Search tips
Search criteria

Results 1-25 (1149)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
more »
1.  Impaired White Matter Development in Extremely Low Birth Weight Infants with Previous Brain hemorrhage 
To evaluate white matter development in extremely low birth weight (ELBW) infants with or without previous brain hemorrhage.
Thirty-three ELBW infants were prospectively enrolled and included in this IRB approved study. Another 10 healthy term infants were included as controls. The medical records of the ELBW infants were reviewed for ultrasound diagnosis of intraventricular hemorrhage (IVH). All infants had an MRI examination at term-equivalent age for detection of previous hemorrhage, and their white matter was scored and compared among different groups. DTI measured fractional anisotropy (FA) values were also compared voxel-wise by tract-based-spatial-statistics (TBSS).
Compared to controls, the white matter score was not significantly different in ELBW infants without blood deposition on MRI (p=0.17), but was significantly worse in ELBW infants with blood deposition on MRI but no IVH diagnosis by ultrasound (p=0.02), in ELBW infants with grade 1 or 2 IVH on ultrasound (p=0.003), and in ELBW infants with grade 3 or 4 IVH on ultrasound (p=0.0001).ELBW infants without blood deposition on MRI did not show any white matter regions with significantly lower FA values than controls. ELBW infants with blood deposition on MRI but no IVH diagnosis did show white matter regions with significantly lower FA,and ELBW infants with IVH diagnosis had widespread white matter regions with lower FA.
Previous brain hemorrhage is associated with abnormal white matter in ELBW infants at term-equivalent age, and ultrasound is not sensitive to minor hemorrhages that are sufficient to cause white matter injury.
PMCID: PMC4207210  PMID: 24874534
2.  Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection 
Nature Communications  2015;6:8020.
Mucosal damage to the gastrointestinal (GI) tract with resulting microbial translocation is hypothesized to significantly contribute to the heightened and persistent chronic inflammation and immune activation characteristic to HIV infection. Here we employ a non-human primate model of chemically induced colitis in SIV-uninfected rhesus macaques that we developed using dextran sulfate sodium (DSS), to directly test this hypothesis. DSS treatment results in GI barrier damage with associated microbial translocation, inflammation and immune activation. The progression and severity of colitis are longitudinally monitored by a magnetic resonance imaging approach. DSS treatment of SIV-infected African green monkeys, a natural host species for SIV that does not manifest GI tract damage or chronic immune activation during infection, results in colitis with elevated levels of plasma SIV RNA, sCD14, LPS, CRP and mucosal CD4+ T-cell loss. Together these results support the hypothesis that GI tract damage leading to local and systemic microbial translocation, and associated immune activation, are important determinants of AIDS pathogenesis.
HIV-1 infection in humans and SIV infection in rhesus macaques are associated with mucosal damage to the gastrointestinal tract, microbial translocation and chronic immune activation. Here the authors develop a non-human primate DSS colitis model that recapitulates these aspects of the disease in uninfected rhesus macaques.
PMCID: PMC4544774  PMID: 26282376
3.  Ultrasound-guided rectus sheath block or wound infiltration in children: A randomized blinded study of analgesia and bupivacaine absorption 
Paediatric anaesthesia  2014;24(9):968-973.
Rectus sheath block can provide analgesia following umbilical hernia repair. However, conflicting reports on its analgesic effectiveness exist. No study has investigated plasma local anesthetic concentration following ultrasound-guided rectus sheath block (USGRSB) in children.
Compare the effectiveness and bupivacaine absorption following USGRSB or wound infiltration (WI) for umbilical hernia repair in children.
A randomized blinded study comparing WI to USGRSB in 40 children undergoing umbilical hernia repair was performed. Group WI (n=20) received wound infiltration 1mg/kg 0.25% bupivacaine. Group RS (n=20) received USGRSB 0.5mg/kg 0.25% bupivacaine per side in the posterior rectus sheath compartment. Pain scores and rescue analgesia were recorded. Blood samples were drawn at 0, 10, 20, 30, 45 and 60 minutes.
Patients in the WI group had a 2-fold increased risk of requiring morphine (Hazard ratio 2.06, 95% CI 1.01, 4.20, p=0.05). When required, median time to first morphine dose was longer in the USGRSB group (65.5 min vs 47.5 min, p=0.049). Peak plasma bupivacaine concentration was higher following USGRSB than WI (median: 631.9 ng/ml IQR: 553.9 – 784.1 vs 389.7 ng/ml IQR: 250.5-502.7, p= 0.002). Tmax was longer in the USGRSB group (median 45 min IQR: 30 - 60 vs 20 min IQR: 20 – 45, p= 0.006).
USGRSB provides more effective analgesia than WI for umbilical hernia repair. USGRSB with 1mg/kg 0.25% bupivacaine is associated with safe plasma bupivacaine concentration that peaks higher and later than WI. Caution against using larger volumes of higher concentration local anesthetic for USGRSB is advised.
PMCID: PMC4125512  PMID: 24853314
Pharmacokinetics; Drugs, regional; Ultrasound, regional; Pain, child; Age, outpatient; Ambulatory, local anesthetics; Drugs
4.  Development and verification of the PAM50-based Prosigna breast cancer gene signature assay 
BMC Medical Genomics  2015;8:54.
The four intrinsic subtypes of breast cancer, defined by differential expression of 50 genes (PAM50), have been shown to be predictive of risk of recurrence and benefit of hormonal therapy and chemotherapy. Here we describe the development of Prosigna™, a PAM50-based subtype classifier and risk model on the NanoString nCounter Dx Analysis System intended for decentralized testing in clinical laboratories.
514 formalin-fixed, paraffin-embedded (FFPE) breast cancer patient samples were used to train prototypical centroids for each of the intrinsic subtypes of breast cancer on the NanoString platform. Hierarchical cluster analysis of gene expression data was used to identify the prototypical centroids defined in previous PAM50 algorithm training exercises. 304 FFPE patient samples from a well annotated clinical cohort in the absence of adjuvant systemic therapy were then used to train a subtype-based risk model (i.e. Prosigna ROR score). 232 samples from a tamoxifen-treated patient cohort were used to verify the prognostic accuracy of the algorithm prior to initiating clinical validation studies.
The gene expression profiles of each of the four Prosigna subtype centroids were consistent with those previously published using the PCR-based PAM50 method. Similar to previously published classifiers, tumor samples classified as Luminal A by Prosigna had the best prognosis compared to samples classified as one of the three higher-risk tumor subtypes. The Prosigna Risk of Recurrence (ROR) score model was verified to be significantly associated with prognosis as a continuous variable and to add significant information over both commonly available IHC markers and Adjuvant! Online.
The results from the training and verification data sets show that the FDA-cleared and CE marked Prosigna test provides an accurate estimate of the risk of distant recurrence in hormone receptor positive breast cancer and is also capable of identifying a tumor's intrinsic subtype that is consistent with the previously published PCR-based PAM50 assay. Subsequent analytical and clinical validation studies confirm the clinical accuracy and technical precision of the Prosigna PAM50 assay in a decentralized setting.
