

Gender profile of principal investigators in a large academic clinical trials group.

Introduction: Gender equity in medicine has become a significant topic of discussion due to consistently low female representation in academia and leadership roles. Gender imbalance directly affects patient care. This study examined the gender and craft group of the Principal Investigators (PI) of clinical trials run by the Australasian Gastro-Intestinal Trials Group (AGITG). Methods: Publicly available data was obtained from the AGITG website. Trials were divided into upper, lower gastrointestinal cancer, miscellaneous (neuroendocrine and gastrointestinal stromal tumours). Where multiple PIs were listed, all were counted. Craft group was assigned as surgical, medical, radiation oncology or other. Results: There were 69 trials with 89 PI, where 52 trials were represented exclusively by male PIs. Of all PIs, 18 were women (20.2%); all were medical oncologists. Prior to 2005, all PIs were male. The craft group distribution of PIs was: 79% medical oncologists, 12% surgical oncologists, 8% radiation oncologist, 1% nuclear medicine physicians. Regarding trials with multiple PI's, there were 19 in total. Of these, 11 had only male PIs, which included 5 surgeons. Females were more likely to be a co-PI (42%) as opposed to sole PI (18%). There was no gender policy publicly available on the AGITG website. Conclusions: There is a low percentage of female PIs in academic oncology trials in the portfolio of this large international trials group. No trial was led by a female surgical or radiation oncologist. There is a need to understand the reasons driving the disparity so that specific strategies can be put in place.

Machine Learning-Derived Prenatal Predictive Risk Model to Guide Intervention and Prevent the Progression of Gestational Diabetes Mellitus to Type 2 Diabetes: Prediction Model Development Study.

BACKGROUND: The increasing prevalence of gestational diabetes mellitus (GDM) is concerning as women with GDM are at high risk of type 2 diabetes (T2D) later in life. The magnitude of this risk highlights the importance of early intervention to prevent the progression of GDM to T2D. Rates of postpartum screening are suboptimal, often as low as 13% in Asian countries. The lack of preventive care through structured postpartum screening in several health care systems and low public awareness are key barriers to postpartum diabetes screening. OBJECTIVE: In this study, we developed a machine learning model for early prediction of postpartum T2D following routine antenatal GDM screening. The early prediction of postpartum T2D during prenatal care would enable the implementation of effective strategies for diabetes prevention interventions. To our best knowledge, this is the first study that uses machine learning for postpartum T2D risk assessment in antenatal populations of Asian origin. METHODS: Prospective multiethnic data (Chinese, Malay, and Indian ethnicities) from 561 pregnancies in Singapore's most deeply phenotyped mother-offspring cohort study-Growing Up in Singapore Towards healthy Outcomes-were used for predictive modeling. The feature variables included were demographics, medical or obstetric history, physical measures, lifestyle information, and GDM diagnosis. Shapley values were combined with CatBoost tree ensembles to perform feature selection. Our game theoretical approach for predictive analytics enables population subtyping and pattern discovery for data-driven precision care. The predictive models were trained using 4 machine learning algorithms: logistic regression, support vector machine, CatBoost gradient boosting, and artificial neural network. We used 5-fold stratified cross-validation to preserve the same proportion of T2D cases in each fold. Grid search pipelines were built to evaluate the best performing hyperparameters. RESULTS: A high performance prediction model for postpartum T2D comprising of 2 midgestation features-midpregnancy BMI after gestational weight gain and diagnosis of GDM-was developed (BMI_GDM CatBoost model: AUC=0.86, 95% CI 0.72-0.99). Prepregnancy BMI alone was inadequate in predicting postpartum T2D risk (ppBMI CatBoost model: AUC=0.62, 95% CI 0.39-0.86). A 2-hour postprandial glucose test (BMI_2hour CatBoost model: AUC=0.86, 95% CI 0.76-0.96) showed a stronger postpartum T2D risk prediction effect compared to fasting glucose test (BMI_Fasting CatBoost model: AUC=0.76, 95% CI 0.61-0.91). The BMI_GDM model was also robust when using a modified 2-point International Association of the Diabetes and Pregnancy Study Groups (IADPSG) 2018 criteria for GDM diagnosis (BMI_GDM2 CatBoost model: AUC=0.84, 95% CI 0.72-0.97). Total gestational weight gain was inversely associated with postpartum T2D outcome, independent of prepregnancy BMI and diagnosis of GDM (P=.02; OR 0.88, 95% CI 0.79-0.98). CONCLUSIONS: Midgestation weight gain effects, combined with the metabolic derangements underlying GDM during pregnancy, signal future T2D risk in Singaporean women. Further studies will be required to examine the influence of metabolic adaptations in pregnancy on postpartum maternal metabolic health outcomes. The state-of-the-art machine learning model can be leveraged as a rapid risk stratification tool during prenatal care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01174875; https://clinicaltrials.gov/ct2/show/NCT01174875.

Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis.

