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Supplementary Tables 1-5 from Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES Is Consistently Increased

Background: Current biomarkers for breast cancer have little potential for detection. We determined whether breast cancer subtypes influence circulating protein biomarkers.Methods: A sandwich ELISA microarray platform was used to evaluate 23 candidate biomarkers in plasma samples that were obtained from subjects with either benign breast disease or invasive breast cancer. All plasma samples were collected at the time of biopsy, after a referral due to a suspicious screen (e.g., mammography). Cancer samples were evaluated on the basis of breast cancer subtypes, as defined by the HER2 and estrogen receptor statuses.Results: Ten proteins were statistically altered in at least one breast cancer subtype, including four epidermal growth factor receptor ligands, two matrix metalloproteases, two cytokines, and two angiogenic factors. Only one cytokine, RANTES, was significantly increased (P < 0.01 for each analysis) in all four subtypes, with areas under the curve (AUC) for receiver operating characteristic values that ranged from 0.76 to 0.82, depending on cancer subtype. The best AUC values were observed for analyses that combined data from multiple biomarkers, with values ranging from 0.70 to 0.99, depending on the cancer subtype. Although the results for RANTES are consistent with previous publications, the multi-assay results need to be validated in independent sample sets.Conclusions: Different breast cancer subtypes produce distinct biomarker profiles, and circulating protein biomarkers have potential to differentiate between true- and false-positive screens for breast cancer.Impact: Subtype-specific biomarker panels may be useful for detecting breast cancer or as an adjunct assay to improve the accuracy of current screening methods. Cancer Epidemiol Biomarkers Prev; 20(7); 1543–51. ©2011 AACR.

Purpose The Morbidity and Mortality (M&M) report of the Scoliosis Research Society (SRS) has been collected since 1965 and since 1968 submission of complications has been required of all members. Since 2009, the SRS has collected information on death, blindness, and neurological deficit, with acute infection being added in 2012 and unintentional return to the operating room (OR) being added in 2017. In this report, we use the most recent data submitted to the SRS M&M database to determine the rate of neurological deficit, blindness, acute infection, unintentional return to the OR, and death, while also comparing this information to previous reports. Methods The SRS M&M database was queried for all cases from 2013 to 2020. The rates of death, vision loss, neurological deficit, acute infection, and unintentional return to the OR were then calculated and analyzed. The rates were compared to previously published data if available. Differences in complication rates between years were analyzed with Poisson regression with significance set at α = 0.05. Results The total number of cases submitted per year varied with a maximum of 49,615 in 2018 and a minimum of 40,464 in 2020. The overall reported complication rate from 2013 to 2020 was 2.86%. The overall mortality rate ranged from 0.09% in 2018 to 0.14% in 2015. The number of patients with visual impairment ranged from 4 to 13 between 2013 and 2015 (no data on visual impairment were collected after 2015). The overall infection rate varied from 0.95 in 2020 to 1.30% in 2015. When the infection rate was analyzed based on spinal deformity group, the neuromuscular scoliosis group consistently had the highest infection rate ranging from 3.24 to 3.94%. The overall neurological deficit rate ranged from 0.74 to 0.94%, with the congenital kyphosis and dysplastic spondylolisthesis groups having the highest rates. The rates of unintentional return to the OR ranged from 1.60 to 1.79%. Multiple groups showed a statistically significant decreasing trend for infection, return to the operating room, neurologic deficit, and death. Conclusions Neuromuscular scoliosis had the highest infection rate among all spinal deformity groups. Congenital kyphosis and dysplastic spondylolisthesis had the highest rate of neurological deficit postoperatively. This is similar to previously published data. Contrary to previous reports, neuromuscular scoliosis did not have the highest annual death rate. Multiple groups showed a statistically significant decreasing trend in complication rates during the reporting period, with only mortality in degenerative spondylolisthesis significantly trending upwards. Level of evidence Level III.

Acute graft-versus-host disease (aGvHD) is a rare complication of liver transplantation associated with high morbidity and mortality. Death typically occurs due to complications related to severe infection, shock, and multiorgan failure. The clinical presentation involves dysfunction of multiple organ systems with overlapping symptoms that often results in a diagnostic delay. As there are a limited number of cases reported in the literature, there are no clear guidelines for treatment. Many different therapeutic measures have been utilized that target various immune system pathways, but steroids remain the first line of therapy. We report on two patients who developed aGvHD after liver transplantation who were treated with ruxolitinib, a novel Janus kinase 1/2 (JAK) inhibitor that has been shown to improve outcomes in steroid refractory cases of aGvHD after allogenic hematopoietic stem cell transplantation. We reviewed the literature to discuss various therapeutic options currently available for aGvHD after liver transplantation.

