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Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. Methods We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria—with no contraindications to influenza vaccination—were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18–64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. Findings Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to

RATIONALE: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. OBJECTIVES: To test differing durations of intravenous antimicrobials for CF exacerbations. METHODS: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7–10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days’ total antimicrobial duration; all others were randomized to 14 or 21 days’ duration. MEASUREMENTS AND MAIN RESULTS: The primary outcome was percent predicted FEV(1) (ppFEV(1)) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV(1) change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV(1) changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. CONCLUSIONS: Among adults with CF with early treatment improvement during exacerbation, ppFEV(1) after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

Industrial symbiosis (IS) is a business model that proposes symbiotic exchanges, allowing the flow of resources, wastes, and utilities between companies. In recent years, IS initiatives have been exponentially growing around the world. This can be attributed to the increasing awareness on the possibility of obtaining economic, environmental, and social benefits through the implementation of this model. Despite the exponential growth of IS initiatives, the companies are still facing problems in the achievement of reliable and permanent synergies. Over the years the literature has identified several factors in the IS emerging process. Incentives are among these factors, being defined as unlocking tools or mechanisms related to diverse dimensions such as economic, political, social, intermediaries, process, and technology. Authors believe that the large-scale implementation of IS incentives has not been properly addressed. In order to promote facilitated IS implementation and achieve a replicator effect, incentives should be fully addressed. In many case studies, it has been observed that the incentives for IS can be threatened by risks, compromising the implementation, and hindering the emerging process. This study developed a dedicated framework that is composed of incentive identification from best practices of IS and expert consultation; a risk assessment model based on risk factors identification and clustering; and finally, the mitigation actions based on the assessment outputs. The main result of this study is one set of mitigations actions that correlate the implementation levels (clusters) and the potential stakeholders involved.

The COVID‐19 pandemic has provided an opportunity to rethink the way the majority of patient consultations are conducted, with a move from face‐to‐face visits to remote consultations. This article, which is applicable to all primary care clinicians undertaking medication review, outlines the main principles of optimising remote consultations, with a focus on older people living with frailty during COVID‐19.

The silver-lipped pearl oyster, Pinctada maxima, is the primary species used for the culture of pearls in the Indo-Pacific region. The Western Australian fishery relies on wild-caught animals, and as such, knowledge of the status and distribution of P. maxima underpins sustainable management of the fishery. Eighty Mile Beach, in tropical Western Australia, is the key harvest area for P. maxima, with oysters collected by divers to depths of ∼35 m, although there are anecdotal accounts of oysters beyond diving depths. Image-based, and acoustic methods were used to elucidate distribution patterns of P. maxima off Eighty Mile Beach, including data from 862 km2 of multibeam survey and 119 towed video transects spanning an area from the 20 to 100 m contour lines. We quantified habitat characters including depth, substrate, and benthic community composition associated with pearl oyster distribution. Multibeam sonar data was also coupled with towed video data to produce predictive statistical models of P. maxima habitat. We found P. maxima to depths of 76 m, although more than 90% of individuals occurred shallower than 40 m and less than 2% were found deeper than 50 m. Oysters occupied flat, sandy habitats with neighbouring benthic communities of filter feeders (>98% of observations). These results show P. maxima predominantly occurs in depths

Numerous oil and gas (O&G) installations worldwide will need to be decommissioned in the near future. Complete removal of subsea structures is often the default approach although some regions retain structures under rigs-to-reefs programs. Here, we reviewed the published literature to understand the status of global research on decommissioning, and specifically identify gaps in ecological knowledge. We estimated the frequency of different research categories (i.e., themes, and spatial/temporal scales), and tested the assumption that the number of papers across the categories of each research aspect was even in distribution. However, the frequency of studies focusing on biodiversity at a local (≤100 km2) scale (relative to regional and oceanic and pan-oceanic scales) were significantly higher; while other theme categories (e.g., eco-toxicology, connectivity, structural-integrity, restoration and other) were significantly lower than expected. Temporally, ≤1-year studies were more frequent than multi-year studies, but these frequencies did not significantly deviate from the assumed distribution of equal frequencies. We propose that further research be carried out to evaluate the benefits of both retention and removal of structures. Ecological research on decommissioning should extend its focus beyond biodiversity, to include eco-toxicology, structural-integrity, connectivity at larger spatial and temporal scales. This would provide a more holistic assessment of ecological impacts to inform sustainable and equitable development choices in multiple Blue Economy sectors, as we transition from offshore O&G to marine renewables.

1.When considering widely distributed marine organisms with low dispersal capabilities, there is often an implication that the distribution of cosmopolitan species is an artefact of taxonomy, constrained by the absence of characters for delimiting either sibling or cryptic species. Few studies have assessed the relationship among populations across the global range of the species' distribution, and the presence of oceanographic barriers that might influence gene flow among populations are underestimated. 2.In this study, evolutionary and ecological drivers of connectivity patterns have been inferred among populations of the cold-water coral Desmophyllum dianthus, a common and widespread solitary scleractinian species, whose reproduction strategy and larval dispersal are still poorly unknown. 3.The genetic structure of D. dianthus was explored using 30 microsatellites in 347 specimens from 13 localities distributed in the Mediterranean Sea and Atlantic and Pacific Oceans. 4.Results clearly reveal genetically differentiated populations in the Northern and Southern Hemispheres (F = 0.16, F = 0.01, F = 0.15, P-values highly significant), and Chilean and New Zealand populations with independent genetic profiles. 5.Marine connectivity patterns at different spatial scales are discussed to characterize larval dispersal and gene flow through the Northern and Southern Hemispheres., This research was supported by the Spanish Ministry of Science and Innovation (CGL2011‐23306), and EU CoCoNET—“Towards COast to COast NETworks of marine protected areas (from the shore to the high and deep sea), coupled with sea‐based wind energy potential”—from FP7‐KKBE of the European Commission (project ID: 287844). This scientific contribution commits to EESF Cocarde, Italian Flag Ritmare, and Region Apulia Biomap programmes. This is scientific publication no. 1888 Ismar‐CNR Bologna. Funding to VH was partially provided through Fondecyt project nos. 1131039 and 1161699.

Listeners can successfully interpret the intended meaning of an utterance even when it contains errors or other unexpected anomalies. The present work combines an online measure of attention to sentence referents (visual world eye-tracking) with offline judgments of sentence meaning to disclose how the interpretation of anomalous sentences unfolds over time in order to explore mechanisms of non-literal processing. We use a metalinguistic judgment in Experiment 1 and an elicited imitation task in Experiment 2. In both experiments, we focus on one morphosyntactic anomaly (Subject-verb agreement; The key to the cabinets literally *were … ) and one semantic anomaly (Without; Lulu went to the gym without her hat ?off) and show that non-literal referents to each are considered upon hearing the anomalous region of the sentence. This shows that listeners understand anomalies by overwriting or adding to an initial interpretation and that this occurs incrementally and adaptively as the sentence unfolds.

