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The Arctic poses many challenges for Earth system and snow physics models, which are commonly unable to simulate crucial Arctic snowpack processes,such as vapour gradients and rain-on-snow-induced ice layers. These limitations raise concerns about the current understanding of Arctic warming and its impact on biodiversity, livelihoods, permafrost, and the global carbon budget. Recognizing that models are shaped by human choices, 18 Arctic researchers were interviewed to delve into the decision-making process behind model construction. Although data availability, issues of scale, internal model consistency, and historical and numerical model legacies were cited as obstacles to developing an Arctic snowpack model, no opinion was unanimous. Divergences were not merely scientific disagreements about the Arctic snowpack but reflected the broader research context. Inadequate and insufficient resources, partly driven by short-term priorities dominating research landscapes, impeded progress. Nevertheless, modellers were found to be both adaptable to shifting strategic research priorities – an adaptability demonstrated by the fact that interdisciplinary collaborations were the key motivation for model development – and anchored in the past. This anchoring and non-epistemic values led to diverging opinions about whether existing models were “good enough” and whether investing time and effort to build a new model was a useful strategy when addressing pressing research challenges. Moving forward, we recommend that both stakeholders and modellers be involved in future snow model intercomparison projects in order to drive developments that address snow model limitations currently impeding progress in various disciplines. We also argue for more transparency about the contextual factors that shape research decisions. Otherwise, the reality of our scientific process will remain hidden, limiting the changes necessary to our research practice.

Abstract Quantifying the structural complexity provided by biogenic habitat structures is important in ecology, conservation and management, and yet remains a challenging task, particularly in deep sea and polar environments, that current photogrammetry tools can alleviate. In this study, we demonstrate how small remotely operated vehicles and compact underwater GoPro® action cameras can be easily integrated into coastal Antarctic surveys to quantify structural complexity of under‐ice benthos via underwater photogrammetry. Forty‐four pairs of 1 m2 quadrats at 1 cm resolution, each comprising an orthomosaic and three‐dimensional reconstructions, were analyzed to describe relationships between benthic cover and structural complexity metrics. The study case provided insights into a unique biogenic habitat, highlighting the role of integrating structural complexity metrics in Antarctic benthic surveys. Although no clear relationships between structural complexity and biodiversity were found, high cover of live reef‐building polychaetes was associated with higher levels of structural complexity, particularly fractal dimension (D). Further, broken biogenic structures, product of disturbance events retain habitat structural complexity known to be associated with larvae settlement and biogenic reef growth. This suggests that D can be used as a metric for detecting subtle changes in biogenic structural complexity. We build from available open‐source code, a reproducible scientific workflow that is expected to facilitate the acquisition and analysis of structural complexity metrics. The workflow presented aims to encourage and accelerate the use of photogrammetry tools for benthic studies aiming to quantify biogenic structural complexity across depths and latitudes.

Abstract Background Actinic keratoses (AK) are pre‐malignant skin lesions caused by chronic sun exposure. Progression from an AK to intraepidermal carcinoma (IEC) and a cutaneous squamous cell carcinoma (SCC) is well known but the rate of transformation to an invasive SCC is highly variable. Since no definitive biomarkers are available, treatment decisions are made ad hoc. Objectives To fully characterise our AK to SCC progression series, we performed microRNA (miRNA) microarray expression profiling of normal and photodamaged skin, as well as AKs, IEC, and invasive SCCs. Methods The study recruited 27 patients who donated fresh biopsies of normal skin, photodamaged skin, AK, IEC, and SCC (n = 67 specimens). All miRbase (v.21) miRNAs were profiled to identify miRNAs related to SCC progression. miRNAs were validated using qRT‐PCR and in vitro phenotypic assays. Results There were 234 robustly expressed miRNAs across the tissue collection, which resulted in 20 miRNA that were differentially expressed ((cor)p ≤ 0.05 and ≥ 10 fold) between normal skin and SCC. Hierarchical clustering all samples illustrated that AKs, IEC, and SCCs were largely indistinguishable, which confirms the premalignant status of an AK. A panel of miRNAs showed significant dysregulation between normal and photodamaged skin and AK. Importantly, we found miR‐34a‐5p and miR‐31‐5p had significant differential expression between AKs and IEC and IEC and SCC respectively. Phenotypic assays determined that the miR‐31 duplex had opposing effects on SCC cell lines which suggests that dysregulation of this duplex may be related to the dynamic control of progression of transformed keratinocytes. Conclusions This study confirmed the continuum of AK with IEC and SCC highlighting that miRNA expression plays a role in keratinocyte transformation. Development of our putative miRNA biomarker candidates is warranted to aid in clinical management of patients experiencing high AK load to determine the most appropriate treatment.