Background Falls are the most common adverse incident of inpatients in Irish hospitals. 6% of inpatient falls cause serious injury. Older inpatients have the highest risk of falling and the highest risk of injury. The post-fall medical review is critical to assess why a patient fell, did the fall cause injury and for the introduction of measures to prevent future falls. We assessed the quality of the post fall reviews in a large hospital. We then introduced a standardised post-fall medical review pro forma and reassessed the quality of the reviews. Methods We reviewed 18 charts of patients that fell in hospital and assessed the documentation of the post fall review in terms of the inclusion of key elements such as patient identifiers, history, examination, injury management and future falls prevention. We then introduced a post-fall standardised pro-forma on five wards in the hospital and following this assessed 19 charts of patients who had fallen looking at the same key elements of the post fall review. We compared the quality of the post-fall review before and after the introduction of the pro forma. Results The post-falls medical review pro forma improved the quality of the post fall medical review. Hip Trauma: 11.1% of doctors asked about hip strike prior to proforma versus 100% who asked with the proforma. Joint examination: 50% assessed this prior to the proforma versus 100% with the pro-forma. Other aspects of the review that improved included head-strike assessment (89% versus 100%), loss of consciousness history (61% versus 95%), medication reviewed (22% versus 68%) and vital signs assessed (67% versus 95%). Conclusion The introduction of a standardised post fall review pro forma improves the quality of this important medical review. It is a useful aid for doctors and provides a framework to follow when reviewing the patient.

Dispersal in many organisms is asymmetric by sex, a pattern that is often identified through the use of genetic tools. Sex-biased dispersal (SBD) is thought to derive from the varying fitness needs of females and males, as mediated by local ecology and life history. SBD is frequently reported in elasmobranchs (sharks, rays), long-lived fishes that often give live birth to well-developed young and are capable of dispersing thousands of kilometers. While many studies point to male-biased dispersal (MBD) being common, results are highly variable and no clear trends have yet emerged, even as the number of case studies has grown over the past decade. Here, we evaluated patterns in sampling regime, molecular marker type, and analysis method for every genetic structure study published to date that allowed for an assessment of SBD in elasmobranchs. We find that while some degree of MBD in elasmobranchs is likely, factors such as the pooling of life stages during data analysis and the inherent characteristics of different marker types, may lead to an overemphasis on male dispersal and potentially obscure genetic signals of female and male reproductive philopatry. The role of life history and biogeography in determining patterns of SBD in sharks and rays is also discussed.

The mechanisms underlying polyandry and female mate choice in certain taxonomic groups remain widely debated. In elasmobranchs, several species have shown varying rates of polyandry based on genetic studies of multiple paternity (MP). We investigated MP in the finetooth shark, Carcharhinus isodon, in order to directly test the encounter rate hypothesis (ERH), which predicts that MP is a result of the frequency of encounters between mature conspecifics during the breeding season, and should therefore increase when more time is available for copulation and sperm storage. Female finetooth sharks in the northern Gulf of Mexico (GoM) have been found to reproduce with both annual periodicity and biennial periodicity, while finetooth sharks from the northwestern Atlantic Ocean have only been found to reproduce biennially, allowing us to compare mating opportunity to frequency of MP. Our results show high rates of MP with no significant difference in frequency between females in the GoM (83.0%) and Atlantic (88.2%, p = .8718) and varying but nonsignificant rates of MP between females in the GoM reproducing annually (93.0%) and biennially (76.6%, p = .2760). While the ERH is not supported by this study, it remains possible that reproductive periodicity and other physiological factors play a role in determining rates of MP in elasmobranchs, with potential benefits to individuals and populations., We investigated multiple paternity in the finetooth shark in order to directly test the encounter rate hypothesis, which predicts that multiple paternity is a result of the frequency of encounters between mature conspecifics during the breeding season. We found high rates of multiple paternity with no significant differences corresponding to reproductive periodicity or location.

Understanding dispersal in large marine fauna is necessary for conservation, but movement patterns often vary widely by sex and life stage. In sharks, genetic studies have shown evidence of widespread male-biased dispersal, though tagging and tracking studies on the same populations show both sexes using site fidelity, including philopatry, and moving similar distances. We used a suite of microsatellite loci and DNA samples from 362 previously-tagged tiger sharks (Galeocerdo cuvier) in the northwestern Atlantic, including a large number of residential juveniles, to evaluate reproductive dispersal in light of demographic and published tracking data. We found that lumping size classes together resulted in genetic panmixia across sites, but systematic removal of large individuals showed significant population-level differentiation and three separate population clusters among juveniles less than 260 cm total length. Tests for relatedness found that 8.9% of our sample set was composed of first-order related pairs (N = 16), including several full siblings from different litters, a sign of multi-cycle genetic monogamy which carries implications for effective population size. By mapping genetic assignments of juveniles, we identified a signature of fine-scale genetic structure suggesting broad biparental site fidelity to reproductive habitat in the northeast Gulf of Mexico, which is concordant with both genetic and tracking data. Taken together, these findings demonstrate how lumping individuals from different life stages in genetic studies may obscure fine-scale genetic structure, confounding future conservation efforts.

