Early Phase Research Articles

Tracing Back a Second-generation Star Stripped from Terzan 5 by the Galactic Bar

Abstract The Galactic bulge hosts the Milky Way’s oldest stars, possibly coming from disrupted globular clusters (GCs) or the bulge’s primordial building blocks, making these stars witnesses to the Galaxy’s early chemical enrichment. The Galactic bar currently dominates the bulge’s region, altering the orbits of objects formed before its formation and complicating the trace of the field stars’ original clusters. Here, we present the discovery of a fossil record of this evolution, SOS1—a star trapped in the bar, exhibiting significant enhancements in nitrogen, sodium, and aluminum, typical of second-generation GC stars. SOS1 also shows an s-process Ce enhancement, suggesting an old age and early enrichment by fast-rotating massive stars in the Galaxy’s earliest phases. With the purpose of finding the SOS1's parent GC, we derive its precise chemodynamical properties by combining high-precision proper motions from Gaia with Apache Point Observatory Galactic Evolution Experiment–detailed chemical abundances. Our analysis suggests that SOS1 was possibly stripped from the GC Terzan 5 by the Galactic bar’s gravitational influence approximately 350 Myr ago. We also found chemical similarities suggesting that SOS1 belonged to the most metal-poor, ancient, and peripheral stellar population of Terzan 5. These results not only support the hypothesis that Terzan 5 is a remnant of a primordial building block of the Galactic bulge but also suggest this cluster continues losing stars to the bar. Our method highlights how powerful the use of chemodynamical properties in the Gaia era is for tracing the Galaxy’s evolutionary history.

Phenological divergence between plants and animals under climate change.

Climate change has altered the timing of recurring biological cycles in both plants and animals. Phenological changes may be unequal within and among trophic levels, potentially impacting the intricate interactions that regulate ecosystem functioning. Here we compile and analyse a global dataset of terrestrial phenological observations, including nearly half a million time series for both plants and animals. Our analysis reveals an increasing phenological asynchronization between plants and animals from 1981 to 2020, with a stronger overall advancement of late-season phenophases for plants than for animals. Almost 30% of temporal variations in plant phenophases can be explained by the timing of the preceding phenophases. This temporal dependency allows the advancement caused by warming to accumulate and propagate through seasons, advancing later phenophases more than earlier phases. By contrast, animals rely on various environmental cues and resource-tracking strategies to initiate their life-cycle activities, which weakens their cross-phenophase linkage and undermines the effect of warming. Our results suggest that future warming may increase phenological asynchronization between plants and animals and potentially disturb trophic interactions and ecosystem stability.

Developing a digital phenotype to subdivide adult immunosuppressed COVID-19 outcomes within the English Primary Care Sentinel Network.

Adults classified as immunosuppressed have been disproportionately affected by the COVID-19 pandemic. Compared to the immunocompetent, certain patients are at increased risk of suboptimal vaccine response and adverse health outcomes if infected. However, there has been insufficient work to pinpoint where these risks concentrate within the immunosuppressed spectrum; surveillance efforts typically treat the immunosuppressed as a single entity, leading to wide confidence intervals. A clinically meaningful and computerised medical record (CMR) compatible method to subdivide immunosuppressed COVID-19 data is urgently needed. We conducted a rapid scoping review into COVID-19 mortality across UK immunosuppressed categories to assess if differential mortality risk was a viable means of subdivision. We converted the risk hierarchy that surfaced into a pilot digital phenotype-a valueset and series of ontological rules ready to extract immunosuppressed patients from CMR data and stratify outcomes of interest in COVID-19 surveillance dataflows. The rapid scoping review returned COVID-19 mortality data for all immunosuppressed subgroups assessed and revealed significant heterogeneity across the spectrum. There was a clear distinction between heightened COVID-19 mortality in haematological malignancy and transplant patients and mortality that approached the immunocompetent baseline amongst cancer therapy recipients, autoimmune patients, and those with HIV. This process, complemented by expert clinical input, informed the curation of the five-part digital phenotype now ready for testing in real-world data; its ontological rules will enable mutually exclusive, hierarchical extraction with nuanced time and treatment conditions. Unique categorisations have been introduced, including 'Bone Marrow Compromised' and those dedicated to differentiating prescriptions related and unrelated to cancer. Codification was supported by existing reference sets of medical codes; absent or redundant codes had to be resolved manually. Although this work is in its earliest phases, the development process we report has been highly informative. Systematic review, clinical consensus building, and implementation studies will test the validity of our results and address criticisms of the rapid scoping exercise they are predicated on. Comprehensive testing for COVID-19 has differentiated mortality risks across the immunosuppressed spectrum. This risk hierarchy has been codified into a digital phenotype for differentiated COVID-19 surveillance; this marks a step towards the needs-based management of these patients that is urgently required.

