Predicting prognosis for adults with depression using individual symptom data: a comparison of modelling approaches.

BACKGROUND: This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data. METHODS: Individual patient data from all six eligible randomised controlled trials were used to develop (k = 3, n = 1722) and test (k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1-3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3-4 months. RESULTS: Models 1-7 all outperformed the null model and model 8. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum scores had little impact. CONCLUSIONS: Any of the modelling techniques (models 1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.

Research Note: Demographic Change on the United States Coast, 2020-2100.

Prospective demographic information of the United States is limited to national-level analyses and subnational analyses of the total population. With nearly 40% of the U.S. population being residents of coastal areas, understanding the anticipated demographic changes in coastal counties is important for long-range planning purposes. In this research note, we use long-range, county-level population projections based on a simplified cohort-component method to discuss demographic changes by age, sex, and race and ethnicity for coastal counties between 2020 and the end of the century, and we compare these changes to inland counties. Presently, coastal counties are statistically significantly different from inland counties by race and ethnicity (more diverse) and sex (more women) but not by age, yet by 2025, we expect coastal counties to become significantly older than inland counties. We note several important trajectories of predicted demographic outcomes in coastal counties across the remainder of the century: (1) the non-Hispanic White population is expected to decrease, both numerically and as a percentage of the population; (2) the population older than 65 is projected to increase, both numerically and as a percentage of the population; and (3) the ratio of women to men remains constant over the century at 1.03. These trends combine to suggest that the future U.S. coastline will likely be both increasingly diverse racially and ethnically and significantly older than it is today.

The importance of transdiagnostic symptom level assessment to understanding prognosis for depressed adults: analysis of data from six randomised control trials.

BACKGROUND: Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes. METHOD: Individual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators. RESULTS: Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms. CONCLUSION: The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.

Accelerated diversification correlated with functional traits shapes extant diversity of the early divergent angiosperm family Annonaceae.

A major goal of phylogenetic systematics is to understand both the patterns of diversification and the processes by which these patterns are formed. Few studies have focused on the ancient, species-rich Magnoliales clade and its diversification pattern. Within Magnoliales, the pantropically distributed Annonaceae are by far the most genus-rich and species-rich family-level clade, with c. 110 genera and c. 2,400 species. We investigated the diversification patterns across Annonaceae and identified traits that show varied associations with diversification rates using a time-calibrated phylogeny of 835 species (34.6% sampling) and 11,211 aligned bases from eight regions of the plastid genome (rbcL, matK, ndhF, psbA-trnH, trnL-F, atpB-rbcL, trnS-G, and ycf1). Twelve rate shifts were identified using BAMM: in Annona, Artabotrys, Asimina, Drepananthus, Duguetia, Goniothalamus, Guatteria, Uvaria, Xylopia, the tribes Miliuseae and Malmeeae, and the Desmos-Dasymaschalon-Friesodielsia-Monanthotaxis clade. TurboMEDUSA and method-of-moments estimator analyses showed largely congruent results. A positive relationship between species richness and diversification rate is revealed using PGLS. Our results show that the high species richness in Annonaceae is likely the result of recent increased diversification rather than the steady accumulation of species via the 'museum model'. We further explore the possible role of selected traits (habit, pollinator trapping, floral sex expression, pollen dispersal unit, anther septation, and seed dispersal unit) in shaping diversification patterns, based on inferences of BiSSE, MuSSE, HiSSE, and FiSSE analyses. Our results suggest that the liana habit, the presence of circadian pollinator trapping, androdioecy, and the dispersal of seeds as single-seeded monocarp fragments are closely correlated with higher diversification rates; pollen aggregation and anther septation, in contrast, are associated with lower diversification rates.

Church leaders' barriers and facilitators before and after implementing a physical activity and nutrition intervention.

Faith-based health promotion programs have been effective in increasing healthy eating (HE) and physical activity (PA). Very few reports exist regarding church leaders' anticipated and experienced barriers and facilitators to program implementation. Pastors (n = 38, 70%) and program coordinators (n = 54, 100%) from churches (N = 54) who attended a program training answered open-ended questions about anticipated barriers and facilitators to implementing the HE and PA parts of the Faith, Activity, and Nutrition (FAN) program. Twelve months later, pastors (n = 49, 92%) and coordinators (n = 53, 98%) answered analogous questions about their experienced barriers and facilitators to implementing the HE and PA parts of the FAN program. Responses were coded using thematic analysis. Similar themes appeared at baseline and follow-up for anticipated and experienced barriers and facilitators. The most common barriers were no anticipated barriers, resistance to change, church characteristics, and lack of participation/motivation. The most common facilitators were internal support, leadership, and communication. Few differences were found between anticipated and experienced barriers and facilitators. Understanding these perspectives, particularly overcoming resistance to change and church characteristics through strong leadership and internal support from church leaders, will improve future program development, resources, and technical assistance in faith-based and non-faith-based communities alike.

