A new Pipistrelle bat from the oceanic Island of Príncipe (Western Central Africa).

We describe a population of pipistrelle-like bats from Príncipe Island (Gulf of Guinea, Western Central Africa) as a new species based on the molecular and morphological characteristics of six specimens collected more than 30 years ago. The description of this new species was not possible until the traditionally entangled systematics of the whole pipistrelle group was clarified in recent years with the inclusion of molecular techniques and adequate species sampling. In this new taxonomic framework, the new species was clearly included within the dark-winged group of the recently described genus Pseudoromicia. The pipistrelles from Príncipe Island present a moderately inflated skull in lateral view with inner upper incisors that are moderately bicuspids and a baculum distinctly long with expanded tips. Besides these morphological characters, the new bat species is distinguished by its dwarfism, being the smallest species recognized within the genus. The ecology and conservation status of this endemic island species are unknown and field studies are urgently needed to evaluate the situation and conservation threats to this new species in its natural habitat.

High Frequency of Neuroimaging Abnormalities Among Pediatric Patients With Sepsis Who Undergo Neuroimaging.

OBJECTIVES: This study was intended to describe and correlate the neuroimaging findings in pediatric patients after sepsis. DESIGN: Retrospective chart review. SETTING: Single tertiary care PICU. PATIENTS: Patients admitted to Cincinnati Children's Hospital Medical Center with a discharge diagnosis of sepsis or septic shock between 2004 and 2013 were crossmatched with patients who underwent neuroimaging during the same time period. INTERVENTIONS: All neuroimaging studies that occurred during or subsequent to a septic event were reviewed, and all new imaging findings were recorded and classified. As many patients experienced multiple septic events and/or had multiple neuroimaging studies after sepsis, our statistical analysis utilized the most recent or "final" imaging study available for each patient so that only brain imaging findings that persisted were included. MEASUREMENTS AND MAIN RESULTS: A total of 389 children with sepsis and 1,705 concurrent or subsequent neuroimaging studies were included in the study. Median age at first septic event was 3.4 years (interquartile range, 0.7-11.5). Median time from first sepsis event to final neuroimaging was 157 days (interquartile range, 10-1,054). The most common indications for final imaging were follow-up (21%), altered mental status (18%), and fever/concern for infection (15%). Sixty-three percentage (n = 243) of final imaging studies demonstrated abnormal findings, the most common of which were volume loss (39%) and MRI signal and/or CT attenuation abnormalities (21%). On multivariable logistic regression, highest Pediatric Risk of Mortality score and presence of oncologic diagnosis/organ transplantation were independently associated with any abnormal final neuroimaging study findings (odds ratio, 1.032; p = 0.048 and odds ratio, 1.632; p = 0.041), although early timing of neuroimaging demonstrated a negative association (odds ratio, 0.606; p = 0.039). The most common abnormal finding of volume loss was independently associated with highest Pediatric Risk of Mortality score (odds ratio, 1.037; p = 0.016) and oncologic diagnosis/organ transplantation (odds ratio, 2.207; p = 0.001) and was negatively associated with early timing of neuroimaging (odds ratio, 0.575; p = 0.037). CONCLUSIONS: The majority of pediatric patients with sepsis and concurrent or subsequent neuroimaging have abnormal neuroimaging findings. The implications of this high incidence for long-term neurologic outcomes and follow-up require further exploration.

Pediatric Sepsis Biomarker Risk Model-II: Redefining the Pediatric Sepsis Biomarker Risk Model With Septic Shock Phenotype.

OBJECTIVE: The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a pediatric sepsis risk model, uses biomarkers to estimate baseline mortality risk for pediatric septic shock. It is unknown how PERSEVERE performs within distinct septic shock phenotypes. We tested PERSEVERE in children with septic shock and thrombocytopenia-associated multiple organ failure (TAMOF), and in those without new onset thrombocytopenia but with multiple organ failure (MOF). DESIGN: PERSEVERE-based mortality risk was generated for each study subject (n = 660). A priori, we determined that if PERSEVERE did not perform well in both the TAMOF and the MOF cohorts, we would revise PERSEVERE to incorporate admission platelet counts. SETTING: Multiple PICUs in the United States. INTERVENTIONS: Standard care. MEASUREMENTS AND MAIN RESULTS: PERSEVERE performed well in the TAMOF cohort (areas under the receiver operating characteristic curves [AUC], 0.84 [95% CI, 0.77-0.90]), but less well in the MOF cohort (AUC, 0.71 [0.61-0.80]). PERSEVERE was revised using 424 subjects previously reported in the derivation phase. PERSEVERE-II had an AUC of 0.89 (0.85-0.93) and performed equally well across TAMOF and MOF cohorts. PERSEVERE-II performed well when tested in 236 newly enrolled subjects. Sample size calculations for a clinical trial testing the efficacy of plasma exchange for children with septic shock and TAMOF indicated PERSEVERE-II-based stratification could substantially reduce the number of patients necessary, when compared with no stratification. CONCLUSIONS: Testing PERSEVERE in the context of septic shock phenotypes prompted a revision incorporating platelet count. PERSEVERE-II performs well upon testing, independent of TAMOF or MOF status. PERSEVERE-II could potentially serve as a prognostic enrichment tool.

Sexual victimization history predicts academic performance in college women.

College women frequently report having experienced sexual victimization (SV) in their lifetime, including child sexual abuse and adolescent/adult sexual assault. Although the harmful mental health sequelae of SV have been extensively studied, recent research suggests that SV is also a risk factor for poorer college academic performance. The current studies examined whether exposure to SV uniquely predicted poorer college academic performance, even beyond contributions from three well-established predictors of academic performance: high school rank, composite standardized test scores (i.e., American College Testing [ACT]), and conscientiousness. Study 1 analyzed longitudinal data from a sample of female college students (N = 192) who were assessed at the beginning and end of one semester. SV predicted poorer cumulative end-of-semester grade point average (GPA) while controlling for well-established predictors of academic performance. Study 2 replicated these findings in a second longitudinal study of female college students (N = 390) and extended the analyses to include follow-up data on the freshmen and sophomore students (n = 206) 4 years later. SV predicted students' GPA in their final term at the university above the contributions of well-established academic predictors, and it was the only factor related to leaving college. These findings highlight the importance of expanding the scope of outcomes of SV to include academic performance, and they underscore the need to assess SV and other adverse experiences on college campuses to target students who may be at risk of poor performance or leaving college. (PsycINFO Database Record

Differential expression of the Nrf2-linked genes in pediatric septic shock.

INTRODUCTION: Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock. METHODS: We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated from whole blood within 24 h of pediatric intensive care unit admission for septic shock and a false discovery rate of 5 %. We compared differentially expressed genes from (1) patients with septic shock and healthy controls and (2) across validated gene expression-based subclasses of pediatric septic shock (endotypes A and B) using several bioinformatic methods. RESULTS: We found upregulation of 123 Nrf2-linked genes in children with septic shock. The top gene network represented by these genes contained primarily enzymes with oxidoreductase activity involved in cellular lipid metabolism that were highly connected to the peroxisome proliferator activated receptor and the retinoic acid receptor families. Endotype A, which had higher organ failure burden and mortality, exhibited a greater downregulation of Nrf2-linked genes than endotype B, with 92 genes differentially regulated between endotypes. CONCLUSIONS: Our findings indicate that Nrf2-linked genes may contribute to alterations in oxidative signaling and intermediary metabolism in pediatric septic shock.

A Multibiomarker-Based Model for Estimating the Risk of Septic Acute Kidney Injury.

OBJECTIVE: The development of acute kidney injury in patients with sepsis is associated with worse outcomes. Identifying those at risk for septic acute kidney injury could help to inform clinical decision making. We derived and tested a multibiomarker-based model to estimate the risk of septic acute kidney injury in children with septic shock. DESIGN: Candidate serum protein septic acute kidney injury biomarkers were identified from previous transcriptomic studies. Model derivation involved measuring these biomarkers in serum samples from 241 subjects with septic shock obtained during the first 24 hours of admission and then using a Classification and Regression Tree approach to estimate the probability of septic acute kidney injury 3 days after the onset of septic shock, defined as at least two-fold increase from baseline serum creatinine. The model was then tested in a separate cohort of 200 subjects. SETTING: Multiple PICUs in the United States. INTERVENTIONS: None other than standard care. MEASUREMENTS AND MAIN RESULTS: The decision tree included a first-level decision node based on day 1 septic acute kidney injury status and five subsequent biomarker-based decision nodes. The area under the curve for the tree was 0.95 (CI95, 0.91-0.99), with a sensitivity of 93% and a specificity of 88%. The tree was superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. In the test cohort, the tree had an area under the curve of 0.83 (0.72-0.95), with a sensitivity of 85% and a specificity of 77% and was also superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. CONCLUSIONS: We have derived and tested a model to estimate the risk of septic acute kidney injury on day 3 of septic shock using a novel panel of biomarkers. The model had very good performance in a test cohort and has test characteristics supporting clinical utility and further prospective evaluation.

Randomized controlled trial evaluating the effectiveness of a web-based stress management program among community college students.

BACKGROUND AND OBJECTIVES: This study evaluated the effectiveness of a web-based stress management program among community college students that focused on increasing perceived control over stressful events. DESIGN: Students (N = 257) were randomly assigned to a Present Control Intervention or a Stress-information only comparison group. METHODS: Primary outcomes were perceived stress and stress symptoms; secondary outcomes were depression and anxiety. Self-report measures were completed online at preintervention, postintervention, and three-week follow-up. Intervention effects were estimated using linear mixed models. Seventy-five percent of the sample (n = 194) completed the pretest and comprised the intent-to-treat sample. RESULTS: Participants in the intervention group reported significant increases in present control, and significant decreases in all four primary and secondary outcome measures from baseline to postintervention and follow-up. Within-group effect sizes were small to medium at postintervention (mean d = -.34) and follow-up (mean d = -.49). The mean between-group effect size on the four outcome measures was d = .35 at postintervention but d = .12 at follow-up, due to unexpected decreases in distress in the comparison group. CONCLUSIONS: Our online program is a cost-effective mental health program for college students. Limitations and future direction are discussed.

Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology.

The temporal version of the pediatric sepsis biomarker risk model (tPERSEVERE) estimates the risk of a complicated course in children with septic shock based on biomarker changes from days 1 to 3 of septic shock. We validated tPERSEVERE performance in a prospective cohort, with an a priori plan to redesign tPERSEVERE if it did not perform well. Biomarkers were measured in the validation cohort (n = 168) and study subjects were classified according to tPERSEVERE. To redesign tPERSEVERE, the validation cohort and the original derivation cohort (n = 299) were combined and randomly allocated to training (n = 374) and test (n = 93) sets. tPERSEVERE was redesigned using the training set and CART methodology. tPERSEVERE performed poorly in the validation cohort, with an area under the curve (AUC) of 0.67 (95% CI: 0.58-0.75). Failure analysis revealed potential confounders related to clinical characteristics. The redesigned tPERSEVERE model had an AUC of 0.83 (0.79-0.87) and a sensitivity of 93% (68-97) for estimating the risk of a complicated course. Similar performance was seen in the test set. The classification tree segregated patients into two broad endotypes of septic shock characterized by either excessive inflammation or immune suppression.

Developing a clinically feasible personalized medicine approach to pediatric septic shock.

RATIONALE: Using microarray data, we previously identified gene expression-based subclasses of septic shock with important phenotypic differences. The subclass-defining genes correspond to adaptive immunity and glucocorticoid receptor signaling. Identifying the subclasses in real time has theranostic implications, given the potential for immune-enhancing therapies and controversies surrounding adjunctive corticosteroids for septic shock. OBJECTIVES: To develop and validate a real-time subclassification method for septic shock. METHODS: Gene expression data for the 100 subclass-defining genes were generated using a multiplex messenger RNA quantification platform (NanoString nCounter) and visualized using gene expression mosaics. Study subjects (n = 168) were allocated to the subclasses using computer-assisted image analysis and microarray-based reference mosaics. A gene expression score was calculated to reduce the gene expression patterns to a single metric. The method was tested prospectively in a separate cohort (n = 132). MEASUREMENTS AND MAIN RESULTS: The NanoString-based data reproduced two septic shock subclasses. As previously, one subclass had decreased expression of the subclass-defining genes. The gene expression score identified this subclass with an area under the curve of 0.98 (95% confidence interval [CI95] = 0.96-0.99). Prospective testing of the subclassification method corroborated these findings. Allocation to this subclass was independently associated with mortality (odds ratio = 2.7; CI95 = 1.2-6.0; P = 0.016), and adjunctive corticosteroids prescribed at physician discretion were independently associated with mortality in this subclass (odds ratio = 4.1; CI95 = 1.4-12.0; P = 0.011). CONCLUSIONS: We developed and tested a gene expression-based classification method for pediatric septic shock that meets the time constraints of the critical care environment, and can potentially inform therapeutic decisions.

Corticosteroids and pediatric septic shock outcomes: a risk stratified analysis.