Successful implementation of industrial symbiosis is highly complex and occurs across multiple dimensions, both internal and external to the firm. We interrogated 25 case studies to build a rich picture of the various approaches that have been adopted to foster resource synergies between organisations. In this chapter, we present a set of critical success factors which we categorised as enablers and barriers with regard to the implementation of industrial symbiosis. The lessons learnt illuminate the processes of consideration, facilitation, and scale up of industrial symbiosis.

Background The ongoing SURPASS trial (NCT04044859) evaluates safety and efficacy of next-generation ADP-A2M4CD8 SPEAR T-cells co-expressing the CD8α co-receptor with the engineered MAGE-A4c1032T cell receptor (TCR). Methods First-in-human trial in HLA-A*02 positive patients (pts) with advanced cancers expressing MAGE-A4 antigen by immunohistochemistry. Eligible pts undergo apheresis, T-cells are isolated, transduced with a Lentiviral vector containing the MAGE-A4c1032 TCR and CD8α co receptor, and expanded. Expansion, transduction level, cellular composition and function of the manufactured product (MP) are assessed in vitro. Prior to infusion, pts receive lymphodepletion with fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 3 days. Results As of 16 July 2020, 5 pts (1 with MRCLS, 2 with esophagogastric junction [EGJ] cancers, 1 with ovarian cancer, and 1 with head and neck cancer) were treated with ADP-A2M4 CD8 (range ~1 to 5.7 billion transduced cells). No DLTs or SAEs have been reported. To date, 1 pt with EGJ cancer had a partial response (PR per RECIST) and has had progression-free survival >6 months. One pt with head and neck cancer also had a PR. All other pts have had best overall response of stable disease.MP expanded by an average of 15.3 fold during manufacturing (range 5.9 to 25.6-fold). On average, 43% of T-cells in the MP expressed the TCR (range 23 to 63%). The fraction of CD4+ cells in the final MP varied (range 45 to 84%). Co-expression of the MAGE-A4 TCR and CD8α in CD4+ T-cells in the patient MP enabled CD4+ T-cells to kill tumor target cells directly in vitro. MAGE-A4 expression in tumor biopsies varied (H-score range 55 to 300). Transduced T-cells were detected in peripheral blood of all pts. IFN-gamma increased transiently in the serum of 1 pt who responded. Conclusions ADP-A2M4CD8 SPEAR T-cells have shown an acceptable safety profile and pts with EGJ cancer and head and neck cancer have demonstrated evidence of antitumor activity. Translational data and early clinical results indicate that co-expression of the CD8α co-receptor on CD4+ SPEAR T-cells may increase the potency of the product by conferring additional killing activity to the helper T-cell subset. This dose escalation trial is ongoing and updated clinical and translational data will be presented. Trial Registration NCT04044859 Ethics Approval The trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines and was approved by local authorities. An independent ethics committee or institutional review board approved the clinical protocol at each participating center. All the patients provided written informed consent before study entry.

Background T-cells attributes for adoptive cell therapy of patients with advanced cancer can be optimized during ex vivo expansion culture. Autologous TCR-engineered T-cells targeting the MAGE-A4 antigen with Specific Peptide Enhanced Affinity Receptors (SPEAR T-cells) have shown promise in the clinic.1 The highly variable leukocyte material obtained from individual patients during apheresis can present a manufacturing challenge for autologous T-cell therapies. The degree of ex vivo expansion and the functional attributes of the expanded T-cell product impact therapeutic efficacy and can be suboptimal for some patient apheresis material. Both TCR and cytokine growth factor signals used for ex vivo T-cell expansion promote robust activation of AKT (Protein Kinase B) signaling, which drives T-cell activation, proliferation, and terminal differentiation. It is hypothesized that inhibition of AKT signaling during T-cell expansion may uncouple proliferation and terminal differentiation, leading to the generation of less differentiated T-cells that may have functional benefit in vivo.2 3 Methods We evaluated use of an AKT inhibitor during SPEAR T-cell manufacturing using leukocytes from healthy donors and patients with advanced solid cancers. Results AKT inhibition resulted in the generation of a more consistent expansion and phenotype of the final T-cell product. This was observed using two SPEAR T-cell constructs, ADP-A2M4 and ADP-A2M4CD8. Ex vivo SPEAR T-cell expansion in the presence of an AKT inhibitor generated CD8+ T-cells that maintained a less differentiated phenotype (based on CCR7+CD45RA+ and CD62L+ expression). AKT inhibition was associated with enhanced antigen-specific responses of SPEAR T-cells in vitro, including effector cytokine production, target-cell killing, ability to proliferate in response to prolonged antigen-stimulation and maintenance of cytotoxic activity following antigen re-stimulation. Conclusions We plan to introduce AKT inhibition into the GMP manufacturing process, and evaluate the efficacy of the resulting products in ongoing clinical studies. Acknowledgements We are extremely grateful to the patients, who were previously enrolled in our clinical trials, and healthy donors for their consent for R&D studies. This was a collaborative cross-functional project, and we are grateful for the contributions of the following Scientists: Garth Hamilton, Adel Toth, Abigail Kay, Sophie Badie, Josh Griffiths, Kaushik Sarkar, Anoop Chandran. Ethics Approval The experimental study was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines and was approved by local authorities. An independent ethics committee or institutional review board approved the clinical protocol at each participating center. All the patients provided written informed consent before study entry. References Hong DS, Van Tine BA, Olszanski AJ, et al, Phase 1 dose escalation and expansion trial to assess safety and efficacy of ADP-A2M4 in advanced solid tumors. J Clin Oncol 2020;38;A102. Klebanoff C, Crompton J, Leonardi A, et al. Inhibition of AKT signaling uncouples T cell differentiation from expansion for receptor-engineered adoptive immunotherapy. JCI Insight 2017;2:e95103. van der Waart A, van de Weem N, Maas F, et al. Inhibition of Akt signaling promotes the generation of superior tumor-reactive T cells for adoptive immunotherapy. Blood. 2014;124;3490-3500

In January 2017, the Colorado Department of Public Health and Environment (CDPHE) identified four epidemiologically linked cases of mumps among persons from a Marshallese community who were members of the same church in the Denver metropolitan area. During 2016-2017, sizable outbreaks of mumps reported in Arkansas, Hawaii, and Washington also affected the Marshallese population (1). CDPHE, the Tri-County Health Department (TCHD), and Denver Public Health collaborated to conduct an outbreak investigation during January-March 2017 using active and passive surveillance that identified 17 confirmed and 30 probable cases. Public health actions included conducting measles-mumps-rubella (MMR) vaccination clinics at local Marshallese churches; these resulted in the vaccination of 126 persons with ≥1 doses of MMR vaccine. Implementation of active surveillance and support from local Marshallese church leaders in promoting vaccination programs likely contributed to interruption of the outbreak.