Human influence on Antarctic marine ecosystems is a growing concern, despite limited information being available. This study investigated the coastal meiofauna and environmental parameters of 10 locations, 4 of which served as reference points (OB1, OB2, OB3, and McGrady) and 6 which were impacted by different levels of human activity in the past and present (Wharf, Wilkes, BBIN, BBMID, BBOUT, and Shannon) in East Antarctica. Environmental variables such as metals, total petroleum hydrocarbons (TPHs), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), grain size, organic matter content, and nutrients were measured for analysis. Locations close to human activities showed higher concentrations of pollutants (metals, TPHs, PBDEs, PCBs) and greater variations in meiofauna diversity compared to the reference sites (OB1, OB2, OB3, and McGrady). In the area impacted by the Casey Station waste dump (Brown Bay), the meiofauna community at the location furthest from the pollution (BBOUT) source exhibited greater diversity compared to the closest location (BBIN). In addition to metals and TPHs, particle size was also correlated with community patterns, with finer sediments associated with more impacted sites, facilitating the accumulation of toxic compounds. These results contribute to the understanding of the role and impact of pollutants on meiofauna biodiversity in Antarctic coastal ecosystems.

Terahertz (THz) imaging has long held promise for skin cancer detection but has been hampered by the lack of practical technological implementation. In this article, we introduce a technique for discriminating several skin pathologies using a coherent THz confocal system based on a THz quantum cascade laser. High resolution in vivo THz images (with diffraction limited to the order of 100 μm) of several different lesion types were acquired and compared against one another using the amplitude and phase values. Our system successfully separated pathologies using a combination of phase and amplitude information and their respective surface textures. The large scan field (50 × 40 mm) of the system allows macroscopic visualization of several skin lesions in a single frame. Utilizing THz imaging for dermatological assessment of skin lesions offers substantial additional diagnostic value for clinicians. THz images contain information complementary to the information contained in the conventional digital images.

The ongoing controversies about the neural basis of tinnitus, whether linked with central neural gain or not, may hamper efforts to develop therapies. We asked to what extent measurable audiometric characteristics of tinnitus without (T) or with co-occurrence of hyperacusis (TH) are distinguishable on the level of cortical responses. To accomplish this, electroencephalography (EEG) and concurrent functional near-infrared spectroscopy (fNIRS) were measured while patients performed an attentionally demanding auditory discrimination task using stimuli within the individual tinnitus frequency (fTin) and a reference frequency (fRef). Resting-state-fMRI-based functional connectivity (rs-fMRI-bfc) in ascending auditory nuclei (AAN), the primary auditory cortex (AC-I), and four other regions relevant for directing attention or regulating distress in temporal, parietal, and prefrontal cortex was compiled and compared to EEG and concurrent fNIRS activity in the same brain areas. We observed no group differences in pure-tone audiometry (PTA) between 10 and 16 kHz. However, the PTA threshold around the tinnitus pitch was positively correlated with the self-rated tinnitus loudness and also correlated with distress in T-groups, while TH experienced their tinnitus loudness at minimal loudness levels already with maximal suffering scores. The T-group exhibited prolonged auditory brain stem (ABR) wave I latency and reduced ABR wave V amplitudes (indicating reduced neural synchrony in the brainstem), which were associated with lower rs-fMRI-bfc between AAN and the AC-I, as observed in previous studies. In T-subjects, these features were linked with elevated spontaneous and reduced evoked gamma oscillations and with reduced deoxygenated hemoglobin (deoxy-Hb) concentrations in response to stimulation with lower frequencies in temporal cortex (Brodmann area (BA) 41, 42, 22), implying less synchronous auditory responses during active auditory discrimination of reference frequencies. In contrast, in the TH-group gamma oscillations and hemodynamic responses in temporoparietal regions were reversed during active discrimination of tinnitus frequencies. Our findings suggest that T and TH differ in auditory discrimination and memory-dependent directed attention during active discrimination at either tinnitus or reference frequencies, offering a test paradigm that may allow for more precise sub-classification of tinnitus and future improved treatment approaches.

