Evidence Suggests a Decrease in the Incidence of Kernicterus in California.

We identified children diagnosed with kernicterus in the California Department of Developmental Services and estimated an incidence of 0.42 per 100 000 births from 1988 to 2014, significantly decreasing to 0.04 per 100 000 births after 2009. We also examined national infant kernicterus mortality from 1979 to 2016 using CDC data. It did not decrease significantly.

Manipulative-based Activity Using Pop Beads for Demonstration of Sanger Sequencing.

Sanger sequencing, also known as dideoxy sequencing, is a widely used method for DNA sequencing, particularly for cloned plasmids and clinical samples. This technique requires a combination of essential biochemistry skills, such as a chain-termination reaction, gel electrophoresis, and fluorescence detection. Unfortunately, there is a lack of activities that replicate the Sanger sequencing process for students to learn and practice these skills. To address this issue, a manipulative-based Sanger sequencing activity was developed that incorporates colorful pop beads to demonstrate a chain-termination reaction, separation of products, and fluorescence detection. The beads represent deoxynucleotides and dideoxynucleotides, allowing for a visual representation of DNA fragment generation. This kinesthetic learning activity offers a high visual impact for students, aiding in their understanding of the Sanger sequencing process, and can also be used to illustrate polymerase chain reaction (PCR)-based techniques.

Rapid Detection of Staphylococcus aureus Using Paper-Derived Electrochemical Biosensors.

Several groups have recently explored the idea of developing electrochemical paper-based wearable devices, specifically targeting metabolites in sweat. While these sensors have the potential to provide a breadth of analytical information, there are several key challenges to address before these sensors can be widely adopted for clinical interventions. Toward this goal, we describe the development of a paper-based electrochemical sensor for the detection of Staphylococcus aureus. Enabling the application, this report describes the use of paper-derived carbon electrodes, which were modified with a thin layer of sputtered gold (that minimizes lateral resistivity and significantly improves the electron transfer process) and with chitosan (used as a binder, to offer flexibility). The resulting material was laser-patterned and applied for the development of an electrochemical biosensor controlled (via a wireless connection) by a custom-built, portable potentiostat. As no interference was observed when exposed to other bacteria or common metabolites, this wearable system (paper-derived electrodes + potentiostat) has the potential to detect the presence of S. aureus in the skin, a commonly misdiagnosed and mistreated infection.

Life Expectancy of 1-Year Survivors of Traumatic Brain Injury, 1988-2019: Updated Results From the TBI Model Systems.

OBJECTIVE: To update the life expectancy estimates according to age, sex, mobility, and feeding skills reported in the 2015 study of Brooks et al. To examine trends in survival over the past decade. DESIGN: Observational cohort study. SETTING: Poisson regression and life table analysis applied to long-term follow-up data on United States (US) Traumatic Brain Injury (TBI) Model Systems patients recorded in the national database. Functional mobility and feeding skills were assessed with FIM. PARTICIPANTS: A total of 14,803 persons with TBI during the years 1988-2019 who underwent inpatient rehabilitation and provided at least 1 long-term assessment of functional skills 1 year or more postinjury (N=14,803). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Survival, mortality rates, and life expectancy. RESULTS: Life expectancy was lower than that of the age- and sex-matched general population. Older age and severity of functional impairments were risk factors for mortality (both P<.0001 in regression models). Among ambulatory individuals, mortality was 51% (95% confidence interval, 35%-69%) higher in men than women. Life expectancy of 20-year-old women who walked well (FIM ambulation score 7) was 55 (SE=0.8) additional years to age 75, representing a reduction of 6.9 years from the normal general population figure. For 20-year-old men who walked well, the life expectancy was 49 (SE=0.5) additional years, representing a reduction of 8.1 years from normal. Life expectancies for men and women who did not walk and were fed by others were much lower. There was no significant change in mortality rates during the study period (hazard ratio, 1.008; P=.07). CONCLUSIONS: There has been no significant change in the long-term survival of persons with TBI in the US since the late 1980s. The life expectancies reported here are similar to those reported in the 2015 study of Brooks et al, although they are more precise because of the larger sample size and longer follow-up.

Life Expectancy after Stroke Based On Age, Sex, and Rankin Grade of Disability: A Synthesis.

