In cellular circumstances where carbohydrates are scarce, plants can use alternative substrates for cellular energetic maintenance. In plants, the main protein reserve is present in the chloroplast, which contains most of the total leaf proteins and represents a rich source of nitrogen and amino acids. Autophagy plays a key role in chloroplast breakdown, a well-recognized symptom of both natural and stress-induced plant senescence. Remarkably, an autophagic-independent route of chloroplast degradation associated with Chloroplast Vesiculation (CV) gene was recently demonstrated. During extended darkness, CV is highly induced in the absence of autophagy, contributing to the early senescence phenotype of atg mutants. To further investigate the role of CV under dark-induced senescence conditions, mutants with low expression of CV ( amircv) and double mutants amircv1xatg5 were characterized. Following darkness treatment, no aberrant phenotypes were observed in amircv single mutants; however, amircv1xatg5 double mutants displayed early senescence and enhanced dismantling of chloroplast and membrane structures under these conditions. Metabolic characterization revealed that the functional lack of both CV and autophagy leads to higher impairment of amino acid release and differential organic acid accumulation during starvation conditions. The data obtained are discussed in the context of the role of CV and autophagy, both in terms of cellular metabolism and the regulation of chloroplast degradation.

Aims: Emodepside is an anthelmintic, originally developed for veterinary use. We investigated the safety, pharmacokinetics, relative bioavailability and dose linearity of four oral formulations of emodepside in healthy male subjects. Methods: Three randomised, parallel‐group, controlled, Phase I studies were conducted using various oral formulations, involving 79 subjects in ten cohorts in the single-ascending-dose study, 24 subjects in three ascending-dose cohorts in the multiple-ascending-dose study and 77 subjects in seven different cohorts in the relative bioavailability study. Pharmacokinetics and safety assessments were performed up to 21, 30 and 7 days, respectively. Results: As a liquid service formulation, emodepside was rapidly absorbed under fasting conditions, with dose-proportional increases in plasma concentrations at doses from 1 mg to 40 mg. The half-life during the first 24 hours after dosing was around 11 hours, followed by a terminal elimination half-life > 500 hours. Emodepside was less bioavailable in the fed state. The rate of absorption was slower and Cmax was lower with the amorphous solid dispersion tablets compared to the liquid service formulation. Emodepside was well tolerated overall with no major safety concerns. Conclusion: These Phase I studies with various dosage forms revealed a pharmacokinetic profile suggesting good tissue distribution of emodepside and a long terminal half‐life. A 15 mg dose with the gastrosoluble tablet is predicted to provide exposure that will achieve the target concentration for clinical efficacy. These data enabled us to select a field-adapted tablet formulation that will open the way for further clinical development of emodepside in individuals with onchocerchiasis.

Rationale, aims and objectives Creating networked business models is one of the innovative approaches that have the ability and potential for meeting market needs. The purpose of this study is to provide a decision making model for a fair profit sharing among the members of a diagnostic laboratory network while providing a distinctive value for the patients. Methods To identify the members of the network of laboratories, a suitable approach to calculate members’ efficiency scores is proposed. Then, the network members are classified into three groups based on their performance scores. The three groups help administrators identify eligible members, members who need to improve their performance in order to meet the minimum requirements, and members who do not qualify for admission to the network. Since the performance of the members should play a significant role in the fair profit sharing mechanism, the fair allocation of profits among network members is done by the use of Shapely’s value based on the efficiency scores of members. Results The results show that for such a fair mechanism, the efficiency and sample size (the number of samples (blood, urine) taken from the patients by the laboratories), as the two effective factors, have a decisive role in the share of profit of laboratory units of the network. In the Laboratory Services Network, members receive a number of samples according to their performance. As a result, the sample size received has a direct impact on the net income of each member. Conclusion In conclusion, it is evident that the use of Shapely value may help managers in the process of sharing profits among network members in a fair way, thereby improving network performance. In this way, incentive strategies may be created for the members of the network and long-term survival of the network may be achieved.

Tyrosine kinase inhibitors (TKIs) have revolutionized the management of chronic myeloid leukemia (CML), and currently in patients with CML in chronic phase (CML-CP) the first-line treatment is based on BCR-ABL targeted therapy with TKIs [1]. Although generally well tolerated, all BCR-ABL TKIs can be associated with hematologic and non-hematologic toxicities [2]. Most of the patients with CML-CP continue receiving TKIs, unless there is lack of optimal response and/or serious toxicities.