Electronic supplementary material
The online version of this article (doi:10.1186/s12920-015-0129-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4546262  PMID: 26297356
6.  Supporting Option B+ scale up and strengthening the prevention of mother-to-child transmission cascade in central Malawi: results from a serial cross-sectional study 
BMC Infectious Diseases  2015;15:328.
We established Safeguard the Family (STF) to support Ministry of Health (MoH) scale-up of universal antiretroviral therapy (ART) for HIV-infected pregnant and breastfeeding women (Option B+) and to strengthen the prevention of mother-to-child transmission (PMTCT) cascade from HIV testing and counseling (HTC) through maternal ART provision and post-delivery early infant HIV diagnosis (EID). To these ends, we implemented the following interventions in 5 districts: 1) health worker training and mentorship; 2) couples’ HTC and male partner involvement; 3) women’s psychosocial support groups; and 4) health and laboratory system strengthening for EID.
We conducted a serial cross-sectional study using facility-level quarterly (Q) program data and individual-level infant HIV-1 DNA PCR data to evaluate STF performance on PMTCT indicators for project years (Y) 1 (April—December 2011) through 3 (January—December 2013), and compared these results to national averages.
Facility-level uptake of HTC, ART, infant nevirapine prophylaxis, and infant DNA PCR testing increased significantly from quarterly baselines of 66 % (n/N = 32,433/48,804), 23 % (n/N = 442/1,958), 1 % (n/N = 10/1,958), and 52 % (n/N = 1,385/2,644) to 87 % (n/N = 39,458/45,324), 96 % (n/N = 2,046/2,121), 100 % (n/N = 2,121/2,121), and 62 % (n/N = 1,462/2,340), respectively, by project end (all p < 0.001). Quarterly HTC, ART, and infant nevirapine prophylaxis uptake outperformed national averages over years 2–3. While transitioning EID laboratory services to MoH, STF provided first-time HIV-1 DNA PCR testing for 2,226 of 11,261 HIV-exposed infants (20 %) tested in the MoH EID program in STF districts from program inception (Y2) through Y3. Of these, 78 (3.5 %) tested HIV-positive. Among infants with complete documentation (n = 608), median age at first testing decreased from 112 days (interquartile range, IQR: 57–198) in Y2 to 76 days (IQR: 46–152) in Y3 (p < 0.001). During Y3 (only year with national data for comparison), non-significantly fewer exposed infants tested HIV-positive (3.6 %) at first testing in STF districts than nationally (4.1 %) (p = 0.4).
STF interventions, integrated within the MoH Option B+ program, achieved favorable HTC, maternal ART, infant prophylaxis, and EID services uptake, and a low proportion of infants found HIV-infected at first DNA PCR testing. Continued investments are needed to strengthen the PMTCT cascade, particularly around EID.
PMCID: PMC4533797  PMID: 26265222
7.  Delivery of siRNA Silencing Runx2 Using a Multifunctional Polymer-Lipid Nanoparticle Inhibits Osteogenesis in a Cell Culture Model of Heterotopic Ossification 
Heterotopic ossification (HO) associated with traumatic neurological or musculoskeletal injuries remains a major clinical challenge. One approach to understanding better and potentially treating this condition is to silence one or more genes believed to be responsible for osteogenesis by small interfering RNA (siRNA) post-injury. Improved methods of delivering siRNA to myoprogenitor cells as well as relevant cell culture models of HO are needed to advance this approach. We utilize a model of HO featuring C2C12 myoprogenitor cells stimulated to the osteogenic phenotype by addition of BMP-2. For siRNA delivery, we utilize a nanocomposite consisting of DOTAP- based cationic liposomes coated with a graft copolymer of poly(propylacrylic acid) grafted with polyetheramine (Jeffamine), as this system has been shown previously to deliver antisense oligonucleotides safely into cells and out of endosomes for gene silencing in vitro and in vivo. Delivery of siRNA targeting Runx2, a transcription factor downstream of BMP-2, to stimulated C2C12 cells produced greater than 60% down-regulation of the Runx2 gene. This level of gene silencing was sufficient to inhibit alkaline phosphatase activity over the course of several days and calcium phosphate deposition over the course of 2 weeks. These results show the utility of the BMP-2/C2C12 model for capturing the cellular cell-fate decision in HO. Further, they suggest DOTAP/PPAA-g-Jeffamine as a promising delivery system for siRNA– based therapy for HO.
PMCID: PMC4534437  PMID: 23146945
8.  An Attenuated Adenovirus, ONYX-015, As Mouthwash Therapy for Premalignant Oral Dysplasia 
Dysplastic lesions of the oral epithelium are known precursors of oral cancer. A significant proportion of oral dysplastic lesions have functional defects in p53 response pathways. The ONYX-015 adenovirus is selectively cytotoxic to cells carrying defects in p53-dependent signaling pathways. The current study sought to establish the feasibility and activity of ONYX-015 administered topically as a mouthwash to patients with clinically apparent and histologically dysplastic lesions of the oral mucosa.
Patients and Methods
A total of 22 patients (19 assessable patients) were enrolled onto the study. ONYX-015 was administered on three different schedules to consecutive cohorts. Biopsies of the involved mucosa were performed to evaluate histologic response and changes in expression of putative markers of malignant potential, including p53, cyclin D1, and Ki-67. Serology was performed to measure antiadenoviral titers.
Histologic resolution of dysplasia was seen in seven (37%) of 19 patients, and the grade of dysplasia improved in one additional patient. The majority of responses were transient. No toxicity greater than grade 2 (febrile episode in one patient) was observed. Only one of seven patients demonstrated an increase in circulating antiadenoviral antibody titer while on therapy. Although responding and resistant lesions had similar mean p53 staining at baseline, histologic response correlated with a decrease in p53 positivity over time. Significant changes in cyclin D1 or Ki-67 were not observed. Viral replication was confirmed in two of three lesions examined.
This novel approach to cancer prevention is tolerable, feasible, and has demonstrable activity.
PMCID: PMC4523388  PMID: 14597742
9.  CD4 Count Outperforms World Health Organization Clinical Algorithm for Point-of Care HIV Diagnosis among Hospitalized HIV-exposed Malawian Infants 
To determine, for the WHO algorithm for point-of-care diagnosis of HIV infection, the agreement levels between pediatricians and non-physician clinicians, and to compare sensitivity and specificity profiles of the WHO algorithm and different CD4 thresholds against HIV PCR testing in hospitalized Malawian infants.
In 2011, hospitalized HIV-exposed infants <12 months in Lilongwe, Malawi were evaluated independently with the WHO algorithm by both a pediatrician and clinical officer. Blood was collected for CD4 and molecular HIV testing (DNA or RNA PCR). Using molecular testing as the reference, sensitivity, specificity, and positive predictive value (PPV) were determined for the WHO algorithm and CD4 count thresholds of 1500 and 2000 cells/mm3 by pediatricians and clinical officers.
