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Coastal areas provide essential habitats for marine turtle nesting and hatching, but they are under increasing threat due to climate change and other anthropogenic impacts. Very little is known about the nesting habitat characteristics of flatback Natator depressus, green Chelonia mydas and loggerhead Caretta caretta turtles in eastern Queensland, which limits our ability to evaluate which nesting beaches are at risk due to anthropogenic and environmental disturbances and prioritise conservation and monitoring actions. Here, we used generalised linear models to investigate the relationship between the presence/absence of flatback, green and loggerhead turtle nests and environmental and topographic characteristics of 237 potential nesting sites along the central and southern coasts of Queensland. The presence of nesting flatback turtles was strongly correlated with the mainland and non-coral cay islands with decreasing latitude, as there is an interaction between site type and latitude. In contrast, green turtles preferred to nest on coral cays rather than mainland and island beaches. Loggerhead turtles were more likely to nest on coral cays, the mainland, then islands, with presence increasing with latitude. Among these site types and higher latitudes, presence was stronger on sheltered than on semi-exposed beaches. Identifying environmental and topographical features influencing the presence of nesting flatback, green and loggerhead turtles is an important first step to improve the conservation of these species by prioritising sites for monitoring and managing threats to important beaches.

Understanding green turtle habitat use during the nesting season is important for informing management decisions relating to green turtles and ecosystems that support them. Despite patterns such as migration being described, few studies investigate behaviour during the inter-nesting period. This research aims to describe and quantify the spatial distribution patterns of green turtles during 2 nesting seasons on Raine Island in the northern Great Barrier Reef. Satellite telemetry data were used to analyse the inter-nesting movements and patterns of green turtles in 2017 (n = 19) and 2018 (n = 20). The inter-nesting period ranged from 51 to 100 d (76.33 ± 15.98 d) across both seasons. The average inter-nesting area of individual turtles did not differ between nesting seasons (2017: 12.31 ± 13.22 km2, 2018: 12.01 ± 21.92 km2). In addition, it was established that 39 individuals are a sufficient sample size to describe the spatial distribution. Approximately half of the tracked individuals remained at the same reef for their entire inter-nesting season (n = 19), and half used habitat on nearby reefs (n = 20). Most turtles showed fidelity to Raine Island as a nesting site (n = 37), laying all their clutches on the island. However, 2 individuals travelled 479 and 337 km during the inter-nesting period. This study thus highlights where the habitats used by green turtles during the inter-nesting season are and how they are used. Therefore, management strategies and conservation decisions can be informed to maintain the viability of these essential habitats.

ABSTRACT: The use of veterinary drugs is of similar importance to that of human drugs in addressing health challenges. In this context, pharmaceuticals and their metabolites inevitably enter soil and water in unknown quantities. Therefore, this study collects and analyzes drug data from 2020 for 50 dairy farms located in Germany. The most frequently used substance group is antibiotics (40.13%), followed by antiphlogistics (18.86%), antiparasitics (13.09%), and hormones (9.29%). Treatment frequencies record the number of days per year on which an average animal on a farm was treated with a substance. The calculated values range from 0.94 to 21.69 d/yr and are distributed heterogeneously across farms. In this study, on average, a cow was treated on 6 d in 2020: 2.34 d with antibiotics, 1.07 d with antiphlogistics, 0.76 d with antiparasitics, and 0.41 d with hormones. In addition to individual farm management practices, other factors are related to treatment frequency. Farms with a veterinary care contract used more hormonal substances than farms without a care contract. In addition, higher milk yield coincides with more frequent treatments with antiphlogistic or hormonal substances. Other related factors include grazing, longevity, farm size, and use of a claw bath. Our study represents an important first step in describing the amounts and determinants of veterinary drugs used in livestock farming. Such insights on magnitudes and farm parameters are essential to estimate potential environmental effects and derive strategies to reduce veterinary drug use.

Leatherback turtles Dermochelys coriacea are a pelagic species, globally endangered due to multiple anthropogenic impacts. Although protected under Australian legislation, species-specific practical protection has been hampered by sparse information about leatherback distribution in Australian waters. To fill this gap, we obtained records of leatherback interactions with fisheries gear, opportunistic sightings at sea, beach stranding events and non-target capture in shark control programs. We evaluated the temporal and geographic distribution of records and assessed potential bias in observation opportunity based on human population density and fishery activity. Based on 1073 leatherback observations from 1990 to 2022, we found that sightings were unevenly distributed right around Australia, encompassing longitudes from 105.4°E to 165.1°E and latitudes from 43.7°S to 10°S. In the extreme southeast of Australia, hotspots were apparent during December to March (austral summer). In temperate and subtropical latitudes to the west and east of Australia, hotspots appeared predominantly during June, July and August (austral winter), but were also apparent, albeit weaker, to the east in all other months. Our results confirm that the species is present around Australia in all months of the year and has a much wider geographic and offshore distribution around Australia than previously reported. Hence, we inferred that Australian waters are highly important for migrating and foraging leatherbacks from subpopulations breeding in the Pacific and Indian Oceans, all of which are at high risk of extinction, and we suggest that Australian management agencies have crucial roles in protecting these endangered animals.

Identifying migration routes and key habitats is critical for the management and conservation of migratory species. Tracking and stable isotope analysis (SIA), particularly of carbon (δ13C) and nitrogen (δ15N), are often used to study animal movements, with SIA particularly useful when animals move through isotopic gradients. Marine turtles are typically highly migratory, moving between nesting and foraging grounds often located 100s-1000s km apart. The flatback turtle Natator depressus is endemic to the Australian continental shelf. Satellite tracking (n = 44) and SIA (n = 33) of females nesting in eastern Queensland, Australia, were used to identify main foraging areas, describe intraspecific variation in the location of foraging areas, and determine if δ13C and/or δ15N values can be used to identify foraging regions. Although foraging grounds were widely dispersed, tracking identified 3 main foraging regions. SIA agreed with tracking, indicating foraging site fidelity. Generalized linear models and linear discriminant analysis (LDA) were used to estimate how well δ13C/δ15N and nesting sites can perform as indicators of broad foraging regions and to predict foraging regions for turtles with no tracking data. δ15N was a strong predictor of the foraging region. LDA correctly classified the foraging region of 94% of individuals and was suitable to predict foraging regions of untracked individuals. A strong negative linear relationship between turtle δ15N and foraging latitude indicates the presence of a δ15N isoscape along the eastern Queensland coast. This is the first demonstration of an isoscape for the region, which should be useful for studying and monitoring the habitat use of flatback turtles and other migratory species.

OBJECTIVE Clerkship grades are a component of determining a residency candidate's competitiveness. In 2017, the University of Minnesota Medical School's pediatric clerkship transitioned its standardized multiple-choice exam, the Aquifer Pediatrics Examination, to pass/fail with eligibility for honors being determined by clinical performance, not exam performance. We assessed the effect this change had on Aquifer exam performance and evaluated for correlation between Aquifer exam performance and clinical evaluation scores in order to gather insight into the validity of each type of assessment with respect to one another. METHODS We analyzed de-identified data from 750 medical students between the academic years of 2016 to 2017 and 2019 to 2020. Individual Aquifer exam scores were compared to individual clinical performance scores. Differences in exam performance before and after the transition to pass/fail were investigated with a two-sample t -test and Cohen's d for effect size. RESULTS No correlation was found between Aquifer exam scores and clinical performance scores. The mean Aquifer exam score prior to the transition to pass/fail was 80.02 ± 7.51 while the mean after the exam was made pass/fail was 77.8 ± 7.42. This difference was statistically significant ( P

To understand how turtles use the nesting habitat at Raine Island across a nesting season, and how the turtles respond to the restoration of the island’s dune systems, we identified 534 nesting events for 39 green turtles Chelonia mydas across 2 breeding seasons using data derived from satellite tags. Tracked turtles laid between 4 and 10 clutches of eggs. Patterns of nesting success varied between individuals, within and between seasons. Nesting success was higher in 2018-19 (57%) than 2017-18 (45%), and in both years, nesting success was lowest between October and early January (50%). The density of female turtles ashore was lower in 2018-19, and likely explains higher nesting success in 2018-19 because competition for nest space was lower. In 2017-18, females had more attempts per clutch, and the attempts were around 90 min longer. Consequently, energy required to lay a clutch of eggs in 2017-18 was significantly higher than in 2018-19, highlighting potential costs of lower nesting success rates on reproductive output. The area of beach re-profiled as an intervention in 2014 and 2017 was a nesting hotspot in 2017-18. However, in 2018-19, the area was not used to the same extent, and the nesting hotspot occurred on the north-eastern unaltered beach. Collectively, the tracking of turtles across the whole nesting season enabled us to assess overall beach use and nesting site fidelity of green turtles at Raine Island. Results will aid future planning and management of beach restoration activities at turtle nesting sites.