This paper describes an in-depth methodical approach to the development of efficient high frequency (HF) antennas for usage in radio frequency identification (RFID) systems operating at 13.56MHz. It presents brief theory relevant to RFID communication and sets up a framework within which features and requirements of antennas are linked to key design parameters such as antenna form-factor and size; RF power level, materials and communication protocol. Tuning circuits necessary to adjust the resonance and power matching characteristics of antennas for good transponder interrogation and response recovery are discussed. To validate the approaches outlined, a complete step-wise antenna design and measurement described. Common practical problems that are often encountered in such design processes are also commented on.

Multi-channel food webs are shaped by the ability of apex predators to link asymmetric energy flows in mesohabitats differing in productivity and community traits. While body size is a fundamental trait underlying life histories and demography, its implications for structuring multi-channel food webs are unexplored. To fill this gap, we develop a framework that links population responses to predation and resource availability to community-level patterns using a tri-trophic food web model with two populations of intermediate consumers and a size-selective top predator. We show that asymmetries in mesohabitat productivities and consumer body sizes drive food web structure, merging previously separate theory on apparent competition and emergent Allee effects (i.e., abrupt collapses of top predator populations). Our results yield theoretical support for empirically observed stability of asymmetric multi-channel food webs and discover three novel types of emergent Allee effects involving intermediate consumers, multiple populations or multiple alternative stable states.

Cubesats have transcended mere demonstration systems to sophisticated missions which invariably require the use of deployable solar arrays for more power generation. The kinematics of deployment have considerable influence on the stability and attitude control of a satellite, especially one with such low mass as Cubesats. This work aimed to model and simulate two-wing deployable solar array, with a sun tracking tilt function for a 1-U CubeSat, with emphasis on the deployment mechanism using materials locally available in the country. The design is such that four panels attached to two wings hinged at Y and – Y directions deploy slowly and smoothly at approximately 2 seconds where the vibration decays exponentially and approaches zero. The model of all parts, as well as the computational analysis were done with SOLIDWORKS software. The system was tested for vibration and stability using the seismic mass-spring-and-damper arrangement and the Bond Graph technique was used to conduct kinematic analysis of the mechanism. A 3-D printing was generated and tested to evaluate its operational performance. The simulated results of the model were validated with the prototype outputs with an error of 0.03% in energy supply reliability, about 400% more power generated than the body mounted solar panels of same satellite specification without a significant impact on system strength and Stability.

Colony is the basic geometric construction of coral reef. However, both the forming regulations of colony and reef are still obscure. In this study, we reconstructed 21 important samples by high-resolution micro-computed tomography to investigate coral growth pattern and parameter. Our skeleton and canal reconstructions revealed characteristics of different coral species and we further visualized the growth axes and growth rings to reveal coral growth directions. We drew a skeleton gray-scale map and calculated coral skeleton void ratios to reveal skeletal diversity, devising a method to quantify coral growth. On the bases of the 3D reconstructions and growth parameters, we investigated growth strategies of different coral species. This work extends the knowledge of how reef-building corals grow their colonies, giving a hint on reef forming regulation. The data of this paper contain large amount of coral growth information, and can be used in further research on reef forming patterns under different conditions. The method used in this study can also be applied in animals with porous skeletons.

Objective: To determine SARS-CoV-2 seroprevalence in a UK pregnancy cohort and assess associations with demographic factors and vaccination timing. Design: Observational cohort study. Setting: UK inner-city maternity centre. Sample: 960 pregnant women attending nuchal scans from July 2020-January 2022. Methods: Blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid (N) and spike (S) proteins. Self-reported demographics, vaccination status and previous Covid-19 infection were extracted from health records. Multivariable regression models determined factors associated with seroprevalence and antibody titers. Main outcome measures: IgG N- and S-protein antibody titers. Results: 196/960 (20.4%) women were SARS-CoV-2 seropositive from previous infection. Of these, 70 (35.7%) self-reported previous infection. Amongst unvaccinated women, black women were most likely to be SARS-CoV-2 seropositive (aRR 1.88 [95% CI, 1.35-2.61], P < 0.001). Women from black and mixed ethnic backgrounds were least likely to have a history of vaccination with seropositivity to S-protein (aRR 0.58 [95% CI, 0.40-0.84], P = 0.004 and aRR 0.56 [95% CI, 0.34-0.92], P = 0.021 respectively). Double vaccinated, previously infected women had higher IgG S-protein antibody titers than unvaccinated, previously infected women (mean difference: 4.76, 95% CI = [2.65, 6.86], P < 0.001). Vaccination timing before vs during pregnancy did not significantly affect IgG S antibody titers (F(1, 77) = [0.07], P = 0.785). Conclusions: This inner-city pregnancy cohort demonstrates high rates of asymptomatic SARS-CoV-2 infection with women of black ethnicity having higher infection risk and lower vaccine uptake. SARS-CoV-2 antibody titers were highest among double vaccinated, previously infected women.