We enrolled 166 infants (50% female, 34% <2 months, 37% HIV-infected). Sensitivity was higher using CD4 thresholds (<1500, 80%; <2000, 95%) than with the algorithm (physicians, 57%; clinical officers, 71%). Specificity was comparable for CD4 thresholds (<1500, 68%, <2000, 50%) and the algorithm (pediatricians, 55%, clinical officers, 50%). The positive predictive values were slightly better using CD4 thresholds (<1500, 59%, <2000, 52%) than the algorithm (pediatricians, 43%, clinical officers 45%) at this prevalence.
Performance by the WHO algorithm and CD4 thresholds resulted in many misclassifications. Point-of-care CD4 thresholds of <1500 cells/mm3 or <2000 cells/mm3 could identify more HIV-infected infants with fewer false positives than the algorithm. However, a point-of-care option with better performance characteristics is needed for accurate, timely HIV diagnosis.
PMCID: PMC4091045  PMID: 24754543
pediatric; point-of-care; Africa; early infant diagnosis; HIV; clinical algorithm
10.  How Many Etiological Subtypes of Breast Cancer: Two, Three, Four, Or More? 
Breast cancer is a heterogeneous disease, divisible into a variable number of clinical subtypes. A fundamental question is how many etiological classes underlie the clinical spectrum of breast cancer? An etiological subtype reflects a grouping with a common set of causes, whereas a clinical subtype represents a grouping with similar prognosis and/or prediction. Herein, we review the evidence for breast cancer etiological heterogeneity. We then evaluate the etiological evidence with mRNA profiling data. A bimodal age distribution at diagnosis with peak frequencies near ages 50 and 70 years is a fundamental characteristic of breast cancer for important tumor features, clinical characteristics, risk factor profiles, and molecular subtypes. The bimodal peak frequencies at diagnosis divide breast cancer overall into a “mixture” of two main components in varying proportions in different cancer populations. The first breast cancer tends to arise early in life with modal age-at-diagnosis near 50 years and generally behaves aggressively. The second breast cancer occurs later in life with modal age near 70 years and usually portends a more indolent clinical course. These epidemiological and molecular data are consistent with a two-component mixture model and compatible with a hierarchal view of breast cancers arising from two main cell types of origin. Notwithstanding the potential added value of more detailed categorizations for personalized breast cancer treatment, we suggest that the development of better criteria to identify the two proposed etiologic classes would advance breast cancer research and prevention.
PMCID: PMC4148600  PMID: 25118203
11.  Oxidative stress resulting from exposure of a human salivary gland cells to paraoxon: an in vitro model for organophosphate oral exposure 
Organophosphate (OP) compounds are used as insecticides, acaracides, and chemical agents and share a common neurotoxic mechanism of action. The biochemical alterations leading to many of the deleterious effects have been studied in neuronal cell lines, however, non-neuronal toxic effects of OPs are far less well characterized in vitro, and specifically in cell lines representing oral routes of exposure. To address this void, the human salivary gland (HSG) cell line, representing likely interactions in the oral cavity, was exposed to the representative OP paraoxon (PX; O,O-diethyl-p-nitrophenoxy phosphate) over a range of concentrations (0.01 μM to 100 μM) and analyzed for cytotoxicity. PX induced cytotoxicity in HSG cells at most of the exposure concentrations as revealed by MTT assay, however, the release of LDH only occurred at the highest concentration of PX tested (100 μM) at 48 h. Slight increases in cellular ATP levels were measured in PX-exposed (10 μM) HSG cells at 24 h. Exposing HSG cells to 10 μM PX also led to an increase in DNA fragmentation prior to loss of cellular membrane integrity implicating reactive oxygen species (ROS) as a trigger of toxicity. The ROS genes gss, gstm2, gstt2 and sod2 were upregulated, and the presence of superoxide following 10 μM PX exposure was determined via dihydroethidium fluorescence studies further implicating PX-induced oxidative stress in HSG cells.
PMCID: PMC4048768  PMID: 24486155
paraoxon; HSG cells; oxidative stress; organophosphate; MTT; DNA fragmentation
12.  Brainstem processing of vestibular sensory exafference: implications for motion sickness etiology 
Experimental brain research  2014;232(8):2483-2492.
The origin of the internal “sensory conflict” stimulus causing motion sickness has been debated for more than four decades. Recent studies show a subclass of neurons in the vestibular nuclei and deep cerebellar nuclei that respond preferentially to passive head movements. During active movement, the semicircular canal and otolith input (“reafference”) to these neurons is cancelled by a mechanism comparing the expected consequences of self-generated movement (estimated with an internal model-presumably located in the cerebellum) with the actual sensory feedback. The un-cancelled component (“exafference”) resulting from passive movement normally helps compensate for unexpected postural disturbances. Notably, the existence of such vestibular “sensory conflict” neurons had been postulated as early as 1982, but their existence and putative role in posture control, motion sickness has been long debated. Here we review the development of “sensory conflict” theories in relation to recent evidence for brainstem and cerebellar reafference cancellation, and identify some open research questions. We propose that conditions producing persistent activity of these neurons, or their targets, stimulates nearby brainstem emetic centers – via an as yet unidentified mechanism. We discuss how such a mechanism is consistent with the notable difference in motion sickness susceptibility of drivers as opposed to passengers, human immunity to normal self-generated movement, and why head restraint or lying horizontal confers relative immunity. Finally, we propose that fuller characterization of these mechanisms, and their potential role in motion sickness could lead to more effective, scientifically based prevention and treatment for motion sickness.
PMCID: PMC4130651  PMID: 24838552
Motion sickness; brainstem; cerebellum; sensory conflict; nausea; vomiting
13.  Comparative Efficacy of Behavior Therapy, Cognitive Therapy and Cognitive Behavior Therapy for Chronic Insomnia: A Randomized Controlled Trial 
To examine the unique contribution of behavior therapy (BT) and cognitive therapy (CT) relative to the full cognitive behavior therapy (CBT) for persistent insomnia.
Participants were 188 adults (117 women; M age = 47.4 years old, SD=12.6) with persistent insomnia (average of 14.5 years duration). They were randomized to eight, weekly, individual sessions consisting of BT (n = 63), CT (n = 65), or CBT (n = 60).
Full CBT was associated with greatest improvements, the improvements associated with BT were faster but not as sustained and the improvements associated with CT were slower and sustained. The proportion of treatment responders was significantly higher in the CBT (67.3%) and BT (67.4%) relative to CT (42.4%) groups at post treatment, while 6-months later CT made significant further gains (62.3%), BT had significant loss (44.4%) and CBT retained its initial response (67.6%). Remission rates followed a similar trajectory, with higher remission rates at post treatment in CBT (57.3%) relative to CT (30.8%), with BT falling in between (39.4%); CT made further gains from post treatment to follow up (30.9% to 51.6%). All three therapies produced improvements of daytime functioning at both post treatment and follow up, with few differential changes across groups.
