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How should we characterize the interaction between moral and aesthetic values in the context of environmental aesthetics? This question is important given the urgency of many environmental problems and the particular role played by aesthetic value in our experience of environment. To address this question, we develop a model of Environmental Virtue Aesthetics (EVA) that, we argue, offers a promising alternative to current theories in environmental aesthetics with respect to the relationship between aesthetics and ethics. EVA counters environmental aesthetic theories that focus more narrowly on scientific knowledge and ground aesthetic value in ways that obfuscate pluralistic modes of appreciation of and relationships with natural and semi-natural environments. To develop EVA, we work with a revised notion of respect and engage with ideas concerning the development of aesthetic sensibilities, care, and virtuous aesthetic appreciation. EVA has the potential to support forms of human-nature co-flourishing, as well as constituting an aesthetic grounding for ecological citizenship.

Purpose This study aims to focus on the experiences of biomedical science students nearing the end of their doctoral programs and the factors that influence their well-being. In addition to identifying general challenges, the study aims to expand understanding of how interactions with principal investigators (PIs) can influence students’ well-being and engagement in wellness practices. Design/methodology/approach This qualitative study presents an analysis of interview data collected from 90 trainees five years after beginning their graduate programs. All were participants in a larger mixed-methods, longitudinal study. Emergent themes and a codebook were established after reviewing interview transcripts and completing memos. Codes were applied to data, and reports were generated to confirm and challenge early interpretations. Findings Participants described four key factors that influenced their well-being: perceived work/life balance; managing progress on research; program completion and job search; and overall faculty relationships. While relationships with PIs could be a source of stress, participants more often described how both interactions with, and observations of their PIs could amplify or mitigate their ability to manage other stressors and overall sense of well-being. Originality/value While researchers in the USA have increasingly considered the factors impacting graduate student mental health, there has been less of an emphasis on wellness and well-being. Furthermore, there has been less attention to how PIs contribute, in positive and negative ways, to these outcomes. This study offers insight into well-being at a specific timepoint, considering dynamics unique to wellness and well-being in the later stages of doctoral training.

Background: Advocacy is widely recognized as a nursing responsibility. Speaking up, a form of advocacy, is known to benefit patient safety and quality of care yet research shows that nurses are hesitant to speak up and face multiple barriers when deciding to do so. Method: A toolkit that included web-based learning modules and simulation experience with a standardized patient was developed to enhance advocacy skills in baccalaureate nursing students. Student perceptions of the efficacy of this approach were used to revise and improve toolkit materials. Results: There were 131 participants over four semesters. Students reported the toolkit helped them understand how to use advocacy skills (87%), allowed them to use critical thinking (97%), and practice advocacy (94%). Conclusion: Educational experiences like this promote development of students' advocacy skills in a safe environment and can be used to bridge the gap between expectation and practice. [ J Nurs Educ . 2022;61(10):599–602.]

Nearly 40% of patients do not continue proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) therapy after 6 months, despite their ability to lower low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular events. Limited work has assessed persistence to PCSK9i therapy in an integrated specialty pharmacy model.To assess rates of persistence to PCSK9i therapy and report reasons for non-persistence in patients serviced within an integrated specialty pharmacy.We conducted a single-center, retrospective review of patients prescribed a PCSK9i at an academic health system between September 2015 and August 2018. Persistence was calculated as a binary measure (yes/no) of whether the patient was still receiving PCSK9i therapy at 3-, 12-, and 24-months; frequency distributions described reasons for non-persistence and descriptive statistics described the change in LDL-C from baseline to 24 months.477 patients met inclusion criteria, 53% were male with median age of 63 years [IQR 56-70]. Median LDL-C at baseline was 157mg/dL and 86% had an atherosclerotic cardiovascular disease indication. Persistence at 3-, 12-, and 24-months was 94%, 80%, and 68%, respectively. Of the 262 patients persistent on PCSK9i therapy at 24 months with LDL-C values available, median LDL-C was 65 mg/dL. The most common reasons for non-persistence at 24 months included medication adverse effects (54%) and loss to follow-up (17%).High rates of persistence to PCSK9i were seen in patients receiving care within an integrated specialty pharmacy model compared with rates in previous studies, suggesting specialty pharmacists may play a role in mitigating many common reasons for PCSK9i non-persistence.