Impact of the COVID-19 Pandemic on People with Dementia and their Caregivers: A Multiphase Observational Study from India.

The COVID-19 pandemic has had multifaceted and enduring impacts on people with dementia and their caregivers; however, our understanding of the long-term outcomes remains limited. We aimed to explore the long-term effects of the COVID-19 pandemic on cognitive symptoms and vaccination rates in people living with dementia. This study was conducted as a part of a longitudinal study design in two specialized hospitals in South India. In this study, patients with dementia and their caregivers assessed in earlier phases ('period of lockdown with phased relaxations - phase-I' and 'cluster of cases transmission phase - phase-II') were telephonically interviewed. We adopted a quantitative approach to understand disease progression during the three-year course of the pandemic. Changes in cognition and disease severity were measured using the Clinical Dementia Rating (CDR) scale. In brief, semistructured interviews were carried out with caregivers of people with dementia to gain insights into vaccination rates. Data obtained from the current study (phase III) were compared against phase I data, which served as the baseline. Among the 72 participants contacted in the current phase, 59 (81·9%) could be reevaluated for dementia severity and vaccination status, whereas 13 (18·0%) had died. Among the 59 participants, 33 (55·9%) had severe dementia (CDR 3). This is in contrast to phases I and II, when 17·6% and 19·2% of the participants, respectively, were classified as CDR 3. A significant difference in dementia severity between the two phases (phases I and III) was observed. In addition, we observed vaccination hesitancy among caregivers of patients with dementia. This study would provide valuable insights into the long-term impact of the COVID-19 pandemic on the cognitive outcomes and vaccination status of patients with dementia. This overall longitudinal study has compared dementia severity between different phases throughout the pandemic, with implications for future studies to tailor home-based support and healthcare interventions in order to meet these evolving needs.

Severity prediction markers in dengue: a prospective cohort study using machine learning approach

Background Dengue virus causes illnesses with or without warning indicators for severe complications. There are no clear prognostic signs linked to the disease outcomes. Methods Clinical and laboratory parameters among 102 adult including 17 severe dengue (SD), 33 with warning and 52 without warning signs during early and critical phases were analysed by statistical and machine learning (ML) models. Results In classical statistics, abnormal ultrasound findings, platelet count and low lymphocytes were significantly linked with SD during the febrile phase, while low creatinine, high sodium and elevated AST/ALT during the critical phase. ML models highlighted AST/ALT and lymphocytes as key markers for distinguishing SD from non-severe dengue, aiding clinical decisions. Conclusion Parameters like liver enzymes, platelet counts and USG findings were linked with SD.USG testing at an earlier phase of dengue and a point-of-care system for the quantification of AST/ALT levels may lead to an early prediction of SD.

A new model of crater degradation on Ceres involving ice sublimation and talus formation

We report on the widespread occurence of talus on cerean crater walls using Dawn framing camera images. This is unexpected for a planetary body with no atmosphere like Ceres since the dominant process in crater degradation was expected to be topographic diffusion associated with impact gardening, like on the Moon or Mercury. To investigate why talus deposits are so common, and whether they could be related to the particular nature of Ceres’ ice-rich crust, we mapped them over the entire surface and studied their morphological characteristics. We classified the features into three different types, indicating their degree of preservation. Our results show that there is no trend between the total surface area of talus (whatever their degree of preservation) and latitude or longitude. However, we found that talus deposits tend to be observed within deep and young impact craters, and that certain craters expose a particularly large surface area of talus deposits: Dantu, Ninsar, Occator, Kupalo and Juling craters. It was also noted that well-preserved talus have a larger surface area than more degraded ones, and have ≈20 % more consolidated outcrops per km2. Age estimates from crater size frequency distributions for the host craters completed these observations, giving a mean age of 20−4+4 Ma for the craters hosting the more preserved talus deposits, and 280−8+8 Ma for the craters hosting the more degraded ones. By studying the slope of the talus deposits, we obtained a value of the angle of repose of the cerean regolith: 34.5°± 2.8°. We also found that the talus facing the poles are approximately 5°steeper than those facing the equator, have an 18 % larger surface area, and exhibit three times as many outcrops compared to talus on crater walls facing other directions. This suggests that the degradation of outcrops, the source of the material making up the scree, is sensitive to insolation. If we assume that the outcrops are made cohesive by the ice they contain, then we can conclude that sublimation of this ice leads to their fragmentation, at the origin of the talus material. We suggest that outcrop wall retreat due to ice sublimation feeding talus slopes is a predominant process in the earlier phase of crater degradation on Ceres supplanting impact gardening and topographic diffusion for some tens of million years. Once the maximum extent of the talus is reached, the progressively reduced debris production leads to a decreasing talus activity. Impact gardening then takes over and talus deposits are slowly degraded during the next few hundreds million years before fully disappearing. This has an influence on age estimations of the surface of Ceres, as the diameters of the craters grow larger over time due to the ice sublimation, resulting in a slight overestimation of the age of the dated cerean areas. In addition, in the perspective of future missions to Ceres, one of whose objectives would be to precisely quantify the ice content of the crust, the outcrops facing the poles and not yet degraded would be among the most interesting targets to explore.