IntroductionThe influence of pre-existing humoral immunity, inter-individual demographic factors, and vaccine-associated reactogenicity on immunogenicity following COVID vaccination remains poorly understood.MethodsTen-fold cross-validated least absolute shrinkage and selection operator (LASSO) and linear mixed effects models were used to evaluate symptoms experienced by COVID+ participants during natural infection and following SARS-CoV-2 mRNA vaccination along with demographics as predictors for antibody (AB) responses to recombinant spike protein in a longitudinal cohort study.ResultsIn previously infected individuals (n=33), AB were more durable and robust following primary vaccination when compared to natural infection alone. Higher AB were associated with experiencing dyspnea during natural infection, as was the total number of symptoms reported during the COVID-19 disease course. Both local and systemic symptoms following 1st and 2nd dose (n=49 and 48, respectively) of SARS-CoV-2 mRNA vaccines were predictive of higher AB after vaccination. Lastly, there was a significant temporal relationship between AB and days since infection or vaccination, suggesting that vaccination in COVID+ individuals is associated with a more robust immune response.DiscussionExperiencing systemic and local symptoms post-vaccine was suggestive of higher AB, which may confer greater protection.

The introduction of real-time imaging by magnetic resonance guided linear accelerators (MR-Linacs) enabled adaptive treatments and gating on the tumor position. Different end-to-end tests monitored the accuracy of our MR-Linac during the first year of clinical operation. We report on the stability of these tests covering a static, adaptive and gating workflow. Film measurements showed gamma passing rates of 96.4% ± 3.4% for the static tests (five measurements) and for the two adaptive tests 98.9% and 99.99%, respectively (criterion 2%/2mm). The gated point dose measurements in the breathing phantom were 2.7% lower than in the static phantom.

Abstract Southern Ocean waters are among the most vulnerable to ocean acidification. The projected increase in the CO2 level will cause changes in carbonate chemistry that are likely to be damaging to organisms inhabiting these waters. A meta‐analysis was undertaken to examine the vulnerability of Antarctic marine biota occupying waters south of 60°S to ocean acidification. This meta‐analysis showed that ocean acidification negatively affects autotrophic organisms, mainly phytoplankton, at CO2 levels above 1,000 μatm and invertebrates above 1,500 μatm, but positively affects bacterial abundance. The sensitivity of phytoplankton to ocean acidification was influenced by the experimental procedure used. Natural, mixed communities were more sensitive than single species in culture and showed a decline in chlorophyll a concentration, productivity, and photosynthetic health, as well as a shift in community composition at CO2 levels above 1,000 μatm. Invertebrates showed reduced fertilization rates and increased occurrence of larval abnormalities, as well as decreased calcification rates and increased shell dissolution with any increase in CO2 level above 1,500 μatm. Assessment of the vulnerability of fish and macroalgae to ocean acidification was limited by the number of studies available. Overall, this analysis indicates that many marine organisms in the Southern Ocean are likely to be susceptible to ocean acidification and thereby likely to change their contribution to ecosystem services in the future. Further studies are required to address the poor spatial coverage, lack of community or ecosystem‐level studies, and the largely unknown potential for organisms to acclimate and/or adapt to the changing conditions.