Background: RO7297089 is a bispecific tetravalent antibody targeting BCMA (Genentech licensed from Affimed GMBH), which is highly expressed on MM cells and CD16a, which is expressed on innate immune cells including natural killer (NK) cells, macrophages, and monocyte subsets. Here we report findings from a Phase I dose-escalation study of RO7297089 in patients with RRMM (GO41582, Study registration NCT04434469). Methods: All patients had RRMM for which no established therapy is available, appropriate, or tolerated. Prior exposure to CAR-T cells, T-cell engaging bispecific antibodies, and therapies targeting BCMA was permitted. Patients received RO7297089 as weekly IV infusions in 14-day cycles with dose escalation guided by a model implementing the Bayesian continuous reassessment method with overdose control. In Arm A the first dose was given over a single-day infusion, and in Arm B the first dose was divided over two consecutive days. Dose limiting toxicities (DLT) were assessed from Cycle 1. Study objectives included safety, pharmacokinetics (PK), and biologic activity as assessed by the IMWG Uniform Response Criteria. Results: As of 30 April 2021, 21 patients received RO7297089 at 5 dose levels (60 mg [n=3], 180 mg [n=5], 360 mg [n=4], 1080 mg [n=6], and 1850 mg [n=3]). Median age was 63 years (range 41-76) and median number of prior lines of therapy was 8 (range 2-11). Patients received a median of 8 doses (range 2-42) of RO7297089; 5 patients had prior BCMA-targeted therapy. The most common AEs were anemia (n=11), infusion related reaction (IRR; n=10), back pain (n=5), ALT increased (n=4), and thrombocytopenia (n=4). Eleven (52%) patients had ≥1 treatment-related adverse event (AE) which included IRR (n=9), C-reactive protein increase (n=3), ALT increase (n=3), AST increase (n=2), and thrombocytopenia (n=2). Grade ≥ 3 AEs included anemia (n=9), and platelet count decreased (n=5). Related Grade ≥ 3 AEs were ALT increase and AST increase and lymphocyte count decreased (both n=1). No DLTs or dose-dependent toxicities were reported. Fifteen patients discontinued study treatment due to disease progression (n=12), clinical relapse (n=2), and symptomatic deterioration (n=1). Four deaths were reported in the AE follow-up period, all due to disease progression. Thirteen IRR events (1 Grade 1, 12 Grade 2) were observed in 10 patients (48%). IRR was most common in Cycle 1 (12 events in 10 patients) and was uncommon in subsequent cycles (1 patient). Symptoms of IRR occurring in >1 patient included fever, rigors/chills, and dyspnea. To mitigate IRRs, additional measures were implemented from the 180 mg dose level including steroid premedication and slow infusion for the first dose. Dividing the first dose over 2 days (Arm B) was also implemented from the 1080 mg dose level for improved convenience. Preliminary PK assessments demonstrated a more than dose proportional increase in the exposure of RO7297089 with increasing dose levels from 60-1080 mg, suggesting non-linear PK and target-mediated drug disposition, with a trend of approaching linear PK at doses higher than 1080 mg. The estimated half-life was supportive of weekly dosing. Preliminary observation showed 1/18 patients with treatment-induced anti-drug antibodies, which did not appear to impact PK. BCMA expression was detected in the bone marrow in all patients regardless of prior BCMA-targeted therapy. Levels of total soluble BCMA and soluble CD16a increased immediately after the first dose as expected suggesting engagement and stabilization of soluble factors by RO7297089. Of the 18 response-evaluable patients, 1 patient experienced a partial response (1080 mg cohort) per IMWG criteria. Ten patients had stable disease as their best response at dose levels of 60 mg (1/3 patients), 180 mg (2/5 patients), 360 mg (3/4 patients), 1080 mg (4/6 patients). One patient who started at the 60 mg dose and gradually escalated to the 1080 mg dose has been on treatment for 9.5 months with stable disease at the time of the clinical cut-off date. Conclusions: Treatment with RO7297089 was well-tolerated at the dose levels tested, although infusion reactions necessitated long infusion duration for the first dose. Modest activity has been observed to date with doses up to 1080 mg. There were no DLTs and a recommended phase 2 dose has not been identified. The latest clinical, biomarker, and PK data will be presented including data from higher dose level cohorts. Disclosures Plesner: AbbVie: Other: Advisor, Research Funding; CSL Behring: Other: Advisor; Genentech: Other: Advisor, Research Funding; Oncopeptides: Other: Advisor, Research Funding; Takeda: Research Funding; Celgene: Other: Advisor, Research Funding; Genmab: Research Funding; Janssen: Other: Advisor, Research Funding. Harrison: Celgene/ Juno/ BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Terumo BCT: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusa: Consultancy, Honoraria, Speakers Bureau. Quach: GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lee: BMS: Other: Advisor, Research Funding; Janssen: Other: Advisor; Amgen: Other: Advisor. Bryant: Sandoz: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Roche: Honoraria. Estell: Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees. Delforge: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Twomey: Genentech: Current Employment. Choeurng: Genentech: Current Employment. Li: Genentech: Current Employment. Hendricks: Genentech: Current Employment. Sumiyoshi: Genentech: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Miller: Genentech: Current Employment. Choi: Genentech: Current Employment. Schjesvold: Schain: Honoraria; AbbVie: Honoraria; Adaptive Biotechnologies: Consultancy; Nordics Nanovector: Current holder of individual stocks in a privately-held company; Sanofi: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Current holder of individual stocks in a privately-held company, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GSK: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; SkyliteDX: Honoraria; Bayer: Consultancy; Celgene/BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria. OffLabel Disclosure: RO7297089 is a Bâ€'Cell maturation antigen (BCMA)-CD16a bispecific antibody intended for use if approved in patients with relapsed/refractory multiple myeloma