Sea turtles are found worldwide, with all 7 species considered species of conservation concern. The public has seen sea turtle rehabilitation centres as an important tool for conserving sea turtle populations. However, educating the public regarding threats to sea turtles and how they can minimise these threats by making a change in their own lives may be more beneficial than rehabilitation alone, in terms of the ability to restore turtle numbers. In order to determine the educational role of rehabilitation centres, 245 surveys were distributed at several Australian-based rehabilitation centres. The survey was in 2 parts. The first part collected information about visitor’s knowledge of threats, their willingness to pay for conservation, and socio-economic information. The second part determined what threats visitors had learned about, whether visitors would make a change to help support sea turtle conservation, and whether they would be willing to pay more for conservation following their visit. Overall, results showed that all visitors to the sea turtle rehabilitation centres were willing to make a change in their lives to help protect sea turtles. Additionally, the majority of visitors were willing to donate annually to sea turtle conservation. The extra revenue raised could be used for conservation purposes and further research to address the threats sea turtles face. Combining the opportunity for visitors to observe sea turtles up close and learn about threats and how they can be minimised at rehabilitation centres will assist in increasing population sizes and protecting them into the future.

Abstract A search is made for charged Higgs bosons predicted by Two-Higgs-Doublet extensions of the Standard Model (2HDM) using electron-positron collision data collected by the OPAL experiment at $\sqrt{s}=189\mbox{--}209\ \mbox{GeV}$ , corresponding to an integrated luminosity of approximately 600 pb−1. Charged Higgs bosons are assumed to be pair-produced and to decay into $\mathrm{q} \bar{\mathrm{q}}$ , τν τ or AW±. No signal is observed. Model-independent limits on the charged Higgs-boson production cross section are derived by combining these results with previous searches at lower energies. Under the assumption $\mathrm{BR} (\mathrm{H}^{\pm} \to \tau\nu_{\tau}) + \mathrm{BR} (\mathrm{H}^{\pm} \to \mathrm{q} \bar{\mathrm{q}}) = 1$ , motivated by general 2HDM type II models, excluded areas on the $[m_{\mathrm{H}^{\pm}} , \mathrm{BR} (\mathrm {H}^{\pm} \to \tau\nu_{\tau})]$ plane are presented and charged Higgs bosons are excluded up to a mass of 76.3 GeV at 95 % confidence level, independent of the branching ratio BR(H±→τν τ). A scan of the 2HDM type I model parameter space is performed and limits on the Higgs-boson masses $m_{\mathrm{H}^{\pm}}$ and m A are presented for different choices of tanβ.

To assess the suitability of asymmetric cyanine dyes for in vivo fluoro-optical molecular imaging, a comprehensive study on the influence of the number of negatively charged sulfonate groups governing the hydrophilicity of the DY-67x family of asymmetric cyanines was performed. Special attention was devoted to the plasma protein binding capacity and related pharmacokinetic properties. Four members of the DY-67x cyanine family composed of the same main chromophore, but substituted with a sequentially increasing number of sulfonate groups (n = 1−4; DY-675, DY-676, DY-677, DY-678, respectively), were incubated with plasma proteins dissolved in phosphate-buffered saline. Protein binding was assessed by absorption spectroscopy, gel electrophoresis, ultrafiltration, and dialysis. Distribution of dye in organs was studied by intraveneous injection of 62 nmol dye/kg body weight into mice (n = 12; up to 180 minutes postinjection) using whole-body near-infrared fluorescence imaging. Spectroscopic studies, gel electrophoresis, and dialysis demonstrated reduced protein binding with increasing number of sulfonate groups. The bovine serum albumin binding constant of the most hydrophobic dye, DY-675, is 18 times higher than that of the most hydrophilic fluorophore, DY-678. In vivo biodistribution analysis underlined a considerable influence of dye hydrophilicity on biodistribution and excretion pathways, with the more hydrophobic dyes, DY-675 and DY-676, accumulating in the liver, followed by strong fluorescence signals in bile and gut owing to accumulation in feces and comparatively hydrophilic DY-678-COOH accumulating in the bladder. Our results demonstrate the possibility of selectively controlling dye-protein interactions and, thus, biodistribution and excretion pathways via proper choice of the fluorophore's substitution pattern. This underlines the importance of structure-property relationships for fluorescent labels. Moreover, our data could provide the basis for the rationalization of future contrast agent developments.

The 4-slice CT that forms part of the GE Infinia Hawkeye-4 SPECT-CT scanner (Hawkeye) is evaluated against the diagnostic 16-slice CT that is incorporated in the GE Discovery ST PET-CT system (DST). The x-ray tube of the slow-rotating Hawkeye system (23 s/rotation) operates at approximately a third of the dose of diagnostic systems as used for conventional diagnostic imaging. Image reconstruction is optimized for low noise. High-contrast spatial resolution significantly falls behind diagnostic figures: the average of MTF50 and MTF10 (resolution where the MTF has fallen to 50% and 10%) is 2.8 ± 0.1 cm[?]1 for Hawkeye and 5.3 ± 0.1 cm[?]1 for the DST (standard reconstruction filters). Resolution in the direction of the couch movement (z coordinate) is governed by the fixed Hawkeye slice width of 5 mm. Reconstruction accuracy is found to be increased by reducing the default z increment from 4.4 mm to 2.2 mm. Low-contrast object detectability is superior compared with diagnostic systems operating in the Hawkeye dose range. In the diagnostic dose regime, however, small low-contrast details remain visible in DST that are not detectable with Hawkeye. Although not of diagnostic quality, the low-dose Hawkeye provides appropriate data for SPECT attenuation correction and anatomical localization capability. [ABSTRACT FROM AUTHOR]

Synthesis and characterization of MgxZr2−xN2 (0.5 ≤ x ≤ 1.8) thin films deposited by reactive magnetron co-sputtering in nitrogen plasma is reported. Composition measurements show that nitrides with low oxygen content (less than 1%) can be formed up to x = 1.0, at which point an increase in oxygen content is observed. Up to composition of x = 1.6 the MgxZr2−xN2 thin films form in a rocksalt-derived crystal structure, as revealed by X-ray diffraction measurements. At x > 1.6 the films rapidly oxidize. The lattice constant of the stoichiometric MgZrN2 composition is a = 4.537 Å, and only small changes in lattice parameter are observed with changing composition. Electrical conductivity decreases by several orders of magnitude with increasing Mg-content. The conductivity of Mg-rich (x ≥ 1) films increases with increasing measurement temperature, indicating semiconducting character of Mg-rich MgxZr2−xN2. Optical absorption measurements of these Mg-rich samples show a clear absorption onset at 1.8 eV, also indicative of semiconducting behavior. [ABSTRACT FROM AUTHOR]

Heterostructures unconstrained by epitaxy have generated considerable excitement due to the discovery of emergent properties—properties not found in either constituent. Heterostructures enable the surfaces on either side of two-dimensional (2D) layers to be used to systematically investigate phenomena such as superconductivity and magnetism in the 2D limit. The ability to choose constituents facilitates the prediction of emergent properties created by the unusual coordination environments at incommensurate interfaces. There have already been many reviews on heterostructures, focusing on a variety of topics that reflect the diverse interest in this area as well as the potential for new technologies. Hence this review focuses mainly on the synthesis and structural characterization of heterostructures containing transition metal dichalcogenides (TMD). This review only briefly discusses 2D materials and TMD/TMD heterostructure devices and the performances that have been achieved. This review provides a historical context for the rapid development of this field and discusses proposed mechanisms for emergent properties. Up to now, the materials used in heterostructures have mainly been materials with 2D structures, as these compounds can be easily cleaved into ultrathin layers. This review discusses the expansion of heterostructure constituents to include materials that do not have 2D structures. Structural changes and charge redistribution between adjacent (or even more distant) layers are likely to be larger for 3D constituents than with 2D constituents based on known misfit layer compounds. Systematic changes in properties with layer thickness, layer sequences, and the identity of constituents will increase our understanding of emergent properties and how they can be optimized. [ABSTRACT FROM AUTHOR]