Melanomas have increased in global incidence and are the leading cause of skin cancer deaths. Whilst the majority of early-stage, non-metastatic melanomas can be cured with surgical excision alone, ~5% of patients with early melanomas will experience recurrence following a variable disease-free interval and progression to metastatic melanoma and ultimately death. This is likely because of primary tumor heterogeneity and progressive clonal divergency resulting in the growth of more aggressive tumor populations. Liquid biomarkers have the advantage of real-time, non-invasive longitudinal monitoring of tumor burden and heterogeneity over tissue markers. Currently, the only serological marker used in the staging and monitoring of melanoma is serum lactate dehydrogenase, which is not sufficiently specific or sensitive, and is not used routinely in all centers. An ideal melanoma biomarker would be used to identify patients who are at high-risk of primary melanoma, screen for relapse, detect early-stage melanoma, provide treatment outcomes to personalize systemic treatment, follow tumor heterogeneity, provide prognostic data before, during and after treatment, and monitor response to treatment. This review provides a summary of the current research in this field with a specific focus on circulating tumor cells, circulating tumor DNA, microRNA, and extracellular vesicles which may serve to suit these goals.

Precision prevention of advanced melanoma is fast becoming a realistic prospect, with personalized, holistic risk stratification allowing patients to be directed to an appropriate level of surveillance, ranging from skin self-examinations to regular total body photography with sequential digital dermoscopic imaging. This approach aims to address both underdiagnosis (a missed or delayed melanoma diagnosis) and overdiagnosis (the diagnosis and treatment of indolent lesions that would not have caused a problem). Holistic risk stratification considers several types of melanoma risk factors: clinical phenotype, comprehensive imaging-based phenotype, familial and polygenic risks. Artificial intelligence computer-aided diagnostics combines these risk factors to produce a personalized risk score, and can also assist in assessing the digital and molecular markers of individual lesions. However, to ensure uptake and efficient use of AI systems, researchers will need to carefully consider how best to incorporate privacy and standardization requirements, and above all address consumer trust concerns.

Processing of sensory information is embedded into ongoing neural processes which contribute to brain states. Electroencephalographic microstates are semi-stable short-lived power distributions which have been associated with subsystem activity such as auditory, visual and attention networks. Here we explore changes in electrical brain states in response to an audiovisual perception and memorization task under conditions of auditory distraction. We discovered changes in brain microstates reflecting a weakening of states representing activity of the auditory system and strengthening of salience networks, supporting the idea that salience networks are active after audiovisual encoding and during memorization to protect memories and concentrate on upcoming behavioural response.

Antarctic benthic ecosystems support high biodiversity but their characterization is limited to a few well-studied areas, due to the extreme environment and remoteness making access and sampling difficult. Our aim was to compare water and sediment as sources of environmental DNA (eDNA) to better characterise Antarctic benthic communities and further develop practical approaches for DNA-based biodiversity assessment in remote environments. We used a cytochrome c oxidase subunit I (COI) metabarcoding approach to characterise metazoan communities in 26 nearshore sites across 12 locations in the Vestfold Hills (East Antarctica) based on DNA extracted from either sediment cores or filtered seawater. We detected a total of 99 metazoan species from 12 phyla across 26 sites, with similar numbers of species detected in sediment and water eDNA samples. However, significantly different communities were detected in the two sample types at sites where both were collected (i.e., where paired samples were available). For example, nematodes and echinoderms were more likely to be detected exclusively in sediment and water eDNA samples, respectively. eDNA from water and sediment core samples are complementary sample types, with epifauna more likely to be detected in water column samples and infauna in sediment. More reference DNA sequences are needed for infauna/meiofauna to increase the proportion of sequences and number of taxa that can be identified. Developing a better understanding of the temporal and spatial dynamics of eDNA at low temperatures would also aid interpretation of eDNA signals from polar environments. Our results provide a preliminary scan of benthic metazoan communities in the Vestfold Hills, with additional markers required to provide a comprehensive biodiversity survey. However, our study demonstrates the choice of sample type for eDNA studies of benthic ecosystems (sediment, water or both) needs to be carefully considered in light of the research or monitoring question of interest.