Attentional Control as a Predictor of Response to Psychological Treatment for Depression and Relapse up to 1 year After Treatment: A Pilot Cohort Study.

BACKGROUND: Identifying depressed patients unlikely to reach remission and those likely to relapse after reaching remission is of great importance, but there are few pre-treatment factors that can help clinicians predict prognosis and together these explain relatively little variance in treatment outcomes. Attentional control has shown promise in studies to date, but has not been investigated prospectively in routine clinical settings with depressed patients. AIMS: This study aimed to pilot the use of a brief self-report measure of attentional control in routine care and investigate the associations between attentional control, psychological treatment response and relapse to depression up to 1 year post-treatment. METHOD: Depressed patients were recruited from two primary care psychological treatment (IAPT) services and completed the Attentional Control Scale (ACS) alongside routine symptom measures at every therapy session. Participants were tracked and followed up for 1 year post-treatment. RESULTS: Baseline ACS scores were associated with remission and residual depressive symptoms post-treatment, and relapse within 12 months of ending treatment, all independent of pre-treatment depressive symptom severity, and the latter also independent of residual symptoms. CONCLUSION: A self-report measure of attentional control can potentially be used to predict levels of depressive symptoms post-treatment and can contribute to predicting risk of relapse to depression in IAPT services, without affecting rates of therapy completion/drop-out or data completion of standard IAPT measures. However, this pilot study had a small overall sample size and a very small number of observed relapses, so replication in a larger study is needed before firm conclusions can be made.

The Impact of Alcohol Use on Drop-out and Psychological Treatment Outcomes in Improving Access to Psychological Therapies Services: an Audit.

BACKGROUND: The impact of alcohol use disorders (AUD) on psychological treatments for depression or anxiety in primary care psychological treatment services is unknown. AIMS: To establish levels of alcohol misuse in an Improving Access to Psychological Therapies (IAPT) service, examine the impact of higher risk drinking on IAPT treatment outcomes and drop-out, and to inform good practice in working with alcohol misuse in IAPT services. METHOD: 3643 patients completed a brief questionnaire on alcohol use pre-treatment in addition to measures of depression, anxiety and functioning. Symptom and functioning measures were re-administered at all treatment sessions. RESULTS: Severity of alcohol misuse was not associated with treatment outcomes, although those scoring eight or more on the AUDIT-C were more likely to drop out from treatment. CONCLUSIONS: IAPT services may be well placed to offer psychological therapies to patients with common mental disorders and comorbid AUD. Patients with AUD can have equivalent treatment outcomes to those without AUD, but some higher risk drinkers may find accessing IAPT treatment more difficult as they are more likely to drop out. Alcohol misuse on its own should not be used as an exclusion criterion from IAPT services. Recommendations are given as to how clinicians can: adjust their assessments to consider the appropriateness of IAPT treatment for patients that misuse alcohol, consider the potential impact of alcohol misuse on treatment, and improve engagement in treatment for higher risk drinkers.

Myeloid-derived suppressor cell-like fibrocytes are increased and associated with preserved lung function in chronic obstructive pulmonary disease.

BACKGROUND: The role of fibrocytes in chronic obstructive pulmonary disease (COPD) is unknown. We sought to enumerate blood and tissue fibrocytes in COPD and determine the association of blood fibrocytes with clinical features of disease. METHODS: Utilizing flow cytometry to identify circulating, collagen type 1+ cells, we found two populations: (i) CD45+ CD34+ (fibrocytes) and (ii) CD45+ CD34- [myeloid-derived suppressor cell (MDSC)-like fibrocytes] cells in stable COPD (n = 41) and control (n = 29) subjects. Lung resection material from a separate group of subjects with (n = 11) or without (n = 11) COPD was collected for tissue fibrocyte detection. We examined circulating fibrocyte populations for correlations with clinical parameters including quantitative computed tomography (qCT) and determined pathways of association between correlated variables using a path analysis model. RESULTS: Blood and tissue fibrocytes were not increased compared to control subjects nor were blood fibrocytes associated with lung function or qCT, but were increased in eosinophilic COPD. Myeloid-derived suppressor cell-like fibrocytes were increased in COPD compared to controls [2.3 (1.1-4.9), P = 0.038]. Our path analysis model showed that collagen type 1 intensity for MDSC-like fibrocytes was positively associated with lung function through associations with air trapping, predominately in the upper lobes. CONCLUSION: We have demonstrated that two circulating populations of fibrocyte exist in COPD, with distinct clinical associations, but are not prevalent in proximal or small airway tissue. Blood MDSC-like fibrocytes, however, are increased and associated with preserved lung function through a small airway-dependent mechanism in COPD.

