Unexpected increase in structural integrity caused by thermally induced dwarfism in large benthic foraminifera.

Climate change is predicted to negatively impact calcification and change the structural integrity of biogenic carbonates, influencing their protective function. We assess the impacts of warming on the morphology and crystallography of Amphistegina lobifera, an abundant benthic foraminifera species in shallow environments. Specimens from a thermally disturbed field area, mimicking future warming, are about 50% smaller compared with a control location. Differences in the position of the ν1 Raman mode of shells between the sites, which serves as a proxy for Mg content and calcification temperature, indicate that calcification is negatively impacted when temperatures are below the thermal range facilitating calcification. To test the impact of thermal stress on the Young's modulus of calcite which contributes to structural integrity, we quantify elasticity changes in large benthic foraminifera by applying atomic force microscopy to a different genus, Operculina ammonoides, cultured under optimal and high temperatures. Building on these observations of size and the sensitivity analysis for temperature-induced change in elasticity, we used finite element analysis to show that structural integrity is increased with reduced size and is largely insensitive to calcite elasticity. Our results indicate that warming-induced dwarfism creates shells that are more resistant to fracture because they are smaller.

Effects of an Educational Intervention Program on Positional Cranial Deformity in Premature Infants.

Positional cranial deformities are associated with prematurity evolving during the first 2 years of life due to the malleable characteristics of the skull, the first year being the main/primary therapeutic window for intervention. The objectives were (a) to describe health characteristics, peri- and postnatal pathologies, and positional cranial deformities in infants enrolled in an early intervention program and (b) to analyze the effects of a parent education-based intervention program on positional cranial deformity in premature infants. A quantitative, analytical, longitudinal study was conducted. It included 103 premature infants enrolled in an early intervention program (EIP) during the year 2017, all under 4 months of corrected age, to whom a parent education-based intervention program was applied. Cranial circumference, cranial width, diagonals, and anteroposterior diameter were measured, and the cranial asymmetry index (CAI) and cephalic index (CI) were calculated at baseline and during two subsequent evaluations separated by a 3-month period. The main results showed that 75.7% of the infants belonged to a very premature gestational age category, and 57.3% had an adequate weight for gestational age. The most frequent pathologies were premature jaundice, premature anemia, and hyaline membrane disease. The most frequent positional cranial deformity was plagiocephaly. The parent education-based intervention program resulted in (1) a significant decrease in the CAI and a significant increase in the IC, (2) plagiocephalies: an increase in the mild category and a decrease in the moderate + severe categories, (3) brachycephalies: a decrease in the absence category and an increase in the moderate + severe category, and (4) dolichocephalies: an increase in the absence category and a decrease in the mild category. In conclusion, the recommended first line of intervention was not enough for this population, and future studies should support the development of national clinical guidelines, where education is complemented with other therapeutic measures.

Positional cranial deformities in preterm infants and their association with health indicators. / Deformidades craneales posicionales en lactantes prematuros y asociación con indicadores de salud.

Prematurity is a risk factor for positional cranial deformities since preterm infants have a more malleable skull and are susceptible to deformities due to external pressures. OBJECTIVES: To describe positional cranial deformities and peri/postnatal pathologies in preterm infants and to analyze the association between gestational age, birth weight, length of hospitalization, and severity of cranial deformities measured by the Cranial Vault Asymmetry Index (CVAI) and the Cephalic Index (CI). PATIENTS AND METHOD: Analytic, cross-sectional study. 103 preterm infants aged under 4 months of corrected age admitted during 2017 to an Early Intervention Program (EIP) were included. Participants were classified according to gestational age as follows: extremely preterm (< 28 weeks), very preterm (28-32 weeks), and moderate-to-late preterm (32-37 weeks). Head circumference, anteroposterior diameter, width, and head diagonals were measured, and the CVAI and CI were calculated. Peri- and postnatal history was obtained from clinical records. RESULTS: 103 preterm infants were evaluated (17 extremely preterm, 78 very preterm, and 8 moderate-to-late preterm). 99 (96.1%) of the preterm infants had positional cranial deformity and, regardless of the degree of prematurity, presented similar cranial anthropometric measurements. Mild plagiocephaly was the most frequent cranial deformity in all groups. We observed a positive association between the days of hospitalization and the CVAI and there was no relationship between the degree of prematurity and the severity of the positional cranial deformation. CONCLUSIONS: Most of the patients admitted to the EIP presented positional cranial deformities, mainly mild plagiocephaly, regardless of the degree of prematurity. The presence of plagiocephaly was positively associated with prolonged periods of hospitalization. No relationship was confirmed between the degree of prematurity and the severity of the positional cranial deformity.

