A revision of the genus Wrangelia (Wrangeliaceae, Ceramiales) in Bermuda resolves six new species including W. ryancraigii from the mesophotic zone.

Four species of the genus Wrangelia are presently known from the western Atlantic Ocean: W. argus, W. bicuspidata, W. penicillata, and W. gordoniae, with the first three historically being reported from Bermuda. Morphological and molecular barcode (COI-5P) and phylogenetic analyses used in this study (SSU, LSU, rbcL) indicated eight species groupings of Wrangelia in Bermuda, excluding two of the historically recognized species, retaining only W. argus while adding seven new species, of which six are formally described. What had been historically reported as W. penicillata from Bermuda was shown to be distinct from Mediterranean Sea specimens (type locality) and was shown to be a mixture of W. hesperia sp. nov. and W. incrassata sp. nov. Along with these two, three other new species (W. laxa sp. nov., W. ryancraigii sp. nov., and W. secundiramea sp. nov.) have complete rhizoidal cortication tightly covering axial cells of indeterminate axes below the apices, distinguishing them from the two local incompletely corticated congeners W. argus and W. abscondita sp. nov., the latter a morphologically cryptic sister species with W. bicuspidata from the Caribbean Sea. Only one of the new species, W. ryancraigii, has thus far been observed in the mesophotic zone off the Bermuda platform, and it is morphologically cryptic with the euphotic zone's W. laxa.

The Dasya baillouviana and D. cryptica complexes (Delesseriaceae, Rhodophyta) in Bermuda with three additional new species from the archipelago.

Continuing molecular studies of the red algal genus Dasya collected off the coast of Bermuda have revealed two new species in the developing D. cryptica species complex-one from each the euphotic and mesophotic zones, D. orae sp. nov. and D. bathypelagica sp. nov., respectively. Furthermore, what was known as D. baillouviana in Bermuda is shown to represent D. hibernae sp. nov., a sibling of D. pedicellata from New England and New York, USA. Despite morphological similarities to the recently described shallow subtidal species from the islands, D. cryptica, molecular sequencing and morphological comparisons demonstrated that a new set of inshore specimens represented D. orae. The larger, new deep-water species, D. bathypelagica, was genetically compared with recent Bermuda collections of D. baillouviana and others worldwide morphologically falling under this epithet and represented a new species also grouping in the D. cryptica complex. The specimens of D. hibernae from Bermuda were shown to be genetically distinct from specimens of D. pedicellata from southern New England and New York. Molecular analyses necessitated the resurrection of D. pedicellata and uncovered undescribed species in the D. baillouviana complex in the western Atlantic. Based upon genetic evidence provided here, the generitype of Rhodoptilum nested among species in the D. baillouviana complex including the generitype. This finding required the synonymy of the genus Rhodoptilum with Dasya and allowed for the reinstatement of D. plumosa. Furthermore, Dasya collinsiana resolved in the lineage including a closely related species to the generitype of Dasysiphonia, necessitating the transfer of this Bermudian species and others worldwide from the genus Dasya to Dasysiphonia.

Nonoperative Treatment of Large (5-7 cm), Node-Negative Non-Small Cell Lung Cancer Commonly Deviates From NCCN Guidelines.

BACKGROUND: Optimal treatment of nonoperative patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. Current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend definitive radiotherapy (RT) with or without sequential chemotherapy and do not include concurrent chemoradiotherapy (chemoRT) as a treatment option. In this study, we identified factors that predict nonadherence to NCCN Guidelines. PATIENTS AND METHODS: Patients who received definitive RT for nonmetastatic, node-negative NSCLC with tumor size of 5 to 7 cm were identified in the National Cancer Database from 2004 through 2016. Patients were evaluated by RT type (stereotactic body RT [SBRT], hypofractionated RT [HFRT], or conventionally fractionated RT [CFRT]) and chemotherapy use (none, sequential, or concurrent with RT). Patients were classified as receiving NCCN-adherent (RT with or without sequential chemotherapy) or NCCN-nonadherent (concurrent chemoRT) treatment. Demographic and clinical factors were assessed with logistic regression modeling. Overall survival was evaluated with Kaplan-Meier, log-rank, and univariable/multivariable Cox proportional hazards regression analyses. RESULTS: Among 2,020 patients in our cohort, 32% received NCCN-nonadherent concurrent chemoRT, whereas others received NCCN-adherent RT alone (51%) or sequential RT and chemotherapy (17%). CFRT was most widely used (64% CFRT vs 22% SBRT vs 14% HFRT). Multivariable analysis revealed multiple factors to be associated with NCCN-nonadherent chemoRT: age ≤70 versus >70 years (odds ratio [OR] , 2.72; P<.001), treatment at a nonacademic facility (OR, 1.65; P<.001), and tumor size 6 to 7 cm versus 5 to 6 cm (OR, 1.27; P=.026). Survival was similar between the NCCN-nonadherent chemoRT and NCCN-adherent groups (hazard ratio, 1.00; P=.992) in multivariable analysis. CONCLUSIONS: A substantial proportion of inoperable patients with large, node-negative NSCLC are not treated according to NCCN Guidelines and receive concurrent chemoRT. Younger patients with larger tumors receiving treatment at nonacademic medical centers were more likely to receive NCCN-nonadherent therapy, but adherence to NCCN Guidelines was not associated with differences in overall survival.