Type-2 cytokines are hypothesized to promote an immune-permissive milieu for cancer to grow. Through scRNAseq and CITEseq on human non-small cell lung cancer (NSCLC) and the krasG12Dp53−/− lung cancer model we previously described a tumor-enriched dendritic cell program of concomitant immunosuppression and activation which we termed the “mregDC,” that was also notable for a strong Th2 immune signature. We subsequently blocked the canonical Th2 cytokine IL-4 in vivo in tumor-bearing mice, and found that this significantly decreased lung tumor burden, which was recapitulated in multiple other tumor models. Furthermore, this effect synergized with PD-L1 blockade. Based on this data, we designed a clinical trial to assess if the addition of dupilumab, an anti-IL-4Ra antibody widely used for treatment of atopic diseases, may rescue responses to checkpoint blockade (NCT05013450). In this Phase 1b/2 trial, up to 21 patients with NSCLC that have progressed on prior anti-PD-(L)1 therapy will be enrolled. Patients continue PD-(L)1 blockade while receiving three doses of dupilumab, administered every three weeks, with initial radiographic assessment of response at 9 weeks. Patients without progression of disease then continue anti-PD-(L)1 alone. The primary endpoint of Phase 1b is safety and tolerability, while the primary endpoint of Phase 2, inclusive of patients from Phase 1b, is efficacy as per RECIST. Patients undergo pre- and on-treatment biopsies, pre-treatment stool collection for microbiome analysis, as well as blood collection at 6 timepoints for PBMCs, plasma and ctDNA. Here we report the Phase 1b portion that has completed accrual in which 6 patients were enrolled in a Phase 1b run-in to confirm safety and tolerability. There were no adverse events attributable to study treatment during Phase 1b in any of the 6 patients treated. Serum proteomic analysis of this cohort revealed that dupilumab treatment induced a profound increase in proinflammatory/tumoricidal immune effector molecules, and reversed a systemic Th2 cytokine signature. Furthermore, mass cytometry of circulating immune populations showed an expansion of cytotoxic lymphocyte populations and a reduction in immunosuppressive myeloid cells. The fourth patient treated on trial who had progressive disease after 9 cycles of consolidation checkpoint blockade following concurrent chemoradiation for squamous NSCLC was enrolled, and had a partial response at 9 weeks, with deepening of the PR at 25 weeks. This patient’s on-treatment biopsy showed a major increase in CD8 T cell tumor infiltration. Histological analysis using spatial transcriptomics and multiplexed imaging from these patients is ongoing, and will be reported at the conference. Based on this promising signal in the initial lead-in, the trial will proceed through Simon’s Two Stage design and enroll a full 21 patients as part of the Phase 2 expansion cohort. This clinical trial is funded entirely through philanthropy support through the Tisch Cancer Institute. Citation Format: Thomas Urban Marron, Nelson M. LaMarche, Matthew D. Park, Samarth Hegde, Bailey Fitzgerald, Clotilde Hennequin, Raphael Mattiuz, Meriem Belabed, Jessica Le Berichel, Barbara Maier, Nicole Hall, Justin Miller, Deborah B. Doroshow, Nicholas Rohs, Rajwanth Veluswamy, Nicholas Venturini, Jorge E. Gomez, Christian Rolfo, David Yankelevitz, Udit Chaddha, Timothy Harkin, Mary B. Beasley, Seunghee Kim-schulze, Sacha Gnjatic, Fred R. Hirsch, Miriam Merad. Rescuing response to ICI by blocking the type-2 immune axis in patients with NSCLC progressing on immunotherapy: A phase 1b/2 trial of dupilumab administered with checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT199.