Knockout of arsenic (+3 oxidation state) methyltransferase is associated with adverse metabolic phenotype in mice: the role of sex and arsenic exposure.

Susceptibility to toxic effects of inorganic arsenic (iAs) depends, in part, on efficiency of iAs methylation by arsenic (+3 oxidation state) methyltransferase (AS3MT). As3mt-knockout (KO) mice that cannot efficiently methylate iAs represent an ideal model to study the association between iAs metabolism and adverse effects of iAs exposure, including effects on metabolic phenotype. The present study compared measures of glucose metabolism, insulin resistance and obesity in male and female wild-type (WT) and As3mt-KO mice during a 24-week exposure to iAs in drinking water (0.1 or 1 mg As/L) and in control WT and As3mt-KO mice drinking deionized water. Results show that effects of iAs exposure on fasting blood glucose (FBG) and glucose tolerance in either WT or KO mice were relatively minor and varied during the exposure. The major effects were associated with As3mt KO. Both male and female control KO mice had higher body mass with higher percentage of fat than their respective WT controls. However, only male KO mice were insulin resistant as indicated by high FBG, and high plasma insulin at fasting state and 15 min after glucose challenge. Exposure to iAs increased fat mass and insulin resistance in both male and female KO mice, but had no significant effects on body composition or insulin resistance in WT mice. These data suggest that As3mt KO is associated with an adverse metabolic phenotype that is characterized by obesity and insulin resistance, and that the extent of the impairment depends on sex and exposure to iAs, including exposure to iAs from mouse diet.

Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: effect of sex and arsenic exposure.

Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL/6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation.

Predictors of surgical site infection after hospital discharge in patients undergoing major vascular surgery.

OBJECTIVE: Surgical site infection (SSI) is one of the most common postoperative complications after vascular reconstruction, producing significant morbidity and hospital readmission. In contrast to SSI that develops while patients are still hospitalized, little is known about the cohort of patients who develop SSI after discharge. In this study, we explore the factors that lead to postdischarge SSI, investigate the differences between risk factors for in-hospital vs postdischarge SSI, and develop a scoring system to identify patients who might benefit from postdischarge monitoring of their wounds. METHODS: Patients who underwent major vascular surgery from 2005 to 2012 for aneurysm and lower extremity occlusive disease were identified from the American College of Surgeons National Surgical Quality Improvement Program Participant Use Files. Patients were categorized as having no SSI, in-hospital SSI, or SSI after hospital discharge. Predictors of postdischarge SSI were determined by multivariable logistic regression and internally validated by bootstrap resampling. Risk scores were assigned to all significant variables in the model. Summative risk scores were collapsed into quartile-based ordinal categories and defined as low, low/moderate, moderate/high, and high risk. Multivariable logistic regression was used to determine predictors of in-hospital SSI. RESULTS: Of the 49,817 patients who underwent major vascular surgery, 4449 (8.9%) were diagnosed with SSI (2.1% in-hospital SSI; 6.9% postdischarge SSI). By multivariable analysis, factors significantly associated with increased odds of postdischarge SSI include female gender, obesity, diabetes, smoking, hypertension, coronary artery disease, critical limb ischemia, chronic obstructive pulmonary disease, dyspnea, neurologic disease, prolonged operative time >4 hours, American Society of Anesthesiology class 4 or 5, lower extremity revascularization or aortoiliac procedure, and groin anastomosis. The model exhibited moderate discrimination (bias-corrected C statistic, 0.691) and excellent internal calibration. The postdischarge SSI rate was 2.1% for low-risk patients, 5.1% for low/moderate-risk patients, 7.8% for moderate/high-risk patients, and 14% for high-risk patients. In a comparative analysis, comorbidities were the primary driver of postdischarge SSI, whereas in-hospital factors (operative time, emergency case status) and complications predicted in-hospital SSI. CONCLUSIONS: The majority of SSIs after major vascular surgery develop following hospital discharge. We have created a scoring system that can select a cohort of patients at high risk for SSI after discharge. These patients can be targeted for transitional care efforts focused on early detection and treatment with the goal of reducing morbidity and preventing readmission secondary to SSI.

