Chain Length Dependence of Electron Transport in an n-Type Conjugated Polymer with a Rigid-Rod Chain Topology.

Most currently known n-type conjugated polymers have a semiflexible chain topology, and their charge carrier mobilities are known to peak at modest chain lengths of below 40-60 repeat units. Herein, we show that the field-effect electron mobility of a model n-type conjugated polymer that has a rigid-rod chain topology grows continuously without saturation, even at a chain length exceeding 250 repeat units. We found the mechanism underlying the novel chain length-dependent electron transport to originate from the reduced structural disorder and energetic disorder with the increasing degree of polymerization inherent to the rigid-rod chain topology. Furthermore, we demonstrate a unique chain length-dependent decay of threshold voltage, which is rationalized by decreased trap densities and trap depths with respect to the degree of polymerization. Our findings provide new insights into the role of polymer chain topology in electron transport and demonstrate the promise of rigid-rod chain architectures for the design of future high-mobility conjugated polymers.

Asthma symptoms, spirometry and air pollution exposure in schoolchildren in an informal settlement and an affluent area of Nairobi, Kenya.

BACKGROUND: Although 1 billion people live in informal (slum) settlements, the consequences for respiratory health of living in these settlements remain largely unknown. This study investigated whether children living in an informal settlement in Nairobi, Kenya are at increased risk of asthma symptoms. METHODS: Children attending schools in Mukuru (an informal settlement in Nairobi) and a more affluent area (Buruburu) were compared. Questionnaires quantified respiratory symptoms and environmental exposures; spirometry was performed; personal exposure to particulate matter (PM2.5) was estimated. RESULTS: 2373 children participated, 1277 in Mukuru (median age, IQR 11, 9-13 years, 53% girls), and 1096 in Buruburu (10, 8-12 years, 52% girls). Mukuru schoolchildren were from less affluent homes, had greater exposure to pollution sources and PM2.5. When compared with Buruburu schoolchildren, Mukuru schoolchildren had a greater prevalence of symptoms, 'current wheeze' (9.5% vs 6.4%, p=0.007) and 'trouble breathing' (16.3% vs 12.6%, p=0.01), and these symptoms were more severe and problematic. Diagnosed asthma was more common in Buruburu (2.8% vs 1.2%, p=0.004). Spirometry did not differ between Mukuru and Buruburu. Regardless of community, significant adverse associations were observed with self-reported exposure to 'vapours, dusts, gases, fumes', mosquito coil burning, adult smoker(s) in the home, refuse burning near homes and residential proximity to roads. CONCLUSION: Children living in informal settlements are more likely to develop wheezing symptoms consistent with asthma that are more severe but less likely to be diagnosed as asthma. Self-reported but not objectively measured air pollution exposure was associated with increased risk of asthma symptoms.

Interaction of pre- and postnatal nutrition on expression of leptin receptor variants and transporter molecules, leptin transport, and functional response to leptin in heifers†.

Perinatal nutrition modulates the hypothalamic neurocircuitries controlling GnRH release, thus programming pubertal maturation in female mammals. Objectives of experiments reported here were to test the hypotheses that prenatal nutrition during mid- to late gestation interacts with postnatal nutrition during the juvenile period in heifer offspring to alter expression of leptin receptor (LepR) variants (ObRa, ObRb, ObRc, ObRt), and lipoprotein transporter molecules (LRP1 and 2) in the choroid plexus, leptin transport across the blood-brain barrier, and hypothalamic-hypophyseal responsiveness to exogenous ovine leptin (oleptin) during fasting. Nutritional programming of heifers employed a 3 × 2 factorial design of maternal (high, H; low, L; and moderate, M) × postnatal (H and L) dietary treatments. Results (Expt. 1) demonstrated that prepubertal heifers born to L dams, regardless of postnatal diet, had reduced expression of the short isoform of ObRc compared to H and M dams, with sporadic effects of undernutrition (L or LL) on ObRb, ObRt, and LRP1. Intravenous administration of oleptin to a selected postpubertal group (HH, MH, LL) of ovariectomized, estradiol-implanted heifers fasted for 56 h (Expt. 2) did not create detectable increases in third ventricle cerebrospinal fluid but increased gonadotropin secretion in all nutritional groups tested. Previous work has shown that leptin enhances gonadotropin secretion during fasting via effects at both hypothalamic and anterior pituitary levels in cattle. Given the apparent lack of robust transfer of leptin across the blood-brain barrier in the current study, effects of leptin at the adenohypophyseal level may predominate in this experimental model.