We developed a new and injectable poly-dicalcium phosphate dihydrate (P-DCPD) forming cement. The key structural difference between P-DCPD and classical DCPD is that P-DCPD is composed of interconnected P-DCPD crystals by interlocking to the polyphosphate chains. In contrast, DCPD is composed of a package of DCPD crystals with weak mutual ionic bonding. The purpose of this continuing study was to compare the physicochemical properties between P-DCPD and DCPD cement particles. Data collected from SEM, X-ray diffraction, and Raman Spectroscopy approaches demonstrated that P-DCPD has a more stable chemical structure than DCPD as evidenced by much less transformation to hydroxyapatite (HA) during setting. Nanoindentation showed a similar hardness while the elastic modulus of P-DCPD is much lower than DCPD that might be due to the much less HA transformation of P-DCPD. P-DCPD has much lower zeta potential and less hydrophilicity than DCPD because of its entangled and interconnected polyphosphate chains. It is expected that superhydrophilic DCPD undergoes faster dissolution than P-DCPD in an aqueous environment. Another interesting finding is that the pH of eluent from P-DCPD is more neutral (6.6-7.1) than DCPD (5.5-6.5). More extensive experiments are currently underway to further evaluate the potential impacts of the different physiochemical performance observed of P-DCPD and DCPD cement particles on the biocompatibility, degradation behavior and bone defect healing efficacy both in vivo and in vitro.

Geological and tectonic analysis of the Eastern Himalayan basins has given rise to a decade-long debate on the geodynamic evolution of the Burmese terrane and on the extent of reorganization of the main SE Asia drainage systems. However, the influence of the Himalayan belt on the Central Myanmar Basin (CMB) system remains poorly documented, although it is key to providing more accurate models for the evolution of the Himalayan-Burmese orogen. In this contribution, we present geochronological, isotopic and geochemical analysis from 2500 zircon, 1700 titanite, 700 rutile and 850 apatite detrital grains from fifteen Cenozoic siliciclastic samples and one Cretaceous igneous rock. The samples were collected within the fore- and back-arc basins of the Central Myanmar Basin domain (CMB) to constrain the provenance, maximum depositional ages, and depositional environments of the west Burma terrane. Nine key lithological units, the Sadwingyi, Ketpanda, Wabo Chaung, Gwegon, Minwun, Padaung, Okmintaung and Irrawaddy formations have detrital age spectra spanning from the Miocene to Paleoarchean. The entire data set has common age peaks at ca. 20, 40, 60, 90, 100 ​Ma, with about 80% of the U–Pb ages younger than ca. 140 Ma and only ca. 1% of the grains predating ca. 3.0 ​Ga. Our results shed light on the current ambiguities on the transport pathways of Himalayan detritus in the CMB. They show that the fore-arc basin was open to the trench and fed by the unroofing of both the Wuntho Popa volcanic arc to the east and possibly from the Burmese basement and/or from Himalayan-derived Bengal Fan detritus to the west during the Eocene, from at least ca. 44 Ma to before ca. 39 Ma. We show that the west Burma Terrane was partitioned into pull-apart basins such as the Minwun Basin, which during the Oligocene recorded the first evidence of a new source contribution into the CMB at ca. 27 Ma. This new source is characterized by detritus highly compatible with the SE Asia basement rocks, which we suggest corresponds to the initiation of the palaeo–Irrawaddy River. This geodynamic evolution does not require any Yarlung Tsangpo-Irrawaddy-Brahmaputra paleodrainage reorganization, since from the Oligocene to the Early Miocene, the Irrawaddy River fed an internally drained basin, and from the Late Miocene onwards, the Yarlung drained into the Brahmaputra in the Bengal Basin.

This paper investigates the viability of commodity exchange in Bhutan and identifies its essential pre-conditions. Challenges and benefits are enumerated using exploratory and qualitative research with open-ended and semi-structured interviews. Bhutan represents an emerging South-Central Asian country successful emergence of which into the global arena in the last fifty years could serve as an example for other small and developing markets. The results of this study put challenges for farmers in two categories, before and after harvest. All post-harvest challenges can be addressed through an established commodity exchange and its three pre-conditions are essential to the development of commodity exchange in Bhutan.