Atherosclerosis is a chronic inflammatory disease effecting large and medium sized arteries that leads to the buildup of plaque that contributes to myocardial infraction, stroke, and other pathologies. Mounting evidence has identified mitochondrial reactive oxygen species (ROS) as a key contributor to plaque formation and progression. A inner mitochondrial membrane enzyme Nicotinamide nucleotide transhydrogenase (NNT) sustains NADPH pools required for the mitochondrial antioxidant systems. We have observed that the expression of NNT is decreased in severe human atherosclerotic plaques leading us to hypothesize that the loss of NNT contributes to increased mitochondrial ROS and drives the progression of atherosclerosis by enhancing endothelial and vascular dysfunction. Utilizing AAV/PCSK9 and HFD induced models of early and late-stage atherosclerosis, we found that NNT knockout (NNT KO) mice display significantly increased VCAM-1 expression in aortic endothelial cells during early atherosclerosis and significantly larger necrotic cores in late-stage atherosclerosis. Additionally, NNT KO mice displayed a significantly thinner fibrous cap in late-stage plaques. Similar results were observed in vitro where the loss of NNT in human aortic endothelial cells exacerbated oxLDL induced VCAM-1 expression that was associated with decreased mitochondrial NADPH levels, glutathione peroxidase (Gpx2) activity, and increased H 2 O 2 production. The observed increase in necrotic core area in NNT KO mice is suggestive of increased inflammatory cell recruitment to the plaque. Furthermore, bone marrow derived macrophages (BMDM) from NNT KO mice display decreased lipid content, poor lipid uptake and a predisposition to differentiate into a proinflammatory M1 phenotype. Based on these studies, we conclude that the loss of NNT contributes to unstable plaques with large necrotic cores, mitochondrial ROS driven endothelial dysfunction, increased inflammatory cell recruitment, and enhanced M1 macrophage activity. The novel relationship between vascular NNT expression and plaque severity in human samples implicates NNT as a novel clinical target in atherosclerosis.

Background: Malignant pleural mesothelioma (MPM) is usually fatal, though multimodality therapy— now including immunotherapy— has improved survival. Recurrence after surgery is close to 100%, even with adjuvant chemotherapy and radiation. Our collaborators have performed deep immunophenotyping of treatment-naïve MPM lesions using mass cytometry (CyTOF) and single-cell RNA sequencing (scRNAseq) to define the tumor microenvironment. A population of rare CD141+ dendritic cells (DC1) is disproportionately represented in some MPM lesions analyzed. These DC1 cells— which express high levels of Toll-like receptor 3 (TLR3)— are among the most potent cross-presenters of antigen and are key to priming anti-tumor CD4+ and CD8+ T cell responses. Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC), is a double-stranded RNA host-targeted therapeutic viral-mimic. Poly-ICLC activates multiple innate immune receptors including TLR3 and melanoma differentiation-associated gene 5 (MDA5), leading to cross-presentation of antigen to T cells and induction of strong Th1 response. We hypothesize that injection of poly-ICLC prior to surgical resection may activate intratumoral (IT) DC1s, increase tumor antigen presentation to cytotoxic T cells, and induce tumor-specific immune surveillance. Methods: This is a phase I/Ib study to evaluate the safety of IT poly-ICLC prior to surgical resection for patients with MPM (NCT04525859). The primary endpoint is safety as assessed by frequency and severity of toxicities by CTCAE 5.0. Secondary endpoints are objective response as measured by RECIST 1.1 and recurrence free survival measured from the time of first poly-ICLC injection. Exploratory endpoints include evaluation of circulating immune cells (including regulatory T cells and NK cells), evaluation of immune cell infiltration in pre-injection tumor biopsy and surgically resected tissue, as well as characterization of immune parameters such as local B cell specificity. The protocol features a Simon’s two-stage design, with six patients enrolled in a phase I safety cohort, proceeding to a phase Ib expansion cohort (additional 13 patients) if no more than 1 dose limiting toxicity occurs. Eligible patients must have MPM deemed operable by the treating thoracic surgeon. Eligible subjects may not have uncontrolled immunocompromised states or autoimmune disorders. After enrollment, patients undergo biopsies at which time 2mg poly-ICLC is injected across two sites in the tumor. Patients then undergo resection of the tumor (pleurectomy/decortication or extra pleural pneumonectomy per standard of care) at day 21+/- 7 after poly-ICLC injection. Blood is drawn at three points (prior to poly-ICLC injection, at time of surgery, and at a post-operative visit) for immune profiling. At the time of submission six patients have been treated and phase Ib accrual is continuing as planned. Interim analysis of phase I safety and exploratory endpoints will be reported in late 2022. Citation Format: Bailey G. Fitzgerald, Thomas U. Marron, Robert Sweeney, Jorge Gomez, Nicole Hall, Daniel O'Grady, Christian Rolfo, Raj Veluswamy, Deborah Doroshow, John Mandeli, David Yankelevitz, Nina Bhardwaj, Sacha Gnjatic, Fred R. Hirsch, Miriam Merad, Alexander Tsankov, Raja Flores, Andrea Wolf. A phase I/Ib trial of intratumoral Poly-ICLC in resectable malignant pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT205.

