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Mehul J Desai,1,2 Nasir Khatri,3,4 Jonathan M Hagedorn,5 Natalie Strand,6 Ryan S D’Souza,7 Vinicius Tieppo Francio,8 Alaa Abd-Elsayed,9 David W Lee,10 Erika Petersen,11 Johnathan H Goree,12 Jacqueline S Weisbein,13 Timothy R Deer14 1International Spine, Pain & Performance Center, Washington, DC, USA; 2George Washington University, School of Medicine & Health Sciences, Washington, DC, USA; 3University of Kansas, Department of Anesthesiology, Kansas City, KS, USA; 4Novant Spine Specialists, Division of Interventional Pain Medicine, Charlotte, NC, USA; 5iSpine Pain Physicians, Maple Grove, MN, USA; 6Mayo Clinic, Division of Pain Medicine, Phoenix, AZ, USA; 7Mayo Clinic, Department of Anesthesiology, Rochester, MN, USA; 8University of Kansas, Department of Rehabilitation Medicine, Kansas City, KS, USA; 9University of Wisconsin, Department of Anesthesiology, Madison, WI, USA; 10Fullerton Orthopedic Surgery Medical Group, Fullerton, CA, USA; 11University of Arkansas, Department of Neurosurgery, Little Rock, AR, USA; 12University of Arkansas, Department of Anesthesiology, Little Rock, AR, USA; 13Interventional Pain Management, Napa Valley Orthopaedic Medical Group, Napa, CA, USA; 14Spine & Nerve Centers of the Virginias, Charleston, WV, USACorrespondence: Mehul J Desai, International Spine, Pain & Performance Center, 2021 K St NW Suite 615, Washington, DC, 20006, USA, Email drdesai@isppcenter.comAbstract: Social media has revolutionized internet communication and become ubiquitous in modern life. Though it originated as a medium for friendship, social media has evolved into an ideal venue for professional networking, scientific exchange, and brand building. As such, it is a powerful tool with which interventional pain physicians should become familiar. However, given the permanence and visibility of online posts, it is prudent for interventional pain physicians to utilize social media in a manner that is consistent with the ethical and professionalism standards to which they are held by their patients, employers, peers, and state medical boards. While there are extensive publications of professional codes of conduct by medical societies, there is a paucity of literature regarding social media best practices guidelines. Further, to date there have been no social media best practices recommendations specific to interventional pain medicine physicians. While not exhaustive, the aim of this document is to provide recommendations to pain physicians on how to maintain an effective professional and ethical online presence. Specifically, we provide guidance on online persona and professional image, patient–physician interactions online, patient privacy, industry relations, patient education, and brand building.Keywords: professionalism, social media, ethics, best practices, LinkedIn, Instagram, Twitter, Facebook

Sacroiliac joint (SIJ) pain is a common cause of low back pain. Traditionally, treatment for SIJ joint pain and dysfunction has consisted of physical therapy, medication management, SIJ injections, and SIJ ablations. Improved recognition of the SIJ as an etiology for back pain has led to advances in treatment options. Radiofrequency of the lateral sacral branches has been shown to be effective, though evidence is fraught with inconsistent patient selection, study design and procedural technique. It also does not directly address the mechanical dysfunction of the SIJ. In order to create a more enduring approach SIJ fusion has become an attractive option to reduce pain and to improve function. This method of SI joint treatment requires guidance in the perioperative phase of care from both the physicians and advanced practice providers (APP). In order to improve care and outcomes of those undergoing posterior SI joint fusion the American Society of Pain and Neuroscience appointed an expert panel of physicians and advanced practice providers to create a best practice for the post operative care of this approach. As with any best practice, the panel considered current peer reviewed literature and clinical expertise to create guidance today. This is intended to be a living document with modifications as additional evidence comes to light in data publication. The goals of this paper are to focus on (1) wound care, (2) medication use, (3) physical activity and (4) therapeutic exercises.

Sayed D, Grider J, Strand N, et al. J Pain Res. 2022;15:3729-3832. The authors have advised that there is an error in Table 32 on page 3797. Row six Gilligan et al 2021, fourth column level of evidence, the text “I-C” should read “I-A”. The correct Table 32 is as follows. Table 32 Evidence Summary for Multifidus Activation via Medial Branch Nerve Stimulation The authors apologize for this error.

The most common presentation of cluneal neuropathy is ipsilateral low back and gluteal pain. Cluneal neuralgia has been described historically in surgical contexts, with much of the description and treatment related to entrapment and decompression, respectively. Treatment options for addressing axial low back pain have evolved with advancements in the field of interventional pain medicine, though clinical results remain inconsistent. Recent attention has turned toward peripheral nerve stimulation. Nonsurgical interventions targeting the superior and medial cluneal nerve branches have been performed in cases of low back and buttock pain, but there is no known review of the resulting evidence to support these practices.In this manuscript we provide a robust exploration and analysis of the available literature regarding treatment options for cluneal neuropathy. We provide clinical manifestations and recommendations for future study direction.Narrative review.This was a systematic, evidence-based narrative, performed after extensive review of the literature to identify all manuscripts associated with interventional treatment of the superior and medial cluneal nerves.Eleven manuscripts fulfilled inclusion criteria. Interventional treatment of the superior and middle cluneal nerves includes blockade with corticosteroid, alcohol neurolysis, peripheral nerve stimulation, radiofrequency neurotomy, and surgical decompression.The supportive evidence for interventions in cluneal neuropathy is largely lacking due to small, uncontrolled, observational studies with multiple confounding factors. There is no standardized definition of cluneal neuropathy.Limited studies promote beneficial effects from interventions intended to target cluneal neuropathy. Despite increased emphasis and treatment options for this condition, there is little consensus on the diagnostic criteria, endpoints, and measures of therapeutics, or procedural techniques for blocks, radiofrequency, and neuromodulation. It is imperative to delineate pathology associated with the cluneal nerves and perform rigorous analysis of associated treatment options.

