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BACKGROUND: Screening for islet autoantibodies in children and adolescents identifies individuals who will later develop type 1 diabetes, allowing patient and family education to prevent diabetic ketoacidosis at onset and to enable consideration of preventive therapies. We aimed to assess whether islet autoantibody screening is effective for predicting type 1 diabetes in adolescents aged 10−18 years with an increased risk of developing type 1 diabetes. METHODS: Data were harmonised from prospective studies from Finland (the Diabetes Prediction and Prevention study), Germany (the BABYDIAB study), and the USA (Diabetes Autoimmunity Study in the Young and the Diabetes Evaluation in Washington study). Autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured at each follow-up visit. Children who were lost to follow-up or diagnosed with type 1 diabetes before 10 years of age were excluded. Inverse probability censoring weighting was used to include data from remaining participants. Sensitivity and the positive predictive value of these autoantibodies, tested at one or two ages, to predict type 1 diabetes by the age of 18 years were the main outcomes. FINDINGS: Of 20 303 children with an increased type 1 diabetes risk, 8682 were included for the analysis with inverse probability censoring weighting. 1890 were followed up to 18 years of age or developed type 1 diabetes between the ages of 10 years and 18 years, and their median follow-up was 18·3 years (IQR 14·5–20·3). 442 (23·4%) of 1890 adolescents were positive for at least one islet autoantibody, and 262 (13·9%) developed type 1 diabetes. Time from seroconversion to diabetes diagnosis increased by 0·64 years (95% CI 0·34–0·95) for each 1-year increment of diagnosis age (Pearson’s correlation coefficient 0·88, 95% CI 0·50–0·97, p=0·0020). The median interval between the last prediagnostic sample and diagnosis was 0·3 years (IQR 0·1–1·3) in the 227 participants who were autoantibody positive and 6·8 years (1·6–9·9) for the 35 who were autoantibody negative. Single screening at the age of 10 years was 90% (95% CI 86–95) sensitive, with a positive predictive value of 66% (60–72) for clinical diabetes. Screening at two ages (10 years and 14 years) increased sensitivity to 93% (95% CI 89–97) but lowered the positive predictive value to 55% (49–60). INTERPRETATION: Screening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials. FUNDING: JDRF International.

BACKGROUND The youth mental health crisis in the United States continues to worsen, and research shows poor treatment outcomes for youth in mental health care. Despite the rise in predictive and personalized treatment, there has been a lack of research conducted with youth. Due to the complex developmental milestones of these periods, there is a need to better understand initial clinical presentation and predictors of treatment engagement to more effectively identify and tailor beneficial treatments. OBJECTIVE This quality improvement investigation sought to identify subgroups of clients attending remote intensive outpatient (IOP) treatment based on clinical acuity data at intake to determine the predictors of outcomes for clients who present in complex developmental periods and with co-occurring conditions. The identification of these subgroups was used to inform programmatic decisions within the remote IOP system for which this quality improvement analysis was conducted. METHODS Data were collected as part of ongoing quality improvement initiatives at a remote IOP for youth and young adults. Clients (N=2924) discharged between July 2021 and February 2023. A latent profile analysis was conducted using five indicators of clinical acuity at treatment entry, and the resulting profiles were assessed for associations with demographic predictors and treatment engagement outcomes. RESULTS Four profiles of clinical acuity emerged: a low acuity profile, characterized by minimal anxiety, depression, and self-harm, and three high acuity profiles defined by moderately severe depression and anxiety but differentiated by rates of self-harm. Age, gender, transgender identity, and sexual orientation were significantly related to profile membership. Clients identifying as sexual and gender marginalized populations were more likely to be classified into high acuity profiles relative to the low acuity profile, while race was unrelated to profile membership. Profile membership was significantly associated with treatment engagement: youth and young adults in the low acuity and high acuity + low self-harm profiles attended an average of 4-5 fewer treatment sessions relative to youth in the high acuity + moderate self-harm and high acuity + high self-harm profiles, ꭓ2(3) = 27.65, P < .001. Individuals in the high acuity + low self-harm profile completed treatment at a significantly lower rate relative to the other two high acuity profiles, ꭓ2(3) = 13.41, P = .004. Finally, those in the high acuity + high self-harm profile were significantly less likely to disengage early relative to youth in all other profiles, ꭓ2(3) = 71.12, P < .001. CONCLUSIONS This investigation represents a novel application of distilling salient variables around which to proactively assign clients to clinical programming. Identifying subgroups that differentially engage in treatment is a critical first step towards personalizing treatment within complex populations. CLINICALTRIAL NA