Aims Type 2 diabetes mellitus (T2DM) can substantially decrease quality of life (QOL). This study examined the effects on QOL-relevant psychosocial measures of a widely available commercial weight loss program enhanced for individuals with T2DM. Methods A year-long multi-site randomized clinical trial compared the Weight Watchers (WW) approach, supplemented with phone and email counseling with a certified diabetes educator (CDE), to brief standard diabetes nutrition counseling and education (Standard Care; SC). Participants were 400 women and 163 men (N = 279 WW; 284 SC) with T2DM [mean (± SD) HbA1c 8.32 ± 1%; BMI = 37.1 ± 5.7 kg/m2; age = 55.1 ± 9.1 years]. Psychosocial outcomes were assessed at baseline, month 6, and month 12 using a diabetes specific psychosocial measure (Diabetes Distress Scale [DDS]), Impact of Weight on Quality of Life-Lite scale (IWQOL), a generic QOL measure (SF-36), and a depression screen (PHQ-9). Results WW participants showed significantly greater improvements than did SC participants on all DDS subscales and total score and on IWQOL total score and physical function, sex life and work domains (all ps Conclusions WW enhanced for individuals with T2DM was superior to SC in improving psychosocial outcomes most specific to T2DM and obesity. Available commercial WL programs, combined with scalable complementary program-specific diabetes counseling, may have benefits that extend to diabetes-related distress and weight-relevant QOL.

The authors discuss a case of a rare complications of vascular access creation in a hemodialysis patient “ischemic monomelic neuropathy”

Objective Modest weight loss from clinical interventions improves glycemic control in type 2 diabetes (T2DM). Data are sparse on the effects of weight loss via commercial weight loss programs. This study examined the effects on glycemic control and weight loss of the standard Weight Watchers program, combined with telephone and email consultations with a certified diabetes educator (WW), compared with standard diabetes nutrition counseling and education (standard care, SC). Methods In a 12-month randomized controlled trial at 16 U.S. research centers, 563 adults with T2DM (HbA1c 7–11%; BMI 27–50 kg/m2) were assigned to either the commercially available WW program (regular community meetings, online tools), plus telephone and email counseling from a certified diabetes educator, or to SC (initial in-person diabetes nutrition counseling/education, with follow-up informational materials). Results Follow-up rate was 86%. Twelve-month HbA1c changes for WW and SC were −0.32 and +0.16, respectively; 24% of WW versus 14% of SC achieved HbA1c

Supplemental Digital Content is available in the text., Clinical interest in the measurement of Cereblon (CRBN), the primary target of the IMiDs immunomodulatory drugs lenalidomide and pomalidomide, has been fueled by its essential requirement for antitumor or immunomodulatory activity of both drugs in multiple myeloma (MM). However, limited analyses of clinical samples for CRBN gene expression or protein levels have utilized unvalidated reagents and assays, raising uncertainty about the interpretation of these results. We previously described a highly specific rabbit monoclonal antibody CRBN65 against 65-76 AA of human Cereblon. Here we describe a validated dual color bright-field Cereblon/CD138 immunohistochemical (IHC) assay utilizing CRBN65 and a commercial mouse monoclonal CD138 antibody. Sensitivity and specificity of the assay was determined and assay precision was shown for both cytoplasmic and nuclear Cereblon in MM bone marrow samples with coefficient of variation values of 5% and 2%, respectively. The dual IHC assay was effective for detecting a continuous range of Cereblon levels in 22 MM patient bone marrow core biopsies and aspirate clots, as shown by average cytoplasmic H-scores ranging from 63 to 267 and nuclear H-scores ranging from 17 to 250. Interpathologist comparison of MM sample H-scores by 3 pathologists demonstrated good concordance (R2=0.73). This dual assay demonstrated superior Cereblon IHC measurement in MM samples compared with the single IHC assay using a published commercial rabbit polyclonal Cereblon antibody and could be used to explore the potential utility of Cereblon as a biomarker in the clinic.

The learning landscape of the higher education environment is changing, with an increased focus over the past decade on how educators might begin to cultivate reflective skills in health professions students. In addition, changing professional requirements demand that health professionals are adequately prepared to practise in today’s complex healthcare systems, including responding to changing demographics of population ageing. In this educational case study, we will share how we (a group of education, medical and nursing academics) developed ‘Depth of Field: Exploring Ageing’ a digital, consumer-driven, interprofessional reflective learning resource that uses photographs, narrative and small-group work to strengthen reflective capacity in current and/or future health professionals.

Objective Weight losses between a group of participants assigned to a weight loss program based in the community [i.e., specifically the methodology used by Weight Watchers (WW)] and a Nutrition Education (NE) control group were compared in this study. Methods In this 6-month trial, 300 participants with overweight or obesity were recruited from Beijing city, China, and randomly assigned to the WW or NE group. Weight, waist circumference, and biochemical parameters were assessed at baseline and 6 months. Results At 6 months, the majority of participants (79% for WW; 89% for NE) completed the study. WW participants lost significantly more weight than the NE group (−4.2 ± 5.6 kg vs. −0.6 ± 3.6 kg). More WW participants lost 5% or 10% of their starting weight [≥5%: 52.0% of WW participants vs. 11.3% of NE participants (odds ratio 8.15, 95% CI: 4.43–14.97)]; [≥10%: 26.0% of WW vs. 3.3% of NE participants (odds ratio 9.39, 95% CI: 3.55–24.83)]. In addition, WW participants reduced waist circumference by 3.9 ± 6.3 cm, while the NE group increased waist circumference by 0.6 ± 5.5 cm. Conclusions The WW program was associated with clinically significant weight loss, demonstrating its potential value as an intervention strategy, based in the community, for the treatment of obesity in China.

BACKGROUND: Residential aged care environments can provide valuable learning opportunities for health professional education. An aged care community-university partnership developed the Beyond the Teaching Nursing Home: Community Partnership of Learning and Care (BTTNH: CPLC) programme, where older adults volunteer in learning activities with health professional students. This article describes medical students' experience of participating in a clinical learning activity as part of the broader programme. METHOD: Fourth-year medical students (enrolled in a 6-year medical degree) on geriatric medicine rotation participated in a half-day clinical visit as part of the BTTNH: CPLC programme. Medical students participated in an interview activity with an older adult from the aged care facility. A survey was administered to evaluate medical students' experience of the structured clinical visit to a residential aged care facility. Residential aged care environments can provide valuable learning opportunities for health professional education RESULTS: Medical students valued the learning experience of interacting with older adults, observation of the residential aged care environment and learning about the needs of older adults living in residential aged care. CONCLUSIONS: Providing meaningful learning opportunities for medical students in residential aged care environments may contribute to a better understanding of residents, aged care environments, development of communication skills, professional role and clinical decision-making skills that are relevant for the care of older adults not only in aged care but also in other care settings.