T-cells in the tumor microenvironment can often become exhausted and dysfunctional due to chronic and prolonged exposure to antigen. The resulting condition of T cell exhaustion represents an important mechanism of clinical resistance to immune checkpoint blockade. The transcription factor NR4A1 is known to be upregulated in tumor-specific T-cells and is a mediator of T cell dysfunction including driving exhaustion during chronic antigen stimulation of T-cells. Pro-oncogenic activities of NR4A1 have been observed in various solid tumors, including colorectal and breast cancers, and co-expression of NR4A1 with known immune checkpoint markers such as PD-L1 and B7 family members has also been observed in various cancer cell lines. These findings have identified NR4A1 as an important target for overcoming resistance to cancer immunotherapy. We hypothesize that targeted silencing of the NR4A1 and other immunomodulatory genes can reverse T-cell exhaustion and expand the clinical benefit of immune checkpoint blockade in solid tumors resistant to immune therapy. To reverse T-cell exhaustion with a targeted approach, we developed T cell targeting SeekRsTM, which are chimeric RNA therapeutics containing dual-flanking aptamer binders connected by a double-stranded bridge containing siRNA silencers that can target multiple immunomodulatory genes. First-generation aptamer-siRNA chimeras designed with a CTLA-4 targeting aptamer containing a STAT3 siRNA demonstrated effectiveness in silencing its target. Modifications to the structure included the addition of chemically modified nucleotides to improve serum stability. Additionally, dimerization of the structure to form a SeekR dimer molecule greatly improved internalization and target silencing compared to the monomeric chimera. Newly developed SeekRs targeting T cells and designed to silence NR4A1 have effectively downregulated NR4A1 in model cell lines and activated T cells. These results demonstrate that dual targeting SeekRs can be used to specifically deliver siRNA to T cells for targeted silencing that can reverse exhaustion and potentially overcome resistance to cancer immunotherapy in the clinic. Citation Format: Marvin O'Ketch, Jeffrey A. Kiefer, Dnyanesh Rasale, Warren S. Weiner, Lizette A. Castaño, Nathalie A. Azorsa, David W. Lee, Kerry M. Barnhart, Spyro Mousses, David O. Azorsa. Activity of novel RNA therapeutics to overcome resistance to immune checkpoint blockade. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4417.

Background Developmental regression (DR) occurs in about one‐third of children with Autism Spectrum Disorder (ASD) yet it is poorly understood. Current evidence suggests that mitochondrial function in not normal in many children with ASD. However, the relationship between mitochondrial function and DR has not been well‐studied in ASD. Methods This cross‐sectional study of 32 children, 2 to 8 years old with ASD, with (n = 11) and without (n = 12) DR, and non‐ASD controls (n = 9) compared mitochondrial respiration and mtDNA damage and copy number between groups and their relation to standardized measures of ASD severity. Results Individuals with ASD demonstrated lower ND1, ND4, and CYTB copy number (Ps

Background The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial. Methods In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4–5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement. Results Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation. Conclusions Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

Background Sacroiliac joint (SIJ) pain is one of the most common causes of low back pain, accounting for 15 to 30% of all cases. Although SIJ dysfunction accounts for a large portion of chronic low back pain prevalence, it is often overlooked or under diagnosed and subsequently under treated. The purpose of this review was to establish a best practices model to effectively diagnose SIJ pain through detailed history, physical exam, review of imaging, and diagnostic block. Methods A literature search was performed on the diagnosis of sacroiliac joint pain and sacroiliac joint dysfunction. The authors proposed diagnostic recommendations based upon the available literature and a detailed understanding of diagnosing SIJ pain. Results The practitioner must focus on the history, location of pain, observed gait pattern, and perform key points of the physical exam including sacroiliac provocative maneuvers. If the patient exhibits at least three provocative maneuvers then the SIJ may be considered as a possible source of pain. Additionally, a thorough review of the imaging should be performed to rule out other etiologies of low back pain. In the absence of any pathognomonic tests or examination findings, diagnostic SIJ blocks have evolved as the diagnostic standard. Conclusion The diagnosis of SIJ pain is a multifaceted process that involves a careful assessment including differentiating other pain generators in the region. This involves careful history taking, appropriate physical examination including provocative maneuvers and diagnostic injections. Once the diagnosis is confirmed, long-term solutions may be considered, including recent advances in sacral lateral branch denervation and sacroiliac joint fusion.

The sacroiliac joint (SIJ) is a large, irregularly shaped, serpentine joint structure bordered anteriorly and posteriorly by the sacroiliac ligaments. With increased recognition of the SIJ as a pain source, treatments have been historically nonsurgical in nature. Common treatments include bracing, medications, activity modification, manual therapy, chiropractic manipulation, physical therapy, and intra-articular SIJ injections. Surgical stabilization and/or fusion of the SIJ may be considered when a patient has persistent moderate to severe pain, functional impairment, and failed conservative management. Surgical stabilization and fusion has traditionally been by way of the transiliac approach. More recent SIJ fusion systems have proposed not only a posterior approach but one that stabilizes the joint space by placing an allograft within the SIJ. Anatomically, a posterior approach is able to avoid neurovascular structures that otherwise are encountered with the transiliac approach and may be performed percutaneously. Preliminary evidence reports consistent pain reduction with minimal complications. This paper is purposed to detail the present evidence of minimally invasive posterior SIJ fusion, as well as highlight the need for further research moving forward.

"Periprocedural myocardial infarction (MI) occurs infrequently in the current era of percutaneous coronary interventions (PCI) and is associated with an increased risk of mortality and morbidity. Periprocedural MI can occur due to acute side branch occlusion, distal embolization, slow flow or no reflow phenomenon, abrupt vessel closure, and nonidentifiable mechanical processes. Therapeutic strategies to reduce the risk of periprocedural MI include dual antiplatelet therapy, intravenous cangrelor in the periprocedural setting, intravenous glycoprotein IIb/IIIa inhibitor in high-risk patients, anticoagulation with unfractionated heparin, low-molecular-weight heparin or bivalirudin, and embolic protection devices during saphenous vein graft interventions."