The health care and societal costs of inherited retinal diseases in Australia: a microsimulation modelling study.

OBJECTIVES: To estimate the health care and societal costs of inherited retinal diseases (IRDs) in Australia. DESIGN, SETTING, PARTICIPANTS: Microsimulation modelling study based on primary data - collected in interviews of people with IRDs who had ophthalmic or genetic consultations at the Children's Hospital at Westmead or the Save Sight Institute (both Sydney) during 1 January 2019 - 31 December 2020, and of their carers and spouses - and linked Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Schedule (PBS) data. MAIN OUTCOME MEASURES: Annual and lifetime costs for people with IRDs and for their carers and spouses, grouped by payer (Australian government, state governments, individuals, private health insurance) and type (health care costs; societal costs: social support, National Disability Insurance Scheme (NDIS), income and taxation, costs associated with caring for family members with IRDs); estimated annual national cost of IRDs. RESULTS: Ninety-four people (74 adults, 20 people under 18 years; 55 girls and women [59%]) and 30 carers completed study surveys (participation rate: adults, 66%; children, 66%; carers, 63%). Total estimated lifetime cost was $5.2 million per person with an IRD, of which 87% were societal and 13% health care costs. The three highest cost items were lost income for people with IRDs ($1.4 million), lost income for their carers and spouses ($1.1 million), and social spending by the Australian government (excluding NDIS expenses: $1.0 million). Annual costs were twice as high for people who were legally blind as for those with less impaired vision ($83 910 v $41 357 per person). The estimated total annual cost of IRDs in Australia was $781 million to $1.56 billion. CONCLUSION: As the societal costs associated with IRDs are much larger than the health care costs, both contributors should be considered when assessing the cost-effectiveness of interventions for people with IRDs. The increasing loss of income across life reflects the impact of IRDs on employment and career opportunities.

Wide-Field Calcium Imaging of Dynamic Cortical Networks during Locomotion.

Motor behavior results in complex exchanges of motor and sensory information across cortical regions. Therefore, fully understanding the cerebral cortex's role in motor behavior requires a mesoscopic-level description of the cortical regions engaged, their functional interactions, and how these functional interactions change with behavioral state. Mesoscopic Ca2+ imaging through transparent polymer skulls in mice reveals elevated activation of the dorsal cerebral cortex during locomotion. Using the correlations between the time series of Ca2+ fluorescence from 28 regions (nodes) obtained using spatial independent component analysis (sICA), we examined the changes in functional connectivity of the cortex from rest to locomotion with a goal of understanding the changes to the cortical functional state that facilitate locomotion. Both the transitions from rest to locomotion and from locomotion to rest show marked increases in correlation among most nodes. However, once a steady state of continued locomotion is reached, many nodes, including primary motor and somatosensory nodes, show decreases in correlations, while retrosplenial and the most anterior nodes of the secondary motor cortex show increases. These results highlight the changes in functional connectivity in the cerebral cortex, representing a series of changes in the cortical state from rest to locomotion and on return to rest.

Staying Together No Matter What: Becoming Young Parents on the Streets of Vancouver.

Among young people who use drugs in the context of entrenched poverty and homelessness, pregnancy is often viewed as an event that can meaningfully change the trajectory of their lives. However, youth's desires and decision-making do not always align with the perspectives of various professionals and systems regarding how best to intervene during pregnancies and early parenting. Drawing on longitudinal interviews and fieldwork with young people in Vancouver, Canada, we explore how their romantic relationships powerfully shaped understandings of what was right and wrong and which actions to take during pregnancy and early parenting, and how these moral worlds frequently clashed with the imperatives of healthcare, criminal justice, and child protection systems. We demonstrate how a disjuncture between youth's desires, decision-making and moralities, and the systems that are intended to help them, can further entrench young people in cycles of loss, defeat, and harm. These cycles are powerfully racialized for young Indigenous people in our context.

Peripheral Skeletal Muscle Impairment in Children After Treatment for Leukemia and Lymphoma.