In response to increasing resource pressures and environmental degradation in relation to the fashion industry, the body of academic work on extending garment lifetimes is growing steadily. Yet there is a lack of knowledge regarding how design strategies for longevity play out in practice. This research aims to bridge that gap by drawing on both theoretical knowledge and empirical data from three case studies conducted in UK-based small and medium-sized enterprises (SMEs). Each case study comprised in-depth interviews and visual observations. The results reveal that a range of design strategies for extended garment lifetimes are evident in practice, as garments are inspired by deep-rooted personal interests rather than fleeting trends; silhouettes are honed and evolve slowly over time; and removable modular elements creating updateable pieces and eternally mendable clothing are found. Furthermore, the longevity of a garment is influenced by a complex interplay between the material objects themselv...

Background: The immunomodulatory receptor TIGIT (T-cell Immunoreceptor with Ig and ITIM domains) is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers. In preclinical models, co-inhibition of the TIGIT and PD-L1/PD-1 pathways improved anti-tumor activity compared to either agent alone. Tiragolumab (tira or MTIG7192A) is a humanized IgG1/kappa monoclonal antibody (mAb) that binds TIGIT to prevent its interaction with its ligand PVR (CD155). In this first-in-human dose-escalation study, we report the preliminary safety and anti-tumor activity of tira as a single agent and in combination with atezolizumab (atezo) in patients with advanced solid tumors. Methods: Enrolled patients, ECOG PS 0-1, had advanced tumors for whom standard therapy did not exist or was ineffective. Patients received escalating doses of tira alone IV Q3W alone (Phase Ia) or in combination with atezo 1200 mg IV Q3W (Phase Ib) to determine the maximum tolerated dose (MTD) and continued until disease progression, intolerable toxicity, or patient/investigator decision. Study objectives included evaluation of safety and tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of tira alone or tira + atezo. Data cut-off date was April 2019. Results: 73 patients with multiple tumor types were treated in dose-escalation (24 in Phase Ia, 49 in Ib with tira + atezo). In Phase Ia and Phase Ib, median age was 60 and 54 years, ECOG 0 for 29% and 27% of patients, and those who received ≥ 3 prior therapies were 67% and 57%, respectively. No DLTs were observed. Across doses, treatment-related AEs occurred in 67% in Phase Ia and 59% in Phase Ib (Grade ≥ 3: 4% and 4%, respectively), and most common AEs were fatigue (38%) in Phase Ia and anemia (31%) in Phase Ib. Exposure of tira increased with increasing dose, and saturation of nonlinear PK occurred at tira doses ≥ 100 mg Q3W. Complete and sustained occupancy of peripheral TIGIT receptors was observed at tira doses ≥ 30 mg Q3W. In Phase Ia, there were no objective responses, but SD of > 4 months duration was observed (n=4). In Phase Ib, there were 3 responses, which all occurred in PD-L1 positive tumors (2 non-small cell lung cancer [NSCLC]: 1 CR, 1 PR; and 1 head/neck squamous cell carcinoma: PR) with two patients not receiving prior immunotherapy (CIT-naïve). Therefore, expansion cohorts were initiated in PD-L1-positive CIT-naïve indications in Phase Ib. In the metastatic NSCLC expansion cohort (n=14) ORR was 50%, with 1 CR and 6 PRs; DCR was 79%, and the safety profile was similar. Conclusions: Tira monotherapy or combined with atezo was well-tolerated and had an acceptable safety profile across all dose levels. Preliminary anti-tumor activity was observed in Phase Ib with tira + atezo in CIT-naïve PD-L1-positive tumors, including NSCLC, and enrollment is ongoing in these expansion cohorts. Citation Format: Johanna C. Bendell, Philippe Bedard, Yung-Jue Bang, Patricia LoRusso, Stephen Hodi, Michael Gordon, Sandra D'Angelo, Sandra D'Angelo, Jayesh Desai, Elena Garralda, Antoine Italiano, Myung-Ju Ahn, Andres Cervantes, Zev Wainberg, Emiliano Calvo, Marta Gil-Martin, Maria Martinez-Garcia, Rastilav Bahleda, Philippe Cassier, Jean-Pierre Delord, Amy Prawira, Ignacio Melero, Leisha Emens, Emanuela Romano, Karen Miller, Robert W. Hsieh, Cloris Xue, Kari Morrissey, Patrick Twomey, Kelly Gash, Namrata S. Patil, Jane Grogan, Raymond Meng, Byoung Cho, Tae Won Kim. Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT302.

Business model experimentation for sustainability is an intentional and systematic approach to identify, test and learn about value creation strategies that could be adopted by a business in response to current unsustainable trajectories. For businesses such as large clothing retailers the need to alter course is acute as pressure builds from economic, environmental and social angles. The circular economy concept provides a potential powerful lever for change. To date, however, scant research has been conducted on how circular business model experimentation is conducted. We present an in-depth action research case study of a large international clothing retailer embarking on a journey of business model experimentation for circularity: the processes, methods, roles and the organisation in light of the need to address broad sustainability challenges in the business. It was found that experimentation activities oscillated between slow and loaded, and faster and un-weighted modes. While an intentional and stepwise process was sought, in reality it was largely emergent and highly iterative. Through this iterative process, new circular business models were generated that co-exist with current non-circular ones. Confidence in experimentation as a business capability also increased through this collaborative project. This study provides insights into how to conduct lean startup type business model experimentation for circularity in a large organisation. For practitioners, the benefits of academic-industry collaboration, and the oscillating dynamics of business model experimentation are illuminated.

The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines recommend postmastectomy radiation therapy (PMRT) for women with N2/N3 breast cancer. We examined the compliance rate of PMRT using the National Cancer Data Base and determined what factors are associated with low compliance rate with PMRT.The National Cancer Data Base, comprising 2,720,368 breast cancer cases diagnosed between 1998 and 2011, was evaluated. From this database, 56,990 women with N2/N3 diseases were evaluated. Statistics used include chi-square test, 2-sample t-test or Wilcoxon rank-sum test, and multivariate analysis.Mean age of the patients was 58 years and median follow-up was 61 months. The majority of patients were from a comprehensive community cancer programs (59%), were Caucasian (81%), had health insurance (96%), resided in urban communities (98%), and had no comorbidities (83%). Approximately 82% received chemotherapy, but only 65% had PMRT. Factors associated with PMRT are tumor grade (p = 0.03), regional lymph node surgery (p = 0.03), readmission within 30 days of surgical discharge (p = 0.03), receipt of chemotherapy (p0.01) and hormonal therapy (p0.01), and 30-day mortality (p0.01). Socioeconomic variables, such as facility type (p = 0.85), facility geographic location (p = 0.27), race/ethnicity (p = 0.12), insurance status (p = 0.10), income level (p = 0.43), education level (p = 0.86), residential location (p = 0.83), and comorbidities (p = 0.83) were not contributory factors. Independent variables predicting compliance with PMRT include receipt of chemotherapy (odds ratio = 4.55; p0.01), readmission within 30 days after surgery (odds ratio = 1.14; p = 0.01), and alive within 30 days after surgery (odds ratio = 1.55; p = 0.04).One third of patients with N2/N3 disease did not receive PMRT. Socioeconomic variables were not contributory factors. Noncompliance with PMRT is related to lack of receipt of chemotherapy, nonreadmission, or death within 30 days after surgery.