Ubiquitination is a metabolic process in eukaryotic cells that modifies proteins with ubiquitin leading to protein degradation via the ubiquitin-proteosome pathway. Cellular levels of ubiquitin are driven by the expression of RPS27A, UBA52, UBB and UBC. In cancer, the dysregulation of ubiquitination can affect various aspects of tumor progression including cell cycle regulation and gene expression. Ubiquitin B (UBB) gene has been shown to be over-expressed in some tumor types, including NSCLC and cervical cancer, and under-expressed in other tumors, in particularly a subset of ovarian cancers. A role for ubiquitin C (UBC) in cancer has not been well established but UBC has been described as a biomarker in renal cancer and CLL. In recent studies, repression of UBB in ovarian cancer cells was associated with sensitivity to UBC knockdown and demonstrated a synthetic lethal relationship. Since both UBB and UBC show substantial sequence homology, we explored the possibility of developing dual targeting siRNA that would silence both UBB and UBC. We identified unique individual siRNA sequences that efficiently silenced both UBB and UBC and led to rapid cytotoxicity in several cancer cell lines including the colon cancer cell line HCT-116, the breast cancer cell line SK-BR3, and the prostate cancer cell line 22Rv1. Treatment with either UBB-specific or UBC-specific siRNA did not show the same lethal phenotype. Dose response assays using the dual targeting siRNA designated U21 indicated EC50 for cytotoxicity between 50–500 pM in several cancer lines. Treatment of cancer cell lines with U21 leads to rapid apoptosis and cell death. Chemical modifications to pharmacologically stabilize the U21 siRNA sequence did not change its activity. The efficient cytotoxic activity of the U21 siRNA sequence has been integrated into our SeekR™ platform to create aptamer-siRNA chimeras for targeted delivery of the lethal U21 payload to specific cancer cell types. Citation Format: David O. Azorsa, David W. Lee, Marvin O'Ketch, Nathalie A. Azorsa, Ioanna Papacharalampous, Lizette A. Castaño, Jeffrey A. Kiefer, Spyro Mousses. Development of novel anticancer RNA therapeutics with dual-targeting siRNA that silences ubiquitin family members [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4096.

T-cell exhaustion describes the dysfunctional state of effector T cells in the tumor microenvironment that results from chronic and prolonged exposure to antigen. It also represents an important mechanism of clinical resistance to immune checkpoint blockade. Recently, the transcription factor NR4A1 has been shown to be upregulated in tumor-specific T cells and plays a role in driving exhaustion during chronic antigen stimulation of T cells. Pro-oncogenic activities of NR4A1 have long been observed in various solid tumors including colorectal and breast cancers, and co-expression of NR4A1 with known immune checkpoint markers such as PD-L1 have also been observed in various cancer cell lines. These findings have identified NR4A1 as an important target for overcoming resistance to cancer immunotherapy. We hypothesize that multi-targeting to simultaneously block PD-1 signaling and silence NR4A1 gene expression can reverse T-cell exhaustion and expand the clinical benefit of PD-1 blockade in immune therapy resistant solid tumors. Using our SeekR™ RNA therapeutics platform, we combined aptamer binders to PD-1 with siRNA against NR4A1, andNR4A1 and evaluated their ability to reverse T-cell exhaustion and re-activate T-cell based anticancer immunity in solid tumors. Specifically, we created SeekR™ therapeutic RNA molecules with dual flanking RNA aptamers binders to PD-1 and other checkpoint inhibitors, connected by a double stranded bridge that encodes for siRNA silencers that target multiple immunomodulatory genes, such as NR4A1. The novel anti-PD-1 RNA aptamer component serve to: A) direct and deliver the SeekR™ RNA oligo therapeutics to exhausted T-cells that express PD-1 receptors; and B) internalize the siRNA component into the T-cells. The siRNA components of the SeekR™ serve to silence NR4A1 which lead to reversal of the cytotoxic T-cell exhausted phenotype following chronic in-vitro stimulation. These results demonstrate that dual targeting of PD-1 and NR4A1 has the potential to reverse T-cell exhaustion and the potential to overcome cancer immunotherapy resistance in the clinic. Citation Format: Marvin O'ketch, Victoria A. Love, Jeffrey A. Kiefer, David W. Lee, Lizette A. Castaño, Spyro Mousses, David O. Azorsa. Development of multi-targeting immunomodulatory SeekR RNA therapeutics to overcome resistance to PD-1 blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4239.

Objectives Spinal cord stimulation (SCS) is an established therapy option in interventional pain medicine. Recent advances in technology have allowed for greater compliance with treatment and improved efficacy in pain control. This article was proposed to fill the gap in the literature addressing this specific patient population and to facilitate further research. Even though there is a lack of consensus among societies and experts on exact parameters of physical therapy (PT) considerations and postoperative limitations in patients with SCS, we propose rehabilitative care for this population should be standardized. As the number of patients with SCS implants grow, it is vital to understand how to appropriately approach patients with implantable devices when additional treatments such as PT are prescribed. Materials and methods A literature search was performed on the use of PT following SCS implantation. Presently, there is no literature to date which addresses the use of PT in this patient population. The lack of data is the largest hurdle in the creation of formal SCS therapy guidelines. The authors therefore proposed recommendations for rehabilitation based upon a detailed understanding of SCS hardware alongside well-studied physiotherapy concepts. Results Considerations when initiating PT in the SCS patient population should include: 1) biomechanics and quality of SCS output; 2) therapeutic exercise and spinal manipulation in association with risk for lead of lead migration and fracture; 3) the application of therapeutic modalities and risk for injury to the patient and/or damage to the SCS componentry; and 4) integration of a biopsychosocial, person-centered approach. Conclusions PT treatment protocol in patients with a recently implanted SCS device should be person-centered addressing individual needs, values, and goals. Further research is needed to fully appreciate the impact of an interprofessional approach to management of SCS patients, particularly following stimulator implantation.