BACKGROUND Pediatric mental health emergency department (ED) visits are increasing at 6-10% per year, at substantial cost, while 13% of youth with psychiatric hospitalizations are re-admitted in the following weeks. Hospitals do not have the resources to meet escalating youth mental health needs. Intensive Outpatient (IOP) programs, which provide multiple hours of care each week, have the power to reduce the number of patients in need of hospitalized care and provide a step-down option for patients discharging from ED’s in order to prevent readmissions. OBJECTIVE The purpose of this program evaluation was to assess 1) whether youth and young adult ED admission rates decreased following participation in a remote, intensive outpatient program and 2) whether there were differences in readmission rates between youth and young adults by gender or sexual identity, race, or ethnicity. METHODS Data were collected from intake and 3-month post-discharge surveys for 735 clients who attended at least six sessions of a remote IOP for youth and young adults. Patients reported if they had been admitted to an emergency room within the previous 30 days and the admission reason. Over half of clients were adolescents (58%) and the rest were young adults (42%) (M = 18.25, SD = 4.94). The sample was diverse in gender (49% female, 29% male, 10% non-binary) and sexual identity (39% heterosexual, 22% bisexual, 10% pansexual, 27% other sexual identity), and represented several races (79% white, 10% Black, 2% Indigenous, 2% Asian, 7% other) and ethnic identities (25% Hispanic, 6% other ethnic identity). RESULTS Mental health-related ED admissions significantly decreased from intake to 3-months post-discharge such that 94.2% of clients with a recent history of mental health-related ED admissions at IOP intake reported no mental health-related ED admissions in the 3 months post-discharge from treatment, χ2(1)=38.88, P CONCLUSIONS This study documents low mental health-related ED readmission rates when youth and young adults engage with intensive outpatient care following emergency room visits, suggesting remote intensive outpatient services provide care that meet youth and young adult mental health acute needs after ED discharge. The similar outcomes across demographic groups indicate that the current tracks of programming are equally meeting needs. Future research could conduct a full return on investment analysis for intensive mental health services for youth and young adults. CLINICALTRIAL NA

Objective To explore posttraumatic growth (PTG) in pediatric patients who have undergone solid organ transplant (SOT) and their caregivers, and to examine potential correlates of PTG. Method Youth and young adults with a history of SOT (heart, kidney, liver) at least 1 month prior to participation and caregivers completed measures of PTG, demographic, and medical factors. In total, 59 youth (M = 12.68 years, SD = 1.91), 21 young adults (M = 19.37, SD = 0.82), and 95 caregivers (M = 37.95 years, SD = 9.37) participated. Results Overall, 67% of youth, 76% of young adults, and 89% of caregivers reported PTG within the medium to very high range. Appreciation of Life was the highest PTG subscale across all groups. Youth and caregiver PTG scores were significantly positively correlated. Religious affiliation and religious coping were positively associated with PTG for caregivers, and the relationship yielded large effect sizes for young adults. Caregivers of children with kidney transplants endorsed lower PTG than other organ types and caregivers of children who had an acute medical condition endorsed greater PTG than caregivers of children who had chronic illness. Conclusion Findings suggest the pediatric SOT experience can yield positive changes such as a greater appreciation of life. Although small sample sizes may have led to reduced power for detecting significant findings for some analyses, results suggest religious, medical, and parent–child relationship factors are likely related to PTG in pediatric SOT and warrant future investigation.