Environmental impacts on the structural integrity of British rhodoliths.

Coralline algae form complex habitats which are biodiversity hotspots. Experimental studies suggest that climate change will decrease coralline algal structural integrity. These experiments, however, lack information on local morphological variability and how much structural change would be needed to threaten habitat formation. Here, using finite element modelling, we assess variability in cellular structure and chemical composition of the carbonate skeleton of four coralline algal species from Britain in contemporary and historical specimens collected over the last 130 years. Cellular and mineral properties are highly variable within species, between sites and through time, with structurally weaker cells in the southern species and contemporary material compared to northern taxa and historical material. Yet, temporal differences in strength were smaller than spatial differences. Our work supports long term experiments which show the adaptation potential of this group. Our results suggest that future anthropogenic climate change may lead to loss of habitat complexity in the south and expansion of structurally weaker southern species into northern sites.

100 million years of turtle paleoniche dynamics enable the prediction of latitudinal range shifts in a warming world.

Past responses to environmental change provide vital baseline data for estimating the potential resilience of extant taxa to future change. Here, we investigate the latitudinal range contraction that terrestrial and freshwater turtles (Testudinata) experienced from the Late Cretaceous to the Paleogene (100.5-23.03 mya) in response to major climatic changes. We apply ecological niche modeling (ENM) to reconstruct turtle niches, using ancient and modern distribution data, paleogeographic reconstructions, and the HadCM3L climate model to quantify their range shifts in the Cretaceous and late Eocene. We then use the insights provided by these models to infer their probable ecological responses to future climate scenarios at different representative concentration pathways (RCPs 4.5 and 8.5 for 2100), which project globally increased temperatures and spreading arid biomes at lower to mid-latitudes. We show that turtle ranges are predicted to expand poleward in the Northern Hemisphere, with decreased habitat suitability at lower latitudes, inverting a trend of latitudinal range contraction that has been prevalent since the Eocene. Trionychids and freshwater turtles can more easily track their niches than Testudinidae and other terrestrial groups. However, habitat destruction and fragmentation at higher latitudes will probably reduce the capability of turtles and tortoises to cope with future climate changes.

Marine protected areas in the context of climate change: key challenges for coastal social-ecological systems.

Climate and ecological emergencies play out acutely in coastal systems with devastating impacts on biodiversity, and the livelihoods of communities and their cultural values. Marine Protected Areas (MPAs) are one of the key management and regulatory tools against biodiversity loss, playing a role in strengthening bio-cultural diversity and sustainability of coastal social-ecological systems. What is unclear though is the effectiveness of static protections under climate change as species move. Next to ecological uncertainty, regulatory uncertainty may play a role in weakening marine conservation. We asked whether MPAs are ecologically effective now and can sustain or improve to be so in the future while facing key climate and regulatory uncertainties. MPAs can support the protection of cultural values and have an impact on activities of sea-users and the sustainability of social-ecological systems. As such, questions surrounding their legitimacy under a changing climate and increased uncertainty are pertinent. We argue that MPA governance must be cognisant of the interdependency between natural and human systems and their joint reaction to climate change impacts based on an integrated, co-developed, and interdisciplinary approach. Focusing on the UK as a case study, we highlight some of the challenges to achieve effective, adaptive and legitimate governance of MPAs. This article is part of the theme issue 'Nurturing resilient marine ecosystems'.

[The Prestige of Housewives in Germany-A Quantitative-Empirical Analysis of Differential Perceptions]. / Das Ansehen von Hausfrauen in Deutschland ­ Eine quantitativ-empirische Analyse differenzieller Wahrnehmungen.