A brief report: Lessons learned using wearable technology to collect data from adults receiving medications for opioid use disorder

ABSTRACT Background Incorporating wearable technology into substance use disorder research enables continuous, objective, and remote data collection, facilitating symptom monitoring to prevent relapse. However, implementation challenges may hinder data collection. This paper aims to assess adherence patterns to a wrist-worn wearable device, and to share lessons learned from incorporating wearable technology to collect physiological data from adults with opioid use disorder. Methods Employing a prospective observational design, we used convenience sampling to recruit adults receiving medications for opioid use disorder in outpatient settings. Wearable adherence was measured by days and nights worn over eight weeks, acceptability by a visual analog scale, and anecdotal notes tracked study activities and challenges. Results Twenty-three participants completed baseline, and 16 (70.0%) completed the study. Daytime and nighttime wearable adherence averaged 60.1% and 47.7%, respectively. Wearable adherence was highest at the earlier phase of the study (67.7%) and plateaued after overtime. User-related and technical challenges included digital illiteracy, protocol nonadherence, low motivation, measurement errors, and short battery life. Unique challenges included wearable design concerns and sleep problems. Conclusions This study demonstrates the feasibility of wearable use and highlights the potential to overcome challenges. Proactively sharing insights can facilitate wearable technology adoption for both participants and researchers.

Mesozoic lithospheric mantle evolution in South China: Evidence from Ar-Ar dating, geochemistry and Sr-Nd-Pb isotopes of lamprophyres

Understanding the Mesozoic lithospheric mantle beneath South China is challenging, primarily because mantle-derived magmatic rocks are rare, whereas granitic magmatism is far more abundant. In this study, we present new 40Ar/39Ar geochronology, major and trace elemental composition, and Sr-Nd-Pb isotopic data for lamprophyres from northern and central Guangxi Province, South China. Our results reveal two intrusion phases: an earlier phase at 207.7 ± 1.2 Ma, and a later phase between 95.6 ± 0.6 Ma and 102.3 ± 0.7 Ma. The earlier phase, represented by the Danyang lamprophyres, is marked by low Cr (330–355 ppm) and Ni (241–258 ppm) contents and strongly fractionated REE patterns with (La/Yb)n ratios of 57.5 to 62.8. The later phase, represented by the Leidong, Nongchang, and Longchang lamprophyres, shows higher Cr (490–781 ppm) and Ni (237–377 ppm) contents, with less fractionated REE patterns and (La/Yb)n ratios of 20.2 to 27.8. Despite their temporal differences, the lamprophyres share similar isotopic characteristics, including high initial 87Sr/86Sr (0.707940–0.721310), negative εNd(t) (−9.19 to −5.31), and radiogenic Pb isotopic compositions (206Pb/204Pb: 18.200–18.331, 207Pb/204Pb: 15.62–15.72, 208Pb/204Pb: 38.53–38.84). These features suggest derivation from low-degree partial melting of a phlogopite-bearing, refractory peridotite lithospheric mantle, modified by olivine and clinopyroxene fractionation. This refractory mantle was metasomatically enriched by Proterozoic subduction processes beneath the Yangtze Craton. By synthesizing published Sr-Nd-Pb isotopic data, we propose that the lithospheric mantle beneath South China shifted from enriched to depleted mantle between ∼220 Ma and ∼ 100 Ma, possibly due to extension associated with the subduction and rollback of the Paleo-Pacific Plate.

Phase 2b program with sonlicromanol in patients with mitochondrial disease due to m.3243A>G mutation.