Purpose: Intracranial hemorrhage (ICH) is a life-threatening condition requiring rapid diagnostic and therapeutic action. This study evaluates whether Artificial intelligence (AI) can provide high-quality ICH diagnostics and turnaround times suitable for routine radiological practice., Methods: A convolutional neural network (CNN) was trained and validated to detect ICHs on DICOM images of cranial CT (CCT) scans, utilizing about 674,000 individually labeled slices. The CNN was then incorporated into a commercial AI engine and seamlessly integrated into three pilot centers in Germany. A real-world test-dataset was extracted and manually annotated by two experienced experts. The performance of the AI algorithm against the two raters was assessed and compared to the inter-rater agreement. The overall time ranging from data acquisition to the delivery of the AI results was analyzed., Results: Out of 6284 CCT examinations acquired in three different centers, 947 (15%) had ICH. Breakdowns of hemorrhage types included 8% intraparenchymal, 3% intraventricular, 6% subarachnoidal, 7% subdural, < 1% epidural hematomas. Comparing the AI's performance on a subset of 255 patients with two expert raters, it achieved a sensitivity of 0.90, a specificity of 0.96, an accuracy of 0.96. The corresponding inter-rater agreement was 0.84, 0.98, and 0.96. The overall median processing times for the three centers were 9, 11, and 12 min, respectively., Conclusion: We showed that an AI algorithm for the automatic detection of ICHs can be seamlessly integrated into clinical workflows with minimal turnaround time. The accuracy was on par with radiology experts, making the system suitable for routine clinical use., Competing Interests: Conflict of interest: L. Spies as owner of jung diagnostics GmbH has potential financial interest in this study. K. Villringer, R. Sokiranski, R. Opfer, M. Hamann, A. Bormann, M. Brehmer, I. Galinovic and J.B. Fiebach declare that they have no competing interests., (© 2024. The Author(s).)

Purpose: To analyze complications and potential risk factors associated with immediate prepectoral direct-to-implant breast reconstruction (DTIBR)., Methods: 295 patients (326 operated breasts) with DTIBR between March 2021 and December 2023 were included in this prospective study. Postoperative complications (postoperative bleeding, seroma, infection, necrosis, wound dehiscence, implant exchange/loss) were analyzed for potential risk factors by descriptive and logistic regression analyses., Results: The implant was covered by TiLOOP® Bra Pocket in 227 breasts (69.6%), by "dual-plane" technique in 20 breasts (6.1%), by acellular dermal matrix (ADM) in 1 breast (0.3%). No additional support was used for 78 breasts (23.9%). The use of mesh did not increase the risk for complications. Major complications requiring surgical revision occurred due to postoperative bleeding in 22 (6.7%), seroma in 2 (0.6%), infection in 13 (4.0%), necrosis in 10 (3.1%), and wound dehiscence in 10 (3.1%) breasts. Thirteen (4.0%) implants were exchanged, and 5 (1.5%) were explanted without substitution. One patient had to switch to autologous reconstruction due to skin necrosis. The main reasons for the removal/exchange of implants were infections (11 breasts, 3.4%) and necrosis (4 breasts, 1.2%). The risk for necrosis, infection, and wound dehiscence was mainly associated with the type of incision, especially skin-reducing incisions, and body mass index (BMI) ≥ 30 kg/m 2 ., Conclusion: Severe complications occurred primarily in patients with a BMI ≥ 30 kg/m 2 and when skin-reducing surgical techniques were performed., Trial Registry: This study was retrospectively registered at the German Clinical Trials Register (DRKS) on 20.06.2024., Drks-Id: DRKS00034493. https://drks.de/search/de/trial/DRKS00034493 ., Competing Interests: Declarations. Conflict of interest: E Bensmann received support from pfm medical GmbH, Applied Medical Germany GmbH, and Polytech Health & Aesthetics GmbH for a surgical workshop at the Department of Gynecology, Breast Center, Red Cross Hospital, Munich, Germany. A Andrulat was principal investigator of the PRO-Pocket study (Sponsor pfm medical GmbH). All other authors have no relevant financial or non-financial interests to disclose. Consent to participate: Informed consent was obtained from all individual participants included in the study. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Technical University Munich (25.11.2020; 660/20 S-EB)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To investigate the sensitivity of fluorescence lifetime imaging ophthalmoscopy (FLIO) to detect retinal laser spots by comparative analysis with other imaging modalities., Methods: A diode laser with a wavelength of 514 nm was applied with pulse durations of 5.2, 12, 20, and 50 µs. The laser pulse energy was increased so that the visibility of the laser spot by slit-lamp fundus examination (SL) under the irradiator's observation covers from the subvisible to visible range immediately after irradiation. The irradiated areas were then examined by fundus color photography (FC), optical coherence tomography (OCT), fundus autofluorescence (AF), FLIO, and fluorescein angiography (FA). The visibility of a total of over 2200 laser spots was evaluated by two independent researchers, and effective dose (ED) 50 laser pulse energy values were calculated for each imaging modality and compared., Results: Among examined modalities, FA showed the lowest mean of ED50 energy value and SL the highest, that is, they had the highest and lowest sensitivity to detect retinal pigment epithalium (RPE)-selective laser spots, respectively. FLIO also detected spots significantly more sensitively than SL at most laser pulse durations and was not significantly inferior to FA. AF was also often more sensitive than SL, but the difference was slightly less significant than FLIO., Conclusion: Considering its high sensitivity in detecting laser spots and previously reported potential of indicating local wound healing and metabolic changes around laser spots, FLIO may be useful as a non-invasive monitoring tool during and after minimally invasive retinal laser treatment., (© 2024. The Author(s).)

This article presents a checklist of metazoan parasites of snakes from Argentina, along with a comprehensive review of the relevant literature published between 1922 and June 2023, covering various aspects of interest. We compiled 34 species of metazoan endoparasites from 28 studies. The subclass Digenea showed the highest number of species (n = 22 species), followed by the phylum Nematoda (n = 8 species), and the subclass Pentastomida (n = 3 species and 1 taxa inquirenda ). Dipsadidae was the family of snakes with the most species examined for metazoan endoparasites (n = 20 species). In contrast, Viperidae had the largest number of specimens surveyed (n = 343). Of 23 provinces, 15 (65.2%) presented at least one report of metazoan endoparasites in snakes. The northeastern provinces showed the highest richness of metazoan endoparasites and host diversity. Many articles focused on taxonomy, but studies on parasite ecology were not found. Although taxonomic accuracy was high in most reports, some records were correctly deposited in zoological collections or geo-referenced. This is the first attempt to include all groups of metazoan endoparasites of snakes from Argentina in a single checklist in the last century.

Purpose: Boswellic acids, active components of frankincense, suppress tumor proliferation in vitro with a strong clinical trial safety profile in patients with inflammatory diseases. We performed a Phase Ia window of opportunity trial of Boswellia serrata (B. serrata) in patients with breast cancer to evaluate its biologic activity and safety., Methods: Patients with invasive breast cancer were treated pre-operatively with B. Serrata (2400 mg/day PO) until the night before surgery for a median of 11 days (SD 6 days; range: 5-23 days). Paraffin-embedded sections from pretreatment diagnostic core biopsies and post-treatment surgical excisions were evaluated using a tunnel assay and immunohistochemistry staining with Ki-67 antibodies. A non-intervention retrospective control arm consisting of core and surgical tissue specimens from untreated patients was used to compare patients treated with B. Serrata. The change in proliferation and apoptosis between diagnostic core specimens and surgical specimens was compared between the control and treatment groups using a two-tailed paired t-test., Results: Twenty-two patients were enrolled, of which 20 received treatment, and 18 had sufficient tissue for IHC. There was an increase in percent change in proliferation from core biopsy to surgical excision in the control group (n = 18) of 54.6 ± 21.4%. In the B. serrata-treated group there was a reduction in proliferation between core biopsy and excision (n = 18) of 13.8 ± 11.7%. This difference was statistically significant between the control and B. serrata-treated groups (p = 0.008). There was no difference in change in apoptosis. There were no serious adverse events related to the drug., Conclusion: Boswellia serrata inhibited breast cancer proliferation and was well-tolerated in a Phase Ia window of opportunity trial., (© 2024. The Author(s).)

