Preserved appendages in a Silurian binodicope: implications for the evolutionary history of ostracod crustaceans.

Ostracod crustaceans originated at least 500 Ma ago. Their tiny bivalved shells represent the most species-abundant fossil arthropods, and ostracods are omnipresent in a wide array of freshwater and marine environments today and in the past. Derima paparme gen. et sp. nov. from the Herefordshire Silurian Lagerstätte (~430 Ma) in the Welsh Borderland, UK, is one of only a handful of exceptionally preserved ostracods (with soft parts as well as the shell) known from the Palaeozoic. A male specimen provides the first evidence of the appendages of Binodicopina, a major group of Palaeozoic ostracods comprising some 135 Ordovician to Permian genera. The appendage morphology of D. paparme, but not its shell, indicates that binodicopes belong to Podocopa. The discovery that the soft-part morphology of binodicopes allies them with podocopes affirms that using the shell alone is an unreliable basis for classifying certain fossil ostracods, and knowledge of soft-part morphology is critical for the task. Current assignment of many fossil ostracods to higher taxa, and therefore the evolutionary history of the group, may require reconsideration.

Ultrafast Photoinduced Phase Change in SnSe.

Time-resolved multiterahertz (THz) spectroscopy is used to observe an ultrafast, nonthermal electronic phase change in SnSe driven by interband photoexcitation with 1.55 eV pump photons. The transient THz photoconductivity spectrum is found to be Lorentzian-like, indicating charge localization and phase segregation. The rise of photoconductivity is bimodal in nature, with both a fast and slow component due to excitation into multiple bands and subsequent intervalley scattering. The THz conductivity magnitude, dynamics, and spectra show a drastic change in character at a critical excitation fluence of approximately 6 mJ/cm^{2} due to a photoinduced phase segregation and a macroscopic collapse of the band gap.

Global food security threatened by potassium neglect.

Food security and healthy ecosystems are placed in jeopardy by poor potassium management. Six actions may prevent declines in crop yield due to soil potassium deficiency, safeguard farmers from potash price volatility and address environmental concerns associated with potash mining.

Reducing the environmental impact of rice production in subtropical India by minimising reactive nitrogen loss.

The future of reactive nitrogen (N) for subtropical lowland rice to be characterised under diverse N-management to develop adequate sustainable practices. It is a challenge to increase the efficiency of N use in lowland rice, as N can be lost in various ways, e.g., through nitrous oxide (N2O) or dinitrogen (N2) emissions, ammonia (NH3) volatilization and nitrate (NO3-) leaching. A field study was carried out in the subsequent wet (2021) and dry (2022) seasons to assess the impacts of different N management strategies on yield, N use efficiency and different N losses in a double-cropped rice system. Seven different N-management practices including application of chemical fertilisers, liquid organic fertiliser, nitrification inhibitors, organic nutrient management and integrated nutrient management (INM) were studied. The application of soil test-based neem-coated urea (NCU) during the wet season resulted in the highest economic yield, while integrated nutrient management showed the highest economic yield during the dry season. Total N losses by volatilization of NH3, N2O loss and leaching were 0.06-4.73, 0.32-2.14 and 0.25-1.93 kg ha-1, corresponding to 0.06-5.84%, 0.11-2.20% and 0.09-1.81% of total applied N, respectively. The total N-uptake in grain and straw was highest in INM (87-89% over control) followed by the soil test-based NCU (77-82% over control). In comparison, recovery efficiency of N was maximum from application of NCU + dicyandiamide during both the seasons. The N footprint of paddy rice ranged 0.46-2.01 kg N-eq. t-1 during both seasons under various N management. Ammonia volatilization was the process responsible for the largest N loss, followed by N2O emissions, and NO3- leaching in these subtropical lowland rice fields. After ranking the different N management practices on a scale of 1-7, soil test-based NCU was considered the best N management approach in the wet year 2021, while INM scored the best in the dry year 2022.

Managing urban development could halve nitrogen pollution in China.