Radiofrequency neurotomy (RFN), also known as radiofrequency ablation (RFA), is a common interventional procedure used to treat pain from an innervated structure. RFN has historically been used to treat chronic facet-joint mediated pain. The use of RFN has more recently expanded beyond facet-joint mediated pain to peripherally innervated targets. In addition, there has also been the emergence of different radiofrequency modalities, including pulsed and cooled RFN. The use of RFN has been particularly important where conservative and/or surgical measures have failed to provide pain relief. With the emergence of this therapeutic option and its novel applications, the American Society of Pain and Neuroscience (ASPN) identified the need for formal evidence-based guidance. The authors formed a multidisciplinary work group tasked to examine the latest evidence-based medicine for the various applications of RFN, including cervical, thoracic, lumbar spine; posterior sacroiliac joint pain; hip and knee joints; and occipital neuralgia. Best practice guidelines, evidence and consensus grading were provided for each anatomical target.

This is a comprehensive review of the superior hypogastric block for the management of chronic pelvic pain. It reviews the background, including etiology, epidemiology, and current treatment available for chronic pelvic pain. It then presents the superior hypogastric block and reviews the seminal and most recent evidence about its use in chronic pelvic pain. Several definitions exist for chronic pelvic pain (CPP), making the diagnosis more challenging for the clinician; however, they commonly describe continuous pain lasting 6 months in the pelvis, with an overwhelming majority of patients being reproductive-aged women. This pain is often one of mechanical, inflammatory, or neuropathic. It is generally underdiagnosed and affects anywhere between 5 and 26% of women. The diagnosis of chronic pelvic pain is clinical, consisting of mainly of a thorough history and physical and ruling out other causes. The pathophysiology is often endometriosis (70%) and also includes PID, adhesions, adenomyosis, uterine fibroids, chronic processes of the GI and urinary tracts, as well as pelvic-intrinsic musculoskeletal causes. Treatment includes physical therapy, cognitive behavioral therapy, and oral and parenteral opioids. Interventional techniques provide an added tier of treatment and may help to reduce the requirement for chronic opioid use. Superior hypogastric plexus block is one of the available interventional techniques; first described in 1990, it has been shown to provide long-lasting relief in 50–70% of patients who underwent the procedure. Two approaches described so far, both under fluoroscopy, have seen similar results. More recently, ultrasound and CT-guided procedures have also been described with similar success. The injectate includes local anesthetic, steroids, and neurolytic agents such as phenol or ethanol. CPP is a common debilitating condition. It is diagnosed clinically and is underdiagnosed globally. Current treatments can be helpful at times but may fall short of satisfactory pain relief. Interventional techniques provide an added layer of treatment as well as reduce the requirement for opioids. Superior hypogastric plexus block provides long-lasting relief in many patients, regardless of approach. Evidence level is limited, and further RCTs could help provide better tools for evaluation and patient selection.

Recently we have demonstrated the potential of a hybrid astrophotonic device, consisting of a multi-core fiber photonic lantern and a 3D waveguide reformatting component, to efficiently reformat the multimode point spread function of a telescope to a diffracted limited pseudo-slit. Here, we report on an investigation into the potential of this device to mitigate modal noise-one of the main hurdles of multi-mode fiber-fed spectrographs. The modal noise performance of the photonic reformatter and other fiber feeds was assessed using a bench-Top spectrograph based on an echelle grating. In a first method of modal noise quantification, we used broadband light as the input, and assessed the modal noise performance based on the variations in the normalized spectrum as the input coupling to the fiber feed is varied. In a second method, we passed the broadband light through an etalon to generate a source with spectrally narrow peaks. We then used the spectral stability of these peaks as the input coupling to the fiber feed was varied as a proxy for the modal noise. Using both of these approaches we found that the photonic reformatter could significantly reduce modal noise compared to the multi-mode fiber feed, demonstrating the potential of photonic reformatters to mitigate modal noise for applications such as near-IR radial velocity measurements of M-dwarf stars.

The performance of astrophotonic instruments is determined by various factors including the quality of optical surfaces and the precise alignment of components. As instruments become more complex and compact, the manufacture and assembly of components is increasingly challenging. We propose that a laser-based glass microfabrication technique known as ultrafast-laser assisted etching (ULAE) is ideally suited to the manufacture of both existing and novel components for astrophotonic instruments. To demonstrate this potential, we will present ULAE manufactured microlenses with integrated passive alignment features for efficient optical fiber coupling. A full physical and optical characterization of the micro-lenses is given. These components have applications in fiber-fed multi-object spectrographs.

The Multi Object Optical and Near-infrared Spectrograph (MOONS) instrument is the next generation multi-object spectrograph for the VLT. This powerful instrument will combine for the first time: the large collecting power of the VLT with a high multipexing capability offered by 1000 optical fibres moved with individual robotic positioners and a novel, very fast spectrograph able to provide both low- and high-resolution spectroscopy simultaneously across the wavelength range 0.64μm - 1.8μm. Such a facility will provide the astronomical community with a powerful, world-leading instrument able to serve a wide range of Galactic, Extragalactic and Cosmological studies. Th final assembly, integration and verification phase of the instrument is now about to start performance testing.

Chronic pain can be recurrent or constant pain that lasts for longer than 3 months and can result in disability, suffering, and a physical disturbance. Related to the complex nature of chronic pain, treatments have a pharmacological and non-pharmacological approach. Due to the opioid epidemic, alternative therapies have been introduced, and components of the plant Cannabis Sativa, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have gained recent interest as a choice of treatment. The exact mechanism for CBD is currently unknown, but unlike the CBD's psychoactive counterpart, THC, the side effects of CBD itself have been shown to be overall much more benign. The current pharmaceutical products for the treatment of chronic pain are known as nabiximols, and they contain a ratio of THC combined with CBD, which has been promising. This review focuses on the treatment efficacy of CBD, THC: CBD-based treatments for chronic pain and adverse events with each.