Abstract Free-ocean CO2 enrichment (FOCE) experiments have been deployed in marine ecosystems to manipulate carbonate system conditions to those predicted in future oceans. We investigated whether the pH/carbonate chemistry of extremely cold polar waters can be manipulated in an ecologically relevant way, to represent conditions under future atmospheric CO2 levels, in an in-situ FOCE experiment in Antarctica. We examined spatial and temporal variation in local ambient carbonate chemistry at hourly intervals at two sites between December and February and compared these with experimental conditions. We successfully maintained a mean pH offset in acidified benthic chambers of −0.38 (±0.07) from ambient for approximately 8 weeks. Local diel and seasonal fluctuations in ambient pH were duplicated in the FOCE system. Large temporal variability in acidified chambers resulted from system stoppages. The mean pH, Ωarag and fCO2 values in the acidified chambers were 7.688 ± 0.079, 0.62 ± 0.13 and 912 ± 150 µatm, respectively. Variation in ambient pH appeared to be mainly driven by salinity and biological production and ranged from 8.019 to 8.192 with significant spatio-temporal variation. This experiment demonstrates the utility of FOCE systems to create conditions expected in future oceans that represent ecologically relevant variation, even under polar conditions.

Knowledge of life on the Southern Ocean seafloor has substantially grown since the beginning of this century with increasing ship-based surveys and regular monitoring sites, new technologies and greatly enhanced data sharing. However, seafloor habitats and their communities exhibit high spatial variability and heterogeneity that challenges the way in which we assess the state of the Southern Ocean benthos on larger scales. The Antarctic shelf is rich in diversity compared with deeper water areas, important for storing carbon (“blue carbon”) and provides habitat for commercial fish species. In this paper, we focus on the seafloor habitats of the Antarctic shelf, which are vulnerable to drivers of change including increasing ocean temperatures, iceberg scour, sea ice melt, ocean acidification, fishing pressures, pollution and non-indigenous species. Some of the most vulnerable areas include the West Antarctic Peninsula, which is experiencing rapid regional warming and increased iceberg-scouring, subantarctic islands and tourist destinations where human activities and environmental conditions increase the potential for the establishment of non-indigenous species and active fishing areas around South Georgia, Heard and MacDonald Islands. Vulnerable species include those in areas of regional warming with low thermal tolerance, calcifying species susceptible to increasing ocean acidity as well as slow-growing habitat-forming species that can be damaged by fishing gears e.g., sponges, bryozoan, and coral species. Management regimes can protect seafloor habitats and key species from fishing activities; some areas will need more protection than others, accounting for specific traits that make species vulnerable, slow growing and long-lived species, restricted locations with optimum physiological conditions and available food, and restricted distributions of rare species. Ecosystem-based management practices and long-term, highly protected areas may be the most effective tools in the preservation of vulnerable seafloor habitats. Here, we focus on outlining seafloor responses to drivers of change observed to date and projections for the future. We discuss the need for action to preserve seafloor habitats under climate change, fishing pressures and other anthropogenic impacts.