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species' population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate 'intactness scores': the remaining proportion of an 'intact' reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region's major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems., (© 2024. The Author(s).)

Background: The handling of fireworks regularly leads to a variety of injuries affecting the periocular region. Due to the COVID-19 lockdown and a sales ban on consumer fireworks for the private sector the number of injuries massively decreased; however, a considerable increase was registered again at the last New Year festivities. The aim of this work was to present the extent and spectrum of such injuries in a maximum care center., Methods: As part of the nationwide survey of firework-associated eye injuries in emergency care eye clinics and hospitals, data from the MHH Eye Hospital in Hannover were compiled over the period of 3 days (30.12.2022-01.01.2023) and evaluated with respect to gender, age, severity, injury pattern, type of fireworks and treatment., Results: Of a total of n = 25 injured patients, n = 19 (76%) were male. Most patients presented on New Year's Day (n = 14, New Year's Eve: n = 9; 30.12.2022: n = 2), with the majority of cases presenting with mild injuries with irritation and erosion of the ocular surface (n = 15; 60%). Of the patients four sustained moderate to severe injuries with bulbar contusion, hyphema, and sometimes iris base tears (16%). Of the patients six suffered severe, mainly open, eye injuries (24%), two of which required primary evisceration. Ignition of fireworks batteries revealed the highest risk of serious injury, affecting mainly males 31-40 years of age. Children up to 12 years of age generally sustained only minor injuries, although there were exceptions as there were among adolescents. The person who caused the fireworks injury was affected in about 52% of the cases; in 48% the victim of the accident was a bystander. In cases of complex injuries, under certain conditions only surgical exploratory diagnostics could lead to the correct diagnosis and best possible care., Conclusion: The extent of firework injuries is manifold and the consequences including blindness are considerable. The burden on physicians on duty on New Year's Eve and New Year's Day was enormous, as with the permission of private fireworks a large number of patients had to be cared for via the emergency room, some of whom required complex surgical care. To prevent serious eye injuries, targeted education about the risks of private fireworks and possibilities to increase safety should be intensified., (© 2023. The Author(s).)

Managers in the healthcare system play a critical role in ensuring high quality patient care, optimization of resources, management of complex situations, creation of a positive work environment and promotion of continuous progress. They set clear goals, support interdisciplinary collaboration, ensure patient safety and quality care, and assist in the development of future leaders. To accomplish these multiple tasks, important qualities such as integrity, communication skills, self-awareness, ability to learn, influence, empathy, courage, respect, ability to delegate and gratitude are essential. We conducted a survey among the followers and members of the Young-DOG to find out their desired characteristics of leaders. In this survey modern aspects of leadership styles such as communication, loyalty, support, reliability and trust were particularly important to young medical professionals. Classical attributes such as expertise and assertiveness were rated as somewhat less significant. This finding underlines the importance of leadership programs such as the Leadership Academy of the German Society of Ophthalmology (DOG) or the European Leadership Development Program of the European Society of Ophthalmology (SOE). The latter is briefly presented in an excursus., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Contrast-enhancing (CE) lesions are an important finding on brain magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) but can be missed easily. Automated solutions for reliable CE lesion detection are emerging; however, independent validation of artificial intelligence (AI) tools in the clinical routine is still rare., Methods: A three-dimensional convolutional neural network for CE lesion segmentation was trained externally on 1488 datasets of 934 MS patients from 81 scanners using concatenated information from FLAIR and T1-weighted post-contrast imaging. This externally trained model was tested on an independent dataset comprising 504 T1-weighted post-contrast and FLAIR image datasets of MS patients from clinical routine. Two neuroradiologists (R1, R2) labeled CE lesions for gold standard definition in the clinical test dataset. The algorithmic output was evaluated on both patient- and lesion-level., Results: On a patient-level, recall, specificity, precision, and accuracy of the AI tool to predict patients with CE lesions were 0.75, 0.99, 0.91, and 0.96. The agreement between the AI tool and both readers was within the range of inter-rater agreement (Cohen's kappa; AI vs. R1: 0.69; AI vs. R2: 0.76; R1 vs. R2: 0.76). On a lesion-level, false negative lesions were predominately found in infratentorial location, significantly smaller, and at lower contrast than true positive lesions (p < 0.05)., Conclusions: AI-based identification of CE lesions on brain MRI is feasible, approaching human reader performance in independent clinical data and might be of help as a second reader in the neuroradiological assessment of active inflammation in MS patients., Critical Relevance Statement: Al-based detection of contrast-enhancing multiple sclerosis lesions approaches human reader performance, but careful visual inspection is still needed, especially for infratentorial, small and low-contrast lesions., (© 2023. The Author(s).)

Introduction: Elderly patients after hospitalisation for acute events on account of age-related diseases (eg, joint or heart valve replacement surgery) are often characterised by a remarkably reduced functional health. Multicomponent rehabilitation (MR) is considered an appropriate approach to restore the functioning of these patients. However, its efficacy in improving functioning-related outcomes such as care dependency, activities of daily living (ADL), physical function and health-related quality of life (HRQL) remains unclarified. We outline the research framework of a scoping review designed to map the available evidence of the effects of MR on the independence and functional capacity of elderly patients hospitalised for age-related diseases in four main medical specialties beyond geriatrics., Methods and Analysis: The biomedical databases (PubMed, Cochrane Library, ICTRP Search Platform, ClinicalTrials) and additionally Google Scholar will be systematically searched for studies comparing centre-based MR with usual care in patients ≥75 years of age, hospitalised for common acute events due to age-related diseases (eg, joint replacement, stroke) in one of the specialties of orthopaedics, oncology, cardiology or neurology. MR is defined as exercise training and at least one additional component (eg, nutritional counselling), starting within 3 months after hospital discharge. Randomised controlled trials as well as prospective and retrospective controlled cohort studies will be included from inception and without language restriction. Studies investigating patients <75 years, other specialties (eg, geriatrics), rehabilitation definition or differently designed will be excluded. Care dependency after at least a 6-month follow-up is set as the primary outcome. Physical function, HRQL, ADL, rehospitalisation and mortality will be additionally considered. Data for each outcome will be summarised, stratified by specialty, study design and type of assessment. Furthermore, quality assessment of the included studies will be performed., Ethics and Dissemination: Ethical approval is not required. Findings will be published in a peer-reviewed journal and presented at national and/or international congresses., Trial Registration Number: https://doi.org/10.17605/OSF.IO/GFK5C., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Plastics, and more specifically, microplastics (MPs, <5 mm) are considered a marine contaminant of emerging concern. To accurately assess the ecological risk of MPs, it is critical to first understand the relationship between MP contamination in organisms with that in their surrounding environment. The goal of this study was to examine the ecological risk of MPs in coral reef ecosystems by assessing the MP contamination found within a simple food web against contamination in the surrounding environment. Taxa representing three trophic levels (zooplankton, benthic crustaceans, and reef fish), as well as the distinct environmental matrices which they inhabit (i.e., mid-column water and sediment) were collected from two mid-shelf reefs in the central Great Barrier Reef, Australia. Microplastics were isolated using validated clarification techniques, visually characterised (i.e., shape, colour, size) by microscopy, chemically confirmed by Fourier transform infrared spectroscopy and recorded in all three trophic levels and all abiotic samples. MPs were found to bioconcentrate, with similar concentrations, polymer types, sizes, shapes, and colours at each trophic level compared to their surrounding environment. However, MP contamination varied across the three trophic levels, with no evidence of bioaccumulation. Further, MP concentrations did not increase up the food web, discounting MP biomagnification. Regardless, given the heterogeneity of MPs found in the marine environment, and the complexity of marine food webs, trophic transfer represents a prominent pathway of exposure from lower to higher trophic levels., Competing Interests: Declaration of competing interest The authors declare that no competing interests exist., (Copyright © 2022. Published by Elsevier B.V.)

