Cascaded subarray design and control method for power efficient, thermal crosstalk optimized optical phased array.

Thermo-optic phase shifters (TOPSs) are commonly used in large-scale silicon photonic integrated optical phased arrays (OPAs). However, fast-response TOPSs consume relatively high power; the elevated temperature floor in the dense region of the TOPSs introduces thermal crosstalk between optical paths, which undermines the control accuracy. We propose a combined method that involves subarray design in the optical power distribution network and array control method to predict, optimize, and redistribute the phase shifts and mitigates thermal crosstalk. Thermal simulations and an array control method for generic OPA models are discussed. A silicon photonic chip prototype of a 4 × 4 OPA with three-level cascaded subarrays is fabricated to demonstrate the proposed method. The experimental and statistical results show that the method effectively reduces the average total power consumption by 31%, the maximum local temperature by 18.4%, and the thermal crosstalk within the OPA.

GNOSIS: an R Shiny app supporting cancer genomics survival analysis with cBioPortal.

Exploratory analysis of cancer consortia data curated by the cBioPortal repository typically requires advanced programming skills and expertise to identify novel genomic prognostic markers that have the potential for both diagnostic and therapeutic exploitation. We developed GNOSIS (GeNomics explOrer using StatistIcal and Survival analysis in R), an R Shiny App incorporating a range of R packages enabling users to efficiently explore and visualise such clinical and genomic data. GNOSIS provides an intuitive graphical user interface and multiple tab panels supporting a range of functionalities, including data upload and initial exploration, data recoding and subsetting, data visualisations, statistical analysis, mutation analysis and, in particular, survival analysis to identify prognostic markers. GNOSIS also facilitates reproducible research by providing downloadable input logs and R scripts from each session, and so offers an excellent means of supporting clinician-researchers in developing their statistical computing skills.

Zilovertamab Vedotin Targeting of ROR1 as Therapy for Lymphoid Cancers.

BACKGROUND: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein present on many cancers. Zilovertamab vedotin (ZV) is an antibody­drug conjugate comprising a monoclonal antibody recognizing extracellular ROR1, a cleavable linker, and the anti-microtubule cytotoxin monomethyl auristatin E. METHODS: In this phase 1, first-in-human, dose-escalation study, we accrued patients with previously treated lymphoid cancers to receive ZV every 3 weeks until the occurrence of cancer progression or unacceptable toxicity had occurred. RESULTS: We enrolled 32 patients with tumor histologies of mantle cell lymphoma (MCL) (n=15), chronic lymphocytic leukemia (n=7), diffuse large B-cell lymphoma (DLBCL) (n=5), follicular lymphoma (n=3), Richter transformation lymphoma (n=1), or marginal zone lymphoma (n=1). Patients had received a median of four previous drug and/or cellular therapies. Starting dose levels were 0.5 (n=1), 1.0 (n=3), 1.5 (n=3), 2.25 (n=11), and 2.5 (n=14) mg per kg of body weight (mg/kg). Pharmacokinetic and pharmacodynamic data documented systemic ZV exposure and exposure-dependent ZV targeting of ROR1 on circulating tumor cells. As expected with an monomethyl auristatin E-containing antibody­drug conjugate, adverse events (AEs) included acute neutropenia and cumulative neuropathy resulting in a recommended ZV dosing regimen of 2.5 mg/kg every 3 weeks. No clinically concerning AEs occurred to suggest ROR1-mediated toxicities or nonspecific ZV binding to normal tissues. ZV induced objective tumor responses in 7 of 15 patients with MCL (47%; 4 partial and 3 complete) and in 3 of 5 patients with DLBCL (60%; 1 partial and 2 complete); objective tumor responses were not observed among patients with other tumor types. CONCLUSIONS: In heavily pretreated patients, ZV demonstrated no unexpected toxicities and showed evidence of antitumor activity, providing clinical proof of concept for selective targeting of ROR1 as a potential new approach to cancer therapy. (ClinicalTrials.gov number, NCT03833180.)

Survival outcomes are associated with genomic instability in luminal breast cancers.