Lung cancer is currently the leading cause of cancer death in both developing and developed countries. Given that lung cancer has poor prognosis in later stages, it is essential to achieve an early diagnosis to maximize patients’ overall survival. Non-small cell lung cancer (NSCLC) is the most common form of primary lung cancer in both smokers and non-smokers. The current standard screening method, low‐dose computed tomography (LDCT), is the only radiological method that demonstrates to have mortality benefits across multiple large randomized clinical trials (RCT). However, these RCTs also found LDCT to have a significant false positive rate that results in unnecessary invasive biopsies being performed. Due to the lack of both sensitive and specific screening methods for the early detection of lung cancer, there is an urgent need for alternative minimally or non-invasive biomarkers that may provide diagnostic, and/or prognostic information. This has led to the identification of circulating biomarkers that can be readily detectable in blood and have been extensively studied as prognosis markers. Circulating microRNA (miRNA) in particular has been investigated for these purposes as an augmentation to LDCT, or as direct diagnosis of lung cancer. There is, however, a lack of consensus across the studies on which miRNAs are the most clinically useful. Besides miRNA, other potential circulating biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNAs) and non-coding RNAs (ncRNAs). In this review, we provide the current outlook of several of these biomarkers for the early diagnosis of NSCLC.

Benign naevi are closely linked to melanoma, as risk factors, simulators, or sites of melanoma formation. There is a heavy genetic overlap between the two lesions, a shared environmental influence of ultraviolet radiation, and many similar cellular features, yet naevi remain locally situated while melanomas spread from their primary site and may progress systemically to distal organs. Untangling the overlapping contributors and predictors of naevi and melanoma is an ongoing area of research and should eventually lead to more personalized prevention and treatment strategies, through the development of melanoma risk stratification tools and early detection of evolving melanomas. This will be achieved through a range of complementary strategies: risk-adjusted primary prevention counseling; the use of lesion imaging technologies such as sequential 3D total body photography and consumer-performed lesion imaging; artificial intelligence deep phenotyping and clinical assistance; a better understanding of genetic drivers of malignancy, risk variants, clinical genetics, and polygenic effects; and the interplay between genetics, phenotype and the environment.

Understanding the vulnerability of marine calcifiers to ocean acidification is a critical issue, especially in the Southern Ocean (SO), which is likely to be the one of the first, and most severely affected regions. Since the industrial revolution, ~30% of anthropogenic CO2 has been absorbed by the global oceans. Average surface seawater pH levels have already decreased by 0.1 and are projected to decline by ~0.3 by the year 2100. This process, known as ocean acidification (OA), is shallowing the saturation horizon, which is the depth below which calcium carbonate (CaCO3) dissolves, likely increasing the vulnerability of many resident marine calcifiers to dissolution. The negative impact of OA may be seen first in species depositing more soluble CaCO3 mineral phases such as aragonite and high-Mg calcite (HMC). Ocean warming could further exacerbate the effects of OA in these particular species. Here we combine a review and a quantitative meta-analysis to provide an overview of the current state of knowledge about skeletal mineralogy of major taxonomic groups of SO marine calcifiers and to make projections about how OA might affect a broad range of SO taxa. We consider a species' geographic range, skeletal mineralogy, biological traits, and potential strategies to overcome OA. The meta-analysis of studies investigating the effects of the OA on a range of biological responses such as shell state, development and growth rate illustrates that the response variation is largely dependent on mineralogical composition. Species-specific responses due to mineralogical composition indicate that taxa with calcitic, aragonitic, and HMC skeletons, could be at greater risk to expected future carbonate chemistry alterations, and low-Mg calcite (LMC) species could be mostly resilient to these changes. Environmental and biological control on the calcification process and/or Mg content in calcite, biological traits, and physiological processes are also expected to influence species-specific responses.

Summary: To better understand the influence of ultraviolet (UV) irradiation on the initial steps of skin carcinogenesis, we examine patches of labeled keratinocytes as a proxy for clones in the interfollicular epidermis (IFE) and measure their size variation upon UVB irradiation. Multicolor lineage tracing reveals that in chronically irradiated skin, patches near hair follicles (HFs) increase in size, whereas those far from follicles do not change. This is explained by proliferation of basal epidermal cells within 60 μm of HF openings. Upon interruption of UVB, patch size near HFs regresses significantly. These anatomical differences in proliferative behavior have significant consequences for the cell of origin of basal cell carcinomas (BCCs). Indeed, a UV-inducible murine BCC model shows that BCC patches are more frequent, larger, and more invasive near HFs. These findings have major implications for the prevention of field cancerization in the epidermis.