Background Acute Myeloid Leukemia (AML) is a malignancy of myeloid precursor cells that arise from genomic alterations in the expression of key growth regulatory genes causing cells to assume an undifferentiated state and continue to proliferate. Recent efforts have focused on developing therapies that target specific protein products of aberrantly expressed genes. However, many of the identified proteins are difficult to target and thought to be “undrugable” because of structural challenges, protein overexpression, or mutations that confer resistance to therapy. A novel technology that circumvents some of these issues is the use of small molecules that stabilize secondary DNA structures present in the promoters of many potential oncogenes and modulate their transcription. Methods This study characterizes the in vitro activity of the G-quadruplex-stabilizing small molecule GQC-05 in AML cells. The effect of GQC-05 on three AML cell lines was analyzed using viability and apoptosis assays. GQC-05 has been shown to down-regulate MYC through G-quadruplex stabilization in Burkitt’s lymphoma cell lines. MYC expression was evaluated through qPCR and immunoblotting in the three AML cell lines following the treatment of GQC-05. In order to identify other therapeutic agents that potentiate the activity of GQC-05, combination drug screening was performed. The drug combinations were validated using in vitro cytotoxicity assays and compared to other commonly used chemotherapeutic agents. Results GQC-05 treatment of KG-1a, CMK and TF-1 cells decreased cell viability and resulted in increased DNA damage and apoptosis. Additionally, treatment of KG-1a, CMK and TF-1 with GQC-05 resulted in decreased expression of MYC mRNA and protein, with a more pronounced effect in KG-1a cells. Combination drug screening identified the Bcl-2/Bcl-XL inhibitor Navitoclax as a compound that potentiated GQC-05 activity. Co-treatment with GQC-05 and Navitoclax showed a synergistic decrease in cell viability of AML cells as determined by Chou-Talalay analysis, and induced more DNA damage, apoptosis, and rapid cytotoxicity. The cytotoxicity induced by GQC-05 and Navitoclax was more potent than that of Navitoclax combined with either cytarabine or doxorubicin. Conclusion These results suggest that the G-quadruplex stabilizing small molecule GQC-05 induces down regulated MYC expression and DNA damage in AML cells. Treatment with both GQC-05 with a Bcl-2/Bcl-XL inhibitor Navitoclax results in increased cytotoxic activity, which is more pronounced than Navitoclax or GQC-05 alone, and more significant than Navitoclax in combination with cytarabine and doxorubicin that are currently being used clinically.

BackgroundDecitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases, which has been studied extensively and is approved for myelodysplastic syndrome in adults but with less focus in children. Accordingly, we conducted a phase 1 multicenter, randomized, open-label study to evaluate decitabine pre-treatment before standard induction therapy in children with newly diagnosed AML to assess safety and tolerability and explore a number of biologic endpoints.ResultsTwenty-four patients were fully assessable for all study objectives per protocol (10 in Arm A, 14 in Arm B). All patients experienced neutropenia and thrombocytopenia. The most common grade 3 and 4 non-hematologic adverse events observed were gastrointestinal toxicities and hypophosphatemia. Plasma decitabine PK were similar to previously reported adult data. Overall CR/CRi was similar for the two arms. MRD negativity at end-induction was 85% in Arm A versus 67% in Arm B patients. DNA methylation measured in peripheral blood over the course of treatment tracked with blast clearance and matched marrow aspirates at day 0 and day 21. Unlike end-point marrow analyses, promoter methylation in blood identified an apparent reversal of response in the lone treatment failure, one week prior to the patient’s marrow aspirate confirming non-response. Decitabine-induced effects of end-induction marrows in Arm A were reflected by changes in DNA methylation and gene expression comparison with matched paired marrow diagnostic aspirates.ConclusionsThis first-in-pediatrics trial demonstrates that decitabine prior to standard combination chemotherapy is feasible and well tolerated in children with newly diagnosed AML. Pre-treatment with decitabine may represent a newer therapeutic option for pediatric AML, especially as it appears to induce important epigenetic alterations. The novel biological correlates studied in this trial offer a clinically relevant window into disease progression and remission. Additional studies are needed to definitively assess whether decitabine can enhance durability responses in children with AML. This trial was registered at www.clinicaltrials.gov as NCT01177540.

Purpose To develop a highly efficient magnetic field gradient coil for head imaging that achieves 200 mT/m and 500 T/m/s on each axis using a standard 1 MVA gradient driver in clinical whole-body 3.0T MR magnet. Methods A 42-cm inner diameter head-gradient used the available 89- to 91-cm warm bore space in a whole-body 3.0T magnet by increasing the radial separation between the primary and the shield coil windings to 18.6 cm. This required the removal of the standard whole-body gradient and radiofrequency coils. To achieve a coil efficiency ~4× that of whole-body gradients, a double-layer primary coil design with asymmetric x-y axes, and symmetric z-axis was used. The use of all-hollow conductor with direct fluid cooling of the gradient coil enabled ≥50 kW of total heat dissipation. Results This design achieved a coil efficiency of 0.32 mT/m/A, allowing 200 mT/m and 500 T/m/s for a 620 A/1500 V driver. The gradient coil yielded substantially reduced echo spacing, and minimum repetition time and echo time. In high b = 10,000 s/mm2 diffusion, echo time (TE) 50% reduction compared with whole-body gradients). The gradient coil passed the American College of Radiology tests for gradient linearity and distortion, and met acoustic requirements for nonsignificant risk operation. Conclusions Ultra-high gradient coil performance was achieved for head imaging without substantial increases in gradient driver power in a whole-body 3.0T magnet after removing the standard gradient coil. As such, any clinical whole-body 3.0T MR system could be upgraded with 3-4× improvement in gradient performance for brain imaging.

After completion of its final-design review last year, it is full steam ahead for the construction of the MOONS instrument - the next generation multi-object spectrograph for the VLT. This remarkable instrument will combine for the first time: the 8 m collecting power of the VLT, 1000 optical fibres with individual robotic positioners and both medium- and high-resolution spectral coverage acreoss the wavelength range 0.65μm - 1.8 μm. Such a facility will allow a veritable host of Galactic, Extragalactic and Cosmological questions to be addressed. In this paper we will report on the current status of the instrument, details of the early testing of key components and the major milestones towards its delivery to the telescope.

We present the first demonstration of ultrafast laser-inscribed waveguides in IG2 chalcogenide glass and their coupling to a mid-infrared quantum cascade laser. The fabrication parameter space has been investigated, resulting in optimized single-mode waveguides that have estimated propagation losses of 1 dB/cm at 7.8 μm. Higher order mode propagation was also observed. The refractive index modification caused by ultrafast laser inscription has been empirically quantified by comparison with modeled waveguide parameters, resulting in Δn = 0.0097–0.0143 over the pulse energy range investigated. We will present these findings, alongside our initial investigation into waveguide bend losses, which prepare the building blocks towards mid-infrared evanescent field coupling and integrated sensing applications.