TPS9139 Background: Although tumor microenvironments may contain chronic inflammatory cells, this milieu can lead to immune evasion and may contribute to resistance to immunotherapy. Dendritic cells are one of the most potent cross presenters of tumor antigen, and their function is crucial to tumor-directed adaptive immune responses. In the KP mouse model of lung adenocarcinoma (KrasG12D; Tp53-/-), we recently identified interleukin-4 (IL-4)-driven suppression of tumor-antigen charged dendritic cells, which was similarly seen in human lung cancer lesions (Maier, B., et al., A conserved dendritic-cell regulatory program limits antitumour immunity. Nature, 2020.580[7802]:257-262). In the mouse model IL-4 blockade resulted in an increase in IL-12, IFNg and TNF in CD8+ T cells and decreased tumor burden, and further antitumor activity was seen when combined with PD-L1 blockade. Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor alpha subunit which disrupts signaling through receptors for both IL-4 and IL-13; it is FDA approved for patients with multiple atopic conditions, in whom series adverse effects are rare. Based on this pre-clinical data, we hypothesize that the addition of dupilumab to anti PD-(L)1 therapy will be well tolerated, and will rescue the anti-tumor effect of immune checkpoint blockade. Methods: This is a phase Ib/II trial. Patients with relapsed/refractory NSCLC who have received prior anti PD-(L)1 treatment are eligible for enrollment. In a phase Ib safety run-in, six patients will be enrolled in a modified set-dose 3+3 design. If no more than 1 DLT is observed during this phase, the trial will proceed to phase II. Phase II will enroll a further 15 patients in a minimax design with early stopping for futility to a maximum total of 21 patients. Patients will undergo pre-treatment biopsies and peripheral blood sampling prior to receiving 3 doses of dupilumab, administered every three weeks, in conjunction with continuing standard-of-care anti-PD-(L)1 therapy. Patients will undergo repeat biopsies 4 weeks after starting therapy. After completion of dupilumab (at 9 weeks) patients will undergo repeat staging. The primary endpoint of phase 1b is safety as measured by frequency and severity of adverse effects. The primary endpoint of phase II is overall response rate as assessed using RECIST 1.1 criteria at the time of post-dupilumab imaging. Exploratory endpoints include analysis of peripheral blood by CyTOF and O-link, and tissue biopsies will be analyzed by multiplex-IHC and bulk-RNA-sequencing. T cell receptor sequencing will be performed on tumor and matched peripheral blood samples, and circulating tumor DNA will be assessed at multiple time points. Phase 1b is currently enrolling as planned. Clinical trial information: NCT05013450.

Uterine atony remains the major cause of postpartum hemorrhage, and of death from postpartum hemorrhage in the United States. While existing guidelines outlining a general approach to postpartum hemorrhage are useful, recent data suggest that greater specificity may be necessary to significantly impact mortality. We present a highly specific and methodical approach to the management of uterine atony, which addresses what we believe to be the most common cause of preventable maternal hemorrhagic death in the US—lack of an intensive, focused approach to atony and perseverance with therapies that are not working. This protocol should result in cessation of hemorrhage by medical or surgical means within 1 hour of diagnosis. We then apply this protocol to a number of illustrative cases of maternal death due to atony. An approach involving the active management of uterine atony may assist clinicians in avoiding severe morbidity and mortality from uterine atony.