Breast cancer is the leading cause of cancer related death among women. Breast cancers are generally diagnosed and treated based on clinical and histopathological features, along with subtype classification determined by the Prosigna Breast Cancer Prognostic Gene Signature Assay (also known as PAM50). Currently the copy number alteration (CNA) landscape of the tumour is not considered. We set out to examine the role of genomic instability (GI) in breast cancer survival since CNAs reflect GI and correlate with survival in other cancers. We focused on the 70% of breast cancers classified as luminal and carried out a comprehensive survival and association analysis using Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data to determine whether CNA Score Quartiles derived from absolute CNA counts are associated with survival. Analysis revealed that patients diagnosed with luminal A breast cancer have a CNA landscape associated with disease specific survival, suggesting that CNA Score can provide a statistically robust prognostic factor. Furthermore, stratification of patients into subtypes based on gene expression has shown that luminal A and B cases overlap, and it is in this region we largely observe luminal A cases with reduced survival outlook. Therefore, luminal A breast cancer patients with quantitatively elevated CNA counts may benefit from more aggressive therapy. This demonstrates how individual genomic landscapes can facilitate personalisation of therapeutic interventions to optimise survival outcomes.

Testing a cognitive model to predict posttraumatic stress disorder following childbirth.

BACKGROUND: One third of women describes their childbirth as traumatic and between 0.8 and 6.9% goes on to develop posttraumatic stress disorder (PTSD). The cognitive model of PTSD has been shown to be applicable to a range of trauma samples. However, childbirth is qualitatively different to other trauma types and special consideration needs to be taken when applying it to this population. Previous studies have investigated some cognitive variables in isolation but no study has so far looked at all the key processes described in the cognitive model. This study therefore aimed to investigate whether theoretically-derived variables of the cognitive model explain unique variance in postnatal PTSD symptoms when key demographic, obstetric and clinical risk factors are controlled for. METHOD: One-hundred and fifty-seven women who were between 1 and 12 months post-partum (M = 6.5 months) completed validated questionnaires assessing PTSD and depressive symptoms, childbirth experience, postnatal social support, trauma memory, peritraumatic processing, negative appraisals, dysfunctional cognitive and behavioural strategies and obstetric as well as demographic risk factors in an online survey. RESULTS: A PTSD screening questionnaire suggested that 5.7% of the sample might fulfil diagnostic criteria for PTSD. Overall, risk factors alone predicted 43% of variance in PTSD symptoms and cognitive behavioural factors alone predicted 72.7%. A final model including both risk factors and cognitive behavioural factors explained 73.7% of the variance in PTSD symptoms, 37.1% of which was unique variance predicted by cognitive factors. CONCLUSIONS: All variables derived from Ehlers and Clark's cognitive model significantly explained variance in PTSD symptoms following childbirth, even when clinical, demographic and obstetric were controlled for. Our findings suggest that the CBT model is applicable and useful as a way of understanding and informing the treatment of PTSD following childbirth.

Population attributable fractions for three perinatal risk factors for autism spectrum disorders, 2002 and 2008 autism and developmental disabilities monitoring network.

PURPOSE: Numerous studies establish associations between adverse perinatal outcomes/complications and autism spectrum disorder (ASD). There has been little assessment of population attributable fractions (PAFs). METHODS: We estimated average ASD PAFs for preterm birth (PTB), small for gestational age (SGA), and Cesarean delivery (CD) in a U.S. population. Average PAF methodology accounts for risk factor co-occurrence. ASD cases were singleton non-Hispanic white, non-Hispanic black, and Hispanic children born in 1994 (n = 703) or 2000 (n = 1339) who resided in 48 U.S. counties included within eight Autism and Developmental Disabilities Monitoring Network sites. Cases were matched on birth year, sex, and maternal county of residence, race-ethnicity, age, and education to 20 controls from U.S. natality files. RESULTS: For the 1994 cohort, average PAFs were 4.2%, 0.9%, and 7.9% for PTB, SGA, and CD, respectively. The summary PAF was 13.0% (1.7%-19.5%). For the 2000 cohort, average PAFs were 2.0%, 3.1%, and 6.7% for PTB, SGA, and CD, respectively, with a summary PAF of 11.8% (7.5%-15.9%). CONCLUSIONS: Three perinatal risk factors notably contribute to ASD risk in a U.S. population. Because each factor represents multiple etiologic pathways, PAF estimates are best interpreted as the proportion of ASD attributable to having a suboptimal perinatal environment resulting in PTB, SGA, and/or CD.