Ultrafast laser inscription (ULI) has previously been employed to fabricate volume diffraction gratings in chalcogenide glasses, which operate in transmission mode in the mid-infrared spectral region. Prior gratings were manufactured for applications in astrophotonics, at wavelengths around 2.5 μm. Rugged volume gratings also have potential use in remote atmospheric sensing and molecular spectroscopy; for these applications, longer wavelength operation is required to coincide with atmospheric transparency windows (3-5 μm) and intense ro-vibrational molecular absorption bands. We report on ULI gratings inscribed in IG2 chalcogenide glass, enabling access to the full 3-5 μm window. High-resolution broadband spectral characterization of fabricated gratings was performed using a Fourier transform spectrometer. The zeroth order transmission was characterized to derive the diffraction efficiency into higher orders, up to the fourth orders in the case of gratings optimized for first order diffraction at 3 μm. The outcomes imply that ULI in IG2 is well suited for the fabrication of volume gratings in the mid infrared, providing the impact of the ULI fabrication parameters on the grating properties are well understood. To develop this understanding, grating modeling was conducted. Parameters studied include grating thickness, refractive index modification, and aspect ratio of the modulation achieved by ULI. Knowledge of the contribution and sensitivity of these parameters was used to inform the design of a 4.3 μm grating expected to achieve > 95% first order efficiency. We will also present the characterization of these latest mid-infrared diffraction gratings in IG2.

Background The five-year-survival-rate for paediatric patients with Acute Myeloid Leukaemia (AML) is from 60-70%. The most common causes of death are disease relapse and chemo-resistance. Typically, drug dose response testing is performed at atmospheric oxygen (21%) in a 2-Dimensional (2-D) format; however, AML cells reside in the hypoxic (1% O2), 3-Dimensional (3-D) bone marrow structure along with other cells. Therefore, the drug response observed in typical culture conditions (2D, 21% O2) do not always translate to the same response in patients. The objectives of the present study were to: (1) develop an in vitro assay reproducing key elements of the bone marrow microenvironment (BMM), and to (2) use this system to evaluate the sensitivity/resistance of AML cell lines towards selected therapeutic agents. Methods A functional drug screen was performed first in 2D normoxia and hypoxia to evaluate the response of AML cell lines to 50 compounds. RNA sequencing was performed to determine global changes of gene expression. Overrepresented genes were further matched to potential pathways using Ingenuity Pathway Analysis. Results were validated using real-time RT-PCR. MV-4-11, an AML cell line with a FLT3 mutation was used to study the effects of 3-D structure on drug response. Cells were seeded in 3D and allowed to grow for 72h, compounds were added for an additional 24 h and cell viability was measured using Cell Titer Glo assay. Results Twelve cell lines were used in the present study. In the initial screen THP1 cells for example were more sensitive in hypoxia to 8 out of 50 different compounds. In MV-4-11 cells, hypoxia and 3-D structure conferred resistance towards YM155, a BIRC5 targeting compound. Mechanistic studies revealed that MCL-1 stabilization may underlie this response. A functional drug screen using 50 compounds in 3-D showed that 10 out of 50 compounds resulted in significantly reduced viability of MV-4-11 cells compared to vehicle indicating that this assay can be used for high-throughput drug screening (HTS). Conclusions Hypoxia and 3D structure alter drug response in AML cells. The proposed 3D assay can be used for HTS. Clinical application of this study may lead to more accurate predictions of therapeutic outcomes. Legal entity responsible for the study The authors. Funding Children Cancer Network. Disclosure All authors have declared no conflicts of interest.

Acute mesenteric ischemia is associated with a high mortality rate and requires emergent evaluation and surgical management. However, patients with chronic mesenteric ischemia can undergo either surgical or endovascular revascularization. Review of recent medical literature suggests lower rates of mortality and complications after endovascular revascularization, but higher rates of primary patency after surgical revascularization. The decision regarding method of revascularization in patients with chronic mesenteric ischemia should be based on the patient's vascular anatomy, comorbidities, and life expectancy.

The hemodynamic features of subacute aortic regurgitation include equalization of the left ventricular pressure and the aortic pressure during diastole, a mildly increased pulse pressure, and systemic hypotension. These findings are distinct from the hemodynamics of chronic aortic regurgitation.

Seedling developmental responses to understory shade combine the effects of reductions in irradiance and changes in spectral quality. We studied the seedling development of two Southeast Asian dipterocarp trees in response to differences in irradiance (photosynthetic photon flux density, PPFD) and spectral quality (red to far-red ratio, R:FR). The two species, Hopea helferei and H. odorata, are taxonomically closely related but differ in their ecological requirements; H. helferei is more drought-tolerant and typically grows in more open habitats. Seedlings were grown in six different replicated shadehouse treatments varying in percentage of solar PPFD and R:FR. The two species differed in the influence of light variables on most seedling characters, particularly for final height, internode distance, branch/trunk internodes, stem length/mass, leaf area/stem length, petiole length, and growth/mol of photons received. Most of the characters in both taxa were primarily influenced by PPFD, but spectral quality also influenced some characters - more so for H. odorata. The latter species grew more rapidly, particularly in the low PPFD treatments, and its leaves were capable of higher photosynthesis rates. However, growth in H. helferei was not reduced in direct sunlight. The growth of this taxon may be constrained by adaptations, particularly in leaves, for drought tolerance.

A model of the cost and schedule of a development program, characterized by three non-dimensional parameters, gives means for estimating the cost and schedule impacts of constraining funding below planned levels, as well as for assessing the realism of the costs and schedules of planned programs. In contrast to models of the Norden-Rayleigh-Weibull class, the model explicitly considers specific components of cost, and captures the distinction between a development program’s value (i.e., the things delivered) and its cost (i.e., the money paid to acquire the value). Treating staff levels, staff productivity and cost, overhead, purchased material costs, and the burdens imposed by staff coordination and by allocating a program’s effort to individual workers or teams and collating the results, the model reflects effects of management actions to make programs optimal by such criteria as minimal cost, minimal time, or minimal cost subject to a maximum-time constraint.