The employment rate of women has increased markedly over the past decades, both internationally and in Germany, whereas the classic male breadwinner model is eroding. Against this background, using current survey data, the aim of this study is to examine the social prestige of the shrinking group of housewives whose main activity is domestic and family work. The analyses address, on the one hand, the question of how high their reputation is generally rated by the population in Germany and, on the other hand, whether the perceptions differ systematically by raters' sociodemographic characteristics. The empirical findings show that the reputation of housewives in Germany is generally rated higher than that of the unemployed and of those in helper jobs but lower than for those in professional jobs at the skilled level. Moreover, the assessments of housewives' prestige vary significantly according to the social group (birth cohort, level of education, labor force participation, gender) to which the respondents belong. Further analyses of interaction effects also reveal a differentiated interaction of the gender variable with the other structural group characteristics. The paper concludes with a detailed discussion of the results and an outlook on future research.

Characterisation of the pathophysiology of neuropathy and sensory dysfunction in a mouse model of recessive dystrophic epidermolysis bullosa.

ABSTRACT: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic condition in which mutations in the type VII collagen gene ( COL7A1 ) lead to decreased expression of this anchoring protein of the skin, causing the loss of stability at the dermo-epidermal junction. Most patients with RDEB experience neuropathic pain and itch due to the development of a small fibre neuropathy, characterised by decreased intraepidermal innervation and thermal hypoaesthesia. To understand the physiopathology of this neuropathy, we used a mouse model of RDEB (Col7a1 flNeo/flNeo ) and performed a detailed characterisation of the somatosensory system. Col7a1 flNeo/flNeo mice showed a decrease in heat sensitivity, an increase in spontaneous scratching, and a significant decrease in intraepidermal nerve fibre density in the hindpaw; these changes were distal because there was no significant loss of unmyelinated or myelinated fibres in the nerve trunk. Of interest, we observed a decrease in axon diameter in both myelinated and unmyelinated fibres. This axonal damage was not associated with inflammation of the dorsal root ganglion or central projection targets at the time of assessment. These results suggest that in RDEB, there is a distal degeneration of axons produced by exclusive damage of small fibres in the epidermis, and in contrast with traumatic and acute neuropathies, it does not induce sustained neuroinflammation. Thus, this animal model emphasizes the importance of a healthy cutaneous environment for maintenance of epidermal innervation and faithfully replicates the pathology in humans, offering the opportunity to use this model in the development of treatments for pain for patients with RDEB.

Exploring the impact of climate change on the global distribution of non-spinose planktonic foraminifera using a trait-based ecosystem model.

Planktonic foraminifera are one of the primary calcifiers in the modern ocean, contributing 23%-56% of total global pelagic carbonate production. However, a mechanistic understanding of how physiology and environmental conditions control their abundance and distribution is lacking, hindering the projection of the impact of future climate change. This understanding is important, not only for ecosystem dynamics, but also for marine carbon cycling because of foraminifera's key role in carbonate production. Here we present and apply a global trait-based ecosystem model of non-spinose planktonic foraminifera ('ForamEcoGEnIE') to assess their ecology and global distribution under future climate change. ForamEcoGEnIE considers the traits of calcium carbonate production, shell size, and foraging. It captures the main characteristic of biogeographical patterns of non-spinose species - with maximum biomass concentrations found in mid- to high-latitude waters and upwelling areas. The model also reproduces the magnitude of global carbonate production relatively well, although the foraminifera standing stock is systematically overestimated. In response to future scenarios of rising atmospheric CO2 (RCP6 and RCP8.5), on a regional scale, the modelled foraminifera biomass and export flux increases in the subpolar regions of the North Atlantic and the Southern Ocean while it decreases everywhere else. In the absence of adaptation, the biomass decline in the low-latitude South Pacific suggests extirpation. The model projects a global average loss in non-spinose foraminifera biomass between 8% (RCP6) and 11% (RCP8.5) by 2050 and between 14% and 18% by 2100 as a response to ocean warming and associated changes in primary production and ecological dynamics. Global calcium carbonate flux associated with non-spinose foraminifera declines by 13%-18% by 2100. That decline can slow down the ocean carbonate pump and create short-term positive feedback on rising atmospheric pCO2 .