Collections from the mesophytic zone off Bermuda reveal three species of Kallymeniaceae (Gigartinales, Rhodophyta) in genera with transoceanic distributions.

A molecular survey of red algae collected by technical divers and submersibles from 90 m in the mesophotic zone off the coast of Bermuda revealed three species assignable to the Kallymeniaceae. Two of the species are representative of recently described genera centered in the western Pacific in Australia and New Zealand, Austrokallymenia and Psaromenia and the third from the Mediterranean Sea and the eastern Atlantic, Nothokallymenia. A phylogenetic analysis of concatenated mitochondrial (COI-5P) and chloroplast (rbcL) genes, as well as morphological characteristics, revealed that two are shown to be new species with distant closest relatives (N. erosa and Psaromenia septentrionalis), while the third represents a deep water western Atlantic species now moved to an Australasian genus (A. westii).

Discovery and optimization of a novel series of pyrazolyltetrahydropyran N-type calcium channel (Cav 2.2) blockers for the treatment of pain.

A novel series of pyrazolyltetrahydropyran N-type calcium channel blockers are described. Structural modifications of the series led to potent compounds in both a cell-based fluorescent calcium influx assay and a patch clamp electrophysiology assay. Representative compounds from the series were bioavailable and showed efficacy in the rat CFA and CCI models of inflammatory and neuropathic pain.

A molecular evaluation of the Liagoraceae sensu lato (Nemaliales, Rhodophyta) in Bermuda including Liagora nesophila sp. nov. and Yamadaella grassyi sp. nov.

We have undertaken a comprehensive, molecular-assisted alpha-taxonomic examination of the rhodophyte family Liagoraceae sensu lato, a group that has not previously been targeted for molecular studies in the western Atlantic. Sequence data from three molecular markers indicate that in Bermuda alone there are 10 species in nine different genera. These include the addition of three genera to the flora - Hommersandiophycus, Trichogloeopsis, and Yamadaella. Liagora pectinata, a species with a type locality in Bermuda, is phylogenetically allied with Indo-Pacific species of Hommersandiophycus, and the species historically reported as L. ceranoides for the islands is morphologically and genetically distinct from that taxon, and is herein described as L. nesophila sp. nov. Molecular sequence data have also uncovered the Indo-Pacific L. mannarensis in Bermuda, a long-distance new western Atlantic record. DNA sequences of Trichogloeopsis pedicellata from the type locality (Bahamas) match with local specimens demonstrating its presence in Bermuda. We described Yamadaella grassyi sp. nov. from Bermuda, a species phylogenetically and morphologically distinct from the generitype, Y. caenomyce of the Indo-Pacific. Our data also indicated a single species each of Ganonema, Gloiocallis, Helminthocladia, Titanophycus, and Trichogloea in the flora.

Etheliaceae fam. nov. (Gigartinales, Rhodophyta), with a clarification of the generitype of Ethelia and the addition of six novel species from warm waters.

Based upon COI-5P, LSU rDNA, and rbcL sequence data and morphological characteristics, six new members of the noncalcified crustose genus of red algae Ethelia are described in a new family, Etheliaceae (Gigartinales), sister to the recently described Ptilocladiopsidaceae. The novel species are described from subtropical to tropical Atlantic and Indo-Pacific Ocean basins; E. mucronata sp. nov. and E. denizotii sp. nov. from southern and northern Western Australia respectively, E. wilcei sp. nov. from the Cocos (Keeling) Islands of Australia, E. suluensis sp. nov. from the Philippines, E. umbricola sp. nov. from Bermuda and E. kraftii sp. nov. from Lord Howe Island, Australia. The generitype, Ethelia biradiata, originally reported from the Seychelles, Indian Ocean, is added to the Western Australian flora.