BACKGROUND: Stroke is a leading cause of death and disability in the developed world. The major factor affecting long term survival (other than age) is known to be the severity of disability. Yet to our knowledge there are no studies reporting life expectancies stratified by both age and severity. Remaining life expectancy is a key measure of health. METHODS: We identified 11 long-term follow-up studies of stroke patients that reported the multivariate effects of age, sex, the modified Rankin Scale (mRS) grade of disability, and other factors. From these we computed the composite effects of these factors on survival, then used these to calculate age-, sex-, and mRS-specific mortality rates. Finally we used the rates to construct life tables, and hence obtain life expectancies. RESULTS: Life expectancy varies by age, sex, and mRS. The life expectancies of males age 70, for example, were 13, 13, 11, 8, 6, and 5 years for Rankin Grades 0-5, respectively, representing reductions of 1, 1, 3, 6, 8, and 9 years from the corresponding general population figure. CONCLUSIONS: These figures demonstrate the importance of rehabilitation following stroke, and can be used in discussion of public policy and benchmarking of future results.

An update on survival after anoxic brain injury in adolescents and young adults.

While much is known about long-term survival after traumatic brain injury, less is known about survival after anoxic/hypoxic brain injury. We previously compared the two and found no significant difference (hazard ratio [HR] 0.97, p=0.92) after controlling for age, sex, and severity of disability. The present study updates this, based on 1,802 patients with TBI and 380 with anoxic, aged 15 to 25, evaluated in 1986 or later, and who survived one year post injury. The anoxic group had higher mortality (HR = 1.13), though again the difference was not statistically significant (p=0.58).

Validation of US cerebral palsy growth charts using a UK cohort.

AIM: Growth charts for cerebral palsy (CP) have been constructed using data for 24 920 Californian patients, covering ages 2 to 20 years, with separate charts for the five severity levels of the Gross Motor Function Classification System (GMFCS). Our aim was to test how the data for British children with CP fit these charts, compared with conventional local charts. METHOD: US CP growth reference was reanalysed using the lambda-mu-sigma (LMS) method to allow calculation of standard deviation z-scores. Growth data for 195 children with CP in Glasgow, UK, were retrieved and converted to z-scores using the CP reference as well as the combined World Health Organization and UK 1990 growth reference (UK-WHO). RESULTS: Compared to the UK-WHO reference, measurements diverged progressively with increasing severity, with mean height for GMFCS level V being close to the second UK-WHO centile. Compared with the CP reference, mean height and weight z-scores were between the 50th and 75th centiles for all severity levels, while body mass index was just below the 50th centile. INTERPRETATION: British children with severe CP seem relatively very small when their growth data are plotted on non-CP charts, but their data for weight and body mass index fit well to US CP charts and reasonably well for height. The LMS look-up tables will make it possible to calculate z-scores and produce charts in local formats.

Optimization of conditions for cadmium selenide quantum dot biosynthesis in Saccharomyces cerevisiae.

The biosynthesis of quantum dots has been explored as an alternative to traditional physicochemical methods; however, relatively few studies have determined optimal synthesis parameters. Saccharomyces cerevisiae sequentially treated with sodium selenite and cadmium chloride synthesized CdSe quantum dots in the cytoplasm. These nanoparticles displayed a prominent yellow fluorescence, with an emission maximum of approximately 540 nm. The requirement for glutathione in the biosynthetic mechanism was explored by depleting its intracellular content through cellular treatments with 1-chloro-2,4-dinitrobenzene and buthionine sulfoximine. Synthesis was significantly inhibited by both of these reagents when they were applied after selenite treatment prior to the addition of cadmium, thereby indicating that glutathione contributes to the biosynthetic process. Determining the optimum conditions for biosynthesis revealed that quantum dots were produced most efficiently at entry into stationary phase followed by direct addition of 1 mM selenite for only 6 h and then immediately incubating these cells in fresh growth medium containing 3 mM Cd (II). Synthesis of quantum dots reached a maximum at 84 h of reaction time. Biosynthesis of 800-µg g-1 fresh weight cells was achieved. For the first time, significant efforts have been undertaken to optimize each aspect of the CdSe biosynthetic procedure in S. cerevisiae, resulting in a 70% increased production.

Long-term survival after traumatic brain injury part I: external validity of prognostic models.