Lithium isotope evidence for enhanced weathering and erosion during the Paleocene-Eocene Thermal Maximum.

The Paleocene-Eocene Thermal Maximum (PETM; ~55.9 Ma) was a geologically rapid warming period associated with carbon release, which caused a marked increase in the hydrological cycle. Here, we use lithium (Li) isotopes to assess the global change in weathering regime, a critical carbon drawdown mechanism, across the PETM. We find a negative Li isotope excursion of ~3‰ in both global seawater (marine carbonates) and in local weathering inputs (detrital shales). This is consistent with a very large delivery of clays to the oceans or a shift in the weathering regime toward higher physical erosion rates and sediment fluxes. Our seawater records are best explained by increases in global erosion rates of ~2× to 3× over 100 ka, combined with model-derived weathering increases of 50 to 60% compared to prewarming values. Such increases in weathering and erosion would have supported enhanced carbon burial, as both carbonate and organic carbon, thereby stabilizing climate.

Thrombopoietin receptor agonists for acquired thrombocytopenia following anti-CD19 CAR-T-cell therapy: a case report.

Chimeric antigen receptor (CAR)-modified T-cells targeting CD19 represent a promising therapy for relapsed or refractory (r/r) lymphoma and leukemia. The most common adverse events are immune related and include cytokine release syndrome and neurotoxicity. However, early and late hematological toxicity has emerged as a substantial clinical hurdle leading among others to an increased risk for infections or bleeding. The underlying pathophysiology remains elusive and supportive measures comprise stem cell support or the use of growth factors. Here, we report a 66-year-old woman with r/r diffuse large B-cell lymphoma that received anti-CD19 CAR-T-cells achieving a complete metabolic remission. At month 3 after adoptive cell transfer, the patient still exhibited a grade 3 anemia and a grade 4 thrombocytopenia. The latter required regular platelet transfusions. Bone marrow smear revealed hypocellularity without dysplasia. Despite reduced megakaryopoiesis, immature platelet fraction was elevated indicating an at least partially consumptive underlying component. Based on the successful use of Romiplostim, a thrombopoietin receptor-agonist, in aplastic anemia and immune thrombocytopenia, we treated our patient accordingly. Platelet count (and hemoglobin levels) increased and the patient remains transfusion-free. Taken together, our therapeutic approach could represent a novel strategy for managing CAR-T-cell-related hematotoxicity but, self-evidently, requires further controlled clinical studies.

Effects of body-oriented yoga: a RCT study for patients with major depressive disorder.

The major depressive disorder is one of the most common mental illnesses worldwide. Current treatment standards recommend a combined therapy with medication and psychotherapy. As an additive component and to further improvements in treatment, physical activity such as yoga may be integrated into conventional treatment. This study investigates the impact of a 3-month body-oriented yoga in patients with major depressive disorder (MDD). In total, n = 83 patients were included. An intervention group received a vigorous Ashtanga-Yoga three times a week. The waiting-list control group obtained a treatment as usual (TAU). As a primary outcome depression scores (Beck Depression Inventory-II (BDI-II), Montgomery Asberg Depression Rating Scale (MADRS)) were tested at three time points. Secondary outcome was the positive and negative affect [Positive and Negative Affect Scale (PANAS)] and remission rates. To analyze the data, multilevel models and effect sizes were conducted. The results showed an improvement in BDI-II scores for both groups over time [γ = - 3.46, t(165) = - 7.99, p < 0.001] but not between groups [γ = 0.98, t(164) = 1.12, p = 0.263]. An interaction effect (time x group) occurred for MADRS [γ = 2.10, t(164) = 2.10, p < 0.038]. Positive affects improved over time for both groups [γ = 1.65, t(165) = 4.03, p < 0.001]. Negative affects decreased for all over time [γ = - 1.00, t(165) = - 2.51, p = 0.013]. There were no significant group differences in PANAS. Post hoc tests revealed a greater symptom reduction within the first 6 weeks for all measurements. The effect sizes for depression scores showed a positive trend. Remission rates indicated a significant improvement in the yoga group (BDI-II: 46.81%, MADRS: 17.02%) compared to the control group (BDI: 33.33%, MADRS: 8.33%). The findings suggest that there is a trendsetting additive effect of Ashtanga-Yoga after 3 months on psychopathology and mood with a greater improvement at the beginning of the intervention. Further research in this field can help to achieve more differentiated results.