Ex vivo characterization of particle transport in mucus secretions coating freshly excised mucosal tissues.

Sustained drug delivery to mucosal surfaces has the potential to improve the effectiveness of prophylactic and therapeutic treatments for numerous diseases and conditions, including inflammatory bowel disease, sexually transmitted diseases, cystic fibrosis, glaucoma, dry eye, and various cancers. Sustained delivery systems such as nanoparticles can be useful for mucosal delivery, but recent work suggests they must penetrate the rapidly cleared mucus barrier that overlies all mucosal epithelia to achieve uniform distribution on epithelial surfaces and enhanced residence time. Thus, it is important to evaluate the mucus-penetrating ability of nanosized delivery systems in preclinical animal studies, and for administration to humans. We describe a simple ex vivo method to visualize and quantify nanoparticle transport in mucus on fresh mucosal tissues. Using this method in murine models, we observed variations in the mucus mesh at different anatomical locations, as well as cyclical variations that may have implications for mucosal delivery.

A focused review of statistical practices for relating radiation dose-volume exposure and toxicity.

PURPOSE: Relating dose-volume histogram (DVH) information to patient outcomes is critical for outcomes research in radiation oncology, but this is statistically challenging. We performed this focused review of DVH toxicity studies to characterize current statistical approaches and determine the need for updated reporting recommendations. METHODS AND MATERIALS: We performed a focused MEDLINE search to identify studies published in 5 radiation oncology specialty journals that associated dosimetry with toxicity outcomes in humans receiving radiotherapy between 2015 and 2021. Elements abstracted from each manuscript included the study outcome, organs-at-risk (OARs) considered, DVH parameters analyzed, summary of the analytic approach, use of multivariable statistics, goodness-of-fit reporting, completeness of model reporting, assessment of multicollinearity, adjustment for multiple comparisons, and methods for dichotomizing variables. Each study was also assessed for sufficient reporting to allow for replication of results. RESULTS: The MEDLINE search returned 2,300 studies for review and 325 met the inclusion criteria for the analysis. DVH variables were dichotomized using cut points in 154 (47.4%) studies. Logistic regression (55.4% of studies) was the most common statistical method used to relate DVH to toxicity outcomes, followed by Cox regression (20.6%) and linear regression (12.0%). Multivariable statistical tests were performed in 226 (69.5%) studies; of these, the possibility of multicollinearity was addressed in 47.8% and model goodness-of-fit were reported in 32.6%. The threshold for statistical significance was adjusted to account for multiple comparisons in 41 of 196 (17.1%) studies that included multiple statistical comparisons. Twenty-eight (8.6%) studies were classified as missing details necessary to reproduce the study results. CONCLUSIONS: Current practices of statistical reporting in DVH outcomes suggest that studies may be vulnerable to threats against internal and external validity. Recommendations for reporting are provided herein to guard against such threats and to promote cohesiveness among radiation oncology outcomes researchers.

Benchmarking Automated Machine Learning-Enhanced Planning With Ethos Against Manual and Knowledge-Based Planning for Locally Advanced Lung Cancer.

Purpose: Currently, there is insufficient guidance for standard fractionation lung planning using the Varian Ethos adaptive treatment planning system and its unique intelligent optimization engine. Here, we address this gap in knowledge by developing a methodology to automatically generate high-quality Ethos treatment plans for locally advanced lung cancer. Methods and Materials: Fifty patients previously treated with manually generated Eclipse plans for inoperable stage IIIA-IIIC non-small cell lung cancer were included in this institutional review board-approved retrospective study. Fifteen patient plans were used to iteratively optimize a planning template for the Daily Adaptive vs Non-Adaptive External Beam Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Trial of an Individualized Approach for Toxicity Reduction (ARTIA-Lung); the remaining 35 patients were automatically replanned without intervention. Ethos plan quality was benchmarked against clinical plans and reoptimized knowledge-based RapidPlan (RP) plans, then judged using standard dose-volume histogram metrics, adherence to clinical trial objectives, and qualitative review. Results: Given equal prescription target coverage, Ethos-generated plans showed improved primary and nodal planning target volume V95% coverage (P < .001) and reduced lung gross tumor volume V5 Gy and esophagus D0.03 cc metrics (P ≤ .003) but increased mean esophagus and brachial plexus D0.03 cc metrics (P < .001) compared with RP plans. Eighty percent, 49%, and 51% of Ethos, clinical, and RP plans, respectively, were "per protocol" or met "variation acceptable" ARTIA-Lung planning metrics. Three radiation oncologists qualitatively scored Ethos plans, and 78% of plans were clinically acceptable to all reviewing physicians, with no plans receiving scores requiring major changes. Conclusions: A standard Ethos template produced lung radiation therapy plans with similar quality to RP plans, elucidating a viable approach for automated plan generation in the Ethos adaptive workspace.