Mislabelling of seafood products has been documented in numerous countries for over three-quarters of a century. With a trend towards increased consumption of seafood, the informed consumer demands accurately labelled products that provide full disclosure of composition. DNA barcoding can be used to accurately identify a seafood product to species based on its genetic signature, and so provides a means to test the authenticity and accuracy of seafood labelling. This can be especially useful for products such as fillets which have few or no unambiguous identifying characters, and can easily be mislabelled. We investigated labelling accuracy in seafood retailers in Tasmania, Australia. Thirty-eight seafood products were obtained from seafood retailers, sequenced for the barcoding gene region cytochrome oxidase subunit 1(CO1), and subsequently identified to species level by querying GenBank and Barcode of Life Data Systems (BOLD) DNA sequence records. Results were compared with standard fish names (SFN) prescribed under the Australian Fish Names Standard (AFNS) and FishBase. Of the 38 samples, none were deemed to have been mislabelled under Australian regulation, although in some cases naming discrepancies and ambiguity may cause confusion for some consumers. Our work, while reflecting high standards in Tasmanian seafood, highlights the need for mandatory standard labelling across all seafood products so as to eliminate any possible misrepresentation.

This panel provides a state of the art review of knowledge management (KM) education approaches in the LIS field. The panelists will share thoughts and experiences pertaining to the current treatment of knowledge management concepts in Library and Information Science education. The panel is comprised of professionals who have experience in both the knowledge management and LIS disciplines, in both academic and in practical roles. Furthermore, panelists represent perspectives from several contributing disciplines.

The hedgehog (Hh) pathway is aberrantly activated in a number of tumors. In medulloblastoma, basal cell carcinoma, and rhabdomyosarcoma, mutations in Hh pathway genes lead to ligand-independent pathway activation. In many other tumor types, ligand-dependent activation of Hh signaling is potentiated through crosstalk with other critical molecular signaling pathways. Among such pathways, RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, EGFR, and Notch are of particular interest because agents that selectively inhibit these pathways are available and can be readily combined with agents such as vismodegib, sonidegib (LDE225), and BMS-833923, which target smoothened-a key Hh pathway regulator. Numerous preclinical studies have revealed the ways in which Hh intersects with each of these pathways, and combination therapies have resulted in improved antitumor efficacy and survival in animal models. Hh also plays an important role in hematopoiesis and in the maintenance of BCR-ABL-driven leukemic stem cells. Thus, combined inhibition of the Hh pathway and BCR-ABL has emerged as a promising potential therapeutic strategy in chronic myeloid leukemia (CML). A number of clinical trials evaluating combinations of Hh inhibitors with other targeted agents are now underway in CML and a variety of solid tumors. This review highlights these trials and summarizes preclinical evidence of crosstalk between Hh and four other actionable pathways-RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, EGFR, and Notch-as well as the role of Hh in the maintenance of BCR-ABL-driven leukemic stem cells.

This poster summarizes results of the IMLS funded University of South Carolina META project that explored the application of meta-analysis techniques to develop a robust model of public library economic value. Completed in 2014, the project approached this topic with two fundamental questions: (1) whether the reviewed public library valuation studies provide mounting evidence concerning the contributions that public libraries make to the economic prosperity of the communities they serve, and (2) what steps need to be taken in order to strengthen this assertion? The results of the analyses performed to answer these questions suggest that Americans typically receive five to six dollars for every dollar they spend on public library services. The results also lead to recommendations concerning strategies that could add strength to this assertion and provide a powerful new argument for the continuance of public library services: more detailed reporting practices, greater methodological consistency, and systematic consideration of intangible benefits.

Twentieth-century US public relations historiography has focused primarily on corporate public relations and agencies, incorporating a “great man” perspective and largely excluding women and minorities. This scholarship allows us to begin to build a narrative, presented here, but the authors call for an expansion of what is considered public relations and of who practiced it. Public relations was often used by people in areas such as politics, churches, higher education institutions, and social service agencies who were not trying to invent public relations; rather they were solving problems by using communication to inform and persuade their audiences. The activism of suffragist and women’s rights advocate Alice Paul, and Henry Lee Moon, NAACP public relations director, illustrates that American public relations history is broad, diverse, and expansive.

The impact of a cultural awareness course among nursing students may affect the particular person for years to come. Cultural awareness can be taught via many methods, often requiring study abroad and/or extreme investment of time, money and effort. There is little research on sustained effects on nursing alumni from such a course. The purpose of this descriptive survey study was to determine the long term outcomes of a cultural awareness course and 2) compare the long term effects between alumni who went abroad and those who chose to complete the course locally. One hundred and twenty-one nursing alumni completed the International Education Survey (IES) (Zorn, 1996) with additional open-ended questions. Quantitative and qualitative results concluded: 1) nursing alumni were influenced long term by a course dedicated to public and global health and 2) all alumni had statistically significant IES scores but alumni who studied abroad had the greatest increase.

Drawing on theories of representative bureaucracy, we examine whether increased representation of women in police forces in England leads to a higher rate of domestic violence arrests. To do so, we use panel regression techniques to analyze the links between gender representation and variations in the arrest of domestic abuse perpetrators when controlling for a range of other relevant variables, including the relative prosperity of the local population and the size of the police force. Our statistical results suggest that the rate of domestic violence arrests varies in terms of the authority and discretion accorded to women police officers. We find that the presence of a female police chief constable is positively associated with the domestic violence arrest rate, but that increased representation of female police officers makes a difference only when they are accorded greater opportunity to carry out frontline police work.