Full CBT is the treatment of choice. Both BT and CT are effective, with a more rapid effect for BT and a delayed action for CT. These different trajectories of changes provide unique insights into the process of behavior change via behavioral versus cognitive routes.
PMCID: PMC4185428  PMID: 24865869
sleep; insomnia; behavior therapy; cognitive therapy; CBT; behavior change
14.  Diffusion Tensor Imaging in Extremely Low Birth Weight Infants Managed with Hypercapnic vs. Normocapnic Ventilation 
Pediatric radiology  2014;44(8):980-986.
Permissive hypercapnia is a ventilatory strategy used to prevent lung injury in ventilated extremely low birth weight (ELBW, birth weight ≤1000 g) infants. However, there is retrospective evidence showing that high CO2 is associated with brain injury.
The objective of this study was to compare brain white matter development at term-equivalent age in ELBW infants randomized to hypercapnic vs. normocapnic ventilation during the first week of life and in healthy non-ventilated term newborns.
Materials and Methods
Twenty-two ELBW infants from a randomized controlled trial were included in this study; 11 received hypercapnic (transcutaneous PCO2 [tcPCO2] 50–60 mm Hg) ventilation and 11 normocapnic (tcPCO2 35–45 mm Hg) ventilation during the first week of life while still intubated. In addition, 10 term healthy newborns served as controls. Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed at term-equivalent age for the ELBW infants and at approximately 2 weeks of age for the control infants. White matter injury on conventional MRI was graded in the ELBW and control infants using a scoring system adopted from literature. Tract-based spatial statistics (TBSS) was used to evaluate for differences in DTI measured fractional anisotropy (FA, spatially normalized to a customized template) among the ELBW and term control infants.
Conventional MRI white matter scores were not different (7.3 ± 1.7 vs. 6.9 ± 1.4, p=0.65) between the hypercapnic and normocapnic ELBW infants. TBSS analysis did not show significant differences (p<0.05, corrected) between the two ELBW infant groups, although before multiple comparisons correction, hypercapnic infants had many regions with lower FA (p<0.05, uncorrected) and no regions with higher FA (p<0.05, uncorrected) compared to normocapnic infants. When compared to the control infants, normocapnic ELBW infants had a few small regions with significantly lower FA, while hypercapnic ELBW infants had more widespread regions with significantly lower FA (p<0.05, fully corrected for multiple comparisons).
Normocapnic ventilation vs. permissive hypercapnia may be associated with improved white matter development at term-equivalent age in ELBW infants. This effect, however, was small and was not apparent on conventional MRI. Further research is needed using larger sample sizes to assess if permissive hypercapnic ventilation in ELBW infants is associated with worse white matter development.
PMCID: PMC4204475  PMID: 24671721
15.  Wild type N-Ras, overexpressed in basal-like breast cancer, promotes tumor formation by inducing IL8 secretion via JAK2 activation 
Cell reports  2015;12(3):511-524.
Basal-like breast cancers (BLBCs) are aggressive, and their drivers are unclear. We have found that wild-type N-RAS is overexpressed in BLBCs, but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, while overexpression enhances these processes even in preinvasive BLBC cells. We identified N-Ras-responsive genes, most of which encode chemokines, e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL8 by binding and activating the cytoplasmic pool of JAK2; IL8 then acts on both the cancer cells and stromal fibroblasts. Thus BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.
Graphical Abstract
PMCID: PMC4512851  PMID: 26166574
16.  A multi-method exploratory study of stress, coping, and substance use among high school youth in private schools 
Frontiers in Psychology  2015;6:1028.
There is growing awareness that students’ experiences of stress may impede academic success, compromise mental health, and promote substance use. We examined these factors in an under-studied population, private/independent high school students, using a multi-method (qualitative and quantitative), iterative data collection and analytic process. We first conducted qualitative interviews with faculty and staff at a number of highly competitive private schools, followed by an anonymous quantitative survey with 128 11th grade students from two of these settings. We then conducted a qualitative exploration of the quantitative results with a subset of students. Next, a set of Expert Panel members participated in qualitative interviews to reflect on and interpret study findings. Overall, we found students experienced high levels of chronic stress, particularly in relation to academic performance and the college admissions process. While students described a range of effective, adaptive coping strategies, they also commonly internalized these serious pressures and turned to alcohol and drugs to cope with chronic stress, although not typically at problematic levels. We discuss study implications for both schools and families derived from the Expert Panel.
PMCID: PMC4511824  PMID: 26257685
stress; coping; adolescents; substance use; private school; high school
17.  Rapamycin Rescues ABT-737 Efficacy in Small Cell Lung Cancer 
Cancer research  2014;74(10):2846-2856.
Overexpression of the antiapoptotic protein Bcl-2 is observed in the majority of small cell lung cancer (SCLC) cases and is associated with resistance to chemotherapy. While targeting Bcl-2 in hematologic malignancies continues to show signs of promise, translating the BH3 mimetic ABT-737 (or ABT-263; navitoclax) to the clinic for solid tumors has remained problematic, with limited single-agent activity in early-phase clinical trials. Here, we used patient-derived xenograft (PDX) models of SCLC to study ABT-737 resistance and demonstrated that responses to ABT-737 are short lived and coincide with decreases in HIF-1α–regulated transcripts. Combining the mTOR inhibitor rapamycin with ABT-737 rescued this resistance mechanism, was highly synergistic in vitro, and provided durable tumor regressions in vivo without notable hematologic suppression. In comparison, tumor regressions did not occur when ABT-737 was combined with etoposide, a gold-standard cytotoxic for SCLC therapy. Rapamycin exposure was consistently associated with an increase in the proapoptotic protein BAX, whereas ABT-737 caused dose-dependent decreases in BAX. As ABT-737 triggers programmed cell death in a BAX/BAK-dependent manner, we provide preclinical evidence that the efficacy of ABT-737 as a single agent is self-limiting in SCLC, but the addition of rapamycin can maintain or increase levels of BAX protein and markedly enhance the anticancer efficacy of ABT-737. These data have direct translational implications for SCLC clinical trials.
PMCID: PMC4510983  PMID: 24614082
19.  Affinity Enhancement by Dendritic Side Chains in Synthetic Carbohydrate Receptors** 
Dendritic side chains have been used to modify the binding environment in anthracene-based synthetic carbohydrate receptors. Control of length, charge, and branching enabled the positioning of side-chain carboxylate groups in such a way that they assisted in binding substrates rather than blocking the cavity. Conformational degeneracy in the dendrimers resulted in effective preorganization despite the flexibility of the system. Strong binding was observed to glucosammonium ions in water, with Ka values up to 7000 m−1. Affinities for uncharged substrates (glucose and N-acetylglucosamine) were also enhanced, despite competition from solvent and the absence of electrostatic interactions.