The first of this two-part series on critical illness in pregnancy dealt with obstetric disorders. In Part II, medical conditions that commonly affect pregnant women or worsen during pregnancy are discussed. ARDS occurs more frequently in pregnancy. Strategies commonly used in nonpregnant patients, including permissive hypercapnia, limits for plateau pressure, and prone positioning, may not be acceptable, especially in late pregnancy. Genital tract infections unique to pregnancy include chorioamnionitis, group A streptococcal infection causing toxic shock syndrome, and polymicrobial infection with streptococci, staphylococci, and Clostridium perfringens causing necrotizing vulvitis or fasciitis. Pregnancy predisposes to VTE; D-dimer levels have low specificity in pregnancy. A ventilation-perfusion scan is preferred over CT pulmonary angiography in some situations to reduce radiation to the mother's breasts. Low-molecular-weight or unfractionated heparins form the mainstay of treatment; vitamin K antagonists, oral factor Xa inhibitors, and direct thrombin inhibitors are not recommended in pregnancy. The physiologic hyperdynamic circulation in pregnancy worsens many cardiovascular disorders. It increases risk of pulmonary edema or arrhythmias in mitral stenosis, heart failure in pulmonary hypertension or aortic stenosis, aortic dissection in Marfan syndrome, or valve thrombosis in mechanical heart valves. Common neurologic problems in pregnancy include seizures, altered mental status, visual symptoms, and strokes. Other common conditions discussed are aspiration of gastric contents, OSA, thyroid disorders, diabetic ketoacidosis, and cardiopulmonary arrest in pregnancy. Studies confined to pregnant women are available for only a few of these conditions. We have, therefore, reviewed pregnancy-specific adjustments in the management of these disorders.

Managing critically ill obstetric patients in the ICU is a challenge because of their altered physiology, different normal ranges for laboratory and clinical parameters in pregnancy, and potentially harmful effects of drugs and interventions on the fetus. About 200 to 700 women per 100,000 deliveries require ICU admission. A systematic five-step approach is recommended to enhance maternal and fetal outcomes: (1) differentiate between medical and obstetric disorders with similar manifestations, (2) identify and treat organ dysfunction, (3) assess maternal and fetal risk from continuing pregnancy and decide if delivery/termination of pregnancy will improve outcome, (4) choose an appropriate mode of delivery if necessary, and (5) optimize organ functions for safe delivery. A multidisciplinary team including the intensivist, obstetrician, maternal-fetal medicine specialist, anesthesiologist, neonatologist, nursing specialist, and transfusion medicine expert is key to optimize outcomes. Severe preeclampsia and its complications, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and amniotic fluid embolism, which cause significant organ failure, are reviewed. Obstetric conditions that were not so common in the past are increasingly seen in the ICU. Thrombotic thrombocytopenic purpura of pregnancy is being diagnosed more frequently. Massive hemorrhage from adherent placenta is increasing because of the large number of pregnant women with scars from previous cesarean section. With more complex fetal surgical interventions being performed for congenital disorders, maternal complications are increasing. Ovarian hyperstimulation syndrome is also becoming common because of treatment of infertility with assisted reproduction techniques. Part II will deal with common medical disorders and their management in critically ill pregnant women.

Background: In children and adolescents with a depressive disorder, predicting who will also go on to exhibit suicide-related behaviors (SRBs), including suicide attempt or self-harm, is a key challenge facing clinicians. Aims: To investigate the relative contributions of depressive disorder severity, hopelessness, family dysfunction, and perceived social support to the risk of suicide-related behaviors. Methods: This was a cross-sectional study of a group of 10–16-year-olds with major depressive disorders and dysthymic disorder. Results: Child-rated depressive disorder symptom severity emerged as the greatest predictor of risk. Hopelessness and family dysfunction were also significant predictors of SRBs. In combination these variables were strong predictors, accounting for 66% of the variance. This is a cross-sectional study design, rather than longitudinal, therefore risk prediction over time was not possible. Conclusions: Understanding the child and adolescents depressive disorder symptom severity from their perspective, their level of hopelessness, as well as their family context is critical in understanding the risk of SRBs. These findings may help to provide direction for targeted interventions to address these clinical risk factors.