Halving nitrogen pollution is crucial for achieving Sustainable Development Goals (SDGs). However, how to reduce nitrogen pollution from multiple sources remains challenging. Here we show that reactive nitrogen (Nr) pollution could be roughly halved by managed urban development in China by 2050, with NH3, NOx and N2O atmospheric emissions declining by 44%, 30% and 33%, respectively, and Nr to water bodies by 53%. While rural-urban migration increases point-source nitrogen emissions in metropolitan areas, it promotes large-scale farming, reducing rural sewage and agricultural non-point-source pollution, potentially improving national air and water quality. An investment of approximately US$ 61 billion in waste treatment, land consolidation, and livestock relocation yields an overall benefit of US$ 245 billion. This underscores the feasibility and cost-effectiveness of halving Nr pollution through urbanization, contributing significantly to SDG1 (No poverty), SDG2 (Zero hunger), SDG6 (Clean water), SDG12 (Responsible consumption and production), SDG14 (Climate Action), and so on.

Prospective Trial of Water Vapor Thermal Therapy for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia in Subjects with a Large Prostate: 6- and 12-month Outcomes.

Background: Current guidelines recommend Rezum water vapor thermal therapy for the treatment of benign prostatic hyperplasia (BPH) for prostate glands ranging in volume from 30 to 80 cm3. Few prospective studies have specifically evaluated the use of Rezum for larger prostates. Objective: To evaluate the safety and efficacy of water vapor thermal therapy in patients with a prostate gland >80 cm3 and ≤150 cm3. Design setting and participants: In this prospective, single-arm study at seven centers in the USA, subjects were males aged >50 yr with symptomatic BPH and prostate volume of >80 cm3 and ≤150 cm3. Intervention: Rezum was used to deliver sterile water vapor via a transurethral approach to ablate targeted areas of prostate tissue. Outcome measurements and statistical analysis: The primary efficacy outcome was response to therapy, defined on a per-patient basis as a ≥30% improvement in International Prostate Symptom Score (IPSS) from baseline to 6 mo. The primary safety outcome was a composite of serious device-related safety events. Secondary outcomes included catheterization for device-related retention. IPSS outcomes over time were analyzed via generalized estimating equations. Results and limitations: Among 47 eligible patients, prostate volume ranged from 80.8 to 148.1 cm3. All patients completed 6-mo follow-up, and 40/47completed 12-mo follow-up. At 6 mo, 83% were treatment responders according to the primary efficacy endpoint. The mean IPSS improvement at 6 mo was 11.9 ± 7.5 points, reflecting significant improvement. The primary safety outcome was met, with no occurrence of device-related composite safety events. The study is limited by the nonrandomized design and early termination, unrelated to safety or effectiveness. Conclusions: Our results are consistent with previous findings for prostate glands of up to 80 cm3, and indicate the safety and efficacy of Rezum for BPH in patients with a larger prostate. Patient summary: Rezum therapy, in which water vapor is used to treat targeted areas of the prostate, is currently recommended for patients with benign enlargement of the prostate and a prostate size of up to 80 cm3. We found that this treatment was also effective and safe in patients with a larger prostate of 80-150 cm3.

Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo.

The Msh2-Msh3 mismatch repair (MMR) complex in Saccharomyces cerevisiae recognizes and directs repair of insertion/deletion loops (IDLs) up to ∼17 nucleotides. Msh2-Msh3 also recognizes and binds distinct looped and branched DNA structures with varying affinities, thereby contributing to genome stability outside post-replicative MMR through homologous recombination, double-strand break repair (DSBR) and the DNA damage response. In contrast, Msh2-Msh3 promotes genome instability through trinucleotide repeat (TNR) expansions, presumably by binding structures that form from single-stranded (ss) TNR sequences. We previously demonstrated that Msh2-Msh3 binding to 5' ssDNA flap structures interfered with Rad27 (Fen1 in humans)-mediated Okazaki fragment maturation (OFM) in vitro. Here we demonstrate that elevated Msh2-Msh3 levels interfere with DNA replication and base excision repair in vivo. Elevated Msh2-Msh3 also induced a cell cycle arrest that was dependent on RAD9 and ELG1 and led to PCNA modification. These phenotypes also required Msh2-Msh3 ATPase activity and downstream MMR proteins, indicating an active mechanism that is not simply a result of Msh2-Msh3 DNA-binding activity. This study provides new mechanistic details regarding how excess Msh2-Msh3 can disrupt DNA replication and repair and highlights the role of Msh2-Msh3 protein abundance in Msh2-Msh3-mediated genomic instability.

Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab')2 fragments.

The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has been used to generate candidate products. In addition to purified IgG, we have refined candidate therapies by removing non-specific IgG via affinity binding along with fragmentation to eliminate the Fc region to create F(ab')2 fragments. These preparations were evaluated for in vitro activity and demonstrated to be strongly neutralising against a range of SARS-CoV-2 strains, including Omicron B2.2. In addition, their protection against disease manifestations and viral loads were assessed using a hamster SARS-CoV-2 infection model. Results demonstrated protective effects of both IgG and F(ab')2, with the latter requiring sequential dosing to maintain in vivo activity due to rapid clearance from the circulation.

A vicissicaudatan arthropod from the Silurian Herefordshire Lagerstätte, UK.

A new arthropod, Carimersa neptuni gen. et sp. nov., is described from the Silurian (Wenlock Series) Herefordshire Konservat-Lagerstätte, UK. The head bears pedunculate eyes and five pairs of appendages. Triflagellate antennae are followed by two pairs of uniramous limbs each with an endopod bearing a pronounced gnathobasic basipod. The posterior two pairs of head limbs and all trunk limbs bear an endopod, exopod and filamentous exite. The trunk consists of 10 appendage-bearing segments followed by an apodous abdomen of four segments. The arthropod resolves as sister taxon to Kodymirus and Eozetetes + Aglaspidida. It is the first representative of Vicissicaudata reported from the Herefordshire Lagerstätte and the first Silurian example with well-preserved appendages. The preservation of a cluster of radiolarians apparently captured by the trunk appendages is the first direct association of predator and prey discovered in the Herefordshire fauna, and suggests that Carimersa was a nektobenthic form that used its gnathobasic basipods in microdurophagy.

Lichens as spatially transferable bioindicators for monitoring nitrogen pollution.

Excess nitrogen is a pollutant and global problem that harms ecosystems and can severely affect human health. Pollutant nitrogen is becoming more widespread and intensifying in the tropics. There is thus a requirement to develop nitrogen biomonitoring for spatial mapping and trend analysis of tropical biodiversity and ecosystems. In temperate and boreal zones, multiple bioindicators for nitrogen pollution have been developed, with lichen epiphytes among the most sensitive and widely applied. However, the state of our current knowledge on bioindicators is geographically biased, with extensive research effort focused on bioindicators in the temperate and boreal zones. The development of lichen bioindicators in the tropics is further weakened by incomplete taxonomic and ecological knowledge. In this study we performed a literature review and meta-analysis, attempting to identify characteristics of lichens that offer transferability of bioindication into tropical regions. This transferability must overcome the different species pools between source information - drawing on extensive research effort in the temperate and boreal zone - and tropical ecosystems. Focussing on ammonia concentration as the nitrogen pollutant, we identify a set of morphological traits and taxonomic relationships that cause lichen epiphytes to be more sensitive, or more resistant to this excess nitrogen. We perform an independent test of our bioindicator scheme and offer recommendations for its application and future research in the tropics.

Controlling the structure of supramolecular fibre formation for benzothiazole based hydrogels with antimicrobial activity against methicillin resistant Staphylococcus aureus.

Antimicrobial resistance is one of the greatest threats to human health. Gram-positive methicillin resistant Staphylococcus aureus (MRSA), in both its planktonic and biofilm form, is of particular concern. Herein we identify the hydrogelation properties for a series of intrinsically fluorescent, structurally related supramolecular self-associating amphiphiles and determine their efficacy against both planktonic and biofilm forms of MRSA. To further explore the potential translation of this hydrogel technology for real-world applications, the toxicity of the amphiphiles was determined against the eukaryotic multicellular model organism, Caenorhabditis elegans. Due to the intrinsic fluorescent nature of these supramolecular amphiphiles, material characterisation of their molecular self-associating properties included; comparative optical density plate reader assays, rheometry and widefield fluorescence microscopy. This enabled determination of amphiphile structure and hydrogel sol dependence on resultant fibre formation.

Microscopic Origins of the Nonlinear Behavior of Particle-Filled Rubber Probed with Dynamic Strain XPCS.

The underlying microscopic response of filler networks in reinforced rubber to dynamic strain is not well understood due to the experimental difficulty of directly measuring filler network behavior in samples undergoing dynamic strain. This difficulty can be overcome with in situ X-ray photon correlation spectroscopy (XPCS) measurements. The contrast between the silica filler and the rubber matrix for X-ray scattering allows us to isolate the filler network behavior from the overall response of the rubber. This in situ XPCS technique probes the microscopic breakdown and reforming of the filler network structure, which are responsible for the nonlinear dependence of modulus on strain, known in the rubber science community as the Payne effect. These microscopic changes in the filler network structure have consequences for the macroscopic material performance, especially for the fuel efficiency of tire tread compounds. Here, we elucidate the behavior with in situ dynamic strain XPCS experiments on industrially relevant, vulcanized rubbers filled (13 vol %) with novel air-milled silica of ultrahigh-surface area (UHSA) (250 m2/g). The addition of a silane coupling agent to rubber containing this silica causes an unexpected and counterintuitive increase in the Payne effect and decrease in energy dissipation. For this rubber, we observe a nearly two-fold enhancement of the storage modulus and virtually equivalent loss tangent compared to a rubber containing a coupling agent and conventional silica. Interpretation of our in situ XPCS results simultaneously with interpretation of traditional dynamic mechanical analysis (DMA) strain sweep experiments reveals that the debonding or yielding of bridged bound rubber layers is key to understanding the behavior of rubber formulations containing the silane coupling agent and high-surface area silica. These results demonstrate that the combination of XPCS and DMA is a powerful method for unraveling the microscale filler response to strain which dictates the dynamic mechanical properties of reinforced soft matter composites. With this combination of techniques, we have elucidated the great promise of UHSA silica when used in concert with a silane coupling agent in filled rubber. Such composites simultaneously exhibit large moduli and low hysteresis under dynamic strain.

Cost-effective mitigation of nitrogen pollution from global croplands.

Cropland is a main source of global nitrogen pollution1,2. Mitigating nitrogen pollution from global croplands is a grand challenge because of the nature of non-point-source pollution from millions of farms and the constraints to implementing pollution-reduction measures, such as lack of financial resources and limited nitrogen-management knowledge of farmers3. Here we synthesize 1,521 field observations worldwide and identify 11 key measures that can reduce nitrogen losses from croplands to air and water by 30-70%, while increasing crop yield and nitrogen use efficiency (NUE) by 10-30% and 10-80%, respectively. Overall, adoption of this package of measures on global croplands would allow the production of 17 ± 3 Tg (1012 g) more crop nitrogen (20% increase) with 22 ± 4 Tg less nitrogen fertilizer used (21% reduction) and 26 ± 5 Tg less nitrogen pollution (32% reduction) to the environment for the considered base year of 2015. These changes could gain a global societal benefit of 476 ± 123 billion US dollars (USD) for food supply, human health, ecosystems and climate, with net mitigation costs of only 19 ± 5 billion USD, of which 15 ± 4 billion USD fertilizer saving offsets 44% of the gross mitigation cost. To mitigate nitrogen pollution from croplands in the future, innovative policies such as a nitrogen credit system (NCS) could be implemented to select, incentivize and, where necessary, subsidize the adoption of these measures.

Disparities in substance use treatment retention: An exploration of reasons for discharge from publicly funded treatment.

Although Delaware is the seventh smallest state in the country (including Washington, D.C.) in terms of population size, it has the second highest drug overdose death rate. The Delaware Division of Substance Abuse and Mental Health has increased attention in identifying disparities in treatment outcomes. We explored reasons for discharge from publicly-funded treatment in Delaware with special attention to populations at risk for health inequities, with a focus on covariates of treatment non-completion. Using secondary data collected from publicly-funded treatment providers, we analyzed data from individuals that were admitted to substance use treatment between 2015 and 2019 and had been discharged in 2019. We did this by using logistic and multinomial regression, focusing on non-completion treatment outcomes such as failure to meet requirements, loss of contact, and treatment refusal. Clients who were Black or African American, compared to white clients, were more likely to be lost contact with, administratively discharged, or marked as failing to meet treatment requirements than having a completed treatment discharge. Women were 30% less likely than men to have "failed to meet treatment requirements" compared to completing treatment. Further investigation is needed into these patterns. While treatment quality cannot be assessed using this data, the results point to a need for closer study of disparities in treatment related to race, ethnicity, gender, employment, criminal justice involvement, and type of drug used. Treatment providers should be made aware of culturally informed care, as well as client-created goals, in order to reduce disparities in exit from treatment.

A Flexible Near-Field Biosensor for Multisite Arterial Blood Flow Detection.

Modern wearable devices show promising results in terms of detecting vital bodily signs from the wrist. However, there remains a considerable need for a device that can conform to the human body's variable geometry to accurately detect those vital signs and to understand health better. Flexible radio frequency (RF) resonators are well poised to address this need by providing conformable bio-interfaces suitable for different anatomical locations. In this work, we develop a compact wearable RF biosensor that detects multisite hemodynamic events due to pulsatile blood flow through noninvasive tissue-electromagnetic (EM) field interaction. The sensor consists of a skin patch spiral resonator and a wearable transceiver. During resonance, the resonator establishes a strong capacitive coupling with layered dielectric tissues due to impedance matching. Therefore, any variation in the dielectric properties within the near-field of the coupled system will result in field perturbation. This perturbation also results in RF carrier modulation, transduced via a demodulator in the transceiver unit. The main elements of the transceiver consist of a direct digital synthesizer for RF carrier generation and a demodulator unit comprised of a resistive bridge coupled with an envelope detector, a filter, and an amplifier. In this work, we build and study the sensor at the radial artery, thorax, carotid artery, and supraorbital locations of a healthy human subject, which hold clinical significance in evaluating cardiovascular health. The carrier frequency is tuned at the resonance of the spiral resonator, which is 34.5 ± 1.5 MHz. The resulting transient waveforms from the demodulator indicate the presence of hemodynamic events, i.e., systolic upstroke, systolic peak, dicrotic notch, and diastolic downstroke. The preliminary results also confirm the sensor's ability to detect multisite blood flow events noninvasively on a single wearable platform.

Primary Cutaneous Anaplastic Large-Cell Lymphoma With Aberrant CD20 Expression: Case Report and Review of the Literature.

ABSTRACT: Cutaneous CD20 + T-cell lymphomas are exceedingly rare. Differentiating cases of T-cell lymphoma with aberrant expression of the B-cell marker CD20 from B-cell lymphoma may be associated with misdiagnosis or delays in diagnosis. We report, to the authors' knowledge, the first case of CD20 + primary cutaneous anaplastic large-cell lymphoma and review the literature to characterize published cases of CD20 + cutaneous T-cell lymphoma (n = 40). There is no accepted explanation for this phenomenon; however, it is suspected that these cases may be due to neoplastic transformation of CD20 + T cells or that CD20 may represent a T-cell activation marker. Expression of CD20 may have clinical significance in prognostication and consideration of treatment options with anti-CD20 therapies such as rituximab.