The composition, spatial structure, diversity and abundance of Antarctic nematode and copepod meiobenthic communities was examined in shallow (5–25 m) marine coastal sediments at Casey Station, East Antarctica. The sampling design incorporated spatial scales ranging from 10 meters to kilometers and included testing for human impacts by comparing polluted (metal and hydrocarbon contaminated sediments adjacent to old waste disposal sites) and control areas. A total of 38 nematode genera and 20 copepod families were recorded with nematodes being dominant, comprising up to 95% of the total abundance. Variation was greatest at the largest scale (km’s) but each location had distinct assemblages. At smaller scales there were different patterns of variation for nematodes and copepods. There were significant differences between communities at control and impacted locations. Community patterns had strong correlations with concentrations of metals introduced by human activity in sediments as well as sediment grain size and total organic content. Given the strong association with environmental patterns, particularly those associated with human impacts, we provide further evidence that meiofauna are very useful indicators of anthropogenic environmental changes in Antarctica.

Amelanotic/hypomelanotic melanoma is a clinicopathologic subtype with absent or minimal melanin. This study assessed previously reported coding variants in albinism genes (TYR, OCA2, TYRP1, SLC45A2, SLC24A5, LRMDA) and common intronic, regulatory variants of OCA2 in individuals with amelanotic/hypomelanotic melanoma, pigmented melanoma cases and controls. Exome sequencing was available for 28 individuals with amelanotic/hypomelanotic melanoma and 303 individuals with pigmented melanoma, which were compared to whole exome data from 1144 Australian controls. Microarray genotyping was available for a further 17 amelanotic/hypomelanotic melanoma, 86 pigmented melanoma, 147 melanoma cases (pigmentation unknown) and 652 unaffected controls. Rare deleterious variants in TYR/OCA1 were more common in amelanotic/hypomelanotic melanoma cases than pigmented melanoma cases (set mixed model association tests P = 0.0088). The OCA2 hypomorphic allele p.V443I was more common in melanoma cases (1.8%) than controls (1.0%, X2 P = 0.02), and more so in amelanotic/hypomelanotic melanoma (4.4%, X2 P = 0.007). No amelanotic/hypomelanotic melanoma cases carried an eye and skin darkening haplotype of OCA2 (including rs7174027), present in 7.1% of pigmented melanoma cases (P = 0.0005) and 9.4% controls. Variants in TYR and OCA2 may play a role in amelanotic/hypomelanotic melanoma susceptibility. We suggest that somatic loss of function at these loci could contribute to the loss of tumor pigmentation, consistent with this we found a higher rate of somatic mutation in TYR/OCA2 in amelanotic/hypomelanotic melanoma vs pigmented melanoma samples (28.6% vs 3.0%; P = 0.021) from The Cancer Genome Atlas Skin Cutaneous Melanoma collection.

Human driven changes such as increases in oceanic CO2, global warming, petroleum hydrocarbons and heavy metals may negatively affect the ability of marine calcifiers to build their skeletons/shells, especially in polar regions. We examine spatio-temporal variability of skeletal Mg-calcite in shallow water Antarctic marine invertebrates using bryozoan and spirorbids as models in a recruitment experiment of settlement tiles in East Antarctica. Mineralogies were determined for 754 specimens belonging to six bryozoan species (four cheilostome and two cyclostome species) and two spirorbid species from around Casey Station. Intra- and interspecific variability in wt% MgCO3 in calcite among most species was the largest source of variation overall. Therefore, the skeletal Mg-calcite in these taxa seem to be mainly biologically controlled. However, significant spatial variability was also found in wt% MgCO3 in calcite, possibly reflecting local environment variation from sources such as freshwater input and contaminated sediments. Species with high-Mg calcite skeletons (e.g. Beania erecta) could be particularly sensitive to multiple stressors under predictions for near-future global ocean chemistry changes such as increasing temperature, ocean acidification and pollution.