BackgroundVisuospatial working memory (VSWM) deficits have not been investigated specifically in children with dysthymic disorder (DD), although they are associated with impairments in attention that commonly occur in DD. This study investigates VSWM impairment in children with DD.MethodA cross-sectional study of VSWM in 6- to 12-year-old children with medication-naive DD (n=26) compared to an age-, gender- and ‘performance IQ’ (PIQ)-matched healthy control group (n=28) was completed.ResultsThe DD group demonstrated impairment in VSWM, including impairment in the spatial span and strategy components of VSWM. Furthermore, the VSWM impairment remained after controlling for spatial span. Inattentive symptoms were significantly associated with the VSWM impairment.ConclusionsThis study of children with DD found deficits in performance on VSWM tasks, suggesting that fronto-striatal–parietal neural networks that underlie processes of attention and the executive component of VSWM are dysfunctional in children with DD. These findings further our understanding of DD and suggest more specific interventions that might improve functioning.

Managers are trying various strategies to cope with increased global competition. One approach is to use expatriate assignments to gain understanding of international operations. But failure rates can be high. What can companies do to boost the chances of success? © 2008 Wiley Periodicals, Inc.

While suicidality is clearly associated with depression in young people, predicting which young people with depression will experience suicidal ideation or attempts is an ongoing dilemma for clinicians. This study examined the association of suicidality in young people with major depressive disorder compared to those with dysthymic disorder to investigate whether major depressive disorder, typically considered a more severe disorder, is associated with greater frequency and severity of suicidality. The study showed no distinction between the diagnoses on the basis of the frequency and severity of suicidality. Clinicians should assess the level of depressive disorder symptom severity as well as suicidality when assessing young people, regardless of depressive disorder type. Any suicidality should be treated and carefully monitored.

Visuospatial memory encoding deficits have been reported in adults with schizophrenia, while adolescents with schizophrenia have not been specifically investigated with visuospatial memory encoding and retrieval paradigms. A cross sectional study of delayed matching-to-sample performance in 19 right handed, male, anti-psychotic medication naïve adolescents with undifferentiated schizophrenia and 28 age, gender, IQ and handedness matched healthy participants was completed. The adolescent-onset schizophrenia group demonstrated significant impairment in visuospatial memory, independent of the degree of delay, consistent with an encoding impairment. The impaired encoding phase of visuospatial memory in the adolescent-onset schizophrenia group is consistent with findings in adult onset schizophrenia samples, suggesting a developmental stage-independent deficit.

Hospitals are no strangers to mistakes and it is well known that errors occur regularly in United States hospitals. In understanding patient safety issues in the healthcare setting the Joint Commission determined that up to “80% of serious medical errors” relate back to communication. Nurses provide a large portion of care in hospital settings and as such are uniquely positioned to speak up when processes aren't followed or improper practices are observed with the potential to prevent errors. In light of the fact that communication is such a significant factor in medical errors, one can understand the importance of a healthcare industry where speaking up is the norm. By supporting the expectation that nurses speak up, organizations can improve patient safety. Factors such as leaders who are good role models and organizations that reward speaking up can be built upon to strengthen a hospital’s culture of safety. Starting a conversation in organizations about the practice of speaking up is needed to end silence in hospitals to help prevent useless loss of function, life, and healthcare dollars.

This study determines that visuospatial working memory (VSWM) deficits are evident in adolescent-onset schizophrenia, while the spatial strategy and spatial span components of VSWM are spared. These findings imply that frontal-striatal-parietal neural networks are dysfunctional in adolescent-onset schizophrenia, while mid-dorsolateral and ventrolateral PFC functions remain intact: the current conceptualisation of schizophrenia as a progressive neurodevelopmental disorder is consistent with these results.

Poly(ɛ-caprolactone)- b -polystyrene with vacant bipyridine coordinating sites and metallated AB type diblock with well-defined metal loci in the polymer chain were synthesized and characterized. Solution atom transfer radical polymerization (ATRP) of styrene where a poly(ɛ-caprolactone) macromonomer acted as initiator and derivative complex of [Ru( p -cymene)Cl 2 ] 2 as catalyst is reported. ATRP reaction conditions with respect to polymer molecular weights and polydispersity indices (PDI) of the target bifunctional polymers were examined. Electronic absorption and emission spectra of the resultant functional polymers provided evidence of the ruthenium metal chromophores in the diblock copolymer. The thermal properties of all polymers were investigated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), and indicated that they possess a high thermal stability and are miscible in the molten state. The semicrystalline nature of the PCL macroligand and the morphology of thin films of the metal free diblocks were also elucidated by combination of atomic force microscopy (AFM), scanning electron microscopy (SEM) and wide angle X-ray diffraction (WAXD) studies.