Mitochondrial disease is a group of rare conditions, with no approved treatment to date, except for Leber hereditary optic neuropathy. Therapeutic options to alleviate the symptoms of mitochondrial disease are urgently needed. Sonlicromanol is a promising candidate, as it positively alters the key metabolic and inflammatory pathways associated with mitochondrial disease. Sonlicromanol is a reductive and oxidative distress modulator, selectively inhibiting microsomal prostaglandin E1 synthase activity. This Phase 2b program, aiming at evaluating sonlicromanol in adults with m.3243A>G mutation and primary mitochondrial disease, consisted of a randomized controlled (RCT) study (dose-selection) followed by a 52-week open-label extension study (EXT, long-term tolerability, safety, and efficacy of sonlicromanol). Patients were randomized (1:1:1) to receive 100- or 50-mg sonlicromanol, or placebo twice daily (bid) for 28 days with ≥2-week wash-out period between treatments. Patients who completed the RCT study entered the EXT study wherein they received 100-mg sonlicromanol bid. Overall, 27 patients were randomized (24 RCT patients completed all periods). 15 patients entered the EXT, and 12 patients were included in the EXT analysis set. All patients reported good tolerability and favourable safety, with pharmacokinetic results comparable to the earlier Phase 2a study. The RCT primary endpoint (change from placebo in the attentional domain of cognition score [IDN: visual identification, Cogstate]) did not reach statistical significance. Using a categorisation of the subject's period baseline a treatment effect over placebo was observed if their baseline was more affected (p=0.0338). Using this approach, there were signals of improvements over placebo in at least one dose in the Beck Depression Inventory (BDI, p=0.0143), Cognitive Failure Questionnaire (CFQ, p=0.0113), and the Depression subscale of the Hospital Anxiety and Depression Scale (p=0.0256). Statistically and/or clinically meaningful improvements were observed in the patient- and clinician-reported outcome measures at the end of the EXT study (Test of attentional performance [TAP] with alarm, p=0.0102; TAP without alarm, p=0.0047; BDI somatic, p=0.0261; BDI Total, p=0.0563; SF12 physical component score, p=0.0008). Seven of nine domains of RAND-Short form-36 like SF-36 pain improved (p=0.0105). Other promising results were observed in Neuro QoL-Fatigue-SF (p=0.0036), MiniBESTest (p=0.0009), McGill Pain Questionnaire (p=0.0105), EQ-5D-5L-VAS (p=0.0213) and EQ-5D-5L-index (p=0.0173). Most patients showed improvement in the 5× sit-to-stand test. Sonlicromanol was well-tolerated and demonstrated a favourable benefit/risk ratio for up to one year. Sonlicromanol was efficacious in patients when affected at baseline, as seen across a variety of clinically relevant domains. Long-term treatment showed more pronounced changes from baseline.

A Systematic Review of Comparative Effectiveness of Interventions for Low Anterior Resection Syndrome: Impacts on Bowel Function and Quality of Life.

Low anterior resection syndrome (LARS) is a common complication following sphincter-preserving surgical resection for rectal cancer, characterized by symptoms such as fecal incontinence, urgency, and altered bowel habits, which significantly affect patients' quality of life. This cluster of symptoms not only limits their day-to-day physical activity but also has a debilitating effect on their emotional and mental well-being, undermining their integration and overall psychological health. This systematic review aimed to evaluate the effectiveness of invasive and non-invasive interventions for LARS, including pelvic floor rehabilitation, transanal irrigation, and various surgical options such as sacral neuromodulation and stoma formation, either as part of primary surgery or as a definitive treatment option for refractory cases. We systematically searched relevant databases for studies published in the last decade, focusing on adult patients diagnosed with LARS post-low anterior resection (LAR), with outcomes assessed through bowel function and quality of life metrics. The review identified six studies that met our eligibility criteria; a pooled cohort of 794 patients was identified, with sample sizes ranging from 37 to 430 participants. Our analysis revealed that pelvic floor rehabilitation significantly improves bowel function and quality of life in patients with LARS; yet, the optimal management approach remains unclear due to variability in patient responses. These findings highlight the inherent complexity and heterogeneity of LARS management, underscoring the necessity for multifaceted and individualized treatment strategies. Although pelvic floor rehabilitation shows promise, especially among motivated patients, its long-term sustainability remains uncertain. Surgical options are typically reserved for severe cases and carry significant risks and psychological impacts. For patients identified as being at high risk for LARS, treatment options must be considered and discussed at an earlier phase of their care. Our review concludes with the need for a tailored, patient-centered approach to managing LARS, highlighting the importance of ongoing research to fill existing evidence gaps. There is a need for translational research across various treatment modalities, comparing their effects, cost-effectiveness, implementation strategies, and the consequent effects on patients' quality of life and mental health.