Ecosystem function after the K/Pg extinction: decoupling of marine carbon pump and diversity.

The ocean biological pump is the mechanism by which carbon and nutrients are transported to depth. As such, the biological pump is critical in the partitioning of carbon dioxide between the ocean and atmosphere, and the rate at which that carbon can be sequestered through burial in marine sediments. How the structure and function of planktic ecosystems in the ocean govern the strength and efficiency of the biological pump and its resilience to disruption are poorly understood. The aftermath of the impact at the Cretaceous/Palaeogene (K/Pg) boundary provides an ideal opportunity to address these questions as both the biological pump and marine plankton size and diversity were fundamentally disrupted. The excellent fossil record of planktic foraminifera as indicators of pelagic-biotic recovery combined with carbon isotope records tracing biological pump behaviour, show that the recovery of ecological traits (diversity, size and photosymbiosis) occurred much later (approx. 4.3 Ma) than biological pump recovery (approx. 1.8 Ma). We interpret this decoupling of diversity and the biological pump as an indication that ecosystem function had sufficiently recovered to drive an effective biological pump, at least regionally in the South Atlantic.

Resolution of vascular inflammation in patients with new-onset giant cell arteritis: data from the RIGA study.

OBJECTIVES: Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. METHODS: Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with MTX or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. RESULTS: We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX and 19 with TOC. PETVAS decreased from 18.9-8.0 units at follow-up in the overall population (P <0.001). PETVAS changes were numerically higher in patients receiving MTX (-12.3 units) or TOC (-11.7 units) compared with PRED (-8.7). Mean cumulative prednisolone dosages were 5637, 4418 and 2984 mg in patients treated with PRED, MTX and TOC (P =0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95% CI: 1.01, 45.29; P =0.049) and 16.25 (95% CI: 2.60, 101.73; P =0.003) for MTX and TOC users compared with PRED users. CONCLUSION: Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.

Individual Calculation of Effective Dose and Risk of Malignancy Based on Monte Carlo Simulations after Whole Body Computed Tomography.

Detailed knowledge about radiation exposure is crucial for radiology professionals. The conventional calculation of effective dose (ED) for computed tomography (CT) is based on dose length product (DLP) and population-based conversion factors (k). This is often imprecise and unable to consider individual patient characteristics. We sought to provide more precise and individual radiation exposure calculation using image based Monte Carlo simulations (MC) in a heterogeneous patient collective and to compare it to phantom based MC provided from the National Cancer Institute (NCI) as academic reference. Dose distributions were simulated for 22 patients after whole-body CT during Positron Emission Tomography-CT. Based on MC we calculated individual Lifetime Attributable Risk (LAR) and Excess Relative Risk (ERR) of cancer mortality. EDMC was compared to EDDLP and EDNCI. EDDLP (13.2 ± 4.5 mSv) was higher compared to EDNCI (9.8 ± 2.1 mSv) and EDMC (11.6 ± 1.5 mSv). Relative individual differences were up to -48% for EDMC and -44% for EDNCI compared to EDDLP. Matching pair analysis illustrates that young age and gender are affecting LAR and ERR significantly. Because of these uncertainties in radiation dose assessment automated individual dose and risk estimation would be desirable for dose monitoring in the future.

Single-cycle induction chemotherapy before chemoradiotherapy or surgery in functionally inoperable head and neck squamous cell carcinoma: 10-year results.

INTRODUCTION: The response to induction chemotherapy (IC) predicts local control after conservative treatment of laryngeal, meso- and hypopharyngeal head and neck squamous cell carcinoma (HNSCC) and can thus help to avoid surgery. Single-cycle induction chemotherapy may help to maintain a low local recurrence rate while keeping the overall toxicity manageable. However, long-term data on single-cycle IC response by tumor location is lacking. METHODS: N = 102 patients with functionally inoperable primary HNSCC of the larynx (n = 43), hypopharynx (n = 42) or mesopharynx/tongue (n = 17) received one cycle of docetaxel (75 mg/m2, d1) plus cisplatin (30 mg/m2, d1-3) or carboplatin (AUC 1.5, d1-3) and a response evaluation 3 weeks later. Responders (≥ 30% tumor size reduction and ≥ 20% SUVmax decrease in 18F-FDG PET/CT) were recommended chemoradiotherapy (CRT), and non-responders surgery. RESULTS: The overall response rate was 72.5%. All 74 responders and 10 non-responders received primary CRT, and 18 patients received primary surgery after single-cycle IC. Overall 10-year local recurrence-free survival (LRFS) was 73.7%. Three-year LRFS was 88.2% (mesopharynx/tongue), 88.2% (larynx), and 73.3% (hypopharynx); p = 0.17. 3-year distant metastasis-free survival (DMFS) was 94.1% (mesopharynx/tongue), 88.0% (larynx) and 76.4% (hypopharynx); p > 0.05. This influenced the 3-year cancer-specific survival (CSS) for larynx (91.2%) vs. hypopharynx tumors (60.8%); p = 0.003, but CSS was not different to tumors in the mesopharynx/tongue (81.4%); p > 0.05. CONCLUSIONS: A single-cycle induction chemotherapy for HNSCC enables surgery plus adjuvant therapy as well as chemoradiotherapy. The long-term local and distant disease control was good but varied between tumors in the larynx and mesopharynx/tongue vs. hypopharynx.

The Distribution of Pelvic Nodal Metastases in Prostate Cancer Reveals Potential to Advance and Personalize Pelvic Radiotherapy.

BACKGROUND: Traditional clinical target volume (CTV) definition for pelvic radiotherapy in prostate cancer consists of large volumes being treated with homogeneous doses without fully utilizing information on the probability of microscopic involvement to guide target volume design and prescription dose distribution. METHODS: We analyzed patterns of nodal involvement in 75 patients that received RT for pelvic and paraaortic lymph node metastases (LNs) from prostate cancer in regard to the new NRG-CTV recommendation. Non-rigid registration-based LN mapping and weighted three-dimensional kernel density estimation were used to visualize the average probability distribution for nodal metastases. As independent approach, the mean relative proportion of LNs observed for each level was determined manually and NRG and non-NRG levels were evaluated for frequency of involvement. Computer-automated distance measurements were used to compare LN distances in individual patients to the spatial proximity of nodal metastases at a cohort level. RESULTS: 34.7% of patients had pelvic LNs outside NRG-consensus, of which perirectal was most common (25.3% of all patients) followed by left common iliac nodes near the left psoas major (6.7%). A substantial portion of patients (13.3%) had nodes at the posterior edge of the NRG obturator level. Observer-independent mapping consistently visualized high-probability hotspots outside NRG-consensus in the perirectal and left common iliac regions. Affected nodes in individual patients occurred in highly significantly closer proximity than at cohort-level (mean distance, 6.6 cm vs. 8.7 cm, p < 0.001). CONCLUSIONS: Based on this analysis, the common iliac level should extend to the left psoas major and obturator levels should extend posteriorly 5 mm beyond the obturator internus. Incomplete coverage by the NRG-consensus was mostly because of perirectal involvement. We introduce three-dimensional kernel density estimation after non-rigid registration-based mapping for the analysis of recurrence data in radiotherapy. This technique provides an estimate of the underlying probability distribution of nodal involvement and may help in addressing institution- or subgroup-specific differences. Nodal metastases in individual patients occurred in highly significantly closer proximity than at a cohort-level, which supports that personalized target volumes could be reduced in size compared to a "one-size-fits-all" approach and is an important basis for further investigation into individualized field designs.