OBJECTIVES: To develop prognostic models for long-term survival in adults with traumatic brain injury (TBI) and to assess their external validity in 2 independent populations. DESIGN: Survival analysis. SETTING: Post-discharge from rehabilitation units and long-term follow-up at regional centers. PARTICIPANTS: Two cohorts of long-term survivors of TBI (N=12,481): the Traumatic Brain Injury Model Systems (TBIMS) cohort comprised 7365 persons who were admitted to a TBIMS facility and were assessed at ≥1 years postinjury, and the California Department of Developmental Services (CDDS) cohort comprised 5116 persons who sustained a TBI and received long-term services from the CDDS. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Survival/mortality. RESULTS: Older age, male sex, and severity of disability in walking and feeding were significant predictors of increased long-term mortality rates (all P<.05, both databases). The CDDS model predicted 623 deaths for persons in the TBIMS cohort, with an observed-to-expected ratio of .94 (95% confidence interval [CI], 0.87-1.02). The TBIMS model predicted a total of 525 deaths for persons in the CDDS cohort, with an observed-to-expected ratio of 1.08 (95% CI, 0.99-1.17). Regression calibration statistics were satisfactory, and both models ranked survival times well from shortest to longest (TBIMS: C index, .78; 95% CI, .76-.80; CDDS: C index, .80; 95% CI, .78-.82). CONCLUSIONS: Long-term survival prognosis in TBI is related to age, sex, and severity of disability. When compared on the basis of these factors, the survival estimates derived from the TBIMS and CDDS cohorts are found to be similar. The close agreement between model predictions and actual mortality rates confirm the external validity of the prognostic models presented herein.

Long-Term Survival After Traumatic Brain Injury Part II: Life Expectancy.

OBJECTIVES: To compute the life expectancy of persons with traumatic brain injury (TBI) based on validated prognostic models from 2 cohorts, to compare mortality and life expectancy of persons with TBI with those of the U.S. general population, and to investigate trends toward improved survival over the last 2 decades. DESIGN: Survival analysis. SETTING: Postdischarge from rehabilitation units and long-term follow-up at regional centers. PARTICIPANTS: Two cohorts of long-term survivors of TBI (N=12,481): the Traumatic Brain Injury Model Systems (TBIMS) cohort comprised 7365 persons who were admitted to a TBIMS facility with moderate to severe TBI and were assessed at ≥1 years postinjury, and the California Department of Developmental Services (CDDS) cohort comprised 5116 persons who sustained a TBI and received long-term services from the CDDS. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Life expectancy. RESULTS: The estimates of age-, sex-, and disability-specific life expectancy of persons with TBI derived from the CDDS and TBIMS were similar. The estimates of age- and sex-specific life expectancy were lower than those of the U.S. general population. Mortality rates of persons with TBI were higher than those of the U.S. general population. Mortality rates did not improve and the standardized mortality ratio increased over the study period from 1988 to 2010. CONCLUSIONS: Life expectancy of persons with TBI is lower than that of the general population and depends on age, sex, and severity of disability. When compared, the survival outcomes in the TBIMS and CDDS cohorts are remarkably similar. Because there have been no marked trends in the last 20 years, the life expectancies presented in this article may remain valid in the future.

Improvements in long-term survival after spinal cord injury?

OBJECTIVE: To investigate whether there have been improvements in long-term survival after spinal cord injury in recent decades. DESIGN: Survival analysis using time-varying covariates. The outcome variable was survival or mortality, and the explanatory variables were age, sex, level and grade of injury, and calendar year. The data were analyzed using the logistic regression model, Poisson regression model with comparison to the general population, and the computation of standardized mortality ratios for various groups. SETTING: National Spinal Cord Injury Model Systems facilities. PARTICIPANTS: Persons (N=31,531) who survived 2 years postinjury, were older than 10 years, and who did not require ventilator support. These persons contributed 484,979 person-years of data, with 8536 deaths over the 1973 to 2012 study period. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Survival; survival relative to the general population; life expectancy. RESULTS: After adjustment for age, sex, race, etiology of injury, time since injury, and level and grade of injury, mortality in persons with spinal cord injury was higher in the 2005 to 2012 period than in 1990 to 2004 or 1980 to 1989, the odds ratios for these 3 periods were .857, .826, and .802 as compared with the 1970 to 1979 reference period. CONCLUSIONS: There was no evidence of improvement. Long-term survival has not changed over the past 30 years.

Angioedema deaths in the United States, 1979-2010.