Despite a growing understanding of the importance of knowledge co-production for just and sustainable urban transformations, early career green infrastructure experts typically lack opportunities to practice transdisciplinary knowledge co-production approaches within their normal training and professional development. However, using online collaboration technologies combined with peer- and problem-based learning can help address this gap by putting early career green infrastructure experts in charge of organizing their own knowledge co-production activities. Using the case study of an online symposia series focused on social-ecological-technological systems approaches to holistic green infrastructure implementation, we discuss how critical pedagogical designs help create favorable conditions for transdisciplinary knowledge co-production. Our work suggests that the early career position offers a unique standpoint from which to better understand the limitations of current institutional structures of expertise, with a view towards their transformation through collective action., Supplementary Information: The online version contains supplementary material available at 10.1186/s42854-023-00051-1., Competing Interests: Competing interestsNone to declare., (© The Author(s) 2023.)

Hypothesis: The morphology of ordinary macro-emulsions is controlled by their high interfacial energies, i.e., by capillarity, leading to well-known structural features which can be tuned only over a narrow range. We claim here that a more explicit control over a much wider range of morphologies can be obtained by producing "elastocapillary emulsions" in which interfacial elasticity acts simultaneously with interfacial tension., Experiments: We develop a model-system composed of PEG-in-PDMS emulsions, in which a catalyst diffuses from the PEG drops into the silicone matrix containing two reactive silicone polymers, which are cross-linked in a non-reactive silicone matrix to form a silicone gel of controlled thickness and mechanical properties on the drop surface. We characterise the cross-linking process of the gel in bulk and at the interface, and we analyse the skin growth kinetics. We then use the obtained understanding to produce emulsions with controlled elastocapillary interfaces using in-flow-chemistry in a purpose-designed millifluidic circuit., Findings: We show that this approach allows to create interfaces over the full range of elastocapillary properties, and that very different emulsion morphologies can be generated depending on whether capillarity or elasticity dominates. These findings advance our fundamental understanding of the morphology of emulsions with complex interfaces, and they are of importance for the design of polymerised High Internal Phase Emulsions (polyHIPEs) with original structure/property relations. They will also be useful for the design of silicone capsules with fine-tuned mechanical properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Manzamine-A is a marine-derived alkaloid which has anti-viral and anti-proliferative properties and is currently being investigated for its efficacy in the treatment of certain viruses (malaria, herpes, HIV-1) and cancers (breast, cervical, colorectal). Manzamine-A has been found to exert effects via modulation of SIX1 gene expression, a gene critical to craniofacial development via the WNT, NOTCH, and PI3K/AKT pathways. To date little work has focused on Manzamine-A and how its use may affect bone. We hypothesize that Manzamine-A, through SIX1, alters bone cell activity. Here, we assessed the effects of Manzamine-A on cells that are responsible for the generation of bone, pre-osteoblasts and osteoblasts. PCR, qrtPCR, MTS cell viability, Caspase 3/7, and functional assays were used to test the effects of Manzamine-A on these cells. Our data suggests Six1 is highly expressed in osteoblasts and their progenitors. Further, osteoblast progenitors and osteoblasts exhibit great sensitivity to Manzamine-A treatment exhibited by a significant decrease in cell viability, increase in cellular apoptosis, and decrease in alkaline phosphatase activity. In silico binding experiment showed that manzamine A potential as an inhibitor of cell proliferation and survival proteins, i.e., Iκb, JAK2, AKT, PKC, FAK, and Bcl-2. Overall, our data suggests Manzamine-A may have great effects on bone health overall and may disrupt skeletal development, homeostasis, and repair.

The globally widespread adoption of Artificial Light at Night (ALAN) began in the mid-20th century. Yet, it is only in the last decade that a renewed research focus has emerged into its impacts on ecological and biological processes in the marine environment that are guided by natural intensities, moon phase, natural light and dark cycles and daily light spectra alterations. The field has diversified rapidly from one restricted to impacts on a handful of vertebrates, to one in which impacts have been quantified across a broad array of marine and coastal habitats and species. Here, we review the current understanding of ALAN impacts in diverse marine ecosystems. The review presents the current state of knowledge across key marine and coastal ecosystems (sandy and rocky shores, coral reefs and pelagic) and taxa (birds and sea turtles), introducing how ALAN can mask seabird and sea turtle navigation, cause changes in animals predation patterns and failure of coral spawning synchronization, as well as inhibition of zooplankton Diel Vertical Migration. Mitigation measures are recommended, however, while strategies for mitigation were easily identified, barriers to implementation are poorly understood. Finally, we point out knowledge gaps that if addressed would aid in the prediction and mitigation of ALAN impacts in the marine realm., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Background: Enhanced recovery after surgery (ERAS) protocols are utilizing a multidisciplinary approach, reassessing physiology to improve clinical outcomes, reducing length of hospital stay (LOS) stay, resulting in cost reduction. Since its introduction in colorectal surgery. the concept has been utilized in various fields and benefits have been recognized also in adult cardiac surgery. However, ERAS concepts in pediatric cardiac surgery are not yet widely established. Therefore, the aim of the present study was to assess the effects of on-table extubation (OTE) after pediatric cardiac surgery compared to the standard approach of delayed extubation (DET) during intensive care treatment. Study Design and Methods: We performed a retrospective analysis of all pediatric cardiac surgery cases performed in children below the age of two years using cardiopulmonary bypass at our institution in 2021. Exclusion criteria were emergency and off pump surgeries as well as children already ventilated preoperatively. Results: OTE children were older (267.3 days vs. 126.7 days, p < 0.001), had a higher body weight (7.0 ± 1.6 kg vs. 4.9 ± 1.9 kg, p < 0.001), showed significantly reduced duration of ICU treatment (75.9 ± 56.8 h vs. 217.2 ± 211.4 h, p < 0.001) and LOS (11.1 ± 10.2 days vs. 20.1 ± 23.4 days; p = 0.001) compared to DET group. Furthermore, OTE children had significantly fewer catecholamine dependencies at 12-, 24-, 48-, and 72-h post-surgery, while DET children showed a significantly increased intrafluid shift relative to body weight (109.1 ± 82.0 mL/kg body weight vs. 63.0 ± 63.0 mL/kg body weight, p < 0.001). After propensity score matching considering age, weight, bypass duration, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality (STATS)-Score, and the outcome variables, including duration of ICU treatment, catecholamine dependencies, and hospital LOS, findings significantly favored the OTE group. Conclusion: Our results suggest that on-table extubation after pediatric cardiac surgery is feasible and in our cohort was associated with a favorable postoperative course.