Aspirin (ASA) is recommended for the prevention of cardiovascular disease; however, the compliance is low. Reported use may not reflect actual use. Serum thromboxane B2 (STxB2) measurement was evaluated to validate reported ASA use. Males aged 45 to 79 years and females aged 55 to 79 years completed a survey and STxB2 measurement (Thromboxane B2 EIA Kit; Cayman Chemical, Ann Arbor, Michigan). The 107 patients were grouped by use of ASA (56 ASA+ and 51 ASA−) and possible interfering medications (INT) such as nonsteroidal anti-inflammatory drugs. The STxB2 levels (ng/mL) were significantly lower in ASA users: ASA+ INT− 3.0 (0.7, 8.4), ASA+ INT+ 2.0 (0.8, 4.9), ASA− INT+ 176 (75, 390), and ASA− INT− 271 (199, 366). The INT use did not cause a significant difference in STxB2 levels. A STxB2 cut point of 25 ng/mL had high sensitivity (94.1%) and specificity (91.1%) for ASA use. The STxB2 was a reliable marker of ASA use and could be used to confirm ASA exposure in population-based health studies.

Design management is widely acknowledged as important in optimizing the contribution of design in organizations, especially where survival in turbulent industries such as fashion retail depends upon design for differentiation, value engineering and an agile response. However, design management in this industry has received scant attention, in spite of the sector's degree of design intensity. This paper seeks to redress this imbalance with interview-based case studies in seven leading UK-based international retailers, by investigating design management activities. The results reveal design management is composed of two distinct cohorts, with true design leaders privileged by formal design education and extensive design experience and others we term ‘managers of design’. From these findings we provide a framework, which more accurately depicts the roles of design management in this dynamic industry, thereby helping to develop understanding in both academic and practical contexts.

During the 1950s and 1960s, U.S. civil rights protesters targeted businesses with demands for service, jobs, and equality. Employing historical method, this study considers the role of public relations by examining magazine, newspaper, and public relations trade press coverage of business responses to the civil rights movement. The analysis shows that, although all five motivations for the adoption of the formal public relations function—profit, legitimacy, recruitment, agitation, and advocacy—were present, business was slow to respond; that riots and concerns about corporate image drove business to take a public stand; and that professional public relations participation appeared to be minimal even as it was cited in press stories as a reason for the failure of many business initiatives. In addition, the analysis demonstrates the existence of a sixth motivation: fear.

Editor's Summary A highlight of the 2012 ASIS&T Annual Meeting, the pre-conference session on the History of ASIS&T and Information Science and Technology Worldwide drew presenters and attendees from around the globe. The day featured papers on four historical themes, starting with the institutional roots of ASIS&T and recognizing decades of research presented in the Annual Review of Information Science and Technology. The evolution of the field was apparent through a review of information revolutions prompted by the printing press, the post-World War II information crisis and the Internet, as well as through presentations on digital curation, ongoing work on relevance, sense-making theory and developments from Croatia to France. Discussion of the historical contexts of technology innovations and impacts considered photographic documentary techniques, binary computing and networking standards. The development of foundational ideas was explored through presentations on pioneering document indexing methods, the semantic challenge of term-oriented retrieval, early European perceptions of classification systems and the French view of communication and information science. Efforts to deepen the historical understanding of information science and technology will continue through oral history interviews, funded research and awards for outstanding papers.

Macromolecular Crystallography (MX) is becoming a big data science straining the capabilities of computers and networks. New techniques of serial crystallography are allowing new science to be done but they are increasing the heterogeneity of the data that must be handled. Two new beamlines at the National Synchrotron Light Source-II, for Frontier Macromolecular Crystallography (FMX) and for highly Automated Macromolecular Crystallography (AMX), are beginning user operation in 2016, and are dealing with these big data issues. This work is contributing to a worldwide High Data-Rate Macromolecular Crystallography (HDRMX) collaboration among crystallographic software developers, beamline scientists and controls people to resolve these issues as new high-brightness beamlines and new fast X-ray detectors come into increasing use.

Objectives. To determine if a widely available weight-management program (Weight Watchers) could achieve sufficient weight loss in persons with prediabetes compared with a Diabetes Prevention Program–based individual counseling program supported by National Diabetes Education Program materials. Methods. We conducted an individual, randomized intervention trial in Indianapolis, Indiana, in 2013 to 2014, in 225 persons with prediabetes. We compared the Weight Watchers weight-management program (n = 112) with Your Game Plan to Prevent Type 2 Diabetes, a program developed by the National Diabetes Education Program. Outcomes were weight and metabolic markers measured at baseline, 6 months, and 12 months. Results. Intervention participants lost significantly more weight than controls at 6 months (5.5% vs 0.8%) and 12 months (5.5% vs 0.2%; both P Conclusions. A large weight-management program is effective for achieving lifestyle changes associated with diabetes prevention. Such programs could significantly increase the availability of diabetes prevention programs worldwide making an immediate and significant public health impact.

Thalidomide and the immunomodulatory drug, lenalidomide, are therapeutically active in hematological malignancies. The ubiquitously expressed E3 ligase protein cereblon (CRBN) has been identified as the primary teratogenic target of thalidomide. Our studies demonstrate that thalidomide, lenalidomide and another immunomodulatory drug, pomalidomide, bound endogenous CRBN and recombinant CRBN-DNA damage binding protein-1 (DDB1) complexes. CRBN mediated antiproliferative activities of lenalidomide and pomalidomide in myeloma cells, as well as lenalidomide- and pomalidomide-induced cytokine production in T cells. Lenalidomide and pomalidomide inhibited autoubiquitination of CRBN in HEK293T cells expressing thalidomide-binding competent wild-type CRBN, but not thalidomide-binding defective CRBN(YW/AA). Overexpression of CRBN wild-type protein, but not CRBN(YW/AA) mutant protein, in KMS12 myeloma cells, amplified pomalidomide-mediated reductions in c-myc and IRF4 expression and increases in p21(WAF-1) expression. Long-term selection for lenalidomide resistance in H929 myeloma cell lines was accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and lenalidomide, CRBN protein was undetectable. Our biophysical, biochemical and gene silencing studies show that CRBN is a proximate, therapeutically important molecular target of lenalidomide and pomalidomide.

This article assesses the nature of partnerships through the research site of local governance in England and Scotland, engaging a range of debates and literature around governance and meta-governance. The research used secondary data of local authority partnership working in England and Scotland as well as primary qualitative data from participant observation and interviews with senior officials of local authorities and partner organisations. There is little to suggest that English and Scottish practices are significantly at variance and the article advances an argument of meta-bureaucracy to describe partnerships’ activities: that is to say, partnerships do not represent a growth of autonomous networks and governance arrangements but rather an extension of bureaucratic controls. State actors remain preeminent within increasingly formalised systems of ‘partnership’.