Exercise intolerance is a common adverse effect of childhood cancer, contributing to impaired health and well-being. While reduced aerobic fitness has been attributed to central cardiovascular deficiencies, the involvement of peripheral musculature has not been investigated. We studied peripheral muscle function in children following cancer treatment using noninvasive phosphorus-31 magnetic resonance spectroscopy. Ten acute lymphoblastic leukemia (ALL) and 1 lymphoma patient 8 to 18 years of age who completed treatment 6 to 36 months prior and 11 healthy controls participated in the study. Phosphorus-31 magnetic resonance spectroscopy was used to characterize muscle bioenergetics at rest and following an in-magnet knee-extension exercise. Exercise capacity was evaluated using a submaximal graded treadmill test. Both analysis of variance and Cohen d were used as statistical methods to determine the statistical significance and magnitude of differences, respectively, on these parameters between the patient and control groups. The patients treated for ALL and lymphoma exhibited lower anaerobic function ( P =0.14, d =0.72), slower metabolic recovery ( P =0.08, d =0.93), and lower mechanical muscle power ( d =1.09) during exercise compared with healthy controls. Patients demonstrated lower estimated VO 2peak (41.61±5.97 vs. 47.71±9.99 mL/min/kg, P =0.11, d =0.76), lower minutes of physical activity (58.3±35.3 vs. 114.8±79.3 min, P =0.12, d =0.99) and higher minutes of inactivity (107.3±74.0 vs. 43.5±48.3 min, d =1.04, P <0.05). Children treated for ALL and lymphoma exhibit altered peripheral skeletal muscle metabolism during exercise. Both deconditioning and direct effects of chemotherapy likely contribute to exercise intolerance in this population.

MUREs: a new member of the URE-CURE family of research opportunities for undergrads.

Undergraduate research experiences are important for the development of scientific identity, appreciation of authentic research, and improvement of persistence toward science careers. We identified a gap in experiential research opportunities for undergraduate Biology students who were seeking a formal yet small-scale research experience that was unique to their own interests and career aspirations. These opportunities may be especially worthwhile for of science, technology, engineering, and mathematics (STEM) students aspiring to nonresearch scientific careers (i.e., medicine, dentistry, forensics, and communication) and underrepresented STEM students. Here, we reflect on the use of small-scale, individualized undergraduate research experiences that are based on established methods. These experiences have helped to fill this gap and create problem-centered learning opportunities for undergraduate students that are as unique as the students themselves.

Fluticasone furoate/vilanterol versus fluticasone propionate in patients with asthma and exercise-induced bronchoconstriction.

Objective: To investigate whether once-daily (OD) fluticasone furoate (FF)/vilanterol (VI) provides greater long-term protection from postexercise fall in forced expiratory volume in 1 s (FEV1) than twice-daily (BD) fluticasone propionate (FP) in patients with asthma and exercise-induced bronchoconstriction. Methods: A randomized, double-blind, crossover study was conducted in patients (aged 12-50 years) on low-/mid-dose maintenance inhaled corticosteroid. Following a 4-week run-in period (FP 250 µg BD), patients with a ≥ 20% decrease in postexercise FEV1 received FF/VI 100/25 µg OD or FP 250 µg BD for 2 weeks. Exercise challenges were carried out 23 h after the first dose of study medication, and 12 and 23 h after evening clinic dose at the end of the 2-week treatment period. After a 2-week washout period (FP 250 µg), patients crossed over treatments, with procedures and tests repeated. The primary endpoint was mean maximal percentage decrease from pre-exercise FEV1 following exercise challenge 12-h postevening dose on Day 14. Results: The mean maximal percentage decrease from pre-exercise FEV1 after the 12-h exercise challenge (Day 14) was 15.02% with FF/VI, and 16.71% with FP (difference, -1.69; 95% confidence interval, -3.76 to 0.39; p = 0.109). After the 23-h exercise challenge (Day 14), respective mean maximal decreases were 11.90% and 14.05% (difference, -2.15; 95% confidence interval, -4.31 to 0.01). Conclusion: The study failed to show a difference between FF/VI and FP at providing long-term protection from exercise-induced bronchoconstriction.

Analysis of Mild Traumatic Brain Injury Outpatient Follow-Up.