Plastic pollution is ubiquitous within the marine environment, including surface waters, water column and benthic sediments. Marine plastic contamination is expected to increase if future projections of increased plastic production eventuate. Conversely, national and international efforts are aiming to reduce marine plastic contamination. In this context, scientists, managers and the general public are increasingly interested in understanding the status and temporal trends of plastic contamination in the marine environment. Presented here is the first temporal assessment of plastic contamination in surface waters of the Great Barrier Reef (GBR), Australia. Specifically, duplicate surface seawater samples (n = 66) were collected at the SS Yongala shipwreck (Central GBR) monthly from September 2016 to September 2019 and analysed for plastic presence and abundance. The processing workflow involved density separation, followed by filtration, visual identification and sizing of putative plastics using stereomicroscopy, and chemical characterisation using Fourier transform infrared spectroscopy. A total of 533 plastic items were identified across all tows, consisting of macro-, meso- and microplastic fragments and fibres, with polypropylene and polyethylene being the most common polymers. Plastic contamination was detected in every replicate tow, bar one. Plastic concentrations fluctuated and spiked every three months, although contamination did not significantly alter across the three-year period. Wind speed, salinity and river discharge volume, but not surface current speed nor sea surface temperature, had a significant influence on the levels of plastic contamination. This study reveals, for the first time, the chronic presence of plastic debris in the surface waters of the GBR highlighting the need for long-term and on-going monitoring of the marine environment for plastic contamination., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Background: Several leech species of the genera Hirudo, Hirudinaria, and Whitmania are widely used in traditional Chinese medicine (TCM) for the oral treatment of disorders associated with blood stasis. Among them, the non-hematophagous leech Whitmania pigra expresses a variety of components that have the potential to act on the vertebrate blood coagulation system., Objective: Whether the thrombin inhibitor hirudin, probably the most prominent leech-derived anticoagulant, is actually present in Whitmania pigra, is still a matter of debate. To answer that open question was the aim of the study., Methods: We identified several putative hirudin-encoding sequences in transcriptome data of Whitmania pigra. Upon gene synthesis and molecular cloning the respective recombinant proteins were expressed in Escherichia coli, purified, processed, and eventually functionally characterized for thrombin-inhibitory potencies in coagulation assays., Results: We were successful in the identification and functional characterization of several putative hirudins in Whitmania pigra. Some, but not all, of these factors are indeed thrombin inhibitors. Whitmania pigra hence expresses both hirudins (factors that inhibit thrombin) and hirudin-like factors (that do not or only very weakly inhibit thrombin). Furthermore, we revealed the exon/intron structures of the corresponding genes. Coding sequences of some putative hirudins of Whitmania pigra were present also in transcriptome datasets of Hirudo nipponia, a hematophagous leech that is likewise used in TCM., Conclusions: Based on both structural and functional data we provide very strong evidence for the expression of hirudins in Whitmania pigra. This is the first description of hirudins in a non-hematophagous leech., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Introduction: The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX®) in patients with 0-3 lymph nodes in a high-volume community hospital., Methods: Patients with non-metastatic HR*/HER2- EBC and 0-3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX® testing were included in this retrospective study. The distribution of clinicopathologic characteristics, recurrence score (RS) risk, and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease-free survival (DFS) and overall survival (OS) were estimated., Results: From 2012 to 2017 ODX® was consecutively performed in 575 (16.4%) of 3,492 women with HR*/HER- EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had an RS of 0 to 25 and 112 (20.3%) had an RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5-year DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p = 0.101) or OS (97.2% vs. 96.0%; p = 0.737) for patients with an RS of 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status., Conclusions: The results of the study confirm the observations from randomized studies on the use of the ODX® in a real-world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR*/HER2- breast cancer with 0-3 positive lymph nodes and RS <25., Competing Interests: M.B. received personal fees (lectures and/or consulting and travel support) from Astra Zeneca, Celgene, Daiichi Sankyo, Exact Sciences, MSD, Novartis, Pfizer, Puma, Roche, Teva; A.A. reports personal fees for lecture honoraria from Astra Zeneca, Exact Sciences, and Roche; M.P. reports personal fees for serving on advisory boards and lecture honoraria from AstraZeneca, Glaxo Smith Cline, Teva, Clovis, and Roche. C.H. reports personal fees for serving on advisory boards and lecture honoraria from Lilly, Novartis, and Roche; A.K., N.S., S.S., M.K., M.H., and O.S. are reporting no general conflict of interest., (Copyright © 2021 by S. Karger AG, Basel.)

The multidrug resistance gene MDR1 (syn. ABCB1) encodes for the multidrug efflux transporter P-glycoprotein (P-gp), which is highly expressed at the blood-brain barrier and protects the brain from potentially neurotoxic compounds, such as ivermectin. MDR1 mutation in dogs is known to be linked to dramatically increased brain accumulation of ivermectin and life-threatening neurological toxicity. The present report describes two suspected ivermectin-sensitive Maine Coon cats, which exhibited neurological toxicity following subcutaneous application of therapeutic doses of ivermectin. Both cats showed a homozygous 2-bp deletion in the MDR1/ABCB1 coding sequence ( ABCB1 1930&#95;1931del TC, syn. MDR1 nt1930(del2)) that had previously been associated with a drug-sensitive phenotype in cats. For cat MDR1 genotyping, a novel TaqMan allelic discrimination assay was established and validated. This assay was used for ABCB1 1930&#95;1931del TC genotyping of the drug-sensitive cats as well as of more than 50 relatives. About half of them had the heterozygous MDR1(+/-) genotype, while none of these related cats with former ivermectin treatment had a history of drug-sensitivity. In conclusion: The present study supports previous findings on drug-sensitivity in cats with homozygous ABCB1 1930&#95;1931del TC mutation. The newly established TaqMan allelic discrimination assay provides a useful and reliable method for routine MDR1 genotyping in cats in order to identify drug-sensitive cats prior to treatment with established P-gp substrates such as ivermectin and other macrocyclic lactones and thus to improve therapeutic safety., Competing Interests: The authors declare that nt230(del4) MDR1 genotyping in dogs is a for-profit licensed and patent-protected diagnostic service of their host institute offered via TransMIT GmbH Center for Pharmacogenetic Diagnostics (PGvet). Joachim Geyer is head of PGvet. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nürnberger, Wagner, Müller, Leiting, Leidolf, Alber, Hamann and Geyer.)

Wildlife health assessments help identify populations at risk of starvation, disease, and decline from anthropogenic impacts on natural habitats. We conducted an overview of available health assessment studies in noncaptive vertebrates and devised a framework to strategically integrate health assessments in population monitoring. Using a systematic approach, we performed a thorough assessment of studies examining multiple health parameters of noncaptive vertebrate species from 1982 to 2020 (n = 261 studies). We quantified trends in study design and diagnostic methods across taxa with generalized linear models, bibliometric analyses, and visual representations of study location versus biodiversity hotspots. Only 35% of studies involved international or cross-border collaboration. Countries with both high and threatened biodiversity were greatly underrepresented. Species that were not listed as threatened on the International Union for Conservation of Nature Red List represented 49% of assessed species, a trend likely associated with the regional focus of most studies. We strongly suggest following wildlife health assessment protocols when planning a study and using statistically adequate sample sizes for studies establishing reference ranges. Across all taxa blood analysis (89%), body composition assessments (81%), physical examination (72%), and fecal analyses (24% of studies) were the most common methods. A conceptual framework to improve design and standardize wildlife health assessments includes guidelines on the experimental design, data acquisition and analysis, and species conservation planning and management implications. Integrating a physiological and ecological understanding of species resilience toward threatening processes will enable informed decision making regarding the conservation of threatened species., (© 2021 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Aged rodents have been used as preclinical models of age-associated cognitive decline. Most of those models displayed substantial impairments in learning and memory. The initial, more subtle changes that precede more severe losses in cognitive abilities have not been well characterized. Here, we established a model detecting initial subtle cognitive changes by comparing the performance of moderately aged Oncins France Strain A Sprague Dawley rats with young rats in the Morris water maze (MWM) and the Open Field (OF) test. Both age groups improved their performance during the training period at a similar rate; however, the older rats performed worse in several parameters measured in the MWM. Our results suggest that already at the age of 18-20 months rats show changes in their approach to solve the spatial memory task while their ability to learn is not yet diminished. The disparate spatial information processing of the moderately aged rats provides a novel animal model for early age-related cognitive alterations that could be useful to test the effect of early intervention strategies. Moreover, our results suggest that the sensitivity of cognitive tests in the elderly could be substantially enhanced if they assess both the improvement after several trials, and the strategy used to solve a certain task., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort., Material and Methods: The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed., Results: The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; p = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR >2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; p = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; p = 0.014)., Conclusion: In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation., Competing Interests: O.G.W., G.S., R.N., and M.A. are employees of Therawis Diagnostics. J.P. is an employee of QIAGEN. O.G.W., R.N., M.A., V.M., M.K., and G.S. are equity owners of Therawis Diagnostics GmbH. W.W. is a member of the following advisory boards: AstraZeneca, Novartis, BMS, MSD, Roche, Pfizer, and Takeda. This work was in part performed under a research agreement supported by Therawis Diagnostics. W.W. has attended advisory boards and served as speaker for Roche, MSD, BMS, AstraZeneca, Pfizer, Merck, Lilly, Boehringer, Novartis, Takeda, Amgen, and Astellas. W.W. receives research funding from Roche, MSD, BMS, and Bruker. M.K. received remuneration for advisory boards, travel costs, and lectures from Celgene, Astra Zeneca, Myriad Genetics, and TEVA. M.H., G.A., K.U., and A.W. report no conflict of interests., (Copyright © 2020 by S. Karger AG, Basel.)