Acute Myeloid Leukemia (AML) is a malignancy of myeloid precursor cells that can occur when genomic changes alter expression of key genes, causing cells to resume an undifferentiated state and proliferate. Ongoing efforts have focused on developing therapies that specifically target the protein products of aberrantly expressed genes. However, many of the identified proteins are difficult to target because of structural challenges, protein overexpression, or mutations that confer resistance to therapy. A type of therapy that circumvents these issues is the use of small molecules that stabilize DNA secondary structures called G-quadruplexes, which are present in the promoters of many potential oncogenes, and have regulatory roles in their transcription. This study analyzes the activity of G-quadruplex stabilizing small molecule GQC-05 that has been shown to down-regulate MYC, which is commonly misregulated in AML. Treatment of MYC-expressing AML cell lines KG-1a, CMK and TF-1 with GQC-05 resulted in decreased expression of MYC mRNA and protein, with the effect more pronounced in KG-1a cells. GQC-05 treatment of the AML cells decreased cell viability, while increasing apoptosis and DNA damage. Combinational drug screening was performed to identify compounds that potentiated the anti-proliferative effects of GQC-05. Results from the screen identified the BCL-2 inhibitor Navitoclax as a compound that potentiated GQC-05 activity. Co-treatment with GQC-05 and Navitoclax showed synergistic effect on cell viability of AML cells as determined by Chou-Talalay analysis. Furthermore, co-treatment with Navitoclax did not affect the downregulation of MYC by GQC-05, but did increase apoptosis and DNA damage leading to rapid cytotoxicity. These results indicate that the G-quadruplex stabilizing small molecule GQC-05 may function more as a DNA damaging agent in AML cells and that combining GQC-05 with a Bcl-2/Bcl-XLinhibitor such as Navitoclax can result in increased cytotoxic activity. Citation Format: Justin J. Montoya, Megan A. Turnidge, Daniel H. Wai, David W. Lee, Apruvi Patel, Vijay Gokhale, Laurence J. Hurley, David O. Azorsa. Activity of G-quadruplex stabilizing small molecule that downregulates MYC and synergizes with Navitoclax in acute myeloid leukemia cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2967.

The purpose of this study was to assess trends in Medicare spending growth for medical imaging relative to other services and the Deficit Reduction Act (DRA).We calculated per-beneficiary Part B Medicare medical imaging expenditures for three-digit Berenson-Eggers Type of Service (BETOS) categories using Physician Supplier Procedure Summary Master Files for 32 million beneficiaries from 2000 to 2011. We adjusted BETOS categories to address changes in coding and payment policy and excluded categories with 2011 aggregate spending less than $500 million. We computed and ranked compound annual growth rates over three periods: pre-DRA (2000-2005), DRA transition period (2005-2007), and post-DRA (2007-2011).Forty-four modified BETOS categories fulfilled the inclusion criteria. Between 2000 and 2006, Medicare outlays for nonimaging services grew by 6.8% versus 12.0% for imaging services. In the ensuing 5 years, annual growth in spending for nonimaging continued at 3.6% versus a decline of 3.5% for imaging. Spending growth for all services during the pre-DRA, DRA, and post-DRA periods were 7.8%, 3.8%, and 2.9 compared with 15.0%, -3.4%, and -2.2% for advanced imaging services. Advanced imaging was among the fastest growing categories of Medicare services in the early 2000s but was in the bottom 2% of spending categories in 2011. Between 2007 and 2011, the fastest growing service categories were evaluation and management services with other specialists (29.1%), nursing home visits (11.2%), anesthesia (9.1%), and other ambulatory procedures (9.0%).Slowing volume growth and massive Medicare payment cuts have left medical imaging near the bottom of all service categories contributing to growth in Medicare spending.

BACKGROUND AND AIMS Blue-green iridescence in the tropical rainforest understorey sedge Mapania caudata creates structural coloration in its leaves through a novel photonic mechanism. Known structures in plants producing iridescent blues consist of altered cellulose layering within cell walls and in special bodies, and thylakoid membranes in specialized plastids. This study was undertaken in order to determine the origin of leaf iridescence in this plant with particular attention to nano-scale components contributing to this coloration. METHODS Adaxial walls of leaf epidermal cells were characterized using high-pressure-frozen freeze-substituted specimens, which retain their native dimensions during observations using transmission and scanning microscopy, accompanied by energy-dispersive X-ray spectroscopy to identify the role of biogenic silica in wall-based iridescence. Biogenic silica was experimentally removed using aqueous Na2CO3 and optical properties were compared using spectral reflectance. KEY RESULTS AND CONCLUSIONS Blue iridescence is produced in the adaxial epidermal cell wall, which contains helicoid lamellae. The blue iridescence from cell surfaces is left-circularly polarized. The position of the silica granules is entrained by the helicoid microfibrillar layers, and granules accumulate at a uniform position within the helicoids, contributing to the structure that produces the blue iridescence, as part of the unit cell responsible for 2 ° Bragg scatter. Removal of silica from the walls eliminated the blue colour. Addition of silica nanoparticles on existing cellulosic lamellae is a novel mechanism for adding structural colour in organisms.

