Introduction and Tribute to Charlie Calisher.

It is a great pleasure to contribute a few words of introduction to this Special Issue of MDPI's Diseases entitled "Recent Studies of Arthropod-, Bat-, and Rodent-Borne Viruses: A Theme Issue in Honor of Professor Charles H [...].

Efficacy and Safety of Intravenous Golimumab Through One Year in Patients With Active Psoriatic Arthritis.

OBJECTIVE: The present study was undertaken to evaluate the safety and efficacy of intravenous (IV) golimumab in patients with active psoriatic arthritis (PsA) through 1 year. METHODS: GO-VIBRANT was a phase III, randomized, placebo-controlled trial of 480 adults with active PsA. Patients were randomized to receive IV placebo (n = 239) or golimumab 2 mg/kg (n = 241) at weeks 0, 4, and every 8 weeks, with placebo crossover to golimumab at weeks 24, 28, and every 8 weeks thereafter. Efficacy through week 52 was assessed using the American College of Rheumatology (ACR) ≥20%, 50%, or 70% improvement criteria (ACR20/50/70), and the Psoriasis Area and Severity Index ≥75% improvement criteria (PASI75). Radiographic progression was measured using the PsA-modified Sharp/van der Heijde score (SHS). Adverse events (AEs) were monitored through week 60. RESULTS: The primary and major secondary end points through week 24 were achieved. At week 52, 76.8% of patients in the golimumab group and 77.0% in the placebo-crossover group achieved an ACR20 response, 58.1% and 53.6%, respectively, achieved an ACR50 response, and 38.6% and 33.9%, respectively, achieved an ACR70 response. Among patients with ≥3% body surface area affected, 71.9% in the golimumab group and 60.6% in the placebo-crossover group achieved a PASI75 response at week 52. Mean change from baseline in total SHS at week 52 was -0.5 in the golimumab group and 0.8 in the placebo-crossover group. Through week 60, 50.9% of all golimumab-treated patients had ≥1 AE, and 5.2% had ≥1 serious AE. There were no opportunistic infections, 2 malignancies, and 1 death in patients treated with golimumab. CONCLUSION: Sustained improvements in joint and skin disease in patients with PsA were maintained through 1 year in the GO-VIBRANT study. No new safety signals for IV golimumab were identified.

Hydroxychloroquine-induced inverse psoriasis.

A 65-year-old woman presented to our rheumatology clinic with pain and swelling of multiple joints of her hands. After a thorough evaluation, she was diagnosed with rheumatoid arthritis and was started on hydroxychloroquine therapy. A week later, she presented to our clinic with an acute condition and reported that after taking hydroxychloroquine for a few days she developed multiple rashes, most prominent at skin folds around her breasts, neck, axillae and buttocks. The rashes were characteristic of inverse psoriasis. Hydroxychloroquine was discontinued and the patient was started on methotrexate therapy that resulted in resolution of her rashes in a week.

Anatomy of the stemmata in the Photuris firefly larva.

Fireflies (Coleoptera: Lampyridae) have distinct visual systems at different stages of development. Larvae have stemmata and adults have compound eyes. Adults use compound eyes to mediate photic communication during courtship. Larvae do not manifest this behavior, yet they are bioluminescent. We investigated the structure of stemmata in Photuris firefly larvae to identify anatomical substrates (i.e., rhabdomeres) conferring visual function. Stemmata were located bilaterally on the antero-lateral surfaces of the head. Beneath the ~ 130 µm diameter lens, we identified a pigmented eye-cup. At its widest point, the eye-cup was ~ 150 µm in diameter. The optic nerve exited the eye-cup opposite the lens. Two distinct regions, asymmetric in size and devoid of pigmentation, were characterized in stemmata cross-sections. We refer to these regions as lobes. Each lobe contained a rhabdom of a radial network of rhabdomeres. Pairs of rhabdomeres formed interdigitating microvilli contributed from neighboring photoreceptor cell bodies. The optic nerve contained 88 axons separable into two populations based on size. The number of axons in the optic nerve together with distinct rhabdoms suggests these structures were formed from 'fusion stemmata.' This structural specialization provides an anatomical substrate for future studies of visually mediated behaviors in Photuris larvae.

Discovery and Description of Ebola Zaire Virus in 1976 and Relevance to the West African Epidemic During 2013-2016.