Spontaneous subthreshold activity in the central nervous system is fundamental to information processing and transmission, as it amplifies and optimizes sub-threshold signals, thereby improving action potential initiation and maintaining reliable firing. This form of spontaneous activity, which is frequently considered noise, is particularly important at auditory synapses where acoustic information is encoded by rapid and temporally precise firing rates. In contrast, when present in excess, this form of noise becomes detrimental to acoustic information as it contributes to the generation and maintenance of auditory disorders such as tinnitus. The most prominent contribution to subthreshold noise is spontaneous synaptic transmission (synaptic noise). Although numerous studies have examined the role of synaptic noise on single cell excitability, little is known about its pre-synaptic modulation owing in part to the difficulties of combining noise modulation with monitoring synaptic release. Here we study synaptic noise in the auditory brainstem dorsal cochlear nucleus (DCN) of mice and show that pharmacological potentiation of Kv3 K + currents reduces the level of synaptic bombardment onto DCN principal fusiform cells. Using a transgenic mouse line (SyG37) expressing SyGCaMP2-mCherry, a calcium sensor that targets pre-synaptic terminals, we show that positive Kv3 K + current modulation decreases calcium influx in a fifth of pre-synaptic boutons. Furthermore, while maintaining rapid and precise spike timing, positive Kv3 K + current modulation increases the synchronization of local circuit neurons by reducing spontaneous activity. In conclusion, our study identifies a unique pre-synaptic mechanism which reduces synaptic noise at auditory synapses and contributes to the coherent activation of neurons in a local auditory brainstem circuit. This form of modulation highlights a new therapeutic target, namely the pre-synaptic bouton, for ameliorating the effects of hearing disorders which are dependent on aberrant spontaneous activity within the central auditory system., Competing Interests: NP was employed by company Autifony Srl. CL was employed by company Autifony Therapeutics Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 OIsen, Capurro, Švent, Pilati, Large, Hartell and Hamann.)

Background: Molecular profiling of breast cancer (BC) classifies several intrinsic subtypes based on different patterns of gene expression. Multigene assays estimate the risk of recurrence and help to select high-risk patients for adjuvant chemotherapy. However, these tests are associated with significant costs. Immunohistochemistry (IHC) offers a surrogate classification for molecular subtypes by determining estrogen (ER) and progesterone receptors (PR), human epidermal growth factor (Her2neu), as well as the proliferation marker Ki67. Core needle biopsy (CNB) is well established in BC diagnosis and allows a pre-operative assessment of biomarkers. The aim of this study was to analyze the concordance of these markers between CNB and surgical specimens to assess whether re-testing of the surgical specimen is mandatory., Materials and Methods: Within a 3-year period, patients with primary BC and paired samples of CNB and surgical specimens were analyzed retrospectively. Concordance rates of ER, PR, Her2neu, Ki67, and the surrogate classification for molecular subtypes were calculated using the Landis and Koch agreement grades., Results: Out of 2254 patients with primary breast cancer, 1307 paired specimens without pre-operative treatment were available for analysis Concordance rates for ER, PR, Her2neu, and Ki67 status showed substantial-to-almost perfect agreement grades (κ = 0.91, 0.75, 0.89, and 0.61, respectively). Though substantial concordance was also found for the subtype classification (κ = 0.70), the molecular subtype changed in 18.5% of patients based on the testing of the surgical specimen, mainly from luminal A-like to luminal B-like., Conclusions: Though the concordance rates for single markers were convincing, a significant proportion of the molecular subtypes differed between CNB and the surgical specimen. Re-testing of PR and Ki67 is mandatory to ensure optimal treatment decisions. Further research is necessary to define safe, efficient, and cost-effective predictive models in adjuvant breast cancer therapy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Microplastics (MPs) have been identified as a threat to global ecosystems. Current projections indicate that the negative impacts of MPs will increase in the environment. Traditional toxicity testing does not account for the diversity of MP particles, the inherent diversity in potential exposure routes, and complex impacts in exposed organisms. Here we present and discuss factors influencing organismal exposure to MPs driven by fate and behavior of MPs in different environmental matrices and organisms behavioral niches. We then provide a structured classification of potential effects of MPs, chemical or particulate, generic or specific to MPs. Using these analyses, we discuss appropriateness and limitations of applying traditional, chemical-based ecotoxicity testing for the study of MPs, and propose practical recommendations and guidelines. Future laboratory based studies can be improved to increase understanding of potential real world effects of MPs by careful selection of appropriate exposure systems and conditions, test organism, MP characteristics, endpoints and required controls. We build upon recommendations provided in previous publications and complement them with a list of parameters and practical information that should be checked and/or reported in MP studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Fluorescence Lifetime (FLT) of intrinsic fluorophores may alter under the change in metabolic state. In this study, the FLT of rabbit retina was investigated in vivo after laser irradiation using fluorescence lifetime imaging ophthalmoscopy (FLIO). The retina of the Chinchilla bastard rabbits was irradiated with a 514 nm diode laser. FLIO, fundus photography, and optical coherence tomography (OCT) were conducted 30 min and 1 to 3 weeks after treatment. After strong coagulation, the FLT at laser spots was significantly elongated immediately after irradiation, conversely shortened after more than a week. Histological examination showed eosinophilic substance and melanin clumping in subretinal space at the coagulation spots older than one week. The FLT was also elongated right around the coagulation spots, which corresponded to the discontinuous ellipsoid zone (EZ) on OCT. This EZ change was recovered after one week, and the FLT became the same level as the surroundings. In addition, there was a region around the laser spot where the FLT was temporarily shorter than the surrounding area. When weak pulse energy was applied to selectively destroy only the RPE, a shortening of the FLT was observed immediately around the laser spot within one week after irradiation. FLIO could serve as a tool to evaluate the structural and metabolic response of the retina to laser treatments.

The multidrug resistance gene MDR1 encodes for an efflux transporter called P-glycoprotein (P-gp). In the canine Mdr1 gene, a nonsense mutation was identified in certain dog breeds causing increased drug sensitivity to various P-gp substrates such as antiparasitic macrocyclic lactones. Symptoms of neurologic toxicity include ataxia, depression, salivation, tremor, apparent blindness, and mydriasis. In the current report, a Thuringian goat developed similar neurological signs after treatment with doramectin, a compound from the macrocyclic lactone class. Therefore, Mdr1 might be defective in this individual goat. For diagnostic purposes, sequencing of the complete mRNA transcript coding for caprine Mdr1 was performed to investigate a potential missense mutation. The Mdr1 transcripts of two related goats without drug sensitivity were also sequenced to allow differential diagnosis and were compared to the suspected drug-sensitive goat. The only position where the Mdr1 sequence from the suspected drug-sensitive goat differed was in the 3'-untranslated region, being a heterozygous single nucleotide polymorphism c.3875C>A. It can be suspected that this variant affects the expression level, stability, or translation efficiency of the Mdr1 mRNA transcript and therefore might be associated with the suspected drug sensitivity. To clarify this, further studies are needed, particularly investigating the Mdr1 mRNA and protein expression levels from brain material of affected goats. In conclusion, Mdr1 variants may exist not only in dogs, but also in individual goats. The current report provides the first Mdr1 mRNA transcript sequence of a goat and therefore represents the basis for more detailed Mdr1 sequence and expression analyses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nürnberger, Müller, Hamann and Geyer.)