Discovery of vinylcycloalkyl-substituted benzimidazole TRPM8 antagonists effective in the treatment of cold allodynia.

Thermosensitive transient receptor potential melastatin 8 (TRPM8) antagonists are considered to be potential therapeutic agents for the treatment of cold hypersensitivity. The discovery of a new class of TRPM8 antagonists that shows in vivo efficacy in the rat chronic constriction injury (CCI)-induced model of neuropathic pain is described.

A novel series of pyrazolylpiperidine N-type calcium channel blockers.

Selective blockers of the N-type calcium channel have proven to be effective in animal models of chronic pain. However, even though intrathecally delivered synthetic ω-conotoxin MVIIA from Conus magnus (ziconotide [Prialt®]) has been approved for the treatment of chronic pain in humans, its mode of delivery and narrow therapeutic window have limited its usefulness. Therefore, the identification of orally active, small-molecule N-type calcium channel blockers would represent a significant advancement in the treatment of chronic pain. A novel series of pyrazole-based N-type calcium channel blockers was identified by structural modification of a high-throughput screening hit and further optimized to improve potency and metabolic stability. In vivo efficacy in rat models of inflammatory and neuropathic pain was demonstrated by a representative compound from this series.

N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles.

For effective airway gene therapy of cystic fibrosis (CF), inhaled gene carriers must first penetrate the hyperviscoelastic sputum covering the epithelium. Whether clinically studied gene carriers can penetrate CF sputum remains unknown. Here, we measured the diffusion of a clinically tested nonviral gene carrier, composed of poly-l-lysine conjugated with a 10 kDa polyethylene glycol segment (CK(30)PEG(10k)). We found that CK(30)PEG(10k)/DNA nanoparticles were trapped in CF sputum. To improve gene carrier diffusion across sputum, we tested adjuvant regimens consisting of N-acetylcysteine (NAC), recombinant human DNase (rhDNase) or NAC together with rhDNase. While rhDNase alone did not enhance gene carrier diffusion, NAC and NAC + rhDNase increased average effective diffusivities by 6-fold and 13-fold, respectively, leading to markedly greater fractions of gene carriers that may penetrate sputum layers. We further tested the adjuvant effects of NAC in the airways of mice with Pseudomonas aeruginosa lipopolysaccharide (LPS)-induced mucus hypersecretion. Intranasal dosing of NAC prior to CK(30)PEG(10k)/DNA nanoparticles enhanced gene expression by up to ~12-fold compared to saline control, reaching levels observed in the lungs of mice without LPS challenge. Our findings suggest that a promising synthetic nanoparticle gene carrier may transfer genes substantially more effectively to lungs of CF patients if administered following adjuvant mucolytic therapy with NAC or NAC + rhDNase.

Patterns of Failure and Optimal Treatment Paradigm for Large, Inoperable, Node-Negative Non-small Cell Lung Cancer.

OBJECTIVES: The ideal non-operative treatment for patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. To inform optimal treatment paradigms for this cohort, we examined patterns of failure and the impact of radiation therapy (RT) and chemotherapy receipt. MATERIALS AND METHODS: Node-negative NSCLC patients with 5+ cm primary tumors receiving definitive RT at our institution were identified. Sites of initial progression were analyzed. Local progression, regional/distant progression, progression-free survival, and overall survival were analyzed via cumulative incidence function and Kaplan-Meier. Associations between local vs. regional/distant progression with treatment and clinicopathologic variables were assessed via univariable and multivariable competing risks regression. RESULTS AND CONCLUSION: We identified 88 patients for analysis. Among patients with recurrent disease (N = 36), initial patterns of failure analysis showed that isolated distant (27.8%) and isolated regional progression (22.2%) were most common. Distant or regional failure as a component of initial failure was seen in 88.9% of patients who progressed, while isolated local failure was uncommon (11.1%). Univariable and multivariable competing risks regression showed that receipt of SBRT was associated with reduced risk of local progression (HR 0.23, P = .012), and receipt of chemotherapy was associated with reduced risk of regional/distant progression (HR 0.12, P = .040). In conclusion, patients with large, node-negative NSCLC treated with definitive RT are at high risk of regional and distant progression. SBRT correlates with a reduced risk of local failure while chemotherapy is associated with reduced regional/distant progression in this patient population. Ideal treatment may include SBRT when feasible with appropriate systemic therapy.