IL-33 drives airway hyper-responsiveness through IL-13-mediated mast cell: airway smooth muscle crosstalk.

BACKGROUND: Mast cell localization within the airway smooth muscle (ASM)-bundle plays an important role in the development of airway hyper-responsiveness (AHR). Genomewide association studies implicate the 'alarmin' IL-33 in asthma, but its role in mast cell-ASM interactions is unknown. OBJECTIVES: We examined the expression and functional role of IL-33 in bronchial biopsies of patients with and without asthma, ex vivo ASM, mast cells, cocultured cells and in a mouse model system. METHODS: IL-33 protein expression was assessed in human bronchial tissue from 9 healthy controls, and 18 mild-to-moderate and 12 severe asthmatic patients by immunohistochemistry. IL-33 and ST2 mRNA and protein expression in human-derived ASM, epithelial and mast cells were assessed by qPCR, immunofluorescence and/or flow cytometry and ELISA. Functional assays were used to assess calcium signalling, wound repair, proliferation, apoptosis and contraction. AHR and inflammation were assessed in a mouse model. RESULTS: Bronchial epithelium and ASM expressed IL-33 with the latter in asthma correlating with AHR. ASM and mast cells expressed intracellular IL-33 and ST2. IL-33 stimulated mast cell IL-13 and histamine secretion independent of FcεR1 cross-linking and directly promoted ASM wound repair. Coculture of mast cells with ASM activated by IL-33 increased agonist-induced ASM contraction, and in vivo IL-33 induced AHR in a mouse cytokine installation model; both effects were IL-13 dependent. CONCLUSION: IL-33 directly promotes mast cell activation and ASM wound repair but indirectly promotes ASM contraction via upregulation of mast cell-derived IL-13. This suggests that IL-33 may present an important target to modulate mast cell-ASM crosstalk in asthma.

Health-economic analysis of real-time continuous glucose monitoring in people with Type 1 diabetes.

AIM: To evaluate the clinical benefits and cost-effectiveness of the sensor-augmented pump compared with self-monitoring of plasma glucose plus continuous subcutaneous insulin infusion in people with Type 1 diabetes. METHODS: The CORE Diabetes Model was used to simulate disease progression in a cohort of people with baseline characteristics taken from a published meta-analysis. Direct and indirect costs for 2010-2011 were calculated from a societal payer perspective, with cost-effectiveness calculated over the patient's lifetime. Discount rates of 3% per annum were applied to the costs and the clinical outcomes. RESULTS: Use of the sensor-augmented pump was associated with an increase in mean discounted, quality-adjusted life expectancy of 0.76 quality-adjusted life years compared with continuous subcutaneous insulin infusion (13.05 ± 0.12 quality-adjusted life years vs 12.29 ± 0.12 quality-adjusted life years, respectively). Undiscounted life expectancy increased by 1.03 years for the sensor-augmented pump compared with continuous subcutaneous insulin infusion. In addition, the onset of complications was delayed (by a mean of 1.15 years) with use of the sensor-augmented pump. This analysis resulted in an incremental cost-effectiveness ratio of 367,571 SEK per quality-adjusted life year gained with the sensor-augmented pump. The additional treatment costs related to the use of the sensor-augmented pump were partially offset by the savings attributable to the reduction in diabetes-related complications and the lower frequency of self-monitoring of plasma glucose. CONCLUSIONS: Analysis using the CORE Diabetes Model showed that improvements in glycaemic control associated with sensor-augmented pump use led to a reduced incidence of diabetes-related complications and a longer life expectancy. Use of the sensor-augmented pump was associated with an incremental cost-effectiveness ratio of 367,571 SEK per quality-adjusted life year gained, which is likely to represent good value for money in the treatment of Type 1 diabetes in Sweden.

Conceptualizing smartphone use in outpatient wound assessment: patients' and caregivers' willingness to use technology.