BACKGROUND: In 1976, the first cases of Ebola virus disease in northern Democratic Republic of the Congo (then referred to as Zaire) were reported. This article addresses who was responsible for recognizing the disease; recovering, identifying, and naming the virus; and describing the epidemic. Key scientific approaches used in 1976 and their relevance to the 3-country (Guinea, Sierra Leone, and Liberia) West African epidemic during 2013-2016 are presented. METHODS: Field and laboratory investigations started soon after notification, in mid-September 1976, and included virus cell culture, electron microscopy (EM), immunofluorescence antibody (IFA) testing of sera, case tracing, containment, and epidemiological surveys. In 2013-2016, medical care and public health work were delayed for months until the Ebola virus disease epidemic was officially declared an emergency by World Health Organization, but research in pathogenesis, clinical presentation, including sequelae, treatment, and prevention, has increased more recently. RESULTS: Filoviruses were cultured and observed by EM in Antwerp, Belgium (Institute of Tropical Medicine); Porton Down, United Kingdom (Microbiological Research Establishment); and Atlanta, Georgia (Centers for Disease Control and Prevention). In Atlanta, serological testing identified a new virus. The 1976 outbreak (280 deaths among 318 cases) stopped in <11 weeks, and basic clinical and epidemiological features were defined. The recent massive epidemic during 2013-2016 (11 310 deaths among 28 616 cases) has virtually stopped after >2 years. Transmission indices (R0) are higher in all 3 countries than in 1976. CONCLUSIONS: An international commission working harmoniously in laboratories and with local communities was essential for rapid success in 1976. Control and understanding of the recent West African outbreak were delayed because of late recognition and because authorities were overwhelmed by many patients and poor community involvement. Despite obstacles, research was a priority in 1976 and recently.

Beyond complications: Comparison of procedural differences and diagnostic success between nurse practitioners and radiologists performing image-guided renal biopsies.

PURPOSE: Radiology-trained nurse practitioners (NPs) may perform image-guided medical renal biopsies with computed tomography (CT). This study evaluates the procedural differences and diagnostic success between biopsies performed by NPs compared to radiologists. DATA SOURCES: A retrospective study was performed on patients who underwent nontargeted, CT-guided renal biopsy between 2009 and 2014. Provider type (NP or radiologist), number of core specimens obtained, sedation medication dose, CT dose index (CTDI), and diagnostic success were recorded. Categorical and continuous variables were analyzed using χ2 and Student's two-tailed t-test, respectively, comparing NPs with radiologists. CONCLUSIONS: A total of 386 patients were included; radiologists performed 215 biopsies and NPs performed 171 biopsies. There was no significant difference in diagnostic success, amount of tissue harvested (number of cores), radiation dose, or sedation dosage between NPs and radiologists performing CT-guided renal biopsies. Only 4% were nondiagnostic (n = 7, radiologists; n = 9, NPs; p = .325). Overall mean number of cores obtained was 3.7, mean CTDI was 176.5 mGy, mean fentanyl dose was 86.3 µg, and mean midazolam was dose 1.54 mg without a statistically significant difference between provider types. IMPLICATIONS FOR PRACTICE: NPs perform image-guided medical renal biopsies in a similar fashion to radiologists with respect to diagnostic success, amount of tissue harvested, total radiation dose exposure, and administration of sedation.

Dose optimization by altering the operating potential and tube current exposure time product in dental cone beam CT: a systematic review.

OBJECTIVES: Current guidelines highlight the need to optimize exposure parameters on CBCT equipment to levels that are as low as diagnostically acceptable. This systematic review aimed to answer the question "Can altering operating potential (kV) and tube current exposure time product (mAs) on CBCT machines reduce radiation dose to patients undergoing dental and/or maxillofacial scans without a detrimental impact on image quality/diagnostic accuracy?" METHODS: Studies were selected and results reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. For each individual study, two authors (RG and JD or KH) independently extracted data using a specifically designed collection form, and an overall quality value was assigned using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Any disagreements in the overall quality value of a study were resolved by discussion between the current authors. RESULTS: Nearly 75% of studies were considered to be of low or very low methodological quality using the GRADE system, and more studies stated that their results applied only in the specific situations they had investigated. However, most studies demonstrated that patient dose reduction is possible without a clinically relevant reduction in image quality. CONCLUSIONS: For many CBCT machines, it should be possible to optimize one, or more, of the investigated exposure parameters and therefore reduce patient radiation dose, while maintaining diagnostic image quality for some diagnostic tasks. However, more rigorous research is still required.

Transmission of Ebola viruses: what we know and what we do not know.