BACKGROUND: Hospital admission data indicate that the angioedema incidence has increased during the past several decades. Little is known about mortality trends. OBJECTIVES: To count the number of deaths associated with angioedema in the United States, investigate correlations with age, sex, race, and other contributory causes, and analyze trends from 1979 to 2010. METHODS: All US death certificates in which angioedema was listed as an underlying or contributing cause of death during 1979 to 2010 were analyzed. Age-adjusted mortality rates were analyzed by age, sex, and race. Other conditions designated as the underlying cause of death were investigated. RESULTS: From 1979 to 2010, there were 5,758 deaths in which angioedema was listed as a contributing cause. The age-adjusted death rate for hereditary angioedema decreased from 0.28 (95% confidence interval [CI] 0.25-0.32) to 0.06 (95% CI 0.05-0.08) per million persons per year. Conversely, mortality for angioedema increased from 0.24 (95% CI 0.21-0.27) to 0.34 (95% CI 0.31-0.37) per million. Blacks constituted 55% of angioedema deaths that were associated with use of angiotensin-converting enzyme inhibitors. On death certificates that listed hereditary angioedema as the underlying cause of death, cancer (frequently lymphoma or leukemia) was the second most commonly listed cause. CONCLUSION: Angioedema-associated deaths were very rare from 1979 to 2010. Hereditary angioedema deaths became even more so, whereas nonhereditary angioedema deaths increased. Risks associated with angiotensin-converting enzyme inhibitors were higher in blacks. Lack of specific coding for acquired angioedema most likely explains the observed association between cancer and hereditary angioedema. In the future, more granular coding systems may help distinguish hereditary from acquired angioedema.

Recent trends in cerebral palsy survival. Part I: period and cohort effects.

AIM: To determine whether the trend of improved survival among individuals with cerebral palsy (CP) in California during the 1980s and 1990s has continued during the most recent decade. METHOD: In an observational cohort study we evaluated individuals with CP, aged 4 years and older, who were clients of the California Department of Developmental Services. Medical diagnoses, functional disabilities, and special health care requirements were assessed with Client Development Evaluation Reports made between 1983 and 2010. Trends in birth cohort survival were analyzed with Kaplan-Meier curves and Cox regression. Calendar year period effects were analyzed with Poisson regression. RESULTS: A total of 51,923 persons with CP (28,789 males [55%], 23,134 females [45%]; mean age 14y 11mo, SD 14y 1mo, range 4y 0mo to 96y 10mo) collectively contributed 662,268 years of follow-up. There were 7690 deaths for an overall mortality rate of 11.6 per 1000 persons per year. No significant birth cohort effects on survival were observed in 4-year-olds who had no severe disabilities. By contrast, children who did not lift their heads in prone position who were born in more recent years had significantly lower mortality rates (Cox hazard ratio 0.971, p<0.001) than those with comparable disabilities born earlier. With regard to calendar year period effects, we found that age-, sex-, and disability-specific mortality rates declined by 1.5% (95% CI 0.9-2.1) year-over-year from 1983 to 2010. The estimate increased to 2.5% (95% CI 1.9-3.1) per year when we additionally controlled for tube-feeding status. Mortality rates in tube fed adolescents and adults, ages 15 to 59 years, declined by 0.9% (95% CI, 0.4-1.4) per year. No improvement was observed for adolescents or adults who fed orally or for those over age 60. In fact, the ratio of age-specific mortality rates for these latter groups to those in the general population, increased by 1.7% (95% CI 1.3-2.0) per year during the study period. INTERPRETATION: The trend toward improved survival has continued throughout the most recent decade. Declines in CP childhood mortality are comparable to the improvements observed in the United States general population (i.e. the mortality ratio in childhood has remained roughly constant over the last three decades). In contrast, the mortality ratio for most adolescents and adults with CP, relative to the general population, has increased.

Recent trends in cerebral palsy survival. Part II: individual survival prognosis.

AIM: The aim of the study was to determine survival probabilities and life expectancies for individuals with cerebral palsy based on data collected over a 28-year period in California. METHOD: We identified all individuals with cerebral palsy, aged 4 years or older, who were clients of the California Department of Developmental Services between 1983 and 2010. Kaplan-Meier survival curves were constructed for 4-year-old children, and the estimated survival probabilities were adjusted to reflect trends in mortality by calendar year. For persons aged 15, 30, 45, and 60 years, separate Poisson regression models were used to estimate age-, sex-, and disability-specific mortality rates. These mortality rates were adjusted to reflect trends of improved survival, and life expectancies were obtained using life table methods. RESULTS: The sample comprised 16,440, 14,609, 11,735, 7023, and 2375 persons at ages 4, 15, 30, 45, and 60 years, respectively. In 1983, 50% of 4-year-old children who did not lift their heads in the prone position and were tube fed lived to age 10.9 years. By 2010, the median age at death had increased to 17.1 years. In ambulatory children the probability of survival to adulthood did not change by more than 1%. Life expectancies for adolescents and adults were lower for those with more severe limitations in motor function and feeding skills, and decreased with advancing age. Life expectancies for tube-fed adolescents and adults increased by 1 to 3 years, depending on age and pattern of disability, over the course of the study period. INTERPRETATION: Over the past three decades in California there have been significant improvements in the survival of children with very severe disabilities. There have also been improvements to the life expectancy of tube-fed adults, though to a lesser extent than in children.

Comparative mortality of persons with intellectual disability in California: an update (2000-2010).

This paper updates our 2003 study on the effect of intellectual disability (ID) on mortality in persons with no significant physical disability. As previously, we used the California Department of Developmental Services database to compute mortality rates by age, sex, and severity of ID. There were 64,207 subjects age 5 and older, who contributed 386,000 person-years of follow-up and 1514 deaths during the 2000 to 2010 study period. The excess death rates increased with age, ranging from 0.1 to 6.8 per 1000 in mild/moderate ID, and 3.4 to 6.7 in severe/profound.

Risk factors of PTSD and substance use disorders in clinical and counseling psychology doctoral students.

OBJECTIVE: This study investigated the prevalence of probable alcohol use disorder (AUD), drug use disorders (DUDs), and posttraumatic stress disorder (PTSD) among psychology doctoral students. Additionally, it explored the unique relationships between risk factors (lifetime trauma, recent stressful experiences, COVID-19-related stress, general stress, financial stress) and AUD, DUD, and PTSD while accounting for demographic factors. METHOD: The sample included 889 clinical and counseling psychology doctoral students, and the Alcohol Use Disorders Identification Test, Screen of Drug Use, and Primary Care PTSD Screen for Diagnostic and Statistical Manual of Mental Disorders (5th ed.) were used to measure current probable AUD, DUD, and PTSD, respectively. RESULTS: Approximately 43.8% had probable AUD, 23.2% had probable DUD, and 14.7% had probable PTSD. The univariate analysis results indicated a pattern of elevated risk among Black, Indigenous, and people of color, lesbian, gay, bisexual, queer, and other (LGBQ+) individuals, and women students. The results of the multivariate logistic regression analyses revealed that increased lifetime trauma and COVID-19-related stress were associated with higher adjusted odds of probable PTSD. Higher adjusted odds of probable AUD were observed among individuals experiencing elevated levels of COVID-19-related stress and among younger, women, and non-Hispanic White individuals. LGBQ+ individuals and those with no religious affiliation were found to have higher adjusted odds of probable DUD. CONCLUSIONS: These findings underscore the alarming prevalence of AUD, DUD, and PTSD in this population, raising concerns that warrant attention. Women; Black, Indigenous, and people of color; and LGBQ+ individuals face heightened risks of PTSD, AUD, and DUD, emphasizing the urgent need for mental health care for psychology doctoral students and marginalized groups. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Correction: The biotoxin BMAA promotes dysfunction via distinct mechanisms in neuroblastoma and glioblastoma cells.

[This corrects the article DOI: 10.1371/journal.pone.0278793.].

Association of busulfan exposure and outcomes after HCT for patients with an inborn error of immunity.

ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment strategy for patients with inborn errors of immunities (IEIs). The objective of this study was to assess the optimal busulfan exposure before allogeneic HCT for patients with an IEI who received an IV busulfan-based conditioning regimen. Patients from 17 international centers were included. The main outcome of interest was event-free survival (EFS). Patients were categorized into 4 IEI subgroups: combined immunodeficiency (CID), severe combined immunodeficiency (SCID), neutrophil disorders, and hemophagocytic lymphohistiocytosis (HLH)-related disorders. Busulfan exposure was calculated by individual centers (area under the curve [AUC]CENTER) and re-estimated using a nonlinear mixed-effects model (NONMEM; exposure defined as AUCNONMEM). Overall, 562 patients were included: 173 (30.8%) with CID, 154 (27.4%) with SCID, 101 (18.0%) with HLH-related disorders, and 134 (23.8%) with neutrophil disorders. The median busulfan AUCNONMEM was 69.0 mg × h/L and correlated poorly with the AUCCENTER (r2 = 0.54). In patients with SCID, HLH-related, and neutrophil disorders with a busulfan AUCNONMEM of 70 to 90 mg × h/L, 2-year EFS was superior to <70 mg × h/L, and >90 mg ×h/L. Full donor chimerism increased with higher busulfan AUCNONMEM, plateauing at 90 mg × h/L. For patients with CID, the optimal AUCNONMEM for donor chimerism was found to be >70 mg × h/L. Improved EFS and higher donor chimerism may be achieved by targeting a cumulative busulfan AUCNONMEM of 80 mg × h/L (range, 70-90). Our study stresses the importance of uniformly using a validated population pharmacokinetic model to estimate AUCNONMEM.