BACKGROUND: Information technology is transforming health care communication. Using smartphones to remotely monitor incisional wounds via digital photos as well as collect postoperative symptom information has the potential to improve patient outcomes and transitional care. We surveyed a vulnerable patient population to evaluate smartphone capability and willingness to adopt this technology. METHODS: We surveyed 53 patients over a 9-mo period on the vascular surgery service at a tertiary care institution. Descriptive statistics were calculated to describe survey item response. RESULTS: A total of 94% of recruited patients (50 of 53) participated. The cohort was 50% female, and the mean age was age 70 y (range: 41-87). The majority of patients owned cell phones (80%) and 23% of these cell phones were smartphones. Ninety percent of patients had a friend or family member that could help take and send photos with a smartphone. Ninety-two percent of patients reported they would be willing to take a digital photo of their wound via a smartphone (68% daily, 22% every other day, 2% less than every other day, and 8% not at all). All patients reported they would be willing to answer questions related to their health via a smartphone. Patients identified several potential difficulties with regard to adopting a smartphone wound-monitoring protocol including logistics related to taking photos, health-related questions, and coordination with caretakers. CONCLUSIONS: Our survey demonstrates that an older patient cohort with significant comorbidity is able and willing to adopt a smartphone-based postoperative monitoring program. Patient training and caregiver participation will be essential to the success of this intervention.

Significance of R1 resection margin in colon cancer resections in the modern era.

AIM: Circumferential resection margin involvement (R1) in rectal cancer is a predictive factor for poor prognosis. The aim of this study was to confirm the prognostic significance of R1 in colon cancer resection and to establish whether the introduction of laparoscopic colorectal surgery influenced this. METHOD: Prospectively collected data on a patient pathway data manager for sequential patients with colon cancer treated at our specialist unit from January 2005 to December 2010 were analysed. There were 1110 colonic resections (elective 865; emergency 245). A circumferential resection margin involvement of < 1 mm was considered positive. RESULTS: The total R1 rate was 13.3% (elective 10.4%; emergency 23.6%; P < 0.001). Other statistically significant risk factors for an R1 resection included tumour perforation (P < 0.001), poorly differentiated carcinoma (P < 0.001), T4 tumour (P < 0.001), vascular invasion (P < 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and palliative resection (P < 0.001). Over half of the elective resections were undertaken laparoscopically (486/865; 56.2%). When compared with elective open resection (379/865; 43.8%), the R1 rate was similar (P = 0.491) with similar disease-free survival (DFS) and overall survival (OS). The overall relapse rate was 18.9% in R0 and 55.5% in R1 resections (P < 0.001). Kaplan-Meier survival analysis showed significant improvements in DFS and OS in R0 over R1 patients. CONCLUSION: The R1 margin in colon cancer resection is an important marker for advanced disease and a prognostic factor for DFS and OS. The introduction of laparoscopic surgery has not influenced the outcome in our unit despite a complex case mix.

Trophodynamics of Protomyctophum (Myctophidae) in the Scotia Sea (Southern Ocean).

This study investigated spatial and temporal patterns in distribution, population structure and diet of Bolin's lanternfish Protomyctophum bolini, Tenison's lanternfish Protomyctophum tenisoni and gaptooth lanternfish Protomyctophum choriodon in the Scotia Sea using data collected by midwater trawl during spring, summer and autumn. Protomyctophum bolini was the most abundant species of the genus encountered throughout the Scotia Sea with the greatest concentrations occurring around the Antarctic Polar Front (APF). This species had a life cycle of 2+ years, but spatial differences in population structure were apparent as the I-group was absent from all regions south of the APF, suggesting that the species does not recruit in the Scotia Sea. Protomyctophum tenisoni occurred mostly in waters characteristic of the APF and was absent from the southern Scotia Sea. It had a limited size range, but there was clear size-related sexual dimorphism with males significantly larger than females. The species had a life cycle of c. 2 years, but the I-group (c. 1 year old, 1 November to 31 October the next year) occurred only in regions close to the APF suggesting that recruitment is restricted to these waters. A seasonal southward migration for P. choriodon is likely as the species occurred mostly to the south-west of South Georgia in summer, but extended to the sea-ice sectors in autumn. Protomyctophum choriodon had a life cycle of 4+ years in the Scotia Sea and the population was dominated by age classes >3 years old. Larval stages were absent during the surveys for all species. Diurnal variations in vertical distribution were apparent for all three species. Interspecific variations in diet were evident, but all species were primarily copepod feeders, with Metridia spp., Rhincalanus gigas and Calanus simillimus generally dominating their diet. Small euphausiids, principally Thysanoessa spp., were also an important component of their diets, particularly for P. choriodon which had the largest body size. The spatial and temporal variations in diet for both P. bolini and P. tenisoni were broadly consistent with underlying abundance patterns within the mesozooplankton community.

Injection parameters and virus dependent choice of promoters to improve neuron targeting in the nonhuman primate brain.