High-fidelity simulation enhances pediatric residents' retention, knowledge, procedural proficiency, group resuscitation performance, and experience in pediatric resuscitation.

OBJECTIVE: The goal of this study was to assess the effect of high-fidelity simulation (HFS) pediatric resuscitation training on resident performance and self-reported experience compared with historical controls. METHODS: In this case-control study, pediatric residents at a tertiary academic children's hospital participated in a 16-hour HFS resuscitation curriculum. Primary outcome measures included cognitive knowledge, procedural proficiency, retention, and self-reported comfort and procedural experience. The intervention group was compared with matched-pair historical controls. RESULTS: Forty-one residents participated in HFS training with 32 matched controls. The HFS group displayed significant initial and overall improvement in knowledge (P < .01), procedural proficiency (P < .05), and group resuscitation performance (P < .01). Significant skill decay occurred in all performance measures (P < .01) with the exception of endotracheal intubation. Compared with controls, the HFS group reported not only greater comfort with most procedures but also performed more than twice the number of successful real-life pediatric intubations (median: 6 vs 3; P = .03). CONCLUSIONS: Despite significant skill decay, HFS pediatric resuscitation training improved pediatric resident cognitive knowledge, procedural proficiency, and comfort. Residents who completed the course were not only more proficient than historical controls but also reported increased real-life resuscitation experiences and related procedures.

DNA strand breaks (comet assay) in blood lymphocytes from wild bottlenose dolphins.

The comet assay was carried out on blood lymphocytes from a large number of wild dolphins (71 from Indian River Lagoon, FL, USA; 51 from Charleston Harbor, SC, USA) and provides a baseline study of DNA strand breaks in wild dolphin populations. There were no significant differences in the comet assay (% DNA in tail) results between the different age and sex categories. Significant difference in DNA strand breaks were found between Charleston Harbor dolphins (median--17.4% DNA in tail) and Indian River Lagoon dolphins (median--14.0% DNA in tail). A strong correlation found between T-cell proliferation and DNA strand breaks in dolphin lymphocytes suggests that dolphins with a high numbers of DNA strand breaks have a decreased ability to respond to infection. Higher concentrations of genotoxic agents in Charleston Harbor compared with Indian River lagoon may have been one of the causes of higher DNA strand breaks in these dolphins.

Early echocardiographic changes after percutaneous implantation of the Edwards SAPIEN transcatheter heart valve in the pulmonary position.

OBJECTIVES: To evaluate echocardiographic changes after SAPIEN valve implantation in the pulmonary position. BACKGROUND: The feasibility of the SAPIEN transcatheter pulmonary valve (TPV) has recently been demonstrated. We evaluated changes in pulmonary valve function and the right ventricle after SAPIEN TPV placement. METHODS: We evaluated echocardiograms at baseline, discharge, 1 and 6 months after TPV placement in 33 patients from 4 centers. Pulmonary insufficiency severity was graded 0-4. TPV peak and mean gradients were measured. Right ventricular (RV) size and function were quantified using routine measures derived from color, spectral, and tissue Doppler indices and two-dimensional echocardiography. RESULTS: At baseline, 94% patients demonstrated pulmonary insufficiency grade 2-4. This decreased to 12% patients at 6 months (P < 0.01). TPV peak (P < 0.01) and mean gradient (P < 0.01) decreased. RV end-diastolic area indexed to body surface area (BSA) (P < 0.01), Tricuspid regurgitation (TR) gradient (P < 0.01), and the ratio of TR jet area to BSA (P < 0.01) decreased. Tricuspid inflow peak E:A, tissue Doppler imaging (TDI): septal E' and A', TDI: tricuspid A' improved between baseline and discharge, but trended back to baseline by 6-month follow-up. Tricuspid valve annulus z-score, RV area change, tricuspid annular plane systolic excursion (TAPSE), RV dP/dt, tricuspid E:E', and TDI: tricuspid annulus E' showed no change. CONCLUSION: Improvements in pulmonary insufficiency and stenosis, RV size, and TR gradient and severity are seen after SAPIEN TPV placement. Selected indices of RV diastolic function improve immediately after TPV implantation, but return to baseline by 6 months. RV systolic function is unchanged.