BACKGROUND: Mild traumatic brain injury (mTBI) remains a prevalent public health concern. Implementation of an mTBI guideline encouraged screening all patients at risk for mTBI, followed by outpatient follow-up in a "concussion clinic." This resulted in an increase in inpatient concussion evaluations, followed by high-volume referral to the concussion clinic. This prompted the routine use of an outpatient mTBI symptom screening tool. The purpose of this quality improvement study was to analyze the characteristics of an mTBI population at outpatient follow-up and describe the clinicians' care recommendations as determined through the use of an mTBI symptom screening tool. METHODS: This is a retrospective review of mTBI patients at a Level 1 trauma center. The study includes patients who completed a concussion screening in the outpatient setting over a 6-month period. Patients were included if older than 16 years, sustained blunt trauma, and had a formal neurocognitive evaluation by a certified speech therapist within 48 hr of initial injury. RESULTS: Of the 247 patients included, 197 (79.8%) were referred to the concussion clinic, 33 (13.4%) had no further outpatient needs, and 17 (6.9%) were referred for outpatient neurocognitive rehabilitation. On follow-up, 97 patients were deemed to have no further postconcussion needs by the trauma nurse practitioner; 57 patients were cleared by the speech therapist. In total, 43 outpatient mTBI follow-up encounters resulted in referral for ongoing therapy. CONCLUSION: Routine screening for concussion symptoms and detailed clinical evaluation allows for prompt recognition of further posttraumatic mTBI needs.

Analysis of an American College of Surgeons Committee on Trauma (ACS-COT) Approved Pilot Project: Increasing Provider Communication During Interhospital Transfer.

The American College of Surgeons Committee on Trauma requires physician-to-physician communication prior to interhospital transfer. This requirement can be difficult to achieve in high-volume trauma centers. This pilot project utilizes trauma advanced practice providers (APPs) as the primary communicator, in lieu of the trauma surgeon, prior to interhospital transfer. The hypothesis suggests that APPs can provide safe recommendations and accurately triage patients for the highest level trauma alert. From January to April 2018, a total of 1,145 patients were transferred to a Level I or Level II trauma center. All interhospital trauma transfers were dispatched through a designated transfer center APP (TCAPP). Descriptive statistics were used to describe the frequency of core TCAPP recommendations, including reversal agents for anticoagulants, antibiotics for open fractures, direct admission criteria, administration of blood products, and triaging to the highest level of trauma activation. TCAPP triage accuracy was analyzed and reported as percentages. Percentages are compared between independent groups using a chi-square test. Prior to implementation of the TCAPP role, provider-to-provider communication occurred in less than 1% of interhospital transfers; TCAPP-to-provider communication occurred 92% of the time (p < .001). During the study period, the TCAPP made 398 care-related recommendations. Three (<1%) TCAPP recommendations were deemed inappropriate. The TCAPP (89.7%) and physician (89.9%) triage accuracy was not significantly different (p = .43). Interhospital transfer communication and recommendations can be performed safely and accurately by a trauma trained APP.

Impaired vascular function in exercising anovulatory premenopausal women is associated with low bone mineral density.

In estrogen-deficient post-menopausal women, osteoporosis shares a common link with cardiovascular disease risk, including endothelial dysfunction. The current study sought to examine associations between bone mineral density (BMD) and endothelial function in estrogen-deficient premenopausal women with exercise-associated menstrual disturbances. Recreationally trained women (24.3 ± 0.8 years; overall mean ± SEM) who were estrogen deficient (amenorrheic or eumenorrheic anovulatory cycles; E2Def; n = 13) or estrogen replete (eumenorrheic ovulatory cycles; E2Rep; n = 14) were studied. Total body and lumbar BMD (L1-L4) were determined using dual-energy X-ray absorptiometry. Serum markers of oxidative stress (oxidized low-density lipoprotein; OxLDL), energy deficiency (triiodothyronine), and bone turnover (osteocalcin, c-telopeptide X, P1NP) were assessed. Estrogen exposure was determined by assessing daily urinary estrone-3-glucuronide (E1G) across a monitoring period. Calf blood flow (CBF), an index of endothelial function, was measured using strain-gauge plethysmography. CBF, total body and L1-L4 BMD, triiodothyronine and E1G were lower (P < 0.05), and c-telopeptide crosslinks higher (P < 0.05) in E2Def. Osteocalcin and OxLDL did not differ (P > 0.05) between groups. L1-L4 BMD, osteocalcin, and E1G were the strongest predictors of CBF (R2 =0.615, P < 0.001). CBF was the strongest predictor of L1-L4 BMD (R2 =0.478, P < 0.001). L1-L4 (r = 0.558, P = 0.008) and CBF (r = 0.534, P = 0.004) were independently correlated with E1G. In young recreationally trained premenopausal women with anovulatory menstrual disturbances, low CBF predicts decreased lumbar BMD, suggesting impaired peripheral endothelial function may predict early unfavorable changes in bone metabolism. This finding may be of relevance in the early detection of cardiovascular and bone health decrements in otherwise healthy estrogen-deficient premenopausal women.