The prognostic impact of therapeutic hypothermia after a sudden cardiac arrest in the course of myocardial infarction.

Mild therapeutic hypothermia (MTH) is one of the treatment methods recommended in post-sudden cardiac arrest (SCA) patients who remain unconscious after cardiopulmonary resuscitation. The present study aimed at assessing the prognostic impact of intravascular MTH on invasively treated patients with an acute myocardial infarction complicated by SCA. The presented data were collected via a single-center retrospective analysis of the hospitalization and follow-up of 54 patients with post-myocardial infarction complicated by SCA. The patients were treated in the years 2014-2020 and the average follow-up period was 1141 ± 163 days. The population was divided into two groups: 28 patients treated with MTH (a therapeutic hypothermia [TH] group) and 26 patients treated without MTH (a non-TH group). The results indicate a trend toward improved in-hospital prognosis in the TH group, but the differences did not reach statistical significance: TH 25.0% vs. non-TH 34.5%, p = 0.554. An additional analysis of younger patients (under 60 years of age) revealed no significant differences between the TH and non-TH subgroups concerning in-hospital survival (in-hospital mortality rate: TH 6.7% vs. non-TH 30.0%, p = 0.267). Still, TH patients aged < 60 achieved a significantly better rate of follow-up survival (p = 0.041). The older (≥ 60) patient group showed no in-hospital mortality rate differences (TH 46.2% vs. non-TH 37.5%, p = 0.638). However, in-hospital bleeding frequency was significantly higher in patients aged ≥ 60 from the hypothermia group (TH 50.0% vs. non-TH 6.7%, p = 0.011). Intravascular MTH may improve the follow-up prognosis in patients aged < 60 with SCA in the early phase of myocardial infarction.

Die „fünfte Suburbanisierung“ – Perspektiven suburbaner Raumentwicklung in den 2020er-Jahren

Germany is currently experiencing a renewed rise of suburbanisation and an associated increase in urban expansion in the peripheries of large cities. How this development—referred to below as the “fifth suburbanisation” in the history of this country—can be characterized in the light of earlier phases of intraregional deconcentration is the topic of this paper. The four historical reference phases are not to be understood as clearly distinguishable and successive developments. Their conceptualization is less temporal than structural-material, socio-spatial, institutional, cultural, economic and political-discursive. The focus is on characteristics of built environments typical of each phase, specific social and economic drivers, dominant housing and planning policies, socio-cultural meanings and values as well as social embedding and negotiation processes. Suburban development of the 2020s will take place in a socio-economically and institutionally changed process field, even though there is still little empirical evidence in this regard. Accordingly, this paper also aims to call for a discussion on new research desiderata and realistic policy designs for suburban spatial development in the 2020s. A historical contextualization of the current development and planning processes is considered essential.

JK-1, a useful erythroleukemic cell line model to study a controlled erythroid differentiation from progenitors to terminal erythropoiesis

New hematopoietic cell models have recently emerged through immortalization of CD34 cells to study and understand various molecular mechanisms of erythropoiesis. Here, we characterize the JK-1 CML-derived cell line, previously shown to spontaneously differentiate without cytokines. Using an epigenetic differentiation inhibitor that keeps JK-1 in an early differentiation phase, we characterized 2 progenitor stages: BFU-E JK-1 and CFU-E JK-1 with CD34+/CD36− and CD34−/CD36 + phenotypes respectively. Then, using the PFI-1 inducer known to synchronously control the terminal differentiation of JK-1 cells, 5 precursor stages were obtained (ProE, Baso1-2, PolyC, OrthoC) and characterized via cell morphology, CD49a and Band3 markers. Enlarged phenotyping was carried out for the earlier phase, and expression kinetics of membrane proteins such as RhAG, RhD/CE, CD47, DARC and CD44 were performed on each stage of the terminal phase. Furthermore, since JK-1 offers the unique property of covering a broad spectrum of differentiation stages, we explored deeper the GATA2/GATA1 and the non-erythroid/erythroid spectrin ‘switching’. The possibility of obtaining large quantities of JK-1 cells at each stage of differentiation, as shown in this study, as well as the potential to genetically modify these cells, via CrisprCas9, makes their use of considerable interest for studying pathologies occurring during erythropoiesis.