Hypofractionated radiation leads to more rapid bleeding cessation in women with vaginal bleeding secondary to gynecologic malignancy.

BACKGROUND: Vaginal bleeding (VB) is common in women with gynecologic (GYN) malignancies. Radiation therapy (RT) is used for the definitive treatment of GYN cancers and palliation of bleeding. The historical dogma is that high dose-per-fraction radiation leads to more rapid bleeding cessation, yet there is scant data supporting this claim. We sought to examine the effect of RT fraction size on VB via retrospective analysis of patients receiving hypofractionated radiation (HFRT) compared to conventionally fractionated radiation (CFRT) for control of bleeding secondary to GYN malignancies. METHODS: We identified patients receiving external beam RT for continuous VB from GYN malignancy treated in our department from 2012 to 2020. RT was classified as HFRT (> 2.0 Gy/fx) or CFRT (1.8-2.0 Gy/fx). Demographic information, disease characteristics, and treatment details were collected. The primary endpoint was days from RT initiation until bleeding resolution. Characteristics between groups were compared via Fisher's exact test. Time to bleeding cessation was assessed via Kaplan-Meier and log-rank test. Univariable and multivariable Cox-proportional hazards were used to identify factors associated with bleeding cessation. RESULTS: We identified 43 patients meeting inclusion criteria with 26 and 17 patients receiving CFRT and HFRT, respectively. Comparison of baseline characteristics revealed patients receiving HFRT were older (p = 0.001), more likely to be post-menopausal (p = 0.002), and less likely to receive concurrent chemotherapy (p = 0.004). Time to bleeding cessation was significantly shorter for patients receiving HFRT (log-rank p < 0.001) with median time to bleeding cessation of 5 days (HFRT) versus 16 days (CFRT). Stratification by dose-per-fraction revealed a dose-response effect with more rapid bleeding cessation with increased dose-per-fraction. While HFRT, age, recurrent disease, prior pelvic RT, and prior systemic therapy were associated with time to bleeding cessation on univariable analysis, HFRT was the only factor significantly associated with time to bleeding cessation in the final multivariable model (HR 3.26, p = 0.008). CONCLUSIONS: Patients with continuous VB from GYN tumors receiving HFRT experienced more rapid bleeding cessation than those receiving CFRT. For patients with severe VB, initiation of HFRT to control malignancy related bleeding quickly may be warranted.

Durable Metastatic Melanoma Remission Following Pembrolizumab and Radiotherapy: A Case Report of Prophylactic Immunosuppression in a Patient with Myasthenia Gravis and Immune-Mediated Colitis.

Immune checkpoint inhibitors (ICIs) and radiotherapy (RT) combinations for various metastatic cancers are increasingly utilized, yet the augmentation of anti-cancer immunity including distant tumor responses by RT remains ill-characterized. Immunosuppressive tumor microenvironments and defective anti-tumor immune activation including immune-related adverse events (irAEs) likely limit dramatic immuno-radiotherapy combinations, though it remains unclear which immune characteristics mediate dramatic systemic tumor regression in only a small subset of patients. Moreover, the efficacy of ICI treatment in patients receiving immunosuppressive therapies for autoimmune conditions or irAEs is convoluted, yet clinically valuable. Here, we report a case of a 75-year-old man with myasthenia gravis and metastatic melanoma who experienced complete and durable systemic regression after receiving pembrolizumab and single-lesion RT while on prednisone for myasthenia gravis prophylaxis and vedolizumab for immune-mediated colitis after previously experiencing mixed response on pembrolizumab monotherapy. We discuss the potential paradoxical effects and clinical considerations of immunosuppressive regimens in patients with underlying autoimmune disease or adverse immune reactions while receiving immuno-radiotherapy combinations.

Radiosensitization of high-grade gliomas through induced hyperthermia: Review of clinical experience and the potential role of MR-guided focused ultrasound.