Physical activity for children with chronic disease; a narrative review and practical applications.

BACKGROUND: Physical activity (PA) is associated with a diverse range of health benefits. International guidelines suggest that children should be participating in a minimum of 60 min of moderate to vigorous intensity PA per day to achieve these benefits. However, current guidelines are intended for healthy children, and thus may not be applicable to children with a chronic disease. Specifically, the dose of PA and disease specific exercise considerations are not included in these guidelines, leaving such children with few, if any, evidence-based informed suggestions pertaining to PA. Thus, the purpose of this narrative review was to consider current literature in the area of exercise as medicine and provide practical applications for exercise in five prevalent pediatric chronic diseases: respiratory, congenital heart, metabolic, systemic inflammatory/autoimmune, and cancer. METHODS: For each disease, we present the pathophysiology of exercise intolerance, summarize the pediatric exercise intervention research, and provide PA suggestions. RESULTS: Overall, exercise intolerance is prevalent in pediatric chronic disease. PA is important and safe for most children with a chronic disease, however exercise prescription should involve the entire health care team to create an individualized program. CONCLUSIONS: Future research, including a systematic review to create evidence-based guidelines, is needed to better understand the safety and efficacy of exercise among children with chronic disease.

Sepsis now a priority: a quality improvement initiative for early sepsis recognition and care.

OBJECTIVE: To develop a triage-based screening algorithm and treatment order-sets aimed at improving the quality of care of all patients with sepsis presenting to our emergency department (ED). DESIGN: Retrospective cohort study conducted during a pre-intervention period from 1 April 2010 to 31 March 2011 and a post-intervention period from 1 September 2014 to 30 April 2015. SETTING: A large teaching hospital located in Toronto, Ontario, Canada with a 35-bed ED. PARTICIPANTS: All patients meeting pre-specified sepsis criteria during the ED encounter. MAIN OUTCOME MEASURES: Process of care measures included time to assessment by emergency physician, lactate measurement, blood culture collection, fluid and antibiotic administration. Intensive care unit (ICU) outcomes including admissions, length of stay (LOS) and deaths were reviewed. RESULTS: There were 346 patients pre-intervention, and 270 patients post-intervention. We significantly improved all process measures including mean time to antibiotics by 60 min (P = 0.003) and proportion of patients receiving fluid resuscitation (64.7% vs. 94.4%, P < 0.001). There was no significant difference in the number of patients admitted to ICU (P = 0.14). The median ICU LOS was shorter in the post-intervention group [2.0 days (interquartile range (IQR) 1.0-4.5 days) vs. 5.0 days (IQR 1.5-10.8 days), P = 0.04], and there was no difference in in-hospital mortality between groups (P = 0.27). CONCLUSIONS: We have demonstrated that a triage-based sepsis screening tool results in expedited and consistent delivery of care, with a significant improvement in initial resuscitation measures.

Clinical and Radiographic Results of Attune and PFC Sigma Knee Designs at 2-Year Follow-Up: A Prospective Matched-Pair Analysis.

BACKGROUND: Anterior knee pain (AKP) and/or crepitation are important causes of dissatisfaction after total knee arthroplasty (TKA). Aim of this prospective, matched-pair study was to compare 2 different designs of patellofemoral (ie, trochlear groove) TKA. The Attune knee has an anatomic trochlear groove with a medialized dome patellar component vs the PFC Sigma with a single radius trochlear groove with a domed shaped patella. METHODS: Between January 2010 and December 2014, 100 consecutive Attune TKAs were matched to 100 PFC Sigma TKAs based on age, gender, side, and body mass index. All surgeries were performed via medial parapatellar approach and used cemented, posterior-stabilized implants with patellar resurfacing. Clinical evaluations were assessed using Knee Society Scores (KSS) and a patient-administered questionnaire at 2-year follow-up (range, 1.5-3 years). RESULTS: Based on the KSS clinical rating system, excellent clinical results were achieved in 89.4% and 90.7% of Attune and PFC Sigma TKAs, respectively. There were no significant differences in the KS pain or function scores. The overall incidence of AKP was significantly lower with the Attune knee compared to that of the PFC Sigma (12.5% vs 25.8%; P = .02). The incidence of hearing or feeling noise was also less with the Attune knee (17.7% vs 30.9%; P = .02). The incidence of painful crepitation was low in both groups (1.0% vs 4.1%) with no significant difference between groups (P = .37). Both groups had similar high satisfaction scores of 8.6 and 8.4 for the Attune and PFC groups, respectively (P = .09). CONCLUSION: At 2-year follow-up, there were no differences between the PFC Sigma and Attune knees in KSS or satisfaction. However, the Attune group had a lesser incidence of AKP and crepitation. Further studies should focus on AKP and noise in cruciate-retaining knees.

A phase 2, multicenter study investigating ofatumumab and bendamustine combination in patients with untreated or relapsed CLL.

The purpose of this study is to assess the safety and efficacy of the combination of ofatumumab and bendamustine in patients with previously untreated or relapsed chronic lymphocytic leukemia. Patients received IV ofatumumab (cycle 1: 300 mg day 1 and 1,000 mg day 8; cycles 2-6: 1,000 mg on day 1 every 28 days) and IV bendamustine 90 mg m(-2) (previously untreated) or 70 mg m(-2) (relapsed) on days 1 and 2 of each 28-day cycle, for up to 6 cycles. Forty-four previously untreated and 53 relapsed patients were enrolled. Median age was 62.5 years (previously untreated) and 68 years (relapsed); relapsed patients had received a median of 1 (range 1-11) prior therapy. The investigator-assessed overall response rate was 95% (43% complete response [CR]) for the previously untreated, and 74% (11% CR) for the relapsed patients. The regimen was well tolerated with 89% (previously untreated) and 85% (relapsed patients) receiving all 6 cycles. No unexpected toxicities were reported. Grade 3/4 events occurred in 57% of previously untreated, and 72% of relapsed patients. At ∼29 months' follow-up, the median progression-free survival (PFS) was not reached for the previously untreated population, and the 28-month PFS estimate was 72.3%. The median PFS for the relapsed population was 22.5 months (95% CI: 14.0-27.3 months). The combination of ofatumumab and bendamustine was well tolerated and effective in these previously untreated or relapsed populations. Am. J. Hematol. 91:900-906, 2016. © 2016 Wiley Periodicals, Inc.

To have your citizen science cake and eat it? Delivering research and outreach through Open Air Laboratories (OPAL).

BACKGROUND: The vast array of citizen science projects which have blossomed over the last decade span a spectrum of objectives from research to outreach. While some focus primarily on the collection of rigorous scientific data and others are positioned towards the public engagement end of the gradient, the majority of initiatives attempt to balance the two. Although meeting multiple aims can be seen as a 'win-win' situation, it can also yield significant challenges as allocating resources to one element means that they may be diverted away from the other. Here we analyse one such programme which set out to find an effective equilibrium between these arguably polarised goals. Through the lens of the Open Air Laboratories (OPAL) programme we explore the inherent trade-offs encountered under four indicators derived from an independent citizen science evaluation framework. Assimilating experience from the OPAL network we investigate practical approaches taken to tackle arising tensions. RESULTS: Working backwards from project delivery to design, we found the following elements to be important: ensuring outputs are fit for purpose, developing strong internal and external collaborations, building a sufficiently diverse partnership and considering target audiences. We combine these 'operational indicators' with four pre-existing 'outcome indicators' to create a model which can be used to shape the planning and delivery of a citizen science project. CONCLUSIONS: Our findings suggest that whether the proverb in the title rings true will largely depend on the identification of challenges along the way and the ability to address these conflicts throughout the citizen science project.