Background Node-positive breast cancer patients are at risk for metastatic disease. A routine metastatic workup might or might not be necessary for all patients with N2 or N3 diseases. The National Comprehensive Cancer Network guidelines recommend a metastatic workup for patients with T3N1 disease, yet no definitive recommendations are made for N2/N3 diseases. We hypothesized that for patients with operable pathologic N2/N3 diseases, a metastatic workup should only be considered for patients with T3/T4 lesions. Study Design Two hundred and fifty-six patients with pathologic N2/N3 diseases were identified from a prospective breast cancer database of 1,329 patients with stage 0 to III breast cancer. A metastatic workup included chest x-rays, bone scans, CT scans, and PET scans. Primary end point was incidence of stage IV disease at the time of diagnosis or within 1 month of definitive surgery. Statistical analysis included chi-square test, independent t- test, Kaplan-Meier Survival method, log-rank test, and Cox proportional hazard model. A p value ≤ 0.05 was considered statistically significant. Results There were 158 patients with N2 disease (62%) and 98 with N3 disease (38%). Overall, 16% had stage IV disease (N2 = 15%, N3=16%). There was no significant difference in age (p = 0.37), tumor size (p = 0.89), tumor grade (p = 0.09), estrogen-receptor status (p = 0.23), or progesterone-receptor status (p = 0.35) between the N2 and N3 groups. Incidences of stage IV disease were T0/T1, 0%; T2, 6%; T3, 22%; and T4, 36%. Multivariate analysis demonstrated that only T stage (p = 0.0006) and grade (p = 0.026) were independent predictors of overall survival. Conclusions A metastatic workup is only indicated for N2/N3 patients with T3 or T4 primary lesions.

The promotion of gender equality has been adopted onto many national policy agendas with the introduction of legislation, public policies and regulatory duties. Yet, gender occupational segregation and discrimination persists. This paper examines the gendered nature of the UK public sector and questions the extent to which public administration scholarship addresses gender bias. The evidence, based on secondary and primary data, reveals that public administration scholarship tends to value masculinity. The intention of the paper is to stimulate a debate by providing a critical reflection of public administration scholarship, and concludes with some tentative suggestions on ways forward for the field of study.

This paper describes two different services within the UK, both of which aim to better address the needs of offenders with personality disorder. Both services have been developed in the light of recent policy and practice guidance, which recognises the need to develop new ways of working with this hard‐to‐reach population.The importance of developing boundaries and optimistic therapeutic relationships in order to foster motivation and engagement is emphasised. It is within these that assessment and interventions to address risk, mental health and social integration issues can be undertaken. In addition, the need for different agencies to work together in partnership to better address these needs is also emphasised.Resettle is a stand‐alone service in the pilot stage whilst the probation link‐work role is a resource within an established community personality disorder service.

Conservation and management of deep-sea corals and coral reefs was the theme of the 4th International Deepsea Coral Symposium held in Wellington, New Zealand from 1 to 5 December 2008. A selection of resulting studies is published here. Recent advances in our understanding of deep-sea corals and associated ecosystems have demonstrated their high diversity, abundance, longevity and widespread global distribution. Such deep-water communities are increasingly threat- ened by anthropogenic environmental change (e.g. ocean acidity, fishing pressures) and require timely management policies and actions to reduce potential deleterious effects. The interdisciplinary nature of deep-sea coral research is a significant strength, helping to provide the broad base of knowledge and resources that are required for the conservation and management of this important ecological group.

PART I: OVERVIEW Introduction In the absence of a general theory that describes the rise and growth of public relations, scholars have tended to organize public relations and its antecedents into time periods that present a progressive evolution from unsophisticated and unethical early roots to planned, strategic, and ethical campaigns of the current day. We argue that such attempts at periodization have obscured our understanding of public relations and its history. Indeed, public relations historians have long called for such a departure, noting the constraints it has imposed on understanding the development of public relations in the United States and around the world (e.g., Brown, 2003; Gower, 2007, 2008 Hoy, Raaz, & Wehmeier, 2007 L'Etang, 2004, 2008; Lamme, 2003 McBride, 1989; Miller, 2000 Pearson, 1990; Piasecki, 2000 Toledano, 2005). We therefore analyzed scholarship about public relations (whether it is called publicity, press agentry, propaganda, or public relations) prior to 1900 to understand the growth of the field in a variety of contexts and time periods. This is not an attempt to catalog additional antecedents to 20th century practices. Instead, this study seeks to break away from the misleading dependence on linear interpretations of the field's past and construct a broad, long-term view of the development and institutionalization of persuasive organizational communication strategies and techniques. In the process, we seek to correct misunderstandings about public relations history which have (mis)informed public relations theory for more than 20 years and to describe and understand the historical relationship between public relations, the mass media, and the historical contexts in which public relations emerged. By doing so, we seek to depart from what L'Etang (2008, p. 321) called the patterning, or colligation, of history, which can artificially inflate or diminish the historical role of people and events, and "reappraise the criteria used to establish the meaning of value in the field" (Creedon, 1989, p. 29). The effect of these efforts, then, will be to remove the spin - the conscious positioning of public relations history that has heretofore dominated scholarly understanding of the field's development. SIGNIFICANCE TO MASS COMMUNICATION Public relations history has been of great interest to disciplines lying outside the mass communication field, such as social history (Ewen, 1996; Pimlott, 1951), business history (Gras, 1945; Marchand, 1998, Raucher, 1968, Tedlow, 1979), political science (Maltese, 1992), cultural history (Leach, 1993), English (Davis, 2007), and history (Billington, 1978; Goldman, 1948, 1978; Nevins, 1963). Mass communication scholars also have contributed studies of significance to American public relations history, largely concerning the press and government (e.g., Cone, 2007; Lumsden, 2000; Oukrop, 1976; Streitmatter, 1990), religion (e.g., Ferre, 1993; Nord, 1984), and the advocacy press (e.g., Burt, 1998, 1999; Steiner, 1983; Folkerts, 1985). The latter, in particular, has been found to serve as a tool for community-building (Steiner, 1983; Folkerts, 1985), for enhancing a movement's legitimacy (Folkerts, 1985), for articulating a movement's message, for propagating a movement's mission, for "recruiting, mobilizing, and sustaining support and membership" (Burt, 2000, p. 73), and for serving as "community bulletin boards" (Burt, 1999, p. 39). Finally, three authors grounded in journalism have, to date, written the most extensively on three 20th century public relations pioneers: Hiebert (1966) on Ivy Lee, Tye (1998) on Edward L. Bernays, and Henry (1997, 1998, 1999) on Doris Fleischman. Within the public relations field, however, scholars have pursued new theoretical ground by looking outside the field to apply multi-tiered analyses and frameworks (e.g., Brown, 2006; L'Etang, 2004; Miller, 2000; and Pearson, 1990). Others have considered public relations history in the context of ethics (McBride, 1989) and ethical propaganda (St. …