PMCID: PMC4506558  PMID: 25645064
carbohydrates; dendrimers; molecular recognition; receptors; supramolecular chemistry
20.  A Novel Fluorine-18 β-Fluoroethoxy Organophosphate Positron Emission Tomography Imaging Tracer Targeted to Central Nervous System Acetylcholinesterase 
ACS Chemical Neuroscience  2014;5(7):519-524.
Radiosynthesis of a fluorine-18 labeled organophosphate (OP) inhibitor of acetylcholinesterase (AChE) and subsequent positron emission tomography (PET) imaging using the tracer in the rat central nervous system are reported. The tracer structure, which contains a novel β-fluoroethoxy phosphoester moiety, was designed as an insecticide-chemical nerve agent hybrid to optimize handling and the desired target reactivity. Radiosynthesis of the β-fluoroethoxy tracer is described that utilizes a [18F]prosthetic group coupling approach. The imaging utility of the [18F]tracer is demonstrated in vivo within rats by the evaluation of its brain penetration and cerebral distribution qualities in the absence and presence of a challenge agent. The tracer effectively penetrates brain and localizes to cerebral regions known to correlate with the expression of the AChE target. Brain pharmacokinetic properties of the tracer are consistent with the formation of an OP-adducted acetylcholinesterase containing the fluoroethoxy tracer group. Based on the initial favorable in vivo qualities found in rat, additional [18F]tracer studies are ongoing to exploit the technology to dynamically probe organophosphate mechanisms of action in mammalian live tissues.
PMCID: PMC4102964  PMID: 24716794
Acetylcholinesterase; organophosphate; fluorine-18; radiotracer; PET imaging; brain
21.  Prognostic B-Cell Signatures using mRNA-Seq in Patients with Subtype-Specific Breast and Ovarian Cancer 
Lymphocytic infiltration of tumors predicts improved survival in breast cancer patients. Previous studies have suggested that this survival benefit is confined predominantly to the basal-like subtype. Immune infiltration in ovarian tumors is also associated with improved prognosis. Currently, it is unclear what aspects of the immune response mediate this improved outcome.
Experimental Design
Using The Cancer Genome Atlas (TCGA) mRNA-seq data and a large microarray data set, we evaluated adaptive immune gene expression by genomic subtype in breast and ovarian cancer. To investigate B-cells observed to be prognostic within specific subtypes, we developed methods to analyze B-cell population diversity and degree of somatic hypermutation (SHM) from B-cell receptor (BCR) sequences in mRNA-seq data.
Improved metastasis-free/progression-free survival was correlated with B-cell gene expression signatures, which were restricted mainly to the basal-like and HER2-enriched breast cancer subtypes and the immunoreactive ovarian cancer subtype. Consistent with a restricted epitope-driven response, a subset of basal-like and HER2-enriched breast tumors and immunoreactive ovarian tumors showed high expression of a low-diversity population of BCR gene segments. More BCR segments showed improved prognosis with increased expression in basal-like breast tumors and immunoreactive ovarian tumors compared with other subtypes. Basal-like and HER2-enriched tumors exhibited more BCR sequence variants in regions consistent with somatic hypermutation.
Taken together, these data suggest the presence of a productive and potentially restricted anti-tumor B-cell response in basal-like breast and immunoreactive ovarian cancers. Immunomodulatory therapies that support B-cell responses may be a promising therapeutic approach to targeting these B-cell infiltrated tumors.
PMCID: PMC4102637  PMID: 24916698
22.  Change Points in the Population Trends of Aerial-Insectivorous Birds in North America: Synchronized in Time across Species and Regions 
PLoS ONE  2015;10(7):e0130768.
North American populations of aerial insectivorous birds are in steep decline. Aerial insectivores (AI) are a group of bird species that feed almost exclusively on insects in flight, and include swallows, swifts, nightjars, and flycatchers. The causes of the declines are not well understood. Indeed, it is not clear when the declines began, or whether the declines are shared across all species in the group (e.g., caused by changes in flying insect populations) or specific to each species (e.g., caused by changes in species’ breeding habitat). A recent study suggested that population trends of aerial insectivores changed for the worse in the 1980s. If there was such a change point in trends of the group, understanding its timing and geographic pattern could help identify potential causes of the decline. We used a hierarchical Bayesian, penalized regression spline, change point model to estimate group-level change points in the trends of 22 species of AI, across 153 geographic strata of North America. We found evidence for group-level change points in 85% of the strata. Change points for flycatchers (FC) were distinct from those for swallows, swifts and nightjars (SSN) across North America, except in the Northeast, where all AI shared the same group-level change points. During the 1980s, there was a negative change point across most of North America, in the trends of SSN. For FC, the group-level change points were more geographically variable, and in many regions there were two: a positive change point followed by a negative change point. This group-level synchrony in AI population trends is likely evidence of a response to a common environmental factor(s) with similar effects on many species across broad spatial extents. The timing and geographic patterns of the change points that we identify here should provide a spring-board for research into the causes behind aerial insectivore declines.