Background: Patients with triple-negative primary breast cancer (TNBC) who have residual invasive carcinoma after neoadjuvant chemotherapy have poor prognosis. Proven adjuvant approaches to reduce the risk of recurrence and improve outcome in patients with non-pathological complete response (non-pCR) are limited., Methods: From our institutional registry, a consecutive case series of patients with operable, unilateral, primary invasive noninflammatory early TNBC of stage I-IIIB and pathologically verified residual cancer cells (no pathological complete response) after neoadjuvant chemotherapy underwent adjuvant treatment with gemcitabine plus cisplatin combined with regional hyperthermia. For quality assurance, we analyzed feasibility, efficacy, and toxicity of all treated patients. Outcome was evaluated for the entire group of patients as well as for the subgroups of patients with or without lymph node involvement at baseline (cN0/ cN+)., Results: From August 2012 to January 2019, we offered this treatment to 53 patients at our center as part of routine care. The median follow-up was 38 months. The majority of patients (64.2%) had cT2 tumors at baseline. Twenty-four patients (45%) were clinically node positive as evaluated by sonography. Thirty-nine patients (74%) had grade 3, and 14 patients (26%) had grade 2 tumors. Forty-one patients (76%) showed a regression grade 1 according to Sinn. Patients received a median of six treatment cycles of gemcitabine and cisplatin (range 1-6) combined with 12 applications of regional hyperthermia (median 12, range 2-12). Disease-free survival (DFS) at 3 years was 57.5%. In patients with no lymph node involvement at baseline (cN0), DFS at 3 years was significantly higher than in initially node-positive (cN+) patients (80 vs. 31%; p = 0.001). Overall survival (OS) at 3 years was 81.6%. In patients with no lymph node involvement at baseline (cN0), OS at 3 years was significantly higher than in node-positive (cN+) patients (93 vs. 70.4%; p = 0.02). Overall, grade 3/4 toxicities were leukopenia (38%), thrombocytopenia (4%), and anemia (4%)., Conclusion: After standard neoadjuvant chemotherapy containing anthracycline plus cyclophosphamide followed by taxanes, addition of adjuvant gemcitabine plus cisplatin in combination with regional hyperthermia was safe and effective in TNBC patients with non-pCR., Competing Interests: O. Stoetzer and C. Salat received honoraria from MedTherm. D. Di Gioia received travel support from PharmaMar, Novartis, Merck, and Lilly. R. Issels received honoraria for invited lectures and reimbursement of travel expenses from PharmaMar, Bayer, Pyrexar, and MedTherm. S. Abdel-Rahman received travel support and honoraria from Dr. Sennewald Medizintechnik and MedTherm. L. Lindner received research and travel support from Dr. Sennewald Medizintechnik; travel support and honoraria from PharmaMar, Novartis, Lilly, Eisai, Bayer, Roche, and EL Medconsult. O. Gluz received advisory board and travel support from Celgene, Amgen, and Roche and honoraria from Genomic Health, Nanostring, Pfizer, Lilly, Novartis, Daiichi and Eisai. R. Würstlein received travel support, honoraria and consultancy from Celgene, Roche, MSD, Eisai, Pfizer, Astra Zeneca, Novartis, and Lilly. M. Braun received advisory board, honoraria and travel expenses from AstraZeneca, Celgene, Genomic Health, Medac, MSD, Novartis, Pfizer, Roche and Teva. All other authors declare no conflicts of interest., (Copyright © 2021 by S. Karger GmbH, Freiburg.)

With increasing use of open access platforms, simulation-based resources are being shared across geographical borders. There are benefits to designing resources with language and content which is understandable and applicable to learners in different countries. This report aims to assess the differences between scenarios from different groups and explore whether common terms can be used to make internationally relevant simulation resources in future. In collaboration between two groups producing Free Open Access Medical Education simulation resources in the UK and USA, we present observations of terms used in our simulation resources. The content within a series of simulation scenarios from both groups was reviewed, with notable differences in language collected. There are areas of overlap between the terms used in the UK and USA. Semantic, cultural and system differences were found which could prevent scenarios from being transferred between countries. The differences we describe highlight that language choice is important if simulation producers are intent on developing scenarios with international impact. There is work to be done to ensure that resources can be used internationally-embracing linguistics has the potential to aid this process, with the use of simplified language and feedback from local communities being key steps., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: To compare the detection rates of sentinel lymph nodes after converting the tracer technique from blue dye to indocyanine green (ICG)., Methods: Patients with uterine or cervical cancer were enrolled for sentinel lymph node (SLN) dissection. A total of 109 consecutive patients were analyzed and compared to a historical cohort of 109 consecutive patients with the sentinel blue dye technique. SLNs were analyzed by ultrastaging., Results: The bilateral mapping rate of sentinel nodes was significantly higher with the ICG (78%; n = 85) compared to the blue dye tracer (61%; n = 67; p = .006). Neither the mean number of SLN nor the rate of low volume metastases showed significant differences between both cohorts. In the subgroup of endometrial cancer patients, the number of systematic lymph node dissection (LND) was significantly lower in the ICG cohort compared to the blue dye cohort (9% vs. 28%, p = .001)., Conclusions: ICG improved the detection rate of pelvic SLN compared to blue dye and may be considered as the superior technique. In clinical practice, the rate of systematic LND further decreased after incorporating SLN mapping with ICG. Reliable safety data are still pending., (© 2020 Wiley Periodicals LLC.)

Background: Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics., Primary Objectives: To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs., Trial Design: A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm)., Major Inclusion/exclusion Criteria: Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1)., Endpoints: The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs., Sample Size: 500 eligible and evaluable patients., Estimated Dates for Completing Accrual and Presenting Results: Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023., Trial Registration: The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025)., Competing Interests: Competing interests: ASVMvdH and NH report a research grant from the Dutch Cancer Society, during the conduct of the PORTEC-4a study. HWN reports non-financial support from Merck, grants from the Dutch Cancer Society, grants from AIMM, outside the submitted work. RAN reports grants from the Dutch Cancer Society, grants from the Dutch Research Council, grants from Elekta, grants from Varian, grants from Accuray, outside the submitted work. CC reports non-financial support from Roche, non-financial support from TherAguix, personal fees from Elekta, personal fees from MSD, personal fees from GSK, outside the submitted work. CLC reports grants from the Dutch Cancer Society, non-financial support from Elekta-Nucletron, during the conduct of the PORTEC-4a study. SK reports personal fees from GSK, personal fees from Roche, personal fees from MSD, personal fees from AstraZeneca, outside the submitted work., (© IGCS and ESGO 2020. Re-use permitted under CC BY. Published by BMJ.)

The impact of a range of different threats has resulted in the listing of six out of seven sea turtle species on the IUCN Red List of endangered species. Disease risk analysis (DRA) tools are designed to provide objective, repeatable and documented assessment of the disease risks for a population and measures to reduce these risks through management options. To the best of our knowledge, DRAs have not previously been published for sea turtles, although disease is reported to contribute to sea turtle population decline. Here, a comprehensive list of health hazards is provided for all seven species of sea turtles. The possible risk these hazards pose to the health of sea turtles were assessed and "One Health" aspects of interacting with sea turtles were also investigated. The risk assessment was undertaken in collaboration with more than 30 experts in the field including veterinarians, microbiologists, social scientists, epidemiologists and stakeholders, in the form of two international workshops and one local workshop. The general finding of the DRA was the distinct lack of knowledge regarding a link between the presence of pathogens and diseases manifestation in sea turtles. A higher rate of disease in immunocompromised individuals was repeatedly reported and a possible link between immunosuppression and environmental contaminants as a result of anthropogenic influences was suggested. Society based conservation initiatives and as a result the cultural and social aspect of interacting with sea turtles appeared to need more attention and research. A risk management workshop was carried out to acquire the insights of local policy makers about management options for the risks relevant to Queensland and the options were evaluated considering their feasibility and effectiveness. The sea turtle DRA presented here, is a structured guide for future risk assessments to be used in specific scenarios such as translocation and head-starting programs., Competing Interests: NO authors have competing interests.

Microplastic (MP) contamination has been well documented across a range of habitats and for a large number of organisms in the marine environment. Consequently, bioaccumulation, and in particular biomagnification of MPs and associated chemical additives, are often inferred to occur in marine food webs. Presented here are the results of a systematic literature review to examine whether current, published findings support the premise that MPs and associated chemical additives bioaccumulate and biomagnify across a general marine food web. First, field and laboratory-derived contamination data on marine species were standardised by sample size from a total of 116 publications. Second, following assignment of each species to one of five main trophic levels, the average uptake of MPs and of associated chemical additives was estimated across all species within each level. These uptake data within and across the five trophic levels were then critically examined for any evidence of bioaccumulation and biomagnification. Findings corroborate previous studies that MP bioaccumulation occurs within each trophic level, while current evidence around bioaccumulation of associated chemical additives is much more ambiguous. In contrast, MP biomagnification across a general marine food web is not supported by current field observations, while results from the few laboratory studies supporting trophic transfer are hampered by using unrealistic exposure conditions. Further, a lack of both field and laboratory data precludes an examination of potential trophic transfer and biomagnification of chemical additives associated with MPs. Combined, these findings indicate that, although bioaccumulation of MPs occurs within trophic levels, no clear sign of MP biomagnification in situ was observed at the higher trophic levels. Recommendations for future studies to focus on investigating ingestion, retention and depuration rates for MPs and chemical additives under environmentally realistic conditions, and on examining the potential of multi-level trophic transfer for MPs and chemical additives have been made., Competing Interests: The authors have declared that no competing interests exist.