Into the Cauldron of the Variant Soup: Insights into the Molecular Epidemiology and Transition to Endemicity of SARS-CoV-2 in Cyprus (November 2022-February 2024).

The coronavirus disease 2019 (COVID-19) pandemic, driven by the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been characterized by the virus's ongoing evolution, leading to the appearance of more transmissible variants that have often triggered infection surges. In this study, we analyzed the SARS-CoV-2 epidemic in Cyprus, utilizing 1627 viral sequences from infected individuals between November 2022 and February 2024. Over this period, 251 distinct lineages and sublineages were identified, predominantly categorized into three groups: Omicron 5, XBB, and JN.1 (parental lineage BA.2.86), all of which harbor S protein mutations linked to enhanced transmissibility and immune escape. Despite the relatively low numbers of new infections during this period, and the lack of any major waves, unlike earlier phases of the pandemic, these lineages demonstrated varying periods of dominance, with Omicron 5 prevailing from November 2022 to February 2023, XBB variants leading from March to November 2023, and JN.1 generating a wavelet from December 2023 to February 2024. These findings suggest that the SARS-CoV-2 epidemic in Cyprus has reached endemicity, with new variants gradually replacing previously circulating variants irrespective of seasonal patterns. This study highlights the critical importance of ongoing surveillance of SARS-CoV-2 evolution in Cyprus and emphasizes the role of preventive measures in limiting virus transmission, providing valuable insights for safeguarding public health.

Model‐based systems engineering and safety assessment: A workflow for mechatronic systems design

AbstractMechatronic systems become ever more complex because of their increasing number of interconnected safety critical components and sophistication. MBSE (Model‐based Systems Engineering) and MBSA (Model‐Based Safety Assessment) are the most commonly adopted approaches to deal with the design and safety analysis of mechatronic systems. Unfortunately, both approaches are normally adopted separately, especially in the earlier phases of system design, thus leading to a lack of communication between system engineers and the safety team. This work aims to fill that gap at a high level, that is, through process interaction. This paper proposes an enhanced V‐model for the design of safety‐critical mechatronic systems. It relates a system development process with specific safety assessment methods. Specifically, the proposed workflow details exchange flows between the RFLP (Requirements, Functional, Logical, Physical) method, the FHA (Functional Hazard Analysis), the FMEA (Failure Mode and Effects Analysis), the MBSA and simulation, and the FTA (Fault Tree Analysis). These analyses are complemented with multiphysics modeling and simulation to observe system behavior in functional and failure scenarios, with the aim of requirements verification. The design workflow has been applied to a winged Unmanned Aerial Vehicle to apply the parallel process and the necessary interaction of MBSE and MBSA approaches. The information flows between the individual activities proved effective for designing a safe system before the verification phase. The main benefit of the proposed workflow is providing both the design and safety team with some interaction points, thus avoiding a lack of safety‐critical analysis in the early phases of system design.

Permeability and Toxicity of Cryoprotective Agents in Silkworm Embryos: Impact on Cryopreservation.

The permeation of cryoprotectants into insect embryos is critical for successful cryopreservation. However, the permeability of silkworm embryos to cryoprotectants and the effects of cryopreservation remain poorly studied. In this study, we evaluated the permeability and toxicity of four cryoprotective agents (CPAs) as well as the vitrification effect on the viability of silkworm embryos. Among the four CPAs, propylene glycol (PG) showed the best permeability. Ethylene glycol (EG) and PG were the least toxic CPAs, but glycerol (GLY) and dimethyl sulfoxide (DMSO) were more toxic. Moreover, we examined several factors including the kind and the concentration of CPAs, exposure time, embryonic stage, and silkworm strains. Embryos at the earlier phases of stage 25 were more tolerant to vitrification using EG. We found that over 21% of embryos treated with EG at the early 2 phase of stage 25: 163 h after egg laying (AEL) developed and progressed to serosa ingestion after vitrification and rewarming. The result was the same in other strains as well. Our results are valuable for the development of new cryopreservation protocols of silkworm embryos.

Impacts of testing and immunity acquired through vaccination and infection on covid-19 cases in Massachusetts elementary and secondary students

BackgroundDuring the 2021–22 academic year, Massachusetts supported several in-school testing programs to facilitate in-person learning. Additionally, COVID-19 vaccines became available to all school-aged children and many were infected with SARS-CoV-2. There are limited studies evaluating the impacts of these testing programs on SARS-CