Increased vesicular dynamics and nanoscale clustering of IL-2 after T cell activation.

T cells coordinate intercellular communication through the meticulous regulation of cytokine secretion. Direct visualization of vesicular transport and intracellular distribution of cytokines provides valuable insights into the temporal and spatial mechanisms involved in regulation. Employing Jurkat E6-1 T cells and interleukin-2 (IL-2) as a model system, we investigated vesicular dynamics using single-particle tracking and the nanoscale distribution of intracellular IL-2 in fixed T cells using superresolution microscopy. Live-cell imaging revealed that in vitro activation resulted in increased vesicular dynamics. Direct stochastic optical reconstruction microscopy and 3D structured illumination microscopy revealed nanoscale clustering of IL-2. In vitro activation correlated with spatial accumulation of IL-2 nanoclusters into more pronounced and elongated clusters. These observations provide visual evidence that accelerated vesicular transport and spatial concatenation of IL-2 clusters at the nanoscale may constitute a potential mechanism for modulating cytokine release by Jurkat T cells.

Quantitative Superresolution Imaging of F-Actin in the Cell Body and Cytoskeletal Protrusions Using Phalloidin-Based Single-Molecule Labeling and Localization Microscopy.

We present single-molecule labeling and localization microscopy (SMLLM) using dye-conjugated phalloidin to achieve enhanced superresolution imaging of filamentous actin (F-actin). We demonstrate that the intrinsic phalloidin dissociation enables SMLLM in an imaging buffer containing low concentrations of dye-conjugated phalloidin. We further show enhanced single-molecule labeling by chemically promoting phalloidin dissociation. Two benefits of phalloidin-based SMLLM are better preservation of cellular structures sensitive to mechanical and shear forces during standard sample preparation and more consistent F-actin quantification at the nanoscale. In a proof-of-concept study, we employed SMLLM to super-resolve F-actin structures in U2OS and dendritic cells (DCs) and demonstrate more consistent F-actin quantification in the cell body and structurally delicate cytoskeletal proportions, which we termed membrane fibers, of DCs compared to direct stochastic optical reconstruction microscopy (dSTORM). Using DC2.4 mouse dendritic cells as the model system, we show F-actin redistribution from podosomes to actin filaments and altered prevalence of F-actin-associated membrane fibers on the culture glass surface after lipopolysaccharide exposure. While our work demonstrates SMLLM for F-actin, the concept opens new possibilities for protein-specific single-molecule labeling and localization in the same step using commercially available reagents.

Cloud microphysical response to entrainment and mixing is locally inhomogeneous and globally homogeneous: Evidence from the lab.

Entrainment of dry air into clouds strongly influences cloud optical and precipitation properties and the response of clouds to aerosol perturbations. The response of cloud droplet size distributions to entrainment-mixing is examined in the Pi convection-cloud chamber that creates a turbulent, steady-state cloud. The experiments are conducted by injecting dry air with temperature (Te) and flow rate (Qe) through a flange in the top boundary, into the otherwise well-mixed cloud, to mimic the entrainment-mixing process. Due to the large-scale circulation, the downwind region is directly affected by entrained dry air, whereas the upwind region is representative of the background conditions. Droplet concentration (Cn) and liquid water content (L) decrease in the downwind region, but the difference in the mean diameter of droplets (Dm) is small. The shape of cloud droplet size distributions relative to the injection point is unchanged, to within statistical uncertainty, resulting in a signature of inhomogeneous mixing, as expected for droplet evaporation times small compared to mixing time scales. As Te and Qe of entrained air increase, however, Cn, L, and Dm of the whole cloud system decrease, resulting in a signature of homogeneous mixing. The apparent contradiction is understood as the cloud microphysical responses to entrainment and mixing differing on local and global scales: locally inhomogeneous and globally homogeneous. This implies that global versus local sampling of clouds can lead to seemingly contradictory results for mixing, which informs the long-standing debate about the microphysical response to entrainment and the parameterization of this process for coarse-resolution models.

Superresolution Imaging with Single-Antibody Labeling.

We present a versatile single-molecule localization microscopy technique utilizing time-lapse imaging of single-antibody labeling. By performing single-molecule imaging in the subminute time scale and tuning the antibody concentration to create sparse single-molecule binding, we captured antibody labeling of subcellular targets to generate superresolution images. Single-antibody labeling enabled dual-target superresolution imaging using dye-conjugated monoclonal and polyclonal antibodies. We further demonstrate a dual-color strategy to increase the sample labeling density. Single-antibody labeling paves a new way to evaluate antibody binding for superresolution imaging in the native cellular environment.

The Human Need for Equilibrium: Qualitative Study on the Ingenuity, Technical Competency, and Changing Strategies of People With Dementia Seeking Health Information.

BACKGROUND: Prior research on health information behaviors of people with dementia has primarily focused on examining the types of information exchanged by people with dementia using various web-based platforms. A previous study investigated the information behaviors of people with dementia within a month of their diagnosis. There is an empirical gap in the literature regarding the evolution of health information needs and behaviors of people with dementia as their condition progresses. OBJECTIVE: Our work primarily investigated the information behaviors of people with dementia who have been living with the condition for several (4 to 26) years. We also aimed to identify their motivations for changing their information behaviors over time. Our primary research questions were as follows: how do people with dementia get informed about their condition, and why do people with dementia seek information about their condition? METHODS: We adopted an action research approach by including 2 people with dementia as members of our research team. Collaboratively, we conducted 16 remote 1-hour contextual inquiry sessions with people living with mild to moderate dementia. During the study sessions, the first 40 minutes included semistructured interviews with participants concerning their information behaviors, followed by a 20-minute demonstration of their information-seeking strategies. Data from these interviews were analyzed using a constructivist grounded theory approach. RESULTS: Participants described their information needs in terms of managing the disrupted physiological, emotional, and social aspects of their lives following a diagnosis of dementia. They used various information behaviors, including active search, ongoing search, monitoring, proxy search, information avoidance, and selective exposure. These information behaviors were not stagnant; however, they were adapted to accommodate the changing circumstances of their dementia and their lives as they worked to re-establish equilibrium to continue to engage in life while living with a degenerative neurological condition. CONCLUSIONS: Our research revealed the motivations, changing abilities, and chosen strategies of people with dementia in their search for information as their condition evolves. This knowledge can be used to develop and improve person-centered information and support services for people with dementia so that they can more easily re-establish equilibrium and continue to engage in life.

Understanding How Sensory Changes Experienced by Individuals with a Range of Age-Related Cognitive Changes Can Effect Technology Use.

Clinical researchers have identified sensory changes people with age-related cognitive changes, such as dementia and mild cognitive impairment, experience that are different from typical age-related sensory changes. Technology designers and researchers do not yet have an understanding of how these unique sensory changes affect technology use. This work begins to bridge the gap between the clinical knowledge of sensory changes and technology research and design through interviews with people with mild to moderate dementia, mild cognitive impairment, subjective cognitive decline, and healthcare professionals. This extended version of our ASSETS conference paper includes people with a range of age-related cognitive changes describing changes in vision, hearing, speech, dexterity, proprioception, and smell. We discuss each of these sensory changes and ways to leverage optimal modes of sensory interaction for accessible technology use with existing and emerging technologies. Finally, we discuss how accessible sensory stimulation may change across the spectrum of age-related cognitive changes.

Barriers to Online Dementia Information and Mitigation.

There is growing interest in HCI to study ways to support access to accurate, accessible, relevant online health information for different populations. Yet, there remains a need to understand the barriers that are posed by the way our platforms are designed as well as how we might overcome these barriers for people with dementia. To address this, we conducted sixteen interviews and observation sessions with people with mild to moderate dementia. Our analysis uncovered four barriers to online health information and corresponding mitigation strategies that participants employed. We discuss how HCI researchers may apply these findings towards new technical approaches and standards concerning information accessibility and credibility for neurodiverse populations. Finally, we broaden the scope of HCI research to include investigations of the accessibility and credibility of online information for people with age-related cognitive impairment independent of proxies.

Variation in management of paediatric isolated bicuspid aortic valve: current practice survey.

BACKGROUND: Prior to the recent release of appropriate use criteria for imaging valvulopathies in children, follow-up of valvular lesions, including isolated bicuspid aortic valve, was not standardised. We describe current follow up, treatment, and intervention strategies for isolated bicuspid aortic valve with varying degrees of stenosis, regurgitation, and dilation in children up to 18 years old and compare them with newly released appropriate use criteria. METHODS: Online survey was sent to members of the American Academy of Pediatrics Section on Cardiology and Cardiac Surgery and PediHeartNet. RESULTS: Totally, 106 responses with interpretable data were received. For asymptomatic patients with isolated BAV without stenosis, regurgitation, or dilation follow-up-intervals increased from 7+/-4 months in the newborn period to 28 +/- 14 months at 18 years of age. Respondents recommended more frequent follow-up for younger patients and those with greater disease severity. More than 80% of respondents treat aortic regurgitation or aortic dilation in the setting of bicuspid aortic valve medically. In general, intervention was recommended once stenosis or regurgitation became severe (stenosis of >4 m/s; regurgitation with LV Z score 4) regardless of age, but was not routinely recommended for younger children (newborn - age 6 years) with severe dilation. Exercise was restricted at 38+/-11 mmHg echocardiographic mean gradient. CONCLUSIONS: Current follow-up, treatment, and intervention strategies for isolated bicuspid aortic valve deviate from appropriate use criteria. Differences between the two highlight the need to better delineate the disease course, clarify recommendations for care, and encourage wider adoption of guidelines.

Rapid statistical discrimination of fluorescence images of T cell receptors on immobilizing surfaces with different coating conditions.

The spatial organization of T cell receptors (TCRs) correlates with membrane-associated signal amplification, dispersion, and regulation during T cell activation. Despite its potential clinical importance, quantitative analysis of the spatial arrangement of TCRs from standard fluorescence images remains difficult. Here, we report Statistical Classification Analyses of Membrane Protein Images or SCAMPI as a technique capable of analyzing the spatial arrangement of TCRs on the plasma membrane of T cells. We leveraged medical image analysis techniques that utilize pixel-based values. We transformed grayscale pixel values from fluorescence images of TCRs into estimated model parameters of partial differential equations. The estimated model parameters enabled an accurate classification using linear discrimination techniques, including Fisher Linear Discriminant (FLD) and Logistic Regression (LR). In a proof-of-principle study, we modeled and discriminated images of fluorescently tagged TCRs from Jurkat T cells on uncoated cover glass surfaces (Null) or coated cover glass surfaces with either positively charged poly-L-lysine (PLL) or TCR cross-linking anti-CD3 antibodies (OKT3). Using 80 training images and 20 test images per class, our statistical technique achieved 85% discrimination accuracy for both OKT3 versus PLL and OKT3 versus Null conditions. The run time of image data download, model construction, and image discrimination was 21.89 s on a laptop computer, comprised of 20.43 s for image data download, 1.30 s on the FLD-SCAMPI analysis, and 0.16 s on the LR-SCAMPI analysis. SCAMPI represents an alternative approach to morphology-based qualifications for discriminating complex patterns of membrane proteins conditioned on a small sample size and fast runtime. The technique paves pathways to characterize various physiological and pathological conditions using the spatial organization of TCRs from patient T cells.

Comparison of three sampling methods for small-bodied fish in lentic nearshore and open water habitats.

We performed a preliminary evaluation of a mobile sampling platform with adjustable push net and live box (Platform) against two common methods for sampling small-bodied fish (i.e., 10-100 mm) in two distinct lentic habitats. Nearshore (NS) littoral habitat was sampled by Platform and beach seine, and open water (OW) pelagic habitat by Platform and Kodiak trawl. Our goal was to evaluate the Platform's ability to describe fish assemblage structure across habitat types in contrast to common techniques restricted to single habitat types that are less comparable due to gear-specific bias. Platform sample speed had a significant positive effect on recapture efficiency of both nearly neutrally buoyant objects and marked fish. Marked fish recapture efficiencies were similar for Platform in NS and OW, indicating similar efficiency across habitat types. Platform capture efficiency was similar to beach seine and greater than Kodiak trawl. With similar sampling time, the Platform collected more individuals and taxa in NS relative to beach seine and in OW relative to Kodiak trawl. Greater taxa detection by the Platform suggests that it may be effective at detecting species that are numerically rare in specific habitats when compared to these methods. Fish CPUE was significantly greater NS regardless of technique. However, by using the Platform, there is greater confidence that this difference was reliable and not a gear selectivity artifact. Overall, this preliminary study demonstrates the Platform's potential to collect standardized data across NS and OW habitats, track ontogenetic habitat shifts, and detect differences in small-bodied fish taxa richness, relative abundance, and density between NS and OW habitats. Continued experimentation beyond a single reservoir and fish size range is required before consensus can be established regarding the utility of this new push net design.

Leveraging the Value of CDISC SEND Data Sets for Cross-Study Analysis: Incidence of Microscopic Findings in Control Animals.

Implementation of the Clinical Data Interchange Standards Consortium (CDISC)'s Standard for Exchange of Nonclinical Data (SEND) by the United States Food and Drug Administration Center for Drug Evaluation and Research (US FDA CDER) has created large quantities of SEND data sets and a tremendous opportunity to apply large-scale data analytic approaches. To fully realize this opportunity, differences in SEND implementation that impair the ability to conduct cross-study analysis must be addressed. In this manuscript, a prototypical question regarding historical control data (see Table of Contents graphic) was used to identify areas for SEND harmonization and to develop algorithmic strategies for nonclinical cross-study analysis within a variety of databases. FDA CDER's repository of >1800 sponsor-submitted studies in SEND format was queried using the statistical programming language R to gain insight into how the CDISC SEND Implementation Guides are being applied across the industry. For each component needed to answer the question (defined as "query block"), the frequency of data population was determined and ranged from 6 to 99%. For fields populated <90% and/or that did not have Controlled Terminology, data extraction methods such as data transformation and script development were evaluated. Data extraction was successful for fields such as phase of study, negative controls, and histopathology using scripts. Calculations to assess accuracy of data extraction indicated a high confidence in most query block searches. Some fields such as vehicle name, animal supplier name, and test facility name are not amenable to accurate data extraction through script development alone and require additional harmonization to confidently extract data. Harmonization proposals are discussed in this manuscript. Implementation of these proposals will allow stakeholders to capitalize on the opportunity presented by SEND data sets to increase the efficiency and productivity of nonclinical drug development, allowing the most promising drug candidates to proceed through development.

SEND harmonization & cross-study analysis: A proposal to better harvest the value from SEND data.

The Standard for Exchange of Nonclinical Data (SEND) identifies an approach for representing nonclinical data in a structured format which has been widely adopted by the pharmaceutical industry as it is required for data submission to the United States Food & Drug Administration (US FDA). The SEND Implementation Guide (SENDIG) allows for considerable flexibility in how data is represented; interpretation of these guidelines has led to significant variability in the approach to SEND dataset creation. The purposes of this manuscript are to identify common variability in certain SEND domains and to describe how variability can be managed to enable valuable cross-study analysis use cases. The example of extracting a commonly used data point, animal age, is used to illustrate the complexity and variability of SEND datasets. Developing a solution framework to the variability problem that includes all stakeholders involved in the creation and use of SEND datasets may enable future, routine analysis of warehoused SEND data. Harmonizing the implementation and use of SEND is expected to benefit all involved stakeholders and to ultimately contribute to the goal of increased productivity in nonclinical research.

Rethinking Essential Services in the Wake of the COVID-19 Health Crisis.

During the COVID-19 global pandemic, Cook Children's Health Care System needed a way to ensure that all employees had a reliable childcare option. This advocacy note details how Child Study Center, an applied behavior analysis facility in North Texas, transitioned into Camp Cook, a free-of-charge childcare facility that operates weekdays from 6:00 a.m. to 8:00 p.m. Closing the doors on our billable services allowed us to open them to the essential health care workers who were fighting on the front lines against COVID-19. Here we describe the redeployment of employees across 3 departments in an effort to ease the burden of childcare within our local community.

Redifferentiated Chondrocytes in Fibrin Gel for the Repair of Articular Cartilage Lesions.

BACKGROUND: Autologous chondrocyte implantation, which uses passaged chondrocytes, commonly leads to the formation of fibrocartilage. When chondrocytes are passaged to increase cell numbers, they lose their phenotype and ability to form hyaline cartilage. The use of transforming growth factor ß (TGFß) to redifferentiate passaged chondrocytes has been validated in vitro; however, it is unknown if redifferentiated chondrocytes will enhance defect repair when implanted in vivo. Furthermore, fibrin gel is used in orthopaedic surgery as a fixative and scaffold and could be an appropriate carrier to enhance retention of cells in the repair site. PURPOSE: To investigate if passaged redifferentiated chondrocytes in fibrin gel have the ability to form cartilage tissue and if these redifferentiated cells will enhance the formation of hyaline cartilage in vivo when implanted into critical-size osteochondral defects. STUDY DESIGN: Controlled laboratory study. METHODS: Rabbit and human chondrocytes were serially passaged twice in monolayer culture. Twice-passaged cells were used directly (dedifferentiated) or redifferentiated in high-density culture with TGFß3. Dedifferentiated or redifferentiated cells were mixed with fibrin gel to form fibrin clots, which were cultured in vitro to assess the use of fibrin gel as a scaffold or implanted in vivo in a critical-size osteochondral defect in New Zealand White rabbit knee joints. Rabbits were sacrificed 6 weeks after implantation, and tissues were assessed histologically and by immunohistochemistry. RESULTS: Redifferentiation of passaged chondrocytes by means of 3-dimensional culture in the presence of TGFß3 improved the formation of cartilaginous tissues in vitro, and culture in fibrin gel did not affect the cell phenotype. Implantation of dedifferentiated cells in vivo resulted in fibrocartilaginous repair tissues. Redifferentiated chondrocyte implants resulted in granulation tissues containing the hyaline cartilage marker collagen type 2. CONCLUSION: Redifferentiated chondrocytes will maintain their chondrogenic differentiation in fibrin clots. Implanted redifferentiated chondrocytes show a different reparative response than dedifferentiated chondrocytes and do not appear to enhance repair at an early time point. Another study of longer duration is required to assess tissue maturation over time. CLINICAL RELEVANCE: Redifferentiation of passaged chondrocytes with TGFß3 before implantation does not improve defect repair in the first 6 weeks.

Color, chlorophyll a, and suspended solids effects on Secchi depth in lakes: implications for trophic state assessment.

Secchi depth (SD), a primary metric to assess trophic state, is controlled in many lakes by algal densities, measured as chlorophyll-a (chl-a) concentration. Two other optically related water quality variables also directly affect SD: non-algal suspended solids (SSNA ) and colored dissolved organic matter (CDOM, expressed as the absorption coefficient at 440 nm, a440 ). Using a database of ~1,460 samples from ~625 inland lake basins in Minnesota and two other Upper Midwest states, Wisconsin and Michigan, we analyzed relationships among these variables, with special focus on CDOM levels that influence SD values and the Minnesota SD standards used to assess eutrophication impairment of lakes. Log-transformed chl-a, total suspended solids (TSS), and SD were strongly correlated with each other; log(a440 ) had major effects on log(SD) but was only weakly correlated with log(chl-a) and log(TSS). Multiple regression models for log(SD) and 1/SD based on the three driving variables (chl-a, SSNA , and CDOM) explained ~80% of the variance in SD in the whole data set, but substantial differences in the form of the best-fit relationships were found between major ecoregions. High chl-a concentrations (> 50 µg/L) and TSS (> 20 mg/L) rarely occurred in lakes with high CDOM (a440  > ~4 m-1 ), and all lakes with a440  > 8 m-1 had SD ≤ 2.0 m despite low chl-a values (<10 µg/L) in most lakes. Further statistical analyses revealed that CDOM has significant effects on SD at a440 values > ~ 4 m-1 . Thus, SD is not an accurate trophic state metric in moderately to highly colored lakes, and Minnesota's 2-m SD criterion should not be the sole metric to assess eutrophication impairment in warm/cool-water lakes of the Northern Lakes and Forest ecoregion. More generally, trophic state assessments using SD in regions with large landscape sources of CDOM need to account for effects of CDOM on SD.

Platelet-rich plasma enhances the integration of bioengineered cartilage with native tissue in an in vitro model.

Current therapies for cartilage repair can be limited by an inability of the repair tissue to integrate with host tissue. Thus, there is interest in developing approaches to enhance integration. We have previously shown that platelet-rich plasma (PRP) improves cartilage tissue formation. This raised the question as to whether PRP could promote cartilage integration. Chondrocytes were isolated from cartilage harvested from bovine joints, seeded on a porous bone substitute and grown in vitro to form an osteochondral-like implant. After 7 days, the biphasic construct was soaked in PRP for 30 min before implantation into the core of a donut-shaped biphasic explant of native cartilage and bone. Controls were not soaked in PRP. The implant-explant construct was cultured for 2-4 weeks. PRP-soaked bioengineered implants integrated with host tissue in 73% of samples, whereas controls only integrated in 19% of samples. The integration strength, as determined by a push-out test, was significantly increased in the PRP-soaked implant group (219 ± 35.4 kPa) compared with controls (72.0 ± 28.5 kPa). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP-treated implant group, compared with untreated controls. Immunohistochemical studies revealed that the integration zone contained collagen type II and aggrecan. The cells at the zone of integration in the PRP-soaked group had a 3.5-fold increase in matrix metalloproteinase-13 gene expression compared with controls. These results suggest that PRP-soaked bioengineered cartilage implants may be a better approach for cartilage repair due to enhanced integration.

Further Evidence for Smoking and Substance Use Disorders in Youth With Bipolar Disorder and Comorbid Conduct Disorder.

OBJECTIVE: Bipolar disorder (BPD) is a highly morbid disorder increasingly recognized in adolescents. The aim of this study was to examine the relative risk for substance use disorders (SUDs; alcohol or drug abuse or dependence) and cigarette smoking in adolescents with BPD. METHODS: We evaluated the relative risk for SUDs and cigarette smoking in a case-controlled, 5-year prospective follow-up of adolescents with (n = 105, mean ± SD baseline age = 13.6 ± 2.5 years) and without ("controls"; n = 98, baseline age = 13.7 ± 2.1 years) BPD. Seventy-three percent of subjects were retained at follow-up (BPD: n = 68; controls: n = 81; 73% reascertainment). Our main outcomes were assessed by blinded structured interviews for DSM-IV criteria. RESULTS: Maturing adolescents with BPD, compared to controls, were more likely to endorse higher rates of SUD (49% vs 26%; hazard ratio [HR] = 2.0; 95% confidence interval (CI), 1.1-3.6; P = .02) and cigarette smoking (49% vs 17%; HR = 2.9; 95% CI, 1.4-6.1; P = .004), as well as earlier onset of SUD (14.9 ± 2.6 [SD] years vs 16.5 ± 1.6 [SD] years; t = 2.6; P = .01). Subjects with conduct disorder (CD) were more likely to have SUD and nicotine dependence than subjects with BPD alone or controls (all P values < .05). When we added conduct disorder to the model with socioeconomic status and parental SUD, all associations lost significance (all P values > .05). Subjects with the persistence of a BPD diagnosis were also more likely to endorse cigarette smoking and SUD in comparison to those who lost a BPD diagnosis or controls at follow-up. CONCLUSIONS: The results provide further evidence that adolescents with BPD, particularly those with comorbid CD, are significantly more likely to endorse cigarette smoking and SUDs when compared to their non-mood disordered peers. These findings indicate that youth with BPD should be carefully monitored for comorbid CD and the development of cigarette smoking and SUDs.

Evaluating multispecies landscape connectivity in a threatened tropical mammal community.