Human activities in coastal areas are accelerating ecosystem changes at an unprecedented pace, resulting in habitat loss, hydrological modifications, and predatory species declines. Understanding how these changes potentially cascade across marine and freshwater ecosystems requires knowing how mobile euryhaline species link these seemingly disparate systems. As upper trophic level predators, bull sharks (Carcharhinus leucas) play a crucial role in marine and freshwater ecosystem health. Telemetry studies in Mobile Bay, Alabama, suggest that bull sharks extensively use the northern portions of the bay, an estuarine–freshwater interface known as the Mobile‐Tensaw Delta. To assess whether bull sharks use freshwater habitats in this region, environmental DNA surveys were conducted during the dry summer and wet winter seasons in 2018. In each season, 5 × 1 L water samples were collected at each of 21 sites: five sites in Mobile Bay, six sites in the Mobile‐Tensaw Delta, and ten sites throughout the Mobile‐Tombigbee and Tensaw‐Alabama Rivers. Water samples were vacuum‐filtered, DNA extractions were performed on the particulate, and DNA extracts were analyzed with Droplet Digital™ Polymerase Chain Reaction using species‐specific primers and an internal probe to amplify a 237‐base pair fragment of the mitochondrial NADH dehydrogenase subunit 2 gene in bull sharks. One water sample collected during the summer in the Alabama River met the criteria for a positive detection, thereby confirming the presence of bull shark DNA. While preliminary, this finding suggests that bull sharks use less‐urbanized, riverine habitats up to 120 km upriver during Alabama's dry summer season., Estuarine, deltaic, and freshwater ecosystems are connected by mobile species that can increase ecosystem resilience by linking these otherwise disparate habitats. However, monitoring populations of mobile link species across multiple, expansive habitats presents logistical challenges. In this study, we use environmental DNA to provide the first evidence of bull shark habitat use 120 km upriver in the Alabama River. While preliminary, our findings provide a basis for further study and demonstrate the usefulness of this technique across similarly dynamic environments.

Candida auris is a yeast that is difficult to eradicate and has caused outbreaks in health care facilities. We report a cluster of 5 patients in 1 intensive care unit who were colonized or infected in 2017. The initial 2 patients were recipients of liver transplants who had cultures that grew C auris within 3 days of each other in June 2017 (days 43 and 30 posttransplant). Subsequent screening cultures identified 2 additional patients with C auris colonization. Respiratory and urine cultures from a fifth patient yielded C auris. All isolates were fluconazole resistant but susceptible to echinocandins. Whole genome sequencing showed the strains were clonal, suggesting in-hospital transmission, and related but distinct from New York/New Jersey strains, consistent with a separate introduction. However, no source or contact was found. Two of the 5 patients died. C auris infection likely contributed to 1 patient death by infecting a vascular aneurysm at the graft anastomosis. Strict infection control precautions were initiated to control the outbreak. Our experience reveals that although severe disease from C auris can occur in transplant recipients, outbreaks can be controlled using recommended infection control practices. We have had no further patients infected with C auris to date.

Scientific professional societies are reviewing diversity, equity, and inclusion (DEI) practices and policies in response to recent calls for much-needed change. Organizations like scientific professional societies contribute to establishing disciplinary norms, and can influence the diversity of disciplinary workforces in multiple ways through both action and inaction. This paper examines these issues using the American Elasmobranch Society (AES), a medium-sized professional scientific society, as a case study. It consists of three parts: (1) an analysis of the demographics of AES members, leaders, and award winners; (2) an evaluation of a diversity initiative created by the society which includes a survey of program alumni focusing on potential improvements to the program; and (3) a synthesis of recommendations of steps that AES and similarly sized societies can take to better support DEI goals. AES’s membership in recent years is more than half women, but 71.5% of all leadership positions in the Society’s history (including all but two Presidents) have been held by men since the society was founded in 1983. AES’s membership has significantly fewer Black/African-American members than the United States scientific workforce overall, with just 1 member out of over 400 identifying as Black in 2019, and 86.6% of Society leadership positions have been held by white-presenting members. The Society’s diversity initiative has led to some limited professional benefits for awardees, but could benefit from additional resources and support to enact suggested expansions and improvements. We provide a series of actionable recommendations that will make the annual meetings of societies like AES, and the field of chondrichthyan science, safer and more inclusive.