Background Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL. Methods Fourteen AML cell lines including the DS-AMKL CMY and CMK from relapsed/refractory AML were used. Cytarabine (Ara-C), bortezomib (BTZ), disulfiram/copper (DSF/Cu2+) were evaluated for cytotoxicity, depletion of ALDH-positive cells, and resistance. BTZ-resistant CMY and CMK variants were generated by continuous BTZ treatment. Cell viability was assessed using CellTiter-Glo®, ALDH activity by ALDELUORTM, and proteasome inhibition by western blot of ubiquitinated proteins and the Proteasome-Glo™ Chymotrypsin-Like (CT-like) assay, apoptosis by Annexin V Fluos/Propidium iodide staining, and mutations were detected using PCR, cloning and sequencing. Results Ara-C-resistant AML cell lines were sensitive to BTZ and DSF/Cu2+. The Ara-C-resistant DS-AMKL CMY cells had a high percentage of ALDHbright “stem-like” populations that may underlie Ara-C resistance. One percent of these cells were still resistant to BTZ but sensitive to DSF/Cu2+. To understand the mechanism of BTZ resistance, BTZ resistant (CMY-BR) and (CMK-BR) were generated. A novel mutation PSMB5 Q62P underlied BTZ resistance, and was associated with an overexpression of the β5 proteasome subunit. BTZ-resistance conferred increased resistance to Ara-C due to G1 arrest in the CMY-BR cells, which protected the cells from S-phase damage by Ara-C. CMY-BR and CMK-BR cells were cross-resistant to CFZ and MG-132 but sensitive to DSF/Cu2+. In this setting, DSF/Cu2+ induced apoptosis and proteasome inhibition independent of CT-like activity inhibition. Conclusions We provide evidence that DSF/Cu2+ overcomes Ara-C and BTZ resistance in cell lines from DS-AMKL patients. A novel mutation underlying BTZ resistance was detected that may identify BTZ-resistant patients, who may not benefit from treatment with CFZ or Ara-C, but may be responsive to DSF/Cu2+. Our findings support the clinical development of DSF/Cu2+ as a less toxic efficacious treatment approach in patients with relapsed/refractory DS-AMKL. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0493-5) contains supplementary material, which is available to authorized users.

NASA’s James Webb Space Telescope (JWST) is a 6.5m diameter, segmented, deployable telescope for cryogenic IR space astronomy (~40K). The JWST Observatory architecture includes the Optical Telescope Element (OTE) and the Integrated Science Instrument Module (ISIM) element that contains four science instruments (SI), including a guider. OSIM is a full field, cryogenic, optical simulator of the JWST OTE. It is the “Master Tool” for verifying the cryogenic alignment and optical performance of ISIM by providing simulated point source/star images to each of the four Science Instruments in ISIM. Included in OSIM is a Pupil Imaging Module (PIM) - a large format CCD used for measuring pupil alignment. Located at a virtual stop location within OSIM, the PIM records superimposed shadow images of pupil alignment reference (PAR) targets located in the OSIM and SI pupils. The OSIM Pupil Imaging Module was described by Brent Bos, et al, at SPIE in 2011 prior to ISIM testing. We have recently completed the third and final ISIM cryogenic performance verification test before ISIM was integrated with the OTE. In this paper, we describe PIM implementation, performance, and measurement results.

The Low Resolution Spectrometer of the MIRI, which forms part of the imager module, will provide R~100 long-slit and slitless spectroscopy from 5 to 12 micron. The design is optimised for observations of compact sources, such as exoplanet host stars. We provide here an overview of the design of the LRS, and its performance as measured during extensive test campaigns, examining in particular the delivered image quality, dispersion, and resolving power, as well as spectrophotometric performance, flatfield accuracy and the effects of fringing. We describe the operational concept of the slitless mode, which is optimally suited to transit spectroscopy of exoplanet atmospheres. The LRS mode of the MIRI was found to perform consistently with its requirements and goals., Comment: published in PASP, vol. 127, issue 953, pp.623-632, 2015

Ultrafast laser inscription is a versatile manufacturing technique which can be used to modify the refractive index of various glasses on a microscopic scale. This enables the production of a number of photonic devices such as waveguides, beam-splitters, photonic lanterns, and diffraction gratings. In this paper, we report on the use of ultrafast laser inscription to fabricate volume phase transmission gratings in mid-infrared transmitting chalcogenide glass. We describe the optimisation of the laser inscription process parameters enhancing grating performances via the combination of spectrally resolved grating transmission measurements and theoretical analysis models. The first order diffraction efficiency of the gratings was measured at mid-infrared wavelengths (3-5 μm), and found to exceed 60% at the Littrow blaze wavelength, compared to a substrate external transmittance of 67%. This impressive result implies the diffraction efficiency should exceed 90% for a grating substrate treated with an anti-reflection coating. There is excellent agreement between the modelled grating efficiency and the measured data, and from a least squares fit to the measured data the refractive index modulation achieved during the inscription process is inferred. These encouraging initial results demonstrate that ultrafast laser inscription of chalcogenide glass may provide a potential new and alternative technology for the manufacture of astronomical diffraction gratings for use at near-infrared and mid-infrared wavelengths.

Plants are clever green strategists (Horn, 1971). By plants, I mean those living on land-or vascular plants. Their evolutionary history goes back to the Silurian, some 430 million years ago. Their evolution in dramatically different environments over that time resulted in the formation of an impressive variety of forms and attributes, in a global diversity that today consists of approximately 260,000 species. Although exceedingly important (one can say, with some justi„cation, that biology is the study of plants and their parasites), our knowledge of them is far exceeded by that of animals. We are more connected to animals (we are animals), more concerned about their conservation, and have studied them much more. Because plants are poor models for human diseases, there is much less research funding available to study them. Some research on plants and biomiomicry has dealt with rapid movements from the storage of energy in tensile organs (Burghart and Franzl, 2009); we seem to be particularly fascinated by plants when they take on the animal-like characteristics of rapid movement (Edwards et al., 2005; Taylor et al., 2006).

Structural colors refer to colors generated by minuscule structures, with the characteristic dimension of the structures on the order of the wavelength of the visible light (i.e., some tens up to hundreds of nanometers). Examples for structural colors are the colors of CDs and DVDs, the colors of soap bubbles, or oil films on water (thin films), or the colors of certain butterfly wings (e.g., photonic crystals), and even plants. Tiny wax crystals in the blue spruce scatter the light (Tyndall scattering), resulting in the blue hue. Thin films in tropical understory plants and diffraction gratings in hibiscus and tulip flowers are just some more examples of the amazing variety of natural nanostructures that are the basis for coloration in some plants. This entry reviews the physics behind structural colors, lists plants, microorganisms, and virus species with nanostructures responsible for their coloration, and also touches upon the multifunctionality of materials in organisms, nanobioconvergence as an emergent science, and biomimetics as a promising field for knowledge transfer from biology to engineering and the arts. Introduction