PMCID: PMC4493114  PMID: 26147572
23.  Measurement of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c(1S)$$\end{document}ηc(1S) production cross-section in proton–proton collisions via the decay \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\eta _c(1S)\,{\rightarrow } \,{{{ p}}} \overline{{{{ p}}}}} $$\end{document}ηc(1S)→pp¯ 
Aaij, R. | Beteta, C. Abellán | Adeva, B. | Adinolfi, M. | Affolder, A. | Ajaltouni, Z. | Akar, S. | Albrecht, J. | Alessio, F. | Alexander, M. | Ali, S. | Alkhazov, G. | Alvarez Cartelle, P. | Alves, A. A. | Amato, S. | Amerio, S. | Amhis, Y. | An, L. | Anderlini, L. | Anderson, J. | Andreassen, R. | Andreotti, M. | Andrews, J. E. | Appleby, R. B. | Aquines Gutierrez, O. | Archilli, F. | Artamonov, A. | Artuso, M. | Aslanides, E. | Auriemma, G. | Baalouch, M. | Bachmann, S. | Back, J. J. | Badalov, A. | Baesso, C. | Baldini, W. | Barlow, R. J. | Barschel, C. | Barsuk, S. | Barter, W. | Batozskaya, V. | Battista, V. | Bay, A. | Beaucourt, L. | Beddow, J. | Bedeschi, F. | Bediaga, I. | Belogurov, S. | Belous, K. | Belyaev, I. | Ben-Haim, E. | Bencivenni, G. | Benson, S. | Benton, J. | Berezhnoy, A. | Bernet, R. | Bettler, M.-O. | van Beuzekom, M. | Bien, A. | Bifani, S. | Bird, T. | Bizzeti, A. | Bjørnstad, P. M. | Blake, T. | Blanc, F. | Blouw, J. | Blusk, S. | Bocci, V. | Bondar, A. | Bondar, N. | Bonivento, W. | Borghi, S. | Borgia, A. | Borsato, M. | Bowcock, T. J. V. | Bowen, E. | Bozzi, C. | Brambach, T. | Bressieux, J. | Brett, D. | Britsch, M. | Britton, T. | Brodzicka, J. | Brook, N. H. | Brown, H. | Bursche, A. | Busetto, G. | Buytaert, J. | Cadeddu, S. | Calabrese, R. | Calvi, M. | Calvo Gomez, M. | Campana, P. | Campora Perez, D. | Carbone, A. | Carboni, G. | Cardinale, R. | Cardini, A. | Carson, L. | Carvalho Akiba, K. | Casse, G. | Cassina, L. | Castillo Garcia, L. | Cattaneo, M. | Cauet, Ch. | Cenci, R. | Charles, M. | Charpentier, Ph. | Chefdeville, M. | Chen, S. | Cheung, S.-F. | Chiapolini, N. | Chrzaszcz, M. | Ciba, K. | Cid Vidal, X. | Ciezarek, G. | Clarke, P. E. L. | Clemencic, M. | Cliff, H. V. | Closier, J. | Coco, V. | Cogan, J. | Cogneras, E. | Cogoni, V. | Cojocariu, L. | Collins, P. | Comerma-Montells, A. | Contu, A. | Cook, A. | Coombes, M. | Coquereau, S. | Corti, G. | Corvo, M. | Counts, I. | Couturier, B. | Cowan, G. A. | Craik, D. C. | Cruz Torres, M. | Cunliffe, S. | Currie, R. | D’Ambrosio, C. | Dalseno, J. | David, P. | David, P. N. Y. | Davis, A. | De Bruyn, K. | De Capua, S. | De Cian, M. | De Miranda, J. M. | De Paula, L. | De Silva, W. | De Simone, P. | Decamp, D. | Deckenhoff, M. | Del Buono, L. | Déléage, N. | Derkach, D. | Deschamps, O. | Dettori, F. | Di Canto, A. | Dijkstra, H. | Donleavy, S. | Dordei, F. | Dorigo, M. | Dosil Suárez, A. | Dossett, D. | Dovbnya, A. | Dreimanis, K. | Dujany, G. | Dupertuis, F. | Durante, P. | Dzhelyadin, R. | Dziurda, A. | Dzyuba, A. | Easo, S. | Egede, U. | Egorychev, V. | Eidelman, S. | Eisenhardt, S. | Eitschberger, U. | Ekelhof, R. | Eklund, L. | El Rifai, I. | Elena, E. | Elsasser, Ch. | Ely, S. | Esen, S. | Evans, H.-M. | Evans, T. | Falabella, A. | Färber, C. | Farinelli, C. | Farley, N. | Farry, S. | Fay, RF | Ferguson, D. | Fernandez Albor, V. | Ferreira Rodrigues, F. | Ferro-Luzzi, M. | Filippov, S. | Fiore, M. | Fiorini, M. | Firlej, M. | Fitzpatrick, C. | Fiutowski, T. | Fol, P. | Fontana, M. | Fontanelli, F. | Forty, R. | Francisco, O. | Frank, M. | Frei, C. | Frosini, M. | Fu, J. | Furfaro, E. | Gallas Torreira, A. | Galli, D. | Gallorini, S. | Gambetta, S. | Gandelman, M. | Gandini, P. | Gao, Y. | García Pardiñas, J. | Garofoli, J. | Garra Tico, J. | Garrido, L. | Gaspar, C. | Gauld, R. | Gavardi, L. | Gavrilov, G. | Geraci, A. | Gersabeck, E. | Gersabeck, M. | Gershon, T. | Ghez, Ph. | Gianelle, A. | Gianì, S. | Gibson, V. | Giubega, L. | Gligorov, V. V. | Göbel, C. | Golubkov, D. | Golutvin, A. | Gomes, A. | Gotti, C. | Grabalosa Gándara, M. | Graciani Diaz, R. | Granado Cardoso, L. A. | Graugés, E. | Graziani, G. | Grecu, A. | Greening, E. | Gregson, S. | Griffith, P. | Grillo, L. | Grünberg, O. | Gui, B. | Gushchin, E. | Guz, Yu. | Gys, T. | Hadjivasiliou, C. | Haefeli, G. | Haen, C. | Haines, S. C. | Hall, S. | Hamilton, B. | Hampson, T. | Han, X. | Hansmann-Menzemer, S. | Harnew, N. | Harnew, S. T. | Harrison, J. | He, J. | Head, T. | Heijne, V. | Hennessy, K. | Henrard, P. | Henry, L. | Hernando Morata, J. A. | van Herwijnen, E. | Heß, M. | Hicheur, A. | Hill, D. | Hoballah, M. | Hombach, C. | Hulsbergen, W. | Hunt, P. | Hussain, N. | Hutchcroft, D. | Hynds, D. | Idzik, M. | Ilten, P. | Jacobsson, R. | Jaeger, A. | Jalocha, J. | Jans, E. | Jaton, P. | Jawahery, A. | Jing, F. | John, M. | Johnson, D. | Jones, C. R. | Joram, C. | Jost, B. | Jurik, N. | Kaballo, M. | Kandybei, S. | Kanso, W. | Karacson, M. | Karbach, T. M. | Karodia, S. | Kelsey, M. | Kenyon, I. R. | Ketel, T. | Khanji, B. | Khurewathanakul, C. | Klaver, S. | Klimaszewski, K. | Kochebina, O. | Kolpin, M. | Komarov, I. | Koopman, R. F. | Koppenburg, P. | Korolev, M. | Kozlinskiy, A. | Kravchuk, L. | Kreplin, K. | Kreps, M. | Krocker, G. | Krokovny, P. | Kruse, F. | Kucewicz, W. | Kucharczyk, M. | Kudryavtsev, V. | Kurek, K. | Kvaratskheliya, T. | La Thi, V. N. | Lacarrere, D. | Lafferty, G. | Lai, A. | Lambert, D. | Lambert, R. W. | Lanfranchi, G. | Langenbruch, C. | Langhans, B. | Latham, T. | Lazzeroni, C. | Le Gac, R. | van Leerdam, J. | Lees, J.