Background. The ability to inhibit inappropriate or unwanted actions is a key element of executive control. The existence of executive function deficits in schizophrenia is consistent with frontal lobe theories of the disorder. Relatively few studies have examined response inhibition in schizophrenia, and none in adolescent patients with early-onset schizophrenia (EOS).Methods. Twenty-one adolescents with the onset of clinically impairing psychosis before 19 years of age and 16 matched controls performed a stop-signal task to assess response inhibition. The patients with EOS were categorized as paranoid (n=10) and undifferentiated subtypes (n=11). The undifferentiated group had higher levels of negative symptomatology. Stop-signal reaction time (SSRT) and go-signal reaction time (Go-RT) were analysed with respect to hand of response.Results. The undifferentiated early-onset patients had significantly longer SSRTs, indicative of poor response inhibition, for the left hand compared to the paranoid early-onset patients and control participants. No differences existed for inhibitory control with the right hand. The three groups did not differ in Go-RT.Conclusions. Our results indicate a specific lateralized impairment of response inhibition in patients with undifferentiated, but not paranoid, EOS. These findings are consistent with reports of immature frontostriatal networks in EOS and implicate areas such as the pre-motor cortex and supplementary motor area (SMA) that are thought to play a role in both voluntary initiation and inhibition of movement.

To describe lessons learned in developing the CEASE tobacco control intervention.Descriptive report.Tobacco use and tobacco smoke exposure harm families in a multitude of ways. The child health care setting is the ideal location to address parental smoking and tobacco smoke exposure in children. Few interventions have been developed specifically for families in the child health care setting. One such intervention, the CEASE program, was developed with assistance from tobacco control experts, pediatric researchers, policy makers, and child health care clinicians to address parental smoking.An effective tobacco cessation intervention can be developed in a systematic way that may not require extensive resources and expertise.

Campylobacter jejuni is a frequent bacterial pathogen causing gastroenteritis worldwide. We report here a mathematically optimized combination of 10 loci selected from 2 previously published binary typing panels. The optimized combination offers advantages of higher differentiation capability, simplicity, cost-effectiveness, and portability for routine surveillance and outbreak investigations of C. jejuni.

OBJECTIVE:To determine prevalence and factors associated with strictly enforced smoke-free car policies among smoking parents.METHODS:As part of a cluster, randomized controlled trial addressing parental smoking, exit interviews were conducted with parents whose children were seen in 10 control pediatric practices. Parents who smoked were asked about smoking behaviors in their car and receipt of smoke-free car advice at the visit. Parents were considered to have a “strictly enforced smoke-free car policy” if they reported having a smoke-free car policy and nobody had smoked in their car within the past 3 months.RESULTS:Of 981 smoking parents, 817 (83%) had a car; of these, 795 parents answered questions about their car smoking policy. Of these 795 parents, 29% reported having a smoke-free car policy, and 24% had a strictly enforced smoke-free car policy. Of the 562 parents without a smoke-free car policy, 48% reported that smoking occurred with children present. Few parents who smoke (12%) were advised to have a smoke-free car. Multivariable logistic regression controlling for parent age, gender, education, and race showed that having a younger child and smoking ≤10 cigarettes per day were associated with having a strictly enforced smoke-free car policy.CONCLUSIONS:The majority of smoking parents exposed their children to tobacco smoke in cars. Coupled with the finding of low rates of pediatricians addressing smoking in cars, this study highlights the need for improved pediatric interventions, public health campaigns, and policies regarding smoke-free car laws to protect children from tobacco smoke.