Effective radiation dose in computed tomographic angiography of the chest and diagnostic cardiac catheterization in pediatric patients.

Computed tomographic angiography (CTA) and cardiac catheterization are useful adjuncts to echocardiography for delineating cardiovascular anatomy in pediatric patients. These studies require ionizing radiation, and it is paramount to understand the amount of radiation pediatric patients receive when these tests are performed. Modern dosimetry methods facilitate the conversion of radiation doses of varying units into an effective radiation dose. To compare the effective radiation dose between nongated CTA of the chest and diagnostic cardiac catheterization in pediatric patients. This is a retrospective cohort study of patients of patients who underwent either nongated CTA of the chest or diagnostic cardiac catheterization between July 2009 and April 2010. Fifty patients were included in each group as consecutive samples at a single tertiary care center. An effective radiation dose (mSv) was formulated using conversion factors for each group. The median effective dose (ED) for the CTA group was 0.74 mSv compared with 10.8 mSv for the catheterization group (p < 0.0001). The median ED for children <1 year of age in the CTA group was 0.76 mSv compared with 13.4 mSv for the catheterization group (p < 0.0001). Nongated CTA of the chest exposes children to 15 times less radiation than diagnostic cardiac catheterization. Unless hemodynamic data are necessary, CTA of the chest should be considered in lieu of diagnostic cardiac catheterization in patients with known or presumed cardiac disease who need additional imaging beyond echocardiography.

Effectiveness of a breath-actuated nebulizer device on asthma care in the pediatric emergency department.

The breath-actuated nebulizer (BAN) is a new respiratory device to deliver short-acting ß-agonists to patients with asthma exacerbations. This pediatric convenience sample experimental study compares the BAN with conventional nebulizers and demonstrates that the BAN allows for shorter treatment times to achieve improved clinical asthma scores with less albuterol, shorter emergency department length of stay, and fewer hospitalizations.

Completeness of case ascertainment for surveillance of autism spectrum disorders using the autism developmental disabilities monitoring network methodology.

BACKGROUND: The Autism and Developmental Disabilities Monitoring Network (ADDM), sponsored by the Centers for Disease Control and Prevention, is the largest-scale project ever undertaken to identify the prevalence of Autism Spectrum Disorders (ASD) in the United States. OBJECTIVE: The objective of the present study was to examine the accuracy of the ADDM methodology in terms of completeness of case ascertainment; that is, to assess the success of the ADDM Network in identifying and accurately classifying all existing cases of ASD among 8-year-old children in the target study areas. METHODS: To accomplish this objective, the ADDM methodology was applied to a selected region of South Carolina for 8-year olds in 2000 (birth year 1992) and again seven years later for the same region and birth year. RESULTS: For this region and birth year, completeness of case ascertainment was high, with prevalence estimates of 7.6 per 1000 at both ages 8- and 15-years. For children common to both surveillance years, concordance in case status was also high (82%). CONCLUSIONS: Given that prevalence did not change within this region and birth year, continued research is needed to better understand the changes in prevalence estimates being found by the ADDM network across surveillance groups.

High prescription drug use and associated costs among Medicaid-eligible children with autism spectrum disorders identified by a population-based surveillance network.

PURPOSE: We assessed medication use and associated costs among 8- and 15-year-old children with autism spectrum disorders (ASD) identified by the South Carolina Autism and Developmental Disabilities Monitoring (SCADDM) Network. METHODS: All Medicaid-eligible SCADDM-identified children with ASD from surveillance years 2006 and 2007 were included (n = 263). Children were classified as ASD cases when documented behaviors consistent with the DSM-IV-TR criteria for autistic disorder, Asperger disorder, or pervasive developmental disorder-not otherwise specified were present in health and education evaluation records. Medication and cost data were obtained by linking population-based and Medicaid data. RESULTS: All 263 SCADDM-identified children had Medicaid data available; 56% (n = 147) had a prescription of any type, 40% (n = 105) used psychotropic medication, and 20% (n = 52) used multiple psychotropic classes during the study period. Common combinations were (1) attention deficit hyperactivity disorder medications and an antihypertensive, antidepressant or antipsychotic; and (2) antidepressants and an antipsychotic. Multiple psychotropic classes were more common among older children. Both the overall distribution of the number of prescription claims and medication costs varied significantly by age. CONCLUSIONS: Results confirm that medication use in ASD, alone or in combination, is common, costly, and may increase with age.