Background: Using alternating orthogonal suture throws with the looped whipstitch technique may allow enhanced suture fixation. Hypothesis: It was hypothesized that this novel multiplanar, perpendicular looped whipstitch (MP) technique would have improved biomechanical properties compared with the standard looped whipstitch (WS) and Krackow stitch (KS). Study Design: Controlled laboratory study. Methods: A total of 30 cadaveric tibialis anterior tendons were randomly assigned into 3 groups of 10. Tendons were secured to a custom clamp, and the other end was sutured using 1 of 3 techniques: the KS, WS, or novel MP. The MP was performed with alternating orthogonal throws starting right to left, then front to back, left to right, and back to front. Each technique used 4 passes of No. 2 FiberWire spaced 5 mm apart and ending 10 mm from the tendon end. Tendons were preloaded to 5 N, pretensioned to 50 N at 100 mm/min for 3 cycles, returned to 5 N for 1 minute, cycled from 5 to 100 N at 200 mm/min for 100 cycles, and then loaded to failure at 20 mm/min. Elongation was recorded after pretensioning and cycling and was measured both across the suture-tendon interface and from the base of the suture-tendon interface to markings on the suture limbs (construct elongation). One-way analyses of variance were performed, with Bonferroni post hoc analysis when appropriate. Results: There were no differences in cross-sectional area or stiffness among the 3 techniques. The ultimate load for WS (183.33 ± 57.44 N) was less compared with both MP (270.76 ± 39.36 N) and KS (298.90 ± 25.94 N) ( P ≤ .001 for both). There was less construct elongation for KS compared with WS and MP for total displacement, measured from pretensioning to the end of cycling ( P < .001). All 3 techniques saw a decrease in length (shortening) at the suture-tendon interface during testing. There was more shortening at the suture-tendon interface for WS compared with KS ( P = .006). Conclusion: The KS appears superior, as it maximized strength while minimizing construct elongation or graft shortening. The ultimate load of the MP technique was greater than that of the standard technique but not significantly different from that of the KS technique. Clinical Relevance: The KS is preferred. If using a WS, multiplanar, perpendicular passes should be considered.

Introduction: This was a single-center retrospective study to evaluate incidence, prognosis, and risk factors in patients with postoperative pleural effusions, a common pulmonary complication following liver transplantation. Methods: A retrospective review was performed on 374 liver transplantation cases through a database within the timeframe of January 1, 2009 through December 31, 2015. Demographics, pulmonary and cardiac function testing, laboratory studies, intraoperative transfusion/infusion volumes, postoperative management, and outcomes were analyzed. Results: In the immediate postoperative period, 189 (50.5%) developed pleural effusions following liver transplantation of which 145 (76.7%) resolved within 3 months. Those who developed pleural effusions demonstrated a lower fibrinogen (149.6 ± 66.3 mg/dL vs 178.4 ± 87.3 mg/dL; P = .009), total protein (5.8 ± 1.0 mg/dL vs 6.1 ± 1.2 mg/dL; P = .04), and hemoglobin (9.8 ± 1.8 mg/dL vs 10.3 ± 1.9 mg/dL; P = .004). There was not a statistically significant difference in 1-year all-cause mortality and in-hospital mortality between liver transplant recipients with and without pleural effusions. Liver transplant recipients who developed pleural effusions had a longer hospital length of stay (16.4 ± 10.9 days vs 14.0 ± 16.5 days; P = .1), but the differences were not statistically significant. However, there was a significant difference in tracheostomy rates (11.6% vs 5.4%; P = .03) in recipients who developed pleural effusions compared to recipients who did not. Conclusions: In summary, pleural effusions are common after liver transplantation and are associated with increased morbidity. Pre- and intraoperative risk factors can offer both predictive and prognostic value for post-transplantation pleural effusions. Further prospective studies will be needed to further evaluate the relevance of these findings to limit instances of postoperative pleural effusions.

Purpose: This study investigated the influence of components of fitness on measures of performance attenuation and recovery following Gaelic football match play. Methods: Measurements of players’ anthropometric characteristics, body composition, running speed, lower-body strength and power, blood lactate concentrations, running economy, and maximal aerobic capacity () were taken over 2 separate days 1 week prior to a competitive match. Creatine kinase, countermovement jump height, drop jump height, contact time, reactive strength index, and perceptual responses were tested prematch, at full time, 24 hours postmatch, and 48 hours postmatch. Results: Multiple components of fitness were associated with reduced performance attenuation and improved recovery responses (adjusted R2 = 9.8%–27.6%; P (higher standard: 57.4 [4.2] mL·kg−1·min−1; lower standard: 45.3 [3.8] mL·kg−1·min−1) and relative squat (higher standard: 1.46 [0.11] 1-repetition-maximum kg·body mass−1; lower standard: 1.20 [0.08] 1-repetition-maximum kg·body mass−1) groups. After adjusting for prematch baseline differences, there were significant differences between groups in drop jump height at 24 hours postmatch (; P ; P ; P ; P ; P Conclusion: Coaches should prioritize the development of aerobic capacity and neuromuscular function as an effective method of reducing performance attenuation and enhancing recovery kinetics in Gaelic football.