Available evidence demonstrates that direct patient contact and contact with infectious body fluids are the primary modes for Ebola virus transmission, but this is based on a limited number of studies. Key areas requiring further study include (i) the role of aerosol transmission (either via large droplets or small particles in the vicinity of source patients), (ii) the role of environmental contamination and fomite transmission, (iii) the degree to which minimally or mildly ill persons transmit infection, (iv) how long clinically relevant infectiousness persists, (v) the role that "superspreading events" may play in driving transmission dynamics, (vi) whether strain differences or repeated serial passage in outbreak settings can impact virus transmission, and (vii) what role sylvatic or domestic animals could play in outbreak propagation, particularly during major epidemics such as the 2013-2015 West Africa situation. In this review, we address what we know and what we do not know about Ebola virus transmission. We also hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread.

Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor α inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study.

INTRODUCTION: The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor-α (TNF)-inhibitor(s). METHODS: Patients enrolled into this multicenter, randomized, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) received placebo (Group 1) or golimumab 50 mg (Group 2) or 100 mg (Group 3) injections every 4 weeks. Patients in Groups 1 and 2 with inadequate response at week 16 escaped to golimumab 50 and 100 mg, respectively. At week 24, Group 1 patients crossed-over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status, and Group 3 maintained dosing. During the long-term-extension (LTE), golimumab 50 mg could be increased to 100 mg, and 100 mg could be decreased to 50 mg. Data through 5 years are reported for all patients (safety) and patients using methotrexate (efficacy, intention-to-treat (ITT) analysis with last-observation-carried-forward for missing data and non-responder imputation for unsatisfactory efficacy discontinuations). RESULTS: In total, 459 of 461 randomized patients received the study agent, 304 of whom were methotrexate-treated and included in efficacy analyses. Through week 256, the proportions of methotrexate-treated patients achieving American-College-of-Rheumatology (ACR) responses were 37.6% to 47.0% for ACR20, 21.4% to 35.0% for ACR50, and 7.8% to 17.0% for ACR70 response across randomized groups. Golimumab safety through week 268 was generally consistent with that at week 24 and week 160 and other anti-TNF agents. CONCLUSIONS: In some patients with active RA discontinuing previous TNF-antagonist therapy, golimumab safety and efficacy, assessed conservatively with ITT analyses, was confirmed through 5 years. TRIAL REGISTRATION: Clinicaltrials.gov NCT00299546 . Registered 03 March 2006.

Comparison of image-guided nonfocal hepatic biopsies performed by physicians and nurse midlevel providers.

Image-guided hepatic biopsies have been performed safely and accurately for a number of years. The advantages of sonographic or CT guidance in avoiding major vital structures, such as large vessels, the gallbladder, or pleura, have been confirmed many times. However, the safety and accuracy of certified nurse practitioners' performing these biopsies have not been described. The authors describe a retrospective review of 418 image-guided hepatic biopsies that demonstrated no significant difference in accuracy or complication rates between biopsies performed by certified nurse practitioners and those performed by radiologists in a single-institution, multihospital academic setting. Appropriately trained advanced practice providers can perform image-guided hepatic biopsies safely and accurately.

The effect of golimumab on haemoglobin levels in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.

OBJECTIVE: To evaluate the effect of golimumab on haemoglobin levels in patients with RA, PsA or AS. METHODS: Secondary analysis was performed on integrated data from five randomized controlled studies: three RA, one PsA and one AS (2303 patients total). Golimumab 50 or 100 mg was injected s.c. every 4 weeks with or without MTX. Control groups received placebo injections plus MTX or background therapy. Patients with haemoglobin levels below the age- and sex-specific normal ranges were considered to have anaemia. Ferritin levels were used to distinguish anaemia of mixed aetiology (≥ 15 and <60 ng/ml) and anaemia of inflammation (≥ 60 ng/ml). Changes from baseline to weeks 14 and 24 in haemoglobin level were compared between treatment groups using an analysis of variance on the van der Waerden normal scores. RESULTS: At baseline, 21% of RA patients, 9% of PsA patients and 15% of AS patients had anaemia. Of these, 24%, 57% and 25%, respectively, had anaemia of inflammation. The median increase from baseline to week 14 in the haemoglobin level of anaemic patients was 0.3 g/dl in the control group and 0.9 g/dl in the golimumab group (P < 0.001). Haemoglobin levels improved within the subgroups of patients with anaemia of mixed aetiology (control, 0.4 g/dl vs golimumab, 0.7 g/dl) (P = 0.305) and with anaemia of inflammation (0.2 vs 1.4 g/dl, respectively) (P < 0.001). CONCLUSION: Compared with the control group, patients receiving golimumab treatment had significantly improved haemoglobin levels, particularly among patients with anaemia of inflammation.

Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind, placebo-controlled phase III trial.

OBJECTIVE: To compare the efficacy of tanezumab versus placebo for reducing pain and improving physical function in patients with osteoarthritis (OA) of the hip. METHODS: This was a 32-week, randomized, double-blind, placebo-controlled, phase III trial. Patients with baseline Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively, and patient's global assessment of OA as "fair," "poor," or "very poor" were treated at baseline and weeks 8 and 16. Coprimary efficacy end points were change from baseline to week 16 in WOMAC Pain and Physical Function subscales and patient's global assessment, analyzed using analysis of covariance. Adverse events (AEs) were monitored throughout. RESULTS: Patients (n = 621) were randomized 1:1:1:1 to treatment with intravenous tanezumab 2.5 mg, 5 mg, or 10 mg or placebo. Each tanezumab group showed significant improvement for the 3 coprimary end points versus placebo (P ≤ 0.001 for all). AE incidence ranged from 55% to 58% across tanezumab groups versus 44% for placebo. Safety findings were similar to those previously reported. The tanezumab OA clinical program was temporarily placed on hold because of AEs leading to joint replacement. Total joint replacements were reported in 8 patients: 1 in the 10 mg, 2 in the 5 mg, 2 in the 2.5 mg, and 3 in the placebo group. A total of 9 joints were replaced (8 hips [7 index joints] and 1 shoulder). CONCLUSION: Our findings indicate that tanezumab provides superior pain relief and improvement in physical function and patient's global assessment versus placebo in patients with painful hip OA, and is generally well tolerated.

Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab.

OBJECTIVE: To determine serum biomarker associations with clinical response to golimumab treatment in patients with psoriatic arthritis (PsA). METHODS: GO-REVEAL was a randomised, placebo-controlled study of golimumab in patients with active PsA. Samples were collected from 100 patients at baseline, week 4 and week 14, and analysed for serum-based biomarkers and protein profiling (total 92 markers); data were correlated with clinical measures at week 14. RESULTS: Serum levels of a subset of proteins (apolipoprotein C III, ENRAGE, IL-16, myeloperoxidase, vascular endothelial growth factor, pyridinoline, matrix metalloproteinase 3, C-reactive protein (CRP), carcinoembryonic antigen, intercellular adhesion molecule 1 and macrophage inflammatory protein 1α) at baseline or week 4 were strongly associated with American College of Rheumatology 20% improvement (ACR20) response and/or disease activity score in 28 joints (DAS28) at week 14. A smaller subset of proteins was significantly associated with a 75% improvement in the psoriasis area and severity index score (PASI75) at week 14, (adiponectin, apolipoprotein CIII, serum glutamic oxaloacetic transaminase, and tumour necrosis factor α). Subsets of proteins were identified as potentially predictive of clinical response for each of the clinical measures, and the power of these biomarker panels to predict clinical response to golimumab treatment was stronger than for CRP alone. CONCLUSIONS: This analysis provides insight into several panels of markers that may have utility in identifying PsA patients likely to have ACR20, DAS28, or PASI75 responses following golimumab treatment.

Virus species polemics: 14 senior virologists oppose a proposed change to the ICTV definition of virus species.

The Executive Committee of the International Committee on Taxonomy of Viruses (ICTV) has recently decided to modify the current definition of virus species (Code of Virus Classification and Nomenclature Rule 3.21) and will soon ask the full ICTV membership (189 voting members) to ratify the proposed controversial change. In this discussion paper, 14 senior virologists, including six Life members of the ICTV, compare the present and proposed new definition and recommend that the existing definition of virus species should be retained. Since the pros and cons of the proposal posted on the ICTV website are not widely consulted, the arguments are summarized here in order to reach a wider audience.

Action research in radiography: What it is and how it can be conducted.

Action research is a form of research that investigates and describes a social or work situation with the aim of achieving a change which results in improvement. This article emphasizes the potential for action research to be a useful research method in radiography. A search was conducted to determine the extent to which action research has been utilized in radiography. Although action research has been used in a number of health-care settings, there are no published examples of action research being utilized in a clinical medical imaging department. Action research is discussed in detail, along with an example guide for an action research study. Action research has been identified as a useful way to affect change, to involve radiographers in the research process, and to introduce evidence-based practice to radiography.