The associations between neurodevelopmental deficits (NDD) and (1) attention deficit hyperactivity disorder, combined type (ADHD-CT) and (2) internalising disorders have been replicated. To date, the specific association between standardized NDD and carefully defined ADHD-CT alone, dysthymic disorder alone and anxiety disorders alone has not been systematically investigated in children of primary school age. A cross-sectional study of NDD in 99 six- to 12-year-old children with categorically and dimensionally defined ADHD-CT alone, dysthymic disorder alone and anxiety disorders alone and 20 age-matched healthy children was undertaken. The ADHD-CT and dysthymic disorder groups had increased total neurological subtle signs, compared to the anxiety disorders group, which, in turn, had increased total neurological subtle signs compared with the healthy children. Interestingly, the dysthymic disorder children had increased conjugate eye gaze difficulties compared with the other three groups. The differences remained after controlling for full scale IQ. These findings suggest a neurobiological underpinning of dysthymic disorder, while confirming that of ADHD-CT in primary school age children. Future studies will explore whether the above more specific neurological subtle signs are developmental phase specific or independent associations.

BackgroundThe CEASE (Clinical Effort Against Secondhand Smoke Exposure) intervention was developed to help pediatricians routinely and effectively address the harms of family smoking behaviors. Based on paper versions of CEASE, we partnered with the American Academy of Pediatrics’ online education department and developed a completely distance-based training, including an online CME training, handouts and education materials for families, and phone and email support.MethodsThe pediatric offices of two low income health clinics with primarily Medicaid populations were selected for the study. Pre and post intervention data by survey of the parents was collected in both practices (Practice 1 n = 470; Practice 2 n = 177). The primary outcome for this study was a comparison of rates of clinician’s asking and advising parents about smoking and smoke-free home and cars.ResultsExit surveys of parents revealed statistically significant increases in rates of clinicians asking about parental smoking (22% vs. 41%), smoke-free rules (25% vs. 44%), and asking about other smoking household members (26% vs. 48%).ConclusionsThrough a completely distance based intervention, we were able to train pediatricians who see low income children to ask parents about smoking, smoke-free home and car rules, and whether other household members smoke. Implementing a system to routinely ask about family tobacco use and smoke-free home and car rules is a first step to effectively addressing tobacco in a pediatric office setting. By knowing which family members use tobacco, pediatricians can take the next steps to help families become completely tobacco-free.Trial registrationClinical trials number:NCT01087177

Background Role conflict can motivate behavior change. No prior studies have explored the association between parent/smoker role conflict and readiness to quit. The objective of the study is to assess the association of a measure of parent/smoker role conflict with other parent and child characteristics and to test the hypothesis that parent/smoker role conflict is associated with a parent’s intention to quit smoking in the next 30 days. As part of a cluster randomized controlled trial to address parental smoking (Clinical Effort Against Secondhand Smoke Exposure—CEASE), research assistants completed exit interviews with 1980 parents whose children had been seen in 20 Pediatric Research in Office Settings (PROS) practices and asked a novel identity-conflict question about “how strongly you agree or disagree” with the statement, “My being a smoker gets in the way of my being a parent.” Response choices were dichotomized as “Strongly Agree” or “Agree” versus “Disagree” or “Strongly Disagree” for the analysis. Parents were also asked whether they were “seriously planning to quit smoking in 30 days.” Chi-square and logistic regression were performed to assess the association between role conflict and other parent/children characteristics. A similar strategy was used to determine whether role conflict was independently associated with intention to quit in the next 30 days. Methods As part of a RTC in 20 pediatric practices, exit interviews were held with smoking parents after their child’s exam. Parents who smoked were asked questions about smoking behavior, smoke-free home and car rules, and role conflict. Role conflict was assessed with the question, “Please tell me how strongly you agree or disagree with the statement: ‘My being a smoker gets in the way of my being a parent.’ (Answer choices were: “Strongly agree, Agree, Disagree, Strongly Disagree.”) Results Of 1980 eligible smokers identified, 1935 (97%) responded to the role-conflict question, and of those, 563 (29%) reported experiencing conflict. Factors that were significantly associated with parent/smoker role conflict in the multivariable model included: being non-Hispanic white, allowing home smoking, the child being seen that day for a sick visit, parents receiving any assistance for their smoking, and planning to quit in the next 30 days. In a separate multivariable logistic regression model, parent/smoker role conflict was independently associated with intention to quit in the next 30 days [AOR 2.25 (95% CI 1.80-2.18)]. Conclusion This study demonstrated an association between parent/smoker role conflict and readiness to quit. Interventions that increase parent/smoker role conflict might act to increase readiness to quit among parents who smoke. Trial registration Clinical trial registration number: NCT00664261.