Habitat corridors are important tools for maintaining connectivity in increasingly fragmented landscapes, but generally they have been considered in single-species approaches. Corridors intended to facilitate the movement of multiple species could increase persistence of entire communities, but at the likely cost of being less efficient for any given species than a corridor intended specifically for that species. There have been few tests of the trade-offs between single- and multispecies corridor approaches. We assessed single-species and multispecies habitat corridors for 5 threatened mammal species in tropical forests of Borneo. We generated maps of the cost of movement across the landscape for each species based on the species' local abundance as estimated through hierarchical modeling of camera-trap data with biophysical and anthropogenic covariates. Elevation influenced local abundance of banded civets (Hemigalus derbyanus) and sun bears (Helarctos malayanus). Increased road density was associated with lower local abundance of Sunda clouded leopards (Neofelis diardi) and higher local abundance of sambar deer (Rusa unicolor). Pig-tailed macaque (Macaca nemestrina) local abundance was lower in recently logged areas. An all-species-combined connectivity scenario with least-cost paths and 1 km buffers generated total movement costs that were 27% and 23% higher for banded civets and clouded leopards, respectively, than the connectivity scenarios for those species individually. A carnivore multispecies connectivity scenario, however, increased movement cost by 2% for banded civets and clouded leopards. Likewise, an herbivore multispecies scenario provided more effective connectivity than the all-species-combined scenario for sambar and macaques. We suggest that multispecies habitat connectivity plans be tailored to groups of ecologically similar, disturbance-sensitive species to maximize their effectiveness.

Difficulties in emotional regulation and substance use disorders: a controlled family study of bipolar adolescents.

BACKGROUND: Self-regulatory mechanisms appear etiologically operant in the context of both substance use disorders (SUD) and bipolar disorder (BD), however, little is known about the role of deficits in emotional self-regulation (DESR) as it relates to SUD in context to mood dysregulation. To this end, we examined to what extent DESR was associated with SUD in a high-risk sample of adolescents with and without BD. METHODS: 203 families were assessed with a structured psychiatric interview. Using the Child Behavior Checklist (CBCL), a subject was considered to have DESR when he or she had an average elevation of 1 standard deviation (SD) above the norm on 3 clinical scale T scores (attention, aggression, and anxiety/depression; scores: 60 × 3 ≥ 180). RESULTS: Among probands and siblings with CBCL data (N=303), subjects with DESR were more likely to have any SUD, alcohol use disorder, drug use disorder, and cigarette smoking compared to subjects with scores <180 (all p values <0.001), even when correcting for BD. We found no significant differences in the risk of any SUD and cigarette smoking between those with 1SD and 2SD above the mean (all p values >0.05). Subjects with cigarette smoking and SUD had more DESR compared to those without these disorders. CONCLUSIONS: Adolescents with DESR are more likely to smoke cigarettes and have SUD. More work is needed to explore DESR in longitudinal samples.

Are obstetrical, perinatal, and infantile difficulties associated with pediatric bipolar disorder?

OBJECTIVES: Despite increasing acknowledgement of bipolar disorder (BD) in childhood, there is a paucity of literature that has investigated obstetrical, perinatal, and infantile difficulties and their potential link with BD. To this end, we examined difficulties during delivery, immediate post-birth, and infancy and the association with BD in childhood. METHODS: From two similarly designed, ongoing, longitudinal, case-control family studies of pediatric BD (N = 327 families), we analyzed 338 children and adolescents [mean (± standard deviation) age: 12.00 ± 3.37 years]. We stratified them into three groups: healthy controls (N = 98), BD probands (N = 120), and their non-affected siblings (N = 120). All families were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and substance use. Mothers were directly questioned regarding the pregnancy, delivery, and infancy difficulties that occurred with each child using a module from the Diagnostic Interview for Children and Adolescents-Parent Version (DICA-P). RESULTS: Mothers of BD subjects were more likely to report difficulties during infancy than mothers of controls [odds ratio (95% confidence interval) = 6.6 (3.0, 14.6)]. Specifically, children with BD were more likely to have been reported as a stiffened infant [7.2 (1.1, 47.1)] and more likely to have experienced 'other' infantile difficulties [including acting colicky; 4.9 (1.3, 18.8)] compared to controls. We found no significant differences between groups in regards to obstetrical or perinatal difficulties (all p values > 0.05). CONCLUSIONS: While our results add to previous literature on obstetrical and perinatal difficulties and BD, they also highlight characteristics in infancy that may be prognostic indicators for pediatric BD.