High-grade gliomas (HGGs) are aggressive primary brain tumors that confer poor prognoses. Despite aggressive combined modality treatment, HGGs invariably recur. Considerable research efforts and resources have focused on identification of novel therapies for HGGs; however, standard treatments have not changed significantly in more than 10 years, since the introduction of concurrent chemoradiation therapy with temozolomide. Hyperthermia (HT) has been shown to enhance the efficacy of radiation treatment (RT) in numerous cancer types through multiple mechanisms, including impairment of DNA repair pathways, increased perfusion/oxygenation of tumors, and immune system activation. In the 1980s and 1990s, the combination of HT with external-beam RT and interstitial brachytherapy was extensively evaluated in HGG, culminating in a randomized controlled trial that demonstrated superior survival in patients receiving combined HT and RT. However, HT was not adopted into common practice for HGG because of the need at that time for invasive implantation procedures, challenges to monitoring and maintaining a homogeneous, localized temperature elevation within the tumor tissue, as well as other technical and logistic challenges. Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is a relatively new technology in clinical use that is capable of highly accurate transcranial HT and has the potential to overcome many of the limitations faced in previous trials combining HT and RT in HGG. In this review, we detail and compile the previous clinical results of combined HT and RT in HGG patients. We also introduce and discuss the potential of MRgFUS as a noninvasive method for HT to radiosensitize HGG.

Measuring the "whole system" outcomes of an educational innovation: experience from the integrative family medicine program.

BACKGROUND AND OBJECTIVES: Six family medicine residency programs in the United States collaborated on the development and implementation of an integrative family medicine (IFM) program, which is a postgraduate training model that combines family medicine residency training with an integrative medicine fellowship. This paper reports on effects of IFM on residency programs and clinical systems in which it was implemented. METHODS: We used the Integrative Medicine Attitudes Questionnaire (IMAQ) to assess participants' attitudes toward integrative medicine before and after the program was implemented. We assessed residency program recruitment success before and after the program was implemented. We conducted interviews with key informants at each program to evaluate the effects of the IFM on the six participating residency programs. RESULTS: IMAQ scores demonstrated a significant increase in the acceptance of integrative medicine after implementation of IFM. Recruiting data showed that participating programs filled at a rate consistently above the national average both before and after implementation. Analysis of interview data showed that programs became more open to an integrative medicine (IM) approach and offered a wider range of clinical services to patients. CONCLUSIONS: Our mixed-methods strategy for evaluation of IFM showed that implementing the program increased acceptance of IM, did not affect residency fill rates, and increased use of IM in clinical practice. The combination of quantitative and qualitative methods was an effective strategy for documenting the "systems level" effects of a new educational program.

Low connectivity between shallow, mesophotic and rariphotic zone benthos.

Worldwide coral reefs face catastrophic damage due to a series of anthropogenic stressors. Investigating how coral reefs ecosystems are connected, in particular across depth, will help us understand if deeper reefs harbour distinct communities. Here, we explore changes in benthic community structure across 15-300 m depths using technical divers and submersibles around Bermuda. We report high levels of floral and faunal differentiation across depth, with distinct assemblages occupying each depth surveyed, except 200-300 m, corresponding to the lower rariphotic zone. Community turnover was highest at the boundary depths of mesophotic coral ecosystems (30-150 m) driven largely by taxonomic turnover and to a lesser degree by ordered species loss (nestedness). Our work highlights the biologically unique nature of benthic communities in the mesophotic and rariphotic zones, and their limited connectivity to shallow reefs, thus emphasizing the need to manage and protect deeper reefs as distinct entities.

How Histopathologic Tumor Extent and Patterns of Recurrence Data Inform the Development of Radiation Therapy Treatment Volumes in Solid Malignancies.

The ability to deliver highly conformal radiation therapy using intensity-modulated radiation therapy and particle therapy provides for new opportunities to improve patient outcomes by reducing treatment-related morbidities following radiation therapy. By reducing the volume of normal tissue exposed to radiation therapy (RT), while also allowing for the opportunity to escalate the dose of RT delivered to the tumor, use of conformal RT delivery should also provide the possibility of expanding the therapeutic index of radiotherapy. However, the ability to safely and confidently deliver conformal RT is largely dependent on our ability to clearly define the clinical target volume for radiation therapy, which requires an in-depth knowledge of histopathologic extent of different tumor types, as well as patterns of recurrence data. In this article, we provide a comprehensive review of the histopathologic and radiographic data that provide the basis for evidence-based guidelines for clinical tumor volume delineation.