Post-copulatory sexual selection, and sperm competition in particular, is a powerful selective force shaping the evolution of sperm morphology. Although mounting evidence suggests that post-copulatory sexual selection influences the evolution of sperm morphology among species, recent evidence also suggests that sperm competition influences variation in sperm morphology at the intraspecific level. However, contradictory empirical results and limited taxonomic scope have led to difficulty in assessing the generality of sperm morphological responses to variation in the strength of sperm competition. Here, we use phylogenetically controlled analyses to explore the effects of sperm competition on sperm morphology and variance in sharks, a basal vertebrate group characterized by wide variation in rates of multiple mating by females, and consequently sperm competition risk. Our analyses reveal that shark species experiencing greater levels of sperm competition produce sperm with longer flagella and that sperm flagellum length is less variable in species under higher sperm competition risk. In contrast, neither the length of the sperm head and midpiece nor variation in sperm head and midpiece length was associated with sperm competition risk. Our findings demonstrate that selection influences both the inter- and intraspecific variation in sperm morphology and suggest that the flagellum is an important target of sexual selection in sharks. These findings provide important insight into patterns of selection on the ejaculate in a basal vertebrate lineage.

Sharpnose sharks (genus Rhizoprionodon) experience extensive fishing pressure throughout their ranges in the Atlantic Ocean. As such, it is important to understand the degree to which intraspecific populations interact across a spatial gradient. The Atlantic sharpnose shark (Rhizoprionodon terraenovae) and Caribbean sharpnose shark (Rhizoprionodon porosus) share a similar appearance and spatial presence within the Gulf of Mexico, though until recently only R. terraenovae was observed north of the Bahamas. We assessed the population structure of R. terraenovae using the mitochondrial control region (650 bp). Our results indicate significant genetic structure (FST= 0.049, P < 0.001; ΦST= 0.017, P = 0.008) between the Gulf of Mexico and the rest of the Atlantic. In addition, we observed R. porosus outside their known range, in South Carolina, Virginia, and northern Florida. Given the overlapping range with R. terraenovae, we assessed the potential for congeneric hybridization with the addition of the nuclear ribosomal internal transcribed spacer 2 gene (1260 bp). Results designate these specimens to be true R. porosus specimens, indicating the need for reevaluation of this species’ range.

The artist Odilon Redon (1840–1916) was a French symbolist known for both the dark, surreal prints and drawings he created in the first half of his career, as well as the colorful pastel works that characterized the second half of his career. This study examines two drawings by Redon in the J. Paul Getty Museum collection—Apparition (ca. 1880–1890) and Head within an Aureole (ca. 1894–1895)—executed during the period in his career in which he was transitioning between these two modes. In order to better understand the materials the artist chose and the methods by which he applied them, two noninvasive, macroscopic characterization techniques—macro X-ray fluorescence (MA-XRF) scanning and reflectance imaging spectroscopy (RIS)—were employed. These techniques allowed the materials present to be distinguished and the relationship between their applications visualized. Coupled with fiber optic reflectance spectroscopy (FORS) and Raman microspectroscopy with principal component analysis (PCA), these results give new insight into the materials and methods used by Redon. Six distinct black drawing materials and a yellow pastel were identified in Apparition, underscoring the complexity of Redon’s noir drawings. As he began using color pastel more frequently he seemed to use a simplified black palette; in Head within an Aureole the artist used only two black drawing materials and three color pastels (two pink and one blue). This research provides a framework for future noninvasive technical analysis of works by Redon in other collections as well as mixed media drawings more generally.

Female multiple mating provides the opportunity for sexual selection to continue after gamete release, generating strong selection on male reproductive traits. In particular, in species where femal ...

Background Biological characterisation of breast cancer subtypes is essential as it informs treatment regimens especially as different subtypes have distinct locoregional patterns. This is related to metabolic phenotype, where altered cellular metabolism is a fundamental adaptation of cancer cells during rapid proliferation. In this context, the metabolism of the essential branched-chain amino acids (BCAAs), catalysed by the human branched-chain aminotransferase proteins (hBCAT), offers multiple benefits for tumour growth. Upregulation of the cytosolic isoform of hBCAT (hBCATc), regulated by c-Myc, has been demonstrated to increase cell migration, tumour aggressiveness and proliferation in gliomas, ovarian and colorectal cancer but the importance of the mitochondrial isoform, hBCATm has not been fully investigated. Methods Using immunohistochemistry, the expression profile of metabolic proteins (hBCAT, IDH) was assessed between breast cancer subtypes, HER2 + , luminal A, luminal B and TNBC. Correlations between the percentage and the intensity of protein expression/co-expression with clinical parameters, such as hormone receptor status, tumour stage, lymph-node metastasis and survival, were determined. Results We show that hBCATc expression was found to be significantly associated with the more aggressive HER2 + and luminal B subtypes, whilst hBCATm and IDH1 associated with luminal A subtype. This was concomitant with better prognosis indicating a differential metabolic reliance between these two subtypes, in which enhanced expression of IDH1 may replenish the α-ketoglutarate pool in cells with increased hBCATm expression. Conclusion The cytosolic isoform of BCAT is associated with tumours that express HER2 receptors, whereas the mitochondrial isoform is highly expressed in tumours that are ER + , indicating that the BCAT proteins are regulated through different signalling pathways, which may lead to the identification of novel targets for therapeutic applications targeting dysregulated cancer metabolism.

Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role in breast cancer progression and was recently shown to bind to the chaperone protein glucose-regulated protein 78 (GRP78), however, the clinical significance of this association remains poorly investigated. Here we report a direct correlation between the expression of GRP78 and IGFBP-3 in breast cancer cell lines and tumour sections. Kaplan&ndash, Meier survival plots revealed that patients with low GRP78 expression that are positive for IGFBP-3 had poorer survival rates than those with low IGFBP-3 levels, and we observed a similar trend in the publicly available METABRIC gene expression database. With breast cancer cells, in vitro IGFBP-3 enhanced induced apoptosis, however when GRP78 expression was silenced the actions of IGFBP-3 were switched from increasing to inhibiting ceramide (C2)-induced cell death and promoted cell invasion. Using immunofluorescence and cell surface biotinylation, we showed that knock-down of GRP78 negated the entry of IGFBP-3 into the cells. Together, our clinical and experimental results suggest that loss of GRP78 reduces IGFBP-3 entry into cells switching its actions to promote tumorigenesis and predicts a poor prognosis in breast cancer patients.

Oral nanomedicines are being investigated as an innovative strategy for targeted drug delivery to treat inflammatory bowel diseases. Preclinical studies have shown that nanoparticles (NPs) can preferentially penetrate inflamed intestinal tissues, allowing for targeted drug delivery. NP size is a critical factor affecting their interaction with the inflamed intestinal barrier and this remains poorly defined. In this study we aimed to assess the impact of NP particle size (PS) and polydispersity (PDI) on cell interaction and uptake in an inflamed epithelial cell model. Using 10, 55 and 100 mg/mL poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG), NPs of 131, 312 and 630 nm PS, respectively, were formulated by solvent dispersion. NP recovery was optimised by differential centrifugation to yield NPs of decreased and unimodal size distribution. NP-cell interaction was assessed in healthy and inflamed caco-2 cell monolayers. Results show that NP interaction with caco-2 cells increased with increasing PS and PDI and was significantly enhanced in inflamed cells. Trypan blue quenching revealed that a significant proportion of multimodal NPs were primarily membrane bound, while monomodal NPs were internalized within cells. These results are interesting as the PS and PDI of NPs can be optimised to allow targeting of therapeutic agents to the epithelial membrane and/or intracellular targets in the inflamed intestinal epithelium.

Environmental DNA (eDNA) is increasingly being used to document species distributions and habitat use in marine systems, with much of the recent effort focused on leveraging advances in next-generation DNA sequencing to assess and track biodiversity across taxonomic groups. Environmental DNA offers a number of important advantages over traditional survey techniques, including non-invasive sampling, sampling where traditional approaches are impractical or inefficient (e.g. deep oceans), reduced cost, and increased detection sensitivity. However, eDNA applications are currently limited because of an insufficient understanding of the influence of sample source, analytical approach, and marker type on eDNA detections. Because approaches vary considerably among eDNA studies, we present a summary of the current state of the field and emerging best practices. The impact of observed variation in rates of eDNA production, persistence, and transport are also discussed and future research needs are highlighted with the goal of expanding eDNA applications, including the development of statistical models to improve the predictability of eDNA detection and quantification.

Late Quaternary Antarctic ice-sheet instability is recorded by ice-rafted debris (IRD) in mid- to high-latitude marine sediment, especially during marine isotope stages (MIS) 2-3, but drivers of this instability remain enigmatic (Labeyrie et al., 1986). A key step in resolving this puzzle is to determine the location of iceberg calving sites, thus highlighting ice sheet sectors exhibiting repeated instability. Single-grain U-Pb provenance analysis applied to clastic IRD provides a suitable high-resolution tool for this task, and also permits discrimination of continental IRD from volcanic material. The application of multiple proxies (apatite, rutile, and zircon) is critical in order to reduce source area fertility biases: for example, the near exclusive occurrence of zircon in felsic-intermediate igneous rocks (e.g., Hietpas et al., 2010).Here, we present detrital apatite, zircon, and rutile U-Pb data from samples taken from a gravity core from the Odyssea contourite drift system, located on the margin of the Ross Sea (Rebesco et al., 2018) and deposited during MIS2-3. Contourites are marine clastic sediment deposits forming by along-slope, bottom currents reworking of fine-grained (clay-silt) sediments delivered by down-slope sedimentary processes (e.g. meltwaters, turbidity currents, debris flows). Crucially, contourite targetting eliminates the challenge of distinguishing IRD from coarse (sand-gravel) turbidite material in basin deposits, as ice-sheet instability is also associated with turbidite production at glaciated shelf margins (e.g., Bart et al., 1999).We couple our analysis with the multi-proxy sediment analyses previously performed by Lucchi et al. (2019). We consider the implications of our data for the advance and retreat of the Antarctic Ice Sheet during MIS 2-3, and discuss the further applicability of our multi-proxy approach around Antarctica.Bart, P.J, et al., 1999, Journal of Sedimentary Research, v. 69, p. 1276–1289, doi:10.2110/jsr.69.1276.Hietpas, J, et al., 2010, Geology, v. 38, p. 167–170, doi:10.1130/G30265.1.Lucchi, R.G, et al., 2019. EGU General Assembly 2019, Vienna April 7th–12th, Geophysical Research Abstracts Vol. 21, EGU2019-10409-1Rebesco, M, et al., 2018, preliminary results, in POLAR 2018 SCAR/IASC Open Science Conference, v. GG2 Arctic, p. 14133.Labeyrie, L, et al., 1986, Nature, v. 322, p. 701–706.