Background: Outcome of children with bladder-prostate rhabdomyosarcoma has improved with multimodal therapies, including surgery and/or radiotherapy for local treatment. Our aim was to report the long-term urological complications after a conservative approach combining conservative surgery and brachytherapy. Patients and methods: Eighty-six patients, free of disease, were retrospectively reviewed. Symptoms related to urinary tract obstruction, incontinence, infection and lithiasis were reported and graded according to CTCAE classification. Only symptomatic patients underwent urodynamic studies. Risk factors for complications were analyzed. Results: There were 76 males and 10 females. The median follow-up was 6.3 years (18 months-24 years). Complications occurred after a median follow up 5 years (0-21). Twenty-two patients had long-term urological complications. Urinary tract obstruction was found in 15 patients, urinary incontinence in 14 patients. Recurrent urinary tract infection and urinary lithiasis were found in 5 patients respectively. Beyond symptom, 3 etiologies were identified: bladder dysfunction in 15 patients, urethral stenosis in 6 and uretero-vesical junction stenosis in 5. Posterior bladder wall dissection used in large prostatic tumors, operation at age less than 2 years and partial prostatectomy were identified as risk factors for these complications. Conclusion: The conservative surgical approach combined with brachytherapy for BPRMS leads to long-term urological complications in 22% of patients free of their disease. Optimizing brachytherapy doses for young children and establishing a clear and long term follow-up protocol, could help to reduce these complications.

Herpes Simplex Encephalitis is the most common cause of infectious encephalitis. Our case is of a 75-year-old woman who presented with dysuria and altered mental status. Our case addresses the difficulties in diagnosis and highlights the importance of early recognition of HSE and its associated neurological sequelae.

Density functional theory (DFT) calculations were adopted in this work to investigate the ability of the B12N12 fullerene like nano-cage for sensing juglone (Jug) and one of its derivative (Jug-OH) using DFT based methods in gas phase, pentyl ethanoate (PE) and water. Results showed that B12N12 is able to adsorbed Jug preferentially by binding to one of the O-atom of its carbonyl groups. Based on NBO analysis, a charge transfer from the oxygen atoms of Jug and Jug-OH to the anti-bonding orbital of B was revealed. QTAIM analysis showed that the B12N12-Jug and B12N12-Jug-OH complexes are stabilized by a partially covalent B-O bond in addition to attractive non covalent interactions. The ability of Jug, Jug-OH as well as their complexes A and A-OH to scavenge radicals has been investigated via the usual hydrogen atom transfer (HAT) mechanism in the three media of study previously stated. Theoretical results revealed that in PE and water, the complexes are better antioxidant than Jug and Jug-OH. These results provide fundamental knowledge for the development of new antioxidant delivery careers.

A 63-year-old male, with a history of coronary artery bypass grafting using bilateral internal thoracic artery grafts, underwent surgical aortic valve replacement. Avoiding the graft injury, we selected the right anterior mini-thoracotomy approach under cardiac arrest with systemic hyperkalemia with remaining bilateral internal thoracic artery grafts open. Deep hypothermia was induced to obtain more reliable myocardial protection. We believe this strategy can be considered as a therapeutic option in patients requiring aortic valve replacement but unsuitable for transcatheter aortic valve replacement.

Introduction: Pneumopericardium is a dreaded complication in esophageal carcinoma. Case description: We report a case of a 62 year old patient with past history of esophageal cancer with spontaneus pneumopericardium, without hemodynamic compromise. Admission echocardiogram that revealed a pneumopericadium with the presence of the “swirling bubbles” and the “air gap” sign. A small esophagopericardial fistula was postulated as the cause of the pneumopericardium. He underwent esophageal stent placement with resolution of the pneumopericardium. Discussion: Pneumopericardium is usually a sign of marked clinical deterioration in neoplasia and leads to patients’ death few weeks. Here we presented a case, in which a more fortunate and unusual outcome happened.