-P. | Lefèvre, R. | Leflat, A. | Lefrançois, J. | Leo, S. | Leroy, O. | Lesiak, T. | Leverington, B. | Li, Y. | Likhomanenko, T. | Liles, M. | Lindner, R. | Linn, C. | Lionetto, F. | Liu, B. | Lohn, S. | Longstaff, I. | Lopes, J. H. | Lopez-March, N. | Lowdon, P. | Lucchesi, D. | Luo, H. | Lupato, A. | Luppi, E. | Lupton, O. | Machefert, F. | Machikhiliyan, I. V. | Maciuc, F. | Maev, O. | Malde, S. | Malinin, A. | Manca, G. | Mancinelli, G. | Mapelli, A. | Maratas, J. | Marchand, J.F. | Marconi, U. | Marin Benito, C. | Marino, P. | Märki, R. | Marks, J. | Martellotti, G. | Martens, A. | Sánchez, A. Martín | Martinelli, M. | Martinez Santos, D. | Martinez Vidal, F. | Martins Tostes, D. | Massafferri, A. | Matev, R. | Mathe, Z. | Matteuzzi, C. | Mazurov, A. | McCann, M. | McCarthy, J. | McNab, A. | McNulty, R. | McSkelly, B. | Meadows, B. | Meier, F. | Meissner, M. | Merk, M. | Milanes, D. A. | Minard, M.-N. | Moggi, N. | Molina Rodriguez, J. | Monteil, S. | Morandin, M. | Morawski, P. | Mordà, A. | Morello, M. J. | Moron, J. | Morris, A.-B. | Mountain, R. | Muheim, F. | Müller, K. | Mussini, M. | Muster, B. | Naik, P. | Nakada, T. | Nandakumar, R. | Nasteva, I. | Needham, M. | Neri, N. | Neubert, S. | Neufeld, N. | Neuner, M. | Nguyen, A. D. | Nguyen, T. D. | Nguyen-Mau, C. | Nicol, M. | Niess, V. | Niet, R. | Nikitin, N. | Nikodem, T. | Novoselov, A. | O’Hanlon, D. P. | Oblakowska-Mucha, A. | Obraztsov, V. | Oggero, S. | Ogilvy, S. | Okhrimenko, O. | Oldeman, R. | Onderwater, G. | Orlandea, M. | Otalora Goicochea, J. M. | Owen, P. | Oyanguren, A. | Pal, B. K. | Palano, A. | Palombo, F. | Palutan, M. | Panman, J. | Papanestis, A. | Pappagallo, M. | Pappalardo, L. L. | Parkes, C. | Parkinson, C. J. | Passaleva, G. | Patel, G. D. | Patel, M. | Patrignani, C. | Alvarez, A. Pazos | Pearce, A. | Pellegrino, A. | Pepe Altarelli, M. | Perazzini, S. | Trigo, E. Perez | Perret, P. | Perrin-Terrin, M. | Pescatore, L. | Pesen, E. | Petridis, K. | Petrolini, A. | Picatoste Olloqui, E. | Pietrzyk, B. | Pilař, T. | Pinci, D. | Pistone, A. | Playfer, S. | Plo Casasus, M. | Polci, F. | Poluektov, A. | Polycarpo, E. | Popov, A. | Popov, D. | Popovici, B. | Potterat, C. | Price, E. | Price, J.D. | Prisciandaro, J. | Pritchard, A. | Prouve, C. | Pugatch, V. | Puig Navarro, A. | Punzi, G. | Qian, W. | Rachwal, B. | Rademacker, J. H. | Rakotomiaramanana, B. | Rama, M. | Rangel, M. S. | Raniuk, I. | Rauschmayr, N. | Raven, G. | Redi, F. | Reichert, S. | Reid, M. M. | dos Reis, A. C. | Ricciardi, S. | Richards, S. | Rihl, M. | Rinnert, K. | Rives Molina, V. | Robbe, P. | Rodrigues, A. B. | Rodrigues, E. | Rodriguez Perez, P. | Roiser, S. | Romanovsky, V. | Romero Vidal, A. | Rotondo, M. | Rouvinet, J. | Ruf, T. | Ruiz, H. | Ruiz Valls, P. | Saborido Silva, J. J. | Sagidova, N. | Sail, P. | Saitta, B. | Salustino Guimaraes, V. | Sanchez Mayordomo, C. | Sanmartin Sedes, B. | Santacesaria, R. | Santamarina Rios, C. | Santovetti, E. | Sarti, A. | Satriano, C. | Satta, A. | Saunders, D.M. | Savrie, M. | Savrina, D. | Schiller, M. | Schindler, H. | Schlupp, M. | Schmelling, M. | Schmidt, B. | Schneider, O. | Schopper, A. | Schune, M.-H. | Schwemmer, R. | Sciascia, B. | Sciubba, A. | Seco, M. | Semennikov, A. | Sepp, I. | Serra, N. | Serrano, J. | Sestini, L. | Seyfert, P. | Shapkin, M. | Shapoval, I. | Shcheglov, Y. | Shears, T. | Shekhtman, L. | Shevchenko, V. | Shires, A. | Silva Coutinho, R. | Simi, G. | Sirendi, M. | Skidmore, N. | Skwarnicki, T. | Smith, N. A. | Smith, E. | Smith, E. | Smith, J. | Smith, M. | Snoek, H. | Sokoloff, M. D. | Soler, F. J. P. | Soomro, F. | Souza, D. | De Paula, B. Souza | Spaan, B. | Sparkes, A. | Spradlin, P. | Sridharan, S. | Stagni, F. | Stahl, M. | Stahl, S. | Steinkamp, O. | Stenyakin, O. | Stevenson, S. | Stoica, S. | Stone, S. | Storaci, B. | Stracka, S. | Straticiuc, M. | Straumann, U. | Stroili, R. | Subbiah, V. K. | Sun, L. | Sutcliffe, W. | Swientek, K. | Swientek, S. | Syropoulos, V. | Szczekowski, M. | Szczypka, P. | Szilard, D. | Szumlak, T. | T’Jampens, S. | Teklishyn, M. | Tellarini, G. | Teubert, F. | Thomas, C. | Thomas, E. | van Tilburg, J. | Tisserand, V. | Tobin, M. | Tolk, S. | Tomassetti, L. | Tonelli, D. | Topp-Joergensen, S. | Torr, N. | Tournefier, E. | Tourneur, S. | Tran, M. T. | Tresch, M. | Tsaregorodtsev, A. | Tsopelas, P. | Tuning, N. | Ubeda Garcia, M. | Ukleja, A. | Ustyuzhanin, A. | Uwer, U. | Vacca, C. | Vagnoni, V. | Valenti, G. | Vallier, A. | Vazquez Gomez, R. | Vazquez Regueiro, P. | Vázquez Sierra, C. | Vecchi, S. | Velthuis, J. J. | Veltri, M. | Veneziano, G. | Vesterinen, M. | Viaud, B. | Vieira, D. | Vieites Diaz, M. | Vilasis-Cardona, X. | Vollhardt, A. | Volyanskyy, D. | Voong, D. | Vorobyev, A. | Vorobyev, V. | Voß, C. | Voss, H. | de Vries, J. A. | Waldi, R. | Wallace, C. | Wallace, R. | Walsh, J. | Wandernoth, S. | Wang, J. | Ward, D. R. | Watson, N. K. | Websdale, D. | Whitehead, M. | Wicht, J. | Wiedner, D. | Wilkinson, G. | Williams, M. P. | Williams, M. | Wilschut, H.W. | Wilson, F. F. | Wimberley, J. | Wishahi, J. | Wislicki, W. | Witek, M. | Wormser, G. | Wotton, S. A. | Wright, S. | Wyllie, K. | Xie, Y. | Xing, Z. | Xu, Z. | Yang, Z. | Yuan, X. | Yushchenko, O. | Zangoli, M. | Zavertyaev, M. | Zhang, L. | Zhang, W. C. | Zhang, Y. | Zhelezov, A. | Zhokhov, A. | Zhong, L. | Zvyagin, A.