Purpose: Stereotactic radiosurgery (SRS) is the preferred primary treatment option for patients with a limited number of asymptomatic brain metastases. In case of relapse after initial SRS the optimal salvage treatment is not well defined. Within this retrospective analysis, we investigated the feasibility of repeated courses of SRS to defer Whole-Brain Radiation Therapy (WBRT) and aimed to derive prognostic factors for patient selection.Materials and Methods: From 2014 until 2017, 42 patients with 197 brain metastases have been treated with multiple courses of SRS at our institution. Treatment was delivered as single fraction (18 or 20 Gy) or hypo-fractionated (6 fractions with 5 Gy) radiosurgery. Regular follow-up included clinical examination and contrast-enhanced cMRI at 3–4 months' intervals. Besides clinical and treatment related factors, brain metastasis velocity (BMV) as a newly described clinical prognostic metric was included and calculated between first and second treatment.Results: A median number of 1 lesion (range: 1–13) per course and a median of 2 courses (range: 2–6) per patient were administered resulting in a median of 4 (range: 2–14) metastases treated over time per patient. The median interval between SRS courses was 5.8 months (range: 0.9–35 months). With a median follow-up of 17.4 months (range: 4.6–45.5 months) after the first course of treatment, a local control rate of 84% was observed after 1 year and 67% after 2 years. Median time to out-of-field-brain-failure (OOFBF) was 7 months (95%CI 4–8 months). WBRT as a salvage treatment was eventually required in 7 patients (16.6%). Median overall survival (OS) has not been reached. Grouped by ds-GPA (≤ 2 vs. >2) the survival curves showed a significant split (p = 0.039). OS differed also significantly between BMV-risk groups when grouped into low vs. intermediate/high risk groups (p = 0.025). No grade 4 or 5 acute or late toxicity was observed.Conclusion: In selected patients with relapse after SRS for brain metastases, repeat courses of SRS were safe and minimized the need for rescue WBRT. The innovative, yet easy to calculate metric BMV may facilitate treatment decisions as a prognostic factor for OS.

The overall 5-year survival for melanoma is 91%. However, if distant metastasis occurs (stage IV), cure rates are

On polar coasts, seasonal sea-ice duration strongly influences shallow marine environments by affecting environmental conditions, such as light, sedimentation, and physical disturbance. Sea-ice dynamics are changing in response to climate, but there is limited understanding of how this might affect shallow marine environments and benthos. Here we present a unique set of physical and biological data from a single region of Antarctic coast, and use it to gain insights into factors shaping polar benthic communities. At sites encompassing a gradient of sea-ice duration, we measured temporal and spatial variation in light and sedimentation and hard-substrate communities at different depths and substrate orientations. Biological trends were highly correlated with sea-ice duration, and appear to be driven by opposing gradients in light and sedimentation. As sea-ice duration decreased, there was increased light and reduced sedimentation, and concurrent shifts in community structure from invertebrate to algal dominance. Trends were strongest on shallower, horizontal surfaces, which are most exposed to light and sedimentation. Depth and substrate orientation appear to mediate exposure of benthos to these factors, thereby tempering effects of sea-ice and increasing biological heterogeneity. However, while light and sedimentation both varied spatially with sea-ice, their dynamics differed temporally. Light was sensitive to the site-specific date of sea-ice breakout, whereas sedimentation fluctuated at a regional scale coincident with the summer phytoplankton bloom. Sea-ice duration is clearly the overarching force structuring these shallow Antarctic benthic communities, but direct effects are imposed via light and sedimentation, and mediated by habitat characteristics.