The prevalence of youth with autism spectrum disorders in the criminal justice system.

Past surveys have reported high rates of youth with disabilities in the juvenile justice system, however, little research has examined the frequency with which youth with Autism spectrum disorders (ASD) are in contact with law enforcement. Using records linkage with the Department of Juvenile Justice and the South Carolina Law Enforcement Division and the South Carolina Autism and Developmental Disabilities Monitoring Program (SC ADDM), this study compares the frequency, type, and outcome of criminal charges for youth with ASD and non-ASD youth. Youth with ASD had higher rates of crimes against persons and lower rates of crimes against property. Youth with ASD were more likely to be diverted into pre-trial interventions and less likely to be prosecuted than comparison youth. When compared to the overall SC ADDM sample, charged youth were less likely to have comorbid intellectual disability.

Changes in autism spectrum disorder prevalence in 4 areas of the United States.

BACKGROUND: We sought to describe autism spectrum disorder (ASD) population characteristics and changes in identified prevalence across 3 time periods. METHODS: Children with a potential ASD were identified through records abstraction at multiple sources with clinician review based on Diagnostic and Statistical Manual (DSM-IV-TR) criteria. Multisite, population-based data from the Autism and Developmental Disabilities Monitoring (ADDM) Network were analyzed from areas of Arizona (AZ), Georgia (GA), Maryland (MD), and South Carolina (SC). Participants were 8-year-old children (born in 1992, 1994, or 1996) in 2000, 2002, or 2004 (and children born in 1988 residing in metropolitan Atlanta in 1996) who had been evaluated for a variety of developmental concerns at education and/or health sources. RESULTS: From 2000 to 2004, the identified prevalence of the ASDs per 1,000 8-year-old children showed significant increases of 38% in GA and 72% in MD and a nonsignificant increase of 26% in AZ. ASD prevalence was relatively stable in SC with a nonsignificant decrease of 17%. Males had a higher identified prevalence of ASD in all years. Increases among racial, ethnic, and cognitive functioning subgroups varied by site and surveillance year. More children were classified with an ASD by community professionals over time, except in AZ. CONCLUSIONS: There was a trend toward increase in identified ASD prevalence among 8-year-old children who met the surveillance case definition in 3 of the 4 study sites from 2000 to 2004. Some of the observed increases are due to improved ascertainment; however, a true increase in ASD symptoms cannot be ruled out. These data confirm that the prevalence of ASDs is undergoing significant change in some areas of the United States and that ASDs continue to be of urgent public health concern.

Autism spectrum disorders in preschool-aged children: prevalence and comparison to a school-aged population.

PURPOSE: The purpose of this study was to determine the prevalence and case characteristics of children with autism spectrum disorders (ASDs) among 4-year-olds and to compare findings to previous prevalence estimates for 8-year-olds in the same geographic area. METHODS: South Carolina (SC) has been a participant in the Centers for Disease Control and Prevention's active, population-based, multiple-site ASD surveillance network for 8-year-olds since 2000. The 8-year-old methodology, designed to identify children both with and without prior diagnosis, was applied in SC with modification to include information sources for younger children. RESULTS: The ASD prevalence among 4-year-olds in 2006 was 8.0 per 1000 (95% confidence interval [CI], 6.1-9.9), or 1 in 125. In comparison, ASD prevalence among 8-year-olds in the same geographic area was 7.6 (95% CI, 5.7-9.5) in 2000 and 7.0 (95% CI 5.1-8.9) in 2002. Developmental concerns were documented at earlier ages across time, and while most cases received services, only 20% to 29% received services specific to ASD. CONCLUSIONS: Findings should provide useful information for the planning of health/education policies and early intervention strategies for ASD.