The production of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) state in proton-proton collisions is probed via its decay to the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p\overline{p}$$\end{document}pp¯ final state with the LHCb detector, in the rapidity range \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.0 < y < 4.5$$\end{document}2.0 6.5 \mathrm{{\,GeV/}{ c}} $$\end{document}pT>6.5GeV/c. The cross-section for prompt production of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) mesons relative to the prompt \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ J}}/{\psi } $$\end{document}J/ψ cross-section is measured, for the first time, to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.74\, \pm \,0.29\, \pm \, 0.28\, \pm \,0.18 _{{\mathcal{B}}}$$\end{document}σηc(1S)/σJ/ψ=1.74±0.29±0.28±0.18B at a centre-of-mass energy \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\sqrt{s}} = 7 {~\mathrm{TeV}}$$\end{document}s=7TeV using data corresponding to an integrated luminosity of 0.7 fb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{{\mathcal{B}}}$$\end{document}σηc(1S)/σJ/ψ=1.60±0.29±0.25±0.17B at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\sqrt{s}} = 8 {~\mathrm{TeV}}$$\end{document}s=8TeV using 2.0 fb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ J}}/{\psi } $$\end{document}J/ψ decays to the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p\overline{p}$$\end{document}pp¯ final state. In addition, the inclusive branching fraction of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${b} $$\end{document}b-hadron decays into \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) mesons is measured, for the first time, to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathcal{B}}( b {\rightarrow } \eta _c X ) = (4.88\, \pm \,0.64\, \pm \,0.29\, \pm \, 0.67 _{{\mathcal{B}}}) \times 10^{-3}$$\end{document}B(b→ηcX)=(4.88±0.64±0.29±0.67B)×10-3, where the third uncertainty includes also the uncertainty on the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ J}}/{\psi } $$\end{document}J/ψ inclusive branching fraction from \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${b} $$\end{document}b-hadron decays. The difference between the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ J}}/{\psi } $$\end{document}J/ψ and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) meson masses is determined to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$114.7 \pm 1.5 \pm 0.1 {\mathrm {\,MeV\!/}c^2} $$\end{document}114.7±1.5±0.1MeV/c2.
PMCID: PMC4498677  PMID: 26190939
24.  Two-Year Follow-up of a Randomized Effectiveness Trial Evaluating MST for Juveniles Who Sexually Offend 
Building on prior efficacy trials (i.e., university based, graduate students as therapists), the primary purpose of this study was to determine whether favorable 12-month outcomes obtained in a randomized effectiveness trial (i.e., implemented by practitioners in a community mental health center) of multisystemic therapy (MST) with juveniles who had sexually offended (JSO) were sustained through a second year of follow-up.
JSO (n = 124 male youth) and their families were randomly assigned to MST, which was family based and delivered by community-based practitioners, or to treatment as usual (TAU), which was primarily group-based cognitive-behavioral interventions delivered by professionals within the juvenile justice system. Youth averaged 14.7 (SD = 1.7) years of age at referral, were primarily African American (54%), and 30% were Hispanic. All youth had been diverted or adjudicated for a sexual offense. Analyses examined whether MST effects reported previously at 1-year follow-up for problem sexual behaviors, delinquency, substance use, and out-of-home placement were sustained through a second year of follow-up. In addition, arrest records were examined from baseline through 2-year follow-up.
During the second year of follow-up, MST treatment effects were sustained for three of four measures of youth problem sexual behavior, self-reported delinquency, and out-of-home placements. The base rate for sexual offense rearrests was too low to conduct statistical analyses, and a between-groups difference did not emerge for other criminal arrests.
For the most part, the 2-year follow-up findings from this effectiveness study are consistent with favorable MST long-term results with JSO in efficacy research. In contrast with many MST trials, however, decreases in rearrests were not observed.
PMCID: PMC4490861  PMID: 24188082
Juvenile sex offender; randomized controlled trial; treatment; follow-up
25.  Radial Head Replacement for Acute Complex Fractures: What Are the Rate and Risks Factors for Revision or Removal? 
When treating complex radial head fractures, important goals include prevention of elbow or forearm instability, with restoration of radiocapitellar contact essential. When open reduction and internal fixation cannot achieve this, radial head replacement is routinely employed, but the frequency of and risk factors for prosthesis revision or removal are not well defined.
We determined (1) the frequency of prosthesis revision or removal after radial head replacement for acute complex unstable radial head fractures, (2) risk factors for revision or removal, and (3) functional outcomes after radial head replacement.
We identified from our prospective trauma database all patients over a 16-year period managed acutely for unstable complex radial head fractures with primary radial head replacement. Of the 119 patients identified, 105 (88%) met our inclusion criteria; mean age was 50 years (range, 16–93 years) and 57 (54%) were female. All implants were uncemented monopolar prostheses, of which 86% were metallic and 14% silastic. We recorded further procedures for prosthesis revision or removal for any cause, with a minimum followup of 1 year (n = 105). Cox regression analysis was used to determine independent factors associated with revision or removal when controlling for baseline patient (age, sex, comorbidities) and fracture (location, classification, associated injury) characteristics. Short-term functional outcomes (Broberg and Morrey score, ROM) were determined from retrospective review of clinic followup (n = 74), with a minimum followup of 3 months.
Twenty-nine patients (28%) underwent prosthesis revision (n = 3) or removal (n = 26) at a mean of 6.7 years (range, 1.8–18 years) after injury. Independent risk factors for removal or revision were silastic implant type and lower age. At a mean of 1.1 years (range, 0.3–5.5 years) after surgery, mean Broberg and Morrey score was 80 out of 100 (range, 40–99). Mean elbow flexion was 133° (range, 90°–159°; SD, 13°), extension 21° (range, 0°–80°; SD, 17°), flexion arc 112° (range, 10°–140°; SD, 25°), pronation 84° (range, 0°–90°; SD, 18°), supination 73° (range, 0°–90°; SD, 28°), and forearm rotation arc 156° (range, 0°–180°; SD, 38°).
We demonstrated a high removal or revision rate after radial head replacement for acute unstable complex fractures, with lower age and silastic implants independent risk factors. Younger patients should be counseled regarding the increased risk of requiring further surgery after radial head replacement. Future work should focus on long-term patient-reported outcomes after these injuries.
Level of Evidence
Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.
PMCID: PMC4048424  PMID: 24549774

Results 1-25 (1149)