Alan Kunz-Lomelin,1 Michael Killian,2 Brittany H Eghaneyan,3,&ast; Katherine Sanchez1,&ast; 1School of Social Work, University of Texas at Arlington, Arlington, TX, USA; 2College of Social Work, Florida State University, Tallahassee, FL, USA; 3Department of Social Work, California State University, Fullerton, CA, USA&ast;These authors contributed equally to this workCorrespondence: Alan Kunz-Lomelin, 3825 Hunters Trail, Carrollton, TX, 75007, USA, Tel +1 (972) 358-0575, Email alan.kunzlomelin@mavs.uta.eduPurpose: We report on antidepressant (AD) adherence among Hispanics seeking mental health services in a community primary care clinic in Texas as an ancillary outcome from a National Institutes of Health-funded study that collected data on Hispanic AD adherence over a period of two years (February 2016–February 2018). Adherence to AD medications was measured throughout the year-long trial and compared across various demographic characteristics. Since Hispanic individuals often experience stigma and cultural barriers related to AD treatment, we sought to understand what factors may increase the likelihood of non-adherence in this population.Patients and Methods: This study focused on 69 patients who were prescribed AD medications while receiving treatment through an integrated health care model. Adherence was measured with the Patient Adherence Questionnaire, a validated 2-item questionnaire that asks patients about their medication use (missed medications or dosage changes) over the past week. We looked at patient adherence at two key time points (4-weeks and 13-weeks) and utilized logistic regression to identify factors that may increase or decrease the likelihood of adherence in Hispanic patients at a community primary care clinic.Results: Non-adherence to AD medication was 49.3% at 4-weeks and 57% at 13-weeks post-treatment initiation. Logistic regression analyses revealed that age was the only significant predictor of AD non-adherence. As age increased, the likelihood of adherence increased by 12.2% at 13-weeks post-treatment initiation and by 11.1% at 4-weeks post-treatment initiation.Conclusion: The likelihood of Hispanic patients to adhere to AD therapy increased with the age of the patient. Since primary care is the most likely place to be prescribed an AD for Hispanic patients, further research to better understand adherence is essential. Integrated health care interventions designed to help identify, reduce, or eliminate barriers to adherence and improve cultural understanding may help address issues of non-adherence in primary care settings.Keywords: medication, primary care, mental health, antidepressant adherence, social work

BACKGROUND Early treatment dropout among youths and young adults (28%-75%) puts them at risk for poorer outcomes. Family engagement in treatment is linked to lower dropout and better attendance in outpatient, in-person treatment. However, this has not been studied in intensive or telehealth settings. OBJECTIVE We aimed to examine whether family members’ participation in telehealth intensive outpatient (IOP) therapy for mental health disorders in youths and young adults is associated with patient’s treatment engagement. A secondary aim was to assess demographic factors associated with family engagement in treatment. METHODS Data were collected from intake surveys, discharge outcome surveys, and administrative data for patients who attended a remote IOP for youths and young adults, nationwide. Data included 1487 patients who completed both intake and discharge surveys and either completed or disengaged from treatment between December 2020 and September 2022. Descriptive statistics were used to characterize the sample’s baseline differences in demographics, engagement, and participation in family therapy. Mann-Whitney U and chi-square tests were used to explore differences in engagement and treatment completion between patients with and those without family therapy. Binomial regression was used to explore significant demographic predictors of family therapy participation and treatment completion. RESULTS Patients with family therapy had significantly better engagement and treatment completion outcomes than clients with no family therapy. Youths and young adults with ≥1 family therapy session were significantly more likely to stay in treatment an average of 2 weeks longer (median 11 weeks vs 9 weeks) and to attend a higher percentage of IOP sessions (median 84.38% vs 75.00%). Patients with family therapy were more likely to complete treatment than clients with no family therapy (608/731, 83.2% vs 445/752, 59.2%; P CONCLUSIONS Youths and young adults whose families participate in any family therapy have lower dropout, greater length of stay, and higher treatment completion than those whose families do not participate in services in a remote IOP program. The findings of this quality improvement analysis are the first to establish a relationship between participation in family therapy and an increased engagement and retention in remote treatment for youths and young patients in IOP programing. Given the established importance of obtaining an adequate dosage of treatment, bolstering family therapy offerings is another tool that could contribute to the provision of care that better meets the needs of youths, young adults, and their families. CLINICALTRIAL