BACKGROUND: The potential benefits of corticosteroids for septic shock may depend on initial mortality risk. OBJECTIVE: We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk. METHODS: We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression was used to model the effects of corticosteroids on 28-day mortality and complicated course, defined as death within 28 days or persistence of two or more organ failures at 7 days. RESULTS: Subjects who received corticosteroids had greater organ failure burden, higher illness severity, higher mortality, and a greater requirement for vasoactive medications, compared to subjects who did not receive corticosteroids. PERSEVERE-based mortality risk did not differ between the two groups. For the entire cohort, corticosteroids were associated with increased risk of mortality (OR 2.3, 95% CI 1.3-4.0, p = 0.004) and a complicated course (OR 1.7, 95% CI 1.1-2.5, p = 0.012). Within each PERSEVERE-based stratum, corticosteroid administration was not associated with improved outcomes. Similarly, corticosteroid administration was not associated with improved outcomes among patients with no comorbidities, nor in groups of patients stratified by PRISM. CONCLUSIONS: Risk stratified analysis failed to demonstrate any benefit from corticosteroids in this pediatric septic shock cohort.

Differential expression of the nuclear-encoded mitochondrial transcriptome in pediatric septic shock.

INTRODUCTION: Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis. METHODS: We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded mitochondrial genes using a false discovery rate of 1%. A series of bioinformatic approaches were applied to compare differentially expressed genes across previously validated gene expression-based subclasses (groups A, B, and C) of pediatric septic shock. RESULTS: In total, 118 genes were differentially regulated in subjects with septic shock compared to healthy controls, including 48 genes that were upregulated and 70 that were downregulated. The top scoring canonical pathway was oxidative phosphorylation, with general downregulation of the 51 genes corresponding to the electron transport system (ETS). The top two gene networks were composed primarily of mitochondrial ribosomal proteins highly connected to ETS complex I, and genes encoding for ETS complexes I, II, and IV that were highly connected to the peroxisome proliferator activated receptor (PPAR) family. There were 162 mitochondrial genes differentially regulated between groups A, B, and C. Group A, which had the highest maximum number of organ failures and mortality, exhibited a greater downregulation of mitochondrial genes compared to groups B and C. CONCLUSIONS: Based on a focused analysis of a pediatric septic shock transcriptomic database, nuclear-encoded mitochondrial genes were differentially regulated early in pediatric septic shock compared to healthy controls, as well as across genotypic and phenotypic distinct pediatric septic shock subclasses. The nuclear genome may be an important mechanism contributing to alterations in mitochondrial bioenergetic function and outcomes in pediatric sepsis.

Further development of the temporal model of control.

The temporal model of control (Frazier, Berman, & Steward, 2001) posits that different temporal aspects of control (i.e., past, present, and future) have markedly different relations with adjustment and need to be clearly distinguished from each other. The Perceived Control over Stressful Events Scale (PCOSES; Frazier, Keenan, et al., 2011) was recently developed to assess these different aspects of control and to advance understanding of the role of perceived control in adjustment to stressful life events. The goals of the 2 studies presented here were to expand the temporal model of control by developing a new subscale of the PCOSES and to gather additional evidence regarding the temporal model. In Study 1, we developed a new future likelihood subscale and found evidence for the internal consistency, test-retest reliability, and construct validity of its scores in a sample of undergraduate students (N = 201). In Study 2, we confirmed the 4-factor structure of the PCOSES with the new future likelihood subscale using confirmatory factor analysis in another sample of undergraduates (N = 1,084). Study 2 also provided additional evidence, consistent with the temporal model, that the PCOSES subscales were differentially related to distress and other forms of adjustment (e.g., physical health) and that present control and future likelihood were associated with less event-related distress after controlling for 4 known correlates of distress (e.g., social support). Implications for counseling psychology research and practice are discussed.

Impact of victimization on risk of suicide among lesbian, gay, and bisexual high school students in San Francisco.

PURPOSE: This study investigated the association between sexual orientation, victimization, and suicide risk-related outcomes among youth attending public high schools in San Francisco. METHODS: Data from the 2009 Youth Risk Behavior Survey were analyzed using bivariate and logistic regression methods for complex samples to examine the relationship between sexual orientation, victimization, and three suicide risk-related outcomes (sadness/depression, suicide planning, and attempting suicide) while controlling for demographics and substance use. RESULTS: Lesbian, gay, or bisexual (LGB) youth reported significantly higher rates of substance use, victimization, and suicide risk-related outcomes than heterosexual youth. However, in the controlled regression models, victimization was a significant predictor of sadness/depression and suicide attempts, regardless of sexual orientation. There was a significant interaction effect between sexual orientation and victimization on suicide planning, with heterosexual youth more affected than LGB youth. CONCLUSIONS: Results underscore the deleterious effect of victimization on suicide risk-related outcomes, regardless of sexual orientation. As LGB youth continue to report higher rates of victimization, effective violence prevention approaches must focus on reducing violence among youth, specifically LGB youth. Additional research should focus on identification of other factors that may help further explain elevated suicide risk among LGB youth.