Environmental DNA (eDNA) is increasingly being used to document species distributions and habitat use in marine systems, with much of the recent effort focused on leveraging advances in next-generation DNA sequencing to assess and track biodiversity across taxonomic groups. Environmental DNA offers a number of important advantages over traditional survey techniques, including non-invasive sampling, sampling where traditional approaches are impractical or inefficient (e.g. deep oceans), reduced cost, and increased detection sensitivity. However, eDNA applications are currently limited because of an insufficient understanding of the influence of sample source, analytical approach, and marker type on eDNA detections. Because approaches vary considerably among eDNA studies, we present a summary of the current state of the field and emerging best practices. The impact of observed variation in rates of eDNA production, persistence, and transport are also discussed and future research needs are highlighted with the goal of expanding eDNA applications, including the development of statistical models to improve the predictability of eDNA detection and quantification.

This study investigated acute changes in markers of fatigue and performance attenuation during and following a competitive senior club-level Gaelic football match. Forty-one players were tested immediately pre-match, at half-time, full-time, 24 h post-match and 48 h post-match. Creatine kinase, drop jump height and contact-time, reactive strength index, countermovement jump height and perceptual responses were assessed at the aforementioned time-points. 18 Hz global positioning system devices were used to record players in-game workload measures. Compared to pre-match, perceptual responses (&minus, 27.6%) and countermovement jump height (&minus, 3.9%) were significantly reduced at full-time (p &lt, 0.05). Drop jump height (&minus, 8.8%), perceptual responses (&minus, 27.6%), reactive strength index (&minus, 15.6%) and countermovement jump height (&minus, 8.6%) were significantly lower 24 h post-match (p &lt, 0.05). Pre-match creatine kinase was significantly increased (+16.2% to +159.9%) when compared to all other time-points (p &lt, 0.05). Total distance, total accelerations, total sprints, sprint distance and average heart rate were all correlated to changes in perceptual responses (r = 0.34 to 0.56, p &lt, 0.05). Additionally, maximum speed achieved (r = 0.34) and sprint distance (r = 0.31) were significantly related to countermovement jump changes (p &lt, 0.05), while impacts (r = 0.36) were correlated to creatine kinase increases (p &lt, 0.05). These results demonstrate that Gaelic football match-play elicits substantial neuromuscular, biochemical and perceptual disturbances.

Dogfish sharks of the genusSqualusare small, deep-water sharks with a slow rate of molecular evolution that has led to their designation as a series of species complexes, with low between-species diversity relative to other taxa. The largest of these complexes is named for the Shortspine spurdog (SqualusmitsukuriiJordan & Snyder), a medium-sized dogfish shark common to warm upper slope and seamount habitats, with a putative circumglobal distribution that has come under investigation recently due to geographic variation in morphology and genetic diversity. The Hawaiian population ofSqualusmitsukuriiwas examined using both morphological and molecular analyses, putting this group in an evolutionary context with animals from the type population in Japan and closely-related congeners. External morphology differs significantly between the Hawaiian and JapaneseS.mitsukurii, especially in dorsal fin size and relative interdorsal length, and molecular analysis of 1,311 base pairs of the mitochondrial genes ND2 and COI show significant, species-level divergence on par with other taxonomic studies of this genus. The dogfish shark in Hawaii represents a new species in the genus, and the nameSqualushawaiiensis, the Hawaiian spurdog, is designated after the type location.

IgG4-related disease is an immune-mediated fibro-inflammatory disease, characterised by distinct pathological features. An increasing number of clinical phenotypes are described, from single-organ disease to a multisystem disorder, which can present to a variety of different specialities. Recognition is key; its protean manifestations can mimic other inflammatory diseases, infection and malignancy. Here, we present three cases to highlight the importance of being familiar with this condition in its various forms