Objective: Biomarkers predicting risk of type 1 diabetes (Stage 3) among children with islet autoantibodies are greatly needed to prevent DKA and facilitate prevention therapies. Research Design and Methods: Children in the prospective TEDDY study (n=707) with confirmed diabetes-associated autoantibodies (GADA, IA-2A and/or IAA) and ≥2 HbA1c measurements were followed to diabetes or median age 11.1 years. Once confirmed autoantibody positive, HbA1c was measured quarterly. Cox models and receiver operative characteristic (ROC) analyses revealed the prognostic utility for risk of Stage 3 on a relative HbA1c increase from the baseline visit or an OGTT 2-hr plasma glucose (2-hPG). This HbA1c approach was then validated in the TrialNet Pathway to Prevention study (n=1190). Results: A 10% relative HbA1c increase from baseline best marked increased risk of Stage 3 in TEDDY (74% sensitive; 88% specific). Significant predictors of risk for HbA1c change were age and HbA1c at baseline test, genetic sex, maximum number of autoantibodies and maximum rate of HbA1c increase by time of change. The multivariable model featuring a HbA1c >10% increase and these additional factors revealed increased risk of Stage 3 in TEDDY (HR=12.74, 95%CI 8.7-18.6, p>10% increase performed similarly to an OGTT 2-hPG composite model (TEDDY AUC=0.88 and 0.85, respectively) and to the HbA1c model in TrialNet (AUC=0.82). Conclusion: An increase of >10% in HbA1c from baseline is as informative as OGTT 2-hPG in predicting risk of Stage 3 in youth with genetic risk and diabetes-associated autoantibodies.

Aims/hypothesis Diabetes diagnosed at Methods We studied 166 infants diagnosed with type 1 diabetes at n = 164) or children with type 1 diabetes diagnosed at 6–24 months of age (n = 152). We assessed the type 1 diabetes genetic risk score (T1D-GRS), islet autoantibodies, C-peptide and clinical features. Results We found an excess of infants with high T1D-GRS: 38% (63/166) had a T1D-GRS >95th centile of healthy individuals, whereas 5% (8/166) would be expected if all were monogenic (p p = 0.2), and had markedly reduced C-peptide levels (median z score −0.89), which were lowest in those diagnosed with type 1 diabetes at z score −1.98). Conclusions/interpretation We provide strong evidence that type 1 diabetes can present before the age of 6 months based on individuals with this extremely early-onset diabetes subtype having the classic features of childhood type 1 diabetes: high genetic risk, autoimmunity and rapid beta cell loss. The early-onset association with reduced birthweight raises the possibility that for some individuals there was reduced insulin secretion in utero. Comprehensive genetic testing for all neonatal diabetes genes remains essential for all individuals diagnosed with diabetes at

OBJECTIVE Biomarkers predicting risk of type 1 diabetes (stage 3) among children with islet autoantibodies are greatly needed to prevent diabetic ketoacidosis and facilitate prevention therapies. RESEARCH DESIGN AND METHODS Children in the prospective The Environmental Determinants of Diabetes in the Young (TEDDY) study (n = 707) with confirmed diabetes-associated autoantibodies (GAD antibody, IA-2A, and/or insulin autoantibody) and two or more HbA1c measurements were followed to diabetes or median age 11.1 years. Once confirmed autoantibody positive, HbA1c was measured quarterly. Cox models and receiver operative characteristic curve analyses revealed the prognostic utility for risk of stage 3 on a relative HbA1c increase from the baseline visit or an oral glucose tolerance test (OGTT) 2-h plasma glucose (2-hPG). This HbA1c approach was then validated in the Type 1 Diabetes TrialNet Pathway to Prevention Study (TrialNet) (n = 1,190). RESULTS A 10% relative HbA1c increase from baseline best marked the increased risk of stage 3 in TEDDY (74% sensitive; 88% specific). Significant predictors of risk for HbA1c change were age and HbA1c at the baseline test, genetic sex, maximum number of autoantibodies, and maximum rate of HbA1c increase by time of change. The multivariable model featuring a HbA1c ≥10% increase and these additional factors revealed increased risk of stage 3 in TEDDY (hazard ratio [HR] 12.74, 95% CI 8.7–18.6, P < 0.0001) and TrialNet (HR 5.09, 95% CI 3.3–7.9, P < 0.0001). Furthermore, the composite model using HbA1c ≥10% increase performed similarly to an OGTT 2-hPG composite model (TEDDY area under the curve [AUC] 0.88 and 0.85, respectively) and to the HbA1c model in TrialNet (AUC 0.82). CONCLUSIONS An increase of ≥10% in HbA1c from baseline is as informative as OGTT 2-hPG in predicting risk of stage 3 in youth with genetic risk and diabetes-associated autoantibodies.