BACKGROUND: The current standard of care for patients with a large brain metastasis and limited intracranial disease burden is surgical resection and post-operative single fraction stereotactic radiosurgery (SRS). However, post-operative SRS can still lead to substantial rates of local failure (LF), radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated treatments may improve local control by allowing delivery of higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) can minimize rates of LF, RN, and MD. METHODS: A retrospective, multi-institutional analysis was conducted and included patients who had pre-operative FSRT for a large or symptomatic brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. A primary measurement was the rate of a composite endpoint of (1) LF, (2) MD, and/or (3) Grade 2 or higher (symptomatic) RN. RESULTS: 53 patients with 55 lesions were eligible for analysis. FSRT was prescribed to a dose of 24-25 Gy in 3-5 fractions. There were 0 LFs, 3 Grade 2-3 RN events, and 1 MD occurrence, which corresponded to an 8% per-patient composite endpoint event rate. CONCLUSIONS: In this study, the composite endpoint of 8% for pre-operative FSRT was improved compared to previously reported rates with post-operative SRS of 49-60% (N107C, Mahajan etal. JCOG0504) and pre-operative SRS endpoints of 20.6% (PROPS-BM). Pre-operative FSRT appears to be safe, effective, and may decrease the incidence of adverse outcomes. Prospective validation is needed.

Prevalence and predictors of metabolically healthy obesity in severely obese Asian children.

BACKGROUND: Obese individuals who have little or no metabolic syndrome components are proposed to be "metabolically healthy obese (MHO)". This study aim to evaluate the prevalence of MHO and examine the predictors associated with MHO in a multi-ethnic Asian cohort of severely obese children. METHODS: This study included a cross-sectional cohort of 406 Chinese, Malay and Indian children aged 5-20 years old with BMI for age ≥ 97th percentile. Metabolic syndrome (MS) and metabolic health (MH) definitions based on the presence or absence of metabolic abnormalities (High triglycerides, low HDL cholesterol, elevated blood pressure and high glucose) were used to define MHO in the cohort. RESULTS: The prevalence of MHO is 63.5% by MS definition and 22.4% by MH definition. Maternal healthy metabolic status (OR: 2.47), age (OR: 0.83, 0.80), paternal obesity (OR: 0.48, 0.53), Malay (OR: 1.97) and Indian ethnicity (OR: 6.38, 3.21) (compared to Chinese ethnicity) are independent predictors for MHO phenotype based on different MHO definitions. CONCLUSIONS: Adiposity measures are not associated with MHO phenotype, but instead younger age, maternal healthy metabolic status, absence of paternal obesity, Malay and Indian ethnicity are independent predictors for MHO phenotype in a multi-ethnic Asian cohort of severely obese children. IMPACT: The prevalence of metabolically healthy obese (MHO) in our multi-ethnic Asian cohort of severely obese children is 63.5% and 22.4%, respectively, based on different MHO definitions. Adiposity measures are not associated with the MHO phenotype. There are other factors that contribute to the metabolic phenotype in obese individuals. Younger age, maternal healthy metabolic status, absence of paternal obesity, Malay and Indian ethnicity are independent predictors for MHO phenotype. Parental influence is important in predicting metabolic health in obese individuals.

Population-centric risk prediction modeling for gestational diabetes mellitus: A machine learning approach.

AIMS: The heterogeneity in Gestational Diabetes Mellitus (GDM) risk factors among different populations impose challenges in developing a generic prediction model. This study evaluates the predictive ability of existing UK NICE guidelines for assessing GDM risk in Singaporean women, and used machine learning to develop a non-invasive predictive model. METHODS: Data from 909 pregnancies in Singapore's most deeply phenotyped mother-offspring cohort study, Growing Up in Singapore Towards healthy Outcomes (GUSTO), was used for predictive modeling. We used a CatBoost gradient boosting algorithm, and the Shapley feature attribution framework for model building and interpretation of GDM risk attributes. RESULTS: UK NICE guidelines showed poor predictability in Singaporean women [AUC:0.60 (95% CI 0.51, 0.70)]. The non-invasive predictive model comprising of 4 non-invasive factors: mean arterial blood pressure in first trimester, age, ethnicity and previous history of GDM, greatly outperformed [AUC:0.82 (95% CI 0.71, 0.93)] the UK NICE guidelines. CONCLUSIONS: The UK NICE guidelines may be insufficient to assess GDM risk in Asian women. Our non-invasive predictive model outperforms the current state-of-the-art machine learning models to predict GDM, is easily accessible and can be an effective approach to minimize the economic burden of universal testing & GDM associated healthcare in Asian populations.

Binocular Integration of Perceptually Suppressed Visual Information in Amblyopia.

Purpose: The purpose of this study was to assess whether motion information from suppressed amblyopic eyes can influence visual perception. Methods: Participants with normal vision (n = 20) and with amblyopia (n = 20; 11 anisometropic and 9 strabismic/mixed) viewed dichoptic, orthogonal drifting gratings through a mirror stereoscope. Participants continuously reported form and motion percepts as gratings rivaled for 60 seconds. Responses were binned into categories ranging from binocular integration to complete suppression. Periods when the grating presented to the nondominant/amblyopic eye was suppressed were analyzed further to determine the extent of binocular integration of motion. Results: Individuals with amblyopia experienced longer periods of non-preferred eye suppression than controls. When the non-preferred eye grating was suppressed, binocular integration of motion occurred 48.1 ± 6.2% and 31.2 ± 5.8% of the time in control and amblyopic participants, respectively. Periods of motion integration from the suppressed eye were significantly non-zero for both groups. Conclusions: Visual information seen only by a suppressed amblyopic eye can be binocularly integrated and influence the overall visual percept. These findings reveal that visual information subjected to interocular suppression can still contribute to binocular vision and suggest the use of appropriate optical correction for the amblyopic eye to improve image quality for binocular combination.

Association of leukocyte telomere length with obesity-related traits in Asian children with early-onset obesity.

BACKGROUND: Leukocyte telomere length (LTL) is associated with obesity and obesity-related traits, and there are ethnic-specific determinants of LTL. OBJECTIVE: To evaluate LTL associations with obesity and metabolic parameters in Asian children with early-onset obesity. METHODS: Genomic DNA was extracted from peripheral blood leukocytes of a cohort of children with (N = 371) and without obesity (N = 23), and LTL was measured using quantitative PCR (qPCR). Blood plasma was used for metabolic phenotyping. Statistical analysis was performed using SPSS and STATA. RESULTS: Children with obesity had shorter LTL (coefficient = -0.683, PAdj = 1.24 × 10-3 ) as compared to children who were lean. LTL was found to be associated with waist circumference (coefficient = -0.326, PAdj = 0.044) and skin-fold measures (coefficient between 0.267 and 0.301, PAdj between 4.27 × 10-4 and 7.06 × 10-7 ) in children with obesity. However, no significant associations were observed between LTL and metabolic parameters, and between LTL and inflammatory cytokines. LTL also did not significantly mediate the risk of non-alcoholic fatty liver disease (NAFLD) in children with obesity. CONCLUSIONS: We showed for the first time that Asian children with severe obesity had shorter LTL, and the shortening of LTL was associated with other adiposity measures including waist circumference and skin-fold measurements.

A Noninvasive Retrograde Flushing System for Shunted Hydrocephalus: Initial Case Series of 25 Patients.

Hydrocephalus is a common neurosurgical pathology associated with high patient morbidity and systemwide healthcare costs. A significant portion of these costs are related to the failure of ventricular shunting systems. Despite decades of research and technological development, the rate of shunt failure and revision has not significantly improved. The Reflow™ Ventricular System (Anuncia, Inc., Lowell, MA) is a recent technological development with the potential to prolong the shunt lifespan. This system introduces a noninvasive means of flushing a shunt proximally with a controlled, repeatable pulse of cerebral spinal fluid (CSF) and of creating a new ventricular opening for occluded shunts. In this multicenter case series, we present the early clinical experiences with this device and discuss its potential.

Self and parent-proxy rated health-related quality of life (HRQoL) in youth with obesity: are parents good surrogates?

PURPOSE: Consideration of health-related quality of life (HRQoL) and wellbeing outcomes is important to guide healthcare services for youth with obesity, yet youth perspectives may differ from their parents. This study compared youth and parental HRQoL reports and evaluated levels of concordance across HRQoL domains and as a function of youth age, youth gender and parent informant (mother and father). METHODS: 376 youths with obesity, recruited from community (N = 223) and hospital settings (N = 153), and their parents (N = 190 mothers; N = 91 fathers), completed the PedsQL. Parental and youth agreement across subgroup dyads (mother; father; child gender; child age) were evaluated using Wilcoxon signed-rank test, intra-correlations coefficients (ICCs) and Bland-Altman plots. RESULTS: Compared to norms, HRQoL levels (youth self-report and parental proxy reports) were lower in all domains. Both mother and fathers' HRQoL reports were significantly lower than youths, most notably in physical HRQoL. Youth-parent concordance ranged from poor to moderate (ICC = 0.230-0.618), with lowest agreement for Physical HRQOL. Mothers were better proxies with ICCs being significant in all domains. Youth-father ICCs were significant only for Social (ICC = 0.428) and School (ICC = 0.303) domains. Girl-mother agreement was significant across all domains, while girl-father agreement was significant only in the Social domain (ICC = 0.653). Both mothers and fathers were poor raters for boys, and younger youths (aged ≤ 12), with non-significant ICCs in most HRQoL domains. CONCLUSIONS: Parents are poor surrogates for youth HRQoL. Clinicians should be cognizant that parents are not necessarily accurate proxies for youths, and exercise caution when interpreting parent-proxy scores.