We, like many others, wish to use modern molecular methods to alter neuronal functionality in primates. For us, this requires expression in a large proportion of the targeted cell population. Long generation times make germline modification of limited use. The size and intricate primate brain anatomy poses additional challenges. We surved methods using lentiviruses and serotypes of adeno-associated viruses (AAVs) to introduce active molecular material into cortical and subcortical regions of old-world monkey brains. Slow injections of AAV2 give well-defined expression of neurons in the cortex surrounding the injection site. Somewhat surprisingly we find that in the monkey the use of cytomegalovirus promoter in lentivirus primarily targets glial cells but few neurons. In contrast, with a synapsin promoter fragment the lentivirus expression is neuron specific at high transduction levels in all cortical layers. We also achieve specific targeting of tyrosine hydroxlase (TH)- rich neurons in the locus coeruleus and substantia nigra with a lentvirus carrying a fragment of the TH promoter. Lentiviruses carrying neuron specific promoters are suitable for both cortical and subcortical injections even when injected quickly.

CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration.

BACKGROUND: Asthma is characterized by variable airflow obstruction, airway inflammation, airway hyper-responsiveness and airway remodelling. Airway smooth muscle (ASM) hyperplasia is a feature of airway remodelling and contributes to bronchial wall thickening. We sought to investigate the expression levels of chemokines in primary cultures of ASM cells from asthmatics vs healthy controls and to assess whether differentially expressed chemokines (i) promote fibrocyte (FC) migration towards ASM and (ii) are increased in blood from subjects with asthma and in sputum samples from those asthmatics with bronchial wall thickening. METHODS: Chemokine concentrations released by primary ASM were measured by MesoScale Discovery platform. The chemokine most highly expressed by ASM from asthmatics compared with healthy controls was confirmed by ELISA, and expression of its cognate chemokine receptor by FCs was examined by immunofluorescence and flow cytometry. The role of this chemokine in FC migration towards ASM was investigated by chemotaxis assays. RESULTS: Chemokine (C-C motif) ligand 2 (CCL2) levels were increased in primary ASM supernatants from asthmatics compared with healthy controls. CCR2 was expressed on FCs. Fibrocytes migrated towards recombinant CCL2 and ASM supernatants. These effects were inhibited by CCL2 neutralization. CCL2 levels were increased in blood from asthmatics compared with healthy controls, and sputum CCL2 was increased in asthmatics with bronchial wall thickening. CONCLUSIONS: Airway smooth muscle-derived CCL2 mediates FC migration and potentially contributes to the development of ASM hyperplasia in asthma.

The 3-year evolution of a preschool physical activity intervention through a collaborative partnership between research interventionists and preschool teachers.

Despite evidence that preschoolers spend the majority of their time in sedentary activities, few physical activity interventions have focused on preschool-age children. Health promotion interventions that can be integrated into the daily routines of a school or other setting are more likely to be implemented. The Study of Health and Activity in Preschool Environments employed a flexible approach to increasing physical activity opportunities in preschools' daily schedules through recess, indoor physical activity and physical activity integrated into academic lessons. Eight preschools were randomly assigned to receive the study's physical activity intervention. Teachers in these schools partnered with university-based interventionists across 3 years to design and implement a flexible and adaptive intervention. The intervention approach included trainings and workshops, site visits and feedback from intervention personnel, newsletters, and physical activity equipment and materials. Teachers reported a high acceptability of the intervention. The purpose of this article is to describe the evolution of a multi-component physical activity intervention in preschools, including (i) a description of the intervention components, (ii) an explanation of the intervention process and approach, and (iii) a report of teachers' perceptions of barriers to implementation.

Health Care Stereotype Threat and Sexual and Gender Minority Well-Being.

Sexual and gender minorities (SGMs) have experienced progressive change over the last 50 years. However, this group still reports worse health and health care experiences. An innovative survey instrument that applies stereotype threat to the health care setting, health care stereotype threat (HCST), offers a new avenue to examine these disparities. We harmonized two national probability data sets of SGMs-Generations and TransPop-capturing 503 gay men, 297 lesbians, 467 bisexuals, and 221 trans people. Using these data, we, first, explored how HCST's association with self-rated health and psychological distress changed while considering more established constructs: discrimination and stigma. Second, we examined how HCST's association varied across SGM groups. Results suggest that HCST is a unique predictor net of the associations with discrimination and stigma. Furthermore, results highlight the more consequential associations for trans people on well-being compared to gay men. We discuss implications of these findings for future research and potential interventions.