We describe a statistical seminar designed to provide a common foundation in core statistical concepts among all students as they enter a social work PhD program. Student feedback surveys assessed students’ statistics preparation prior to entering the program, and pre- and posttests were compared for increases in statistical knowledge. Nearly half (42.1%) reported no prior statistics training, and exposure to IBM SPSS Statistics software was low (M=1.54 out of 5, SD=1.38). Students showed significant gains in posttest knowledge. Findings suggest substantial variability in students’ statistical preparedness, and for many, knowledge of basic concepts is rudimentary. Such a seminar may allow programs to begin with more advanced quantitative course work and move to increasingly more complex topics over time (e.g., multilevel modeling).

Ireland has a mixed model of healthcare delivery with a public healthcare system funded by general taxation and a large private healthcare insurance system, covering 43% of the population in 2012 and 2016. We set out to examine disparities in outcomes among patients with breast cancer treated in a private hospital compared to national outcomes over a comparable period.Medical records of patients diagnosed with early (Stage 1-3 as per AJCC version 5) breast cancer between 2010 and 2015 at Bon Secours Hospital, Cork, Ireland were reviewed. Staging was confirmed and 5-year disease specific survival (DSS) and overall survival (OS) were calculated. DSS was compared to 5-year net survival (NS) figures from the National Cancer Registry of Ireland (NCRI) for a comparable period (2010-2014).DSS (Bon Secours) and NS (NCRI) are summarized in Table 5 and Fig. 2. 5-year survival figures are numerically higher in the private hospital compared with national data for individual stage. Taking stages 1 to 3 combined, the 95% confidence intervals do not cross, indicating statistical significance.We found evidence of superior outcomes in patients with early breast cancer treated at a private hospital compared with national outcome figures. This was demonstrated in 'all comers' (stages 1-3 combined), and particularly in patients with stage 3 breast cancer. Potential reasons for this disparity include differences in socioeconomic status, health-seeking behaviours and/or underlying health status between the two populations included. Differences in extent or timeliness of access to therapies may also contribute.

Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire is a brief 15-item self-report measure of quality of life and life satisfaction originally developed for clinical populations (6 to 17 years old). The current paper examines the initial factor structure proposed by the developers and underlying psychometric properties of the measure in a non-clinical population of teens. A cross-sectional adolescent sample (N = 3222) completed self-report measures as part of mental health promotion program. A confirmatory factor analysis was conducted with construct validity analyses. The original factor structure was replicated with strong internal consistency (Cronbach α = .912). Strong construct validity (e.g. resilience, well-being, depression, and anxiety) was found. Minimal differences were found based on gender, race, and ethnicity. PQ-LES-Q has strong, replicable psychometric properties, which makes it a generally reliable and valid assessment tool to evaluate the quality of life and life satisfaction in adolescents.

IA sensitively predict future T1D, but onset often occurs many years after seroconversion. Early diagnosis results in less DKA and milder initial disease, especially in young children. Using the international TEDDY cohort, we asked if quarterly HbA1c testing could predict T1D among pre-pubertal subjects with ≥1 persistent IA (GADA, IA2A, IAA). Mean(SD) age at seroconversion and T1D onset was 43(29) and 73(22) months respectively. Of 8,504 HLA high risk children, 456 had persistent confirmed IA, had undergone at least 3 quarterly HbA1c tests in the prior 12 months, and were not on diabetes drugs or diets. Of these, 104 progressed to T1D and 352 did not. Subjects were split into training (292 total, 62 progressors) and test (164 total, 40 progressors) datasets with similar characteristics. The optimal maximum HbA1c cutpoint within 1 year pre-onset to predict T1D, by ROC analysis, was similar in training and test datasets (p=0.66). For both, HbA1c ≥5.6% gave the best Youden index. Other factors significant for T1D risk in the training dataset included age at HbA1c test, month of HbA1c test, continent and IA2A titer, but not gender, family history, HLA type, seroconversion age, IAA titer nor T1D-related SNP genotypes. Adjusted for significant factors, the optimal HbA1c cutpoint of ≥5.6% for quarterly testing was 91% sensitive, 91% specific, 73% PPV and 98% NPV to predict T1D within 1 year in children with HLA and IA risk. The final predictive model fit both training and test data similarly (p=0.28). Median(SD) time from first HbA1c ≥5.6% to diagnosis was 8.6(4.5) months, enabling monitoring and education for earlier treatment. Quarterly HbA1c surveillance is cost-effective and clinically accessible. A hierarchical plan for pediatric T1D prediction is proposed comprising initial genetic screening, then IA surveillance of those at genetic risk, then HbA1c surveillance of those with IA, and finally close glycemic surveillance of those with HbA1c ≥5.6% to ascertain metabolic onset. Disclosure M. Killian: None. K. Vehik: None. R.R. Little: None. H. Elding Larsson: None. M.J. Haller: None. M. Rewers: None. J. She: None. J. Toppari: None. B. Akolkar: None. J. Krischer: None. W. Hagopian: None.

M. Knip on TEDDY Study Grp -työryhmän jäsen. Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.

Saliva offers a relatively noninvasive method for measuring analytes such as cortisol, holding particular promise for use in pediatric populations on a large scale if a rigorous collection protocol is feasible in diverse settings. The Environmental Determinants of Diabetes in the Young study protocol, conducted in centers in the United States, Sweden, Finland, and Germany, used salivary collection to assess cortisol level as a physiologic marker of stress. Saliva was collected using Sorbettes from subjects at 3.5, 4.5, and 5.5 years of age. Parents collected a morning sample, and staff collected pre- and post-blood draw samples. Feasibility was assessed based on protocol completion, adherence with instructions, factors affecting adherence, and sufficiency of saliva sample for cortisol determination. Collection of saliva samples in a diverse pediatric population is feasible. Establishing non-invasive and acceptable methods for collecting physiological parameters of stress will allow better exploration of determinants of health in this important population.

BACKGROUND & AIMS: It is not clear how intake of gluten during infancy affects subsequent risk of celiac disease. We investigated whether gluten intake before 2 years of age increases risk for celiac disease in genetically susceptible children. METHODS: We performed a case-control study of 436 pairs of children, generated from a database of 2525 children with genetic susceptibility to celiac disease in Sweden, matched for sex, birth year, and HLA genotype from September 2004 and February 2010. Children were screened annually for celiac disease using an assay for tissue transglutaminase autoantibodies (tTGA). Intestinal biopsies were collected from children who tested positive for tTGA to confirm the presence of celiac disease. Gluten intake was calculated from 3-day food records collected when the children were 9, 12, 18 and 24 months old. RESULTS: Breastfeeding duration (median 32 weeks) and age at first introduction to gluten (median 22 weeks) did not differ between cases and tTGA-negative children (controls). At the visit prior to tTGA seroconversion, cases reported a larger intake of gluten (median 4.9 g/day) than controls (median 3.9 g/day) (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13-1.46; P=.0002). More cases consumed amounts of gluten in the upper 3rd tertile (i.e. >5.0 g/day) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70-4.13; P

The objective of this project is to improve the efficiency of truck drivelines through reduction of friction and parasitic losses in transmission and drive axles. Known efficiencies for these products exceeded 97 percent, so the task was not trivial. The project relied on a working relationship between modeling and hardware testing. Modeling was to shorten the development cycle by guiding the selection of materials, processes and strategies. Bench top and fixture tests were to validate the models. Modeling was performed at a world class, high academic level, but in the end, modeling did not impact the hardware development as much as intended. Insights leading to the most significant accomplishments came from bench top and fixture tests and full scale dynamometer tests. A key development in the project was the formulation of the implementation strategy. Five technical elements with potential to minimize friction and parasitic losses were identified. These elements included churning, lubrication, surface roughness, coatings and textures. An interesting fact is that both Caterpillar and Eaton independently converged on the same set of technical elements in formulating their implementation strategies. Exploiting technical elements of the implementation strategy had a positive impact on transmission and drive axle efficiencies. During one dynamometermore » test of an Eaton Best Tech 1 transmission, all three gear ranges tested: Under drive, direct drive and over drive, showed efficiencies greater than 99 percent. Technology boosts to efficiency for transmissions reached 1 percent, while efficiency improvements to drive axle pushed 2 percent. These advancements seem small, but the accomplishment is large considering that these products normally run at greater than 97 percent efficiency. Barriers and risks to implementing these technology elements are clear. Schemes using a low fill sump and spray tubes endanger the gears and bearings by lubricant starvation. Gear coatings have exhibited durability issues, stripping away under conditions less demanding than 750,000 miles in service on the road. Failed coatings compound the problem by contaminating the lubricant with hard particles. Under the most severe conditions, super finished surfaces may polish further, reaching a surface roughness unable to support the critical oil film thickness. Low viscosity and low friction lubricants may not protect the gears and bearings adequately leading to excessive pitting, wear and noise. Additives in low friction oils may not stay in solution or suspended thus settling to the bottom and unavailable when they are needed most. Technical barriers and risks can be overcome through engineering, but two barriers remain formidable: (1) cost of the technology and (2) convincing fleet owners that the technology provides a tangible benefit. Dry sumps lower lubricant operating temperatures so the removal of heat exchangers and hoses and reduced demand on engine cooling systems justify their use. The benefits of surface texturing are varied and remain unproven. Lubricant costs seem manageable, but the cost of super finishing and gear coating are high. These are issues of scale and processing technology. Going across the board with gear super finishing and coating will reduce costs. Pushing the envelope to applications with higher torque and higher power density should drive the adoption of these technologies. Fleet owners are an educated and seasoned lot. Only technology measureable in dollars returned is used on truck fleets. To convince fleet owners of the benefit of these technologies, new precision in measuring fuel efficiency must be introduced. Legislation for a minimum standard in truck miles per gallon would also enable the use of these technologies. Improving the efficiency of truck transmissions and axle will make a noticeable impact on the fuel consumption by heavy vehicles in the United States. However, the greatest benefit will come when all the individual efficiency technologies like hybrid power, aerodynamic fairings, auxiliary power units, super single aluminum wheels, single wide tires and reduced cross section radiators are combined synergistically in a single vehicle, the high efficiency truck.« less

Due to their high level of integration, dynamic random access memories (DRAMs) place vigorous requirements on the tools needed for internal signal analysis. In this regard, electron-beam testing proves an invaluable analysis tool for design and process optimization. The e-beam tester described here enables testing of a 4 Mbit DRAM, as well as of the future generation which will utilize submicron interconnections. Major development effort has been carried out with respect to the electron optics to fulfill the required e-beam tester performance. Other important verification criteria include the associated test hardware and degree of CAD integration, as well as improved circuit layout for e-beam testability at chip level. Typical 4 Mbit DRAM verification procedures will be outlined: basic logic verification, graphical comparison of simulated and measured signals by CAD integration and precision waveform measurements being the main topics. Finally, future demands will be discussed.

We prepared infection-free HIV-1 envelope proteins (HIVenv) from genetically homogeneous R5-HIV-1 occurring in plasma (PHIV) of donors before anti-HIV response. Such an immunogen could elicit broadly neutralizing antibodies (bnAb) against viruses transmitted in humans. PHIV was co-cultured with PBMCs and virions from culture supernatants were isolated by ultracentrifugation, and purified to remove contaminating microvesicles with anti-CD45. Membrane cholesterol was extracted with beta-cyclodextrin (BCD) to permeabilize virions and expel p24, RT and virion RNA, removable by 100kD Centricon. The residual host/viral DNA/RNA were hydrolyzed with protease-free Benzonase (BZ) and filtered through 30kD Centricon to obtain mHIVenv. This was tested for infectivity by PBMC cocultures, by inoculating SCID-hu Thy/Liv mice, and by EM for virions. Immunometric analyses of mHIVenv bound to DC-SIGN lipoparticles was done with anti-gp41 (1240) and anti-gp120 (b12) MoAb. A prototype HIV-1280 isolate after inactivation by BCD-BZ yielded mHIVenv with residual 0.28% p24 and retention of 91.9% gp120, and HIV RNA reduced by 7.4 logs. The mHIVenv proved noninfectious in vitro and in vivo and showed no virion particles by EM. The mHIVenv bound to DC-SIGN lipoparticles through gp120 revealed noncovalently bound gp41, with relative luminescence paralleling that of gp120. Infection-free mHIVenv protein subunits concentrated on DC-SIGN lipoparticles fulfil the need for an HIV vaccine candidate.

A 33-ns 64-Mb DRAM with a master-wordline architecture that allows for wordline boosting has been successfully designed and fabricated. The master-wordline scheme incorporates a high-threshold PFET which enables the boost voltage to be controlled by standard CMOS levels. The high-threshold PFET also generates a stable low-power reference voltage for the boost system.