Advanced Practice Nursing Committee on Process Improvement in Trauma: An Innovative Application of the Strong Model.

This article aims to summarize the successes and future implications for a nurse practitioner-driven committee on process improvement in trauma. The trauma nurse practitioner is uniquely positioned to recognize the need for clinical process improvement and enact change within the clinical setting. Application of the Strong Model of Advanced Practice proves to actively engage the trauma nurse practitioner in process improvement initiatives. Through enhancing nurse practitioner professional engagement, the committee aims to improve health care delivery to the traumatically injured patient. A retrospective review of the committee's first year reveals trauma nurse practitioner success in the domains of direct comprehensive care, support of systems, education, and leadership. The need for increased trauma nurse practitioner involvement has been identified for the domains of research and publication.

Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci.

Psoriasis (PS) and Crohn disease (CD) have been shown to be epidemiologically, pathologically, and therapeutically connected, but little is known about their shared genetic causes. We performed meta-analyses of five published genome-wide association studies on PS (2,529 cases and 4,955 controls) and CD (2,142 cases and 5,505 controls), followed up 20 loci that showed strongest evidence for shared disease association and, furthermore, tested cross-disease associations for previously reported PS and CD risk alleles in additional 6,115 PS cases, 4,073 CD cases, and 10,100 controls. We identified seven susceptibility loci outside the human leukocyte antigen region (9p24 near JAK2, 10q22 at ZMIZ1, 11q13 near PRDX5, 16p13 near SOCS1, 17q21 at STAT3, 19p13 near FUT2, and 22q11 at YDJC) shared between PS and CD with genome-wide significance (p < 5 × 10(-8)) and confirmed four already established PS and CD risk loci (IL23R, IL12B, REL, and TYK2). Three of the shared loci are also genome-wide significantly associated with PS alone (10q22 at ZMIZ1, p(rs1250544) = 3.53 × 10(-8), 11q13 near PRDX5, p(rs694739) = 3.71 × 10(-09), 22q11 at YDJC, p(rs181359) = 8.02 × 10(-10)). In addition, we identified one susceptibility locus for CD (16p13 near SOCS1, p(rs4780355) = 4.99 × 10(-8)). Refinement of association signals identified shared genome-wide significant associations for exonic SNPs at 10q22 (ZMIZ1) and in silico expression quantitative trait locus analyses revealed that the associations at ZMIZ1 and near SOCS1 have a potential functional effect on gene expression. Our results show the usefulness of joint analyses of clinically distinct immune-mediated diseases and enlarge the map of shared genetic risk loci.

Osteoprotegerin and fractures in men and women with chronic kidney disease.

Fractures are common in men and women with chronic kidney disease (CKD) but the best tool to identify those at high risk is unknown. Increased circulating osteoprotegerin(OPG) is associated with fractures in postmenopausal women. We determined if serum OPG was associated with prevalent fractures (self-reported low trauma fractures since 40 years of age and/or prevalent vertebral fractures identified by radiographs) in men (n = 97) and women (n = 67) with stage 3­5 CKD. Analyses were performed unadjusted and adjusted for stage of CKD. Results are expressed as mean ± standard deviation(SD), and as odds ratio (OR) per SD increase in OPG with 95 % confidence intervals (CI). The mean age was 62.7 ± 16.3 years, and mean weight was 78.9 ± 18.7 kg. Compared to those without fractures, those with fractures(n = 55) were older (p < 0.01). Serum OPG increased as kidney function decreased, and OPG was higher in those with fractures compared to those without (9.42 ± 4.08 vs 8.06 ± 3.11 pmol/L, p = 0.02). After adjusting for stage of CKD, increased OPG was associated with an increased fracture risk (OR 1.13, 95 % CI 1.02­1.25); however, OPG did not discriminate fracture status well (area under the receiver operating characteristic curve 0.61, 95 % CI 0.52­0.70). OPG is associated with fractures in men and women with stage 3­5 CKD; however, the ability of OPG to discriminate fracture status is poor and cannot be used in isolation to assess fracture risk. Further studies should examine the ability of OPG in combination with other risk factors to better discriminate fracture status in men and women with CKD.