Prevalence and characteristics of children with autism-spectrum disorders.

PURPOSE: The purpose of this study was to determine the prevalence of autism spectrum disorders (ASD) and associated characteristics among 8-year-old children. METHODS: This is an ongoing active, population-based surveillance program conducted in South Carolina as part of the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network. Cases from the state's first two study years (2000 and 2002) have been combined for analysis, resulting in surveillance of 47,726 children who are 8 years of age. RESULTS: A total of 295 children met criteria for ASD, yielding a prevalence of 6.2 per 1000. The racial distribution of cases was similar to that of 8-year-old children in the study area, with boys more commonly affected than girls (3.1:1). Seventy-nine percent of cases were served in special education, 36% of these under Autism classification. Analyses by gender showed differences in diagnostic criteria and intellectual functioning. Girls more often were cognitively impaired (IQ

Mandibular first molar relation to variable lower face skeletal components.

OBJECTIVE: To evaluate the position of the mandibular first permanent molar in the mandible relative to several factors. MATERIALS AND METHODS: A total of 185 untreated Class I and Class II patients were randomly selected from a sample of 350 patients from a single office. The palatal and mandibular planes were related to Frankfort horizontal to create the interjaw or "B" angle. Age and the mesial contact of the mandibular first molars were used. The landmarks were projected at right angles to the Frankfort horizontal for effective mandibular dimension lengths. Actual-length dimensions were projected at right angles to the mandibular plane. Pearson product moment correlation coefficients were computed to evaluate the effect of age, cranial length, and mandibular contribution to the molar's sagittal position in the mandible. Significance was reported only when P < .05 to determine a 95% confidence level. RESULTS: Statistically significant positive correlations indicated that the mandibular molar is located more forward with increasing age, longer mandibular body length, and increasing posterior facial height. In contrast, significant negative correlations to the interjaw, mandibular plane, ramal inclination angles, and the linear ramal contribution corresponded to a more posterior position of the molar with increasing angles. CONCLUSIONS: The mandibular first permanent molar is located more anteriorly with an older patient, a longer mandibular body, greater posterior facial height, and an acute interjaw angle. In contrast, an increase in the forward tip of the ramus places the molar in a more posterior location.

Pleural effusions in a series of 181 outpatients with sarcoidosis.

OBJECTIVES: Pleural effusion (PE) is considered to be a rare manifestation of pulmonary sarcoidosis. We performed thoracic ultrasonography prospectively in consecutive outpatients with sarcoidosis to determine the frequency of PEs caused by sarcoidosis and to define their pleural fluid characteristics. DESIGN: Consecutive outpatients aged >/= 18 years with biopsy-proven sarcoidosis underwent ultrasonography. SETTING: University hospital, outpatient sarcoidosis clinic. RESULTS: One hundred eighty-one outpatients were enrolled into the study. The subjects were predominately African-American and female. Most were between 30 and 60 years of age. The Scadding radiograph stages were fairly evenly distributed across all five stages (0 through 4). Five (2.8%) of 181 patients were found to have pleural fluid. Two patients had a unilateral left-sided PE, and three patients had bilateral PEs. Pleural fluid analysis (PFA) was performed in four patients. The PFA showed a lymphocyte-predominant exudate using protein criterion in only two patients, which is consistent with sarcoidosis-related PE; one patient underwent pleural biopsy, which was consistent with the diagnosis of sarcoidosis. A sarcoidosis-related PE was seen in 1 of 9 patients (11.1%) who had an exacerbation of pulmonary sarcoidosis compared to 1 of 172 patients (0.6%) who did not have an exacerbation (p < 0.4). CONCLUSION: PEs are rare in outpatients with sarcoidosis, even when a sensitive technique, such as ultrasonography, is used. The frequency of PEs was 2.8% (5 of 181 patients) with only 2 of the 181 PEs (1.1%) caused by sarcoid pleural involvement. PE in patients with sarcoidosis should not be assumed to be related to sarcoidosis. Discordance between levels of pleural fluid total protein and lactate dehydrogenase may be a characteristic finding in patients with sarcoid PE. An exacerbation of pulmonary sarcoidosis was not an independent risk factor for the development of sarcoid-related PE.