Introduced alien species have direct and indirect effects on native communities, leading to lower taxonomic diversity and negative impacts on ecosystem functioning. Moreover, other aspects of diversity could be negatively affected, through alteration of functional and phylogenetic diversity of a community. This is particularly evident in habitats where human disturbance may favour alien species, posing an additional stressor on native communities. Following the community resistance hypothesis (higher diversity, higher resistance to invasion), we hypothesized: i) higher taxonomic, functional and phylogenetic diversity (TD, FD and PD respectively) in non-invaded bird communities (i.e. no alien bird species); and, ii) lower alien species impact on all diversity metrics in less human-disturbed areas. We surveyed bird communities in a modified Mediterranean landscape subject to varying levels of human disturbance. We tested whether TD, FD and PD indices were significantly different between non-invaded and invaded bird communities, and assessed the effect of landscape composition and configuration on these indices. We found that non-invaded communities retained higher TD and FD than invaded communities. Alien birds occupied novel parts of the functional space in invaded communities, but that they did not fully compensate for the taxonomic and functional diversity loss caused by the absence of native species. These results were consistent across different habitats, suggesting weak environmental filtering of communities. Generally, both communities were negatively affected by more human-disturbed areas (e.g. agriculture and urban areas) and enhanced by forest areas and by landscape heterogeneity. Our results suggest that the occurrence of alien birds negatively affects TD and FD (but not PD) of bird community assemblages, but that this impact is stronger in human-modified landscapes. Therefore, since the conservation of biodiversity in anthropogenic habitats is a worldwide challenge, researchers should prioritize efforts to assess the effects of alien species on communities inhabiting those habitats.

Original Manuscript ID: BJOG-21-1723.R1 Descriptive: The Impact of Respectful and Compassionate Bereavement Care Following Stillbirth Running Title: Respectful Bereavement Care After Stillbirth Author information: Mehali Patel, Senior Research Officer, Saving Babies’ Lives Team, Sands Contact Details: 07709602633 [email protected] Sands Office, CAN Mezzanine, 49-51 East Road, London, N1 6AH

Purpose: Pediatric patients with medulloblastoma in LMICs are most treated with 3D conformal photon craniospinal irradiation (CSI), a time-consuming, complex treatment to plan, especially in resource-constrained settings. Therefore, we developed and tested a 3D conformal CSI autoplanning tool for varying patient lengths. Methods and Materials: Autocontours were generated with a deep learning model trained:tested (80:20 ratio) on 143 pediatric medulloblastoma CT scans (patient ages, 2-19 years, median=7 years). Using the verified autocontours, the autoplanning tool generated 2 lateral brain fields matched to a single spine field, an extended single spine field, or 2 matched spine fields. Additional spine sub-fields were added to optimize the corresponding dose distribution. Feathering was implemented (yielding 9-12 fields) to give a composite plan. Each planning approach was tested on 6 patients (ages, 3-10 years). A pediatric radiation oncologist assessed clinical acceptability of each autoplan. Results: The autocontoured structures’ average Dice similarity coefficient ranged from 0.65-0.98. The average V95 for the brain/spinal canal for single, extended, and multi-field spine configurations was 99.9±0.06%/99.9±0.10%, 99.9±0.07%/99.4±0.30%, and 99.9±0.06%/99.4±0.40%, respectively. The average maximum dose across all field configurations to the brainstem, eyes (L/R), lenses (L/R) and spinal cord were 23.7±0.08 Gy, 24.1±0.28 Gy, 13.3±5.27 Gy, 25.5±0.34 Gy, respectively (prescription=23.4 Gy/13 fractions). Of the 18 plans tested, all were scored as clinically acceptable as-is or clinically acceptable with minor, time-efficient edits preferred or required. No plans were scored as clinically unacceptable. Conclusion: The autoplanning tool successfully generated pediatric CSI plans for varying patient lengths in 3.50 ± 0.4 minutes on average, indicating potential for an efficient planning aid in resource-constrained settings.

During the COVID-19 pandemic, many specialists doctors found themselves in a situation that they had not faced for a long time: treating patients out of their subarea of expertise. The possibilities of teaching and learning through the modalities of webinars brought to these days the urgent necessity for teamwork and interdisciplinary approach, taking advantage of different areas of expertise to the same patient. With the amount of papers published and the speed at which data are accessed, and analyzed it is impossible to be aware of new findings in all medical areas. The lesson that the COVID-19 pandemic brought to us was the urgent need for the interdisciplinary approach to treating better our patients, and not only each disease they present with. We must review our traditional approach to medical students, residents, colleagues, and patients in which we became stuck to distance and time obstacles. We must use the technology on our behalf to offer the best treatment and follow-up for patients. We live now in the Medicine 4.0 era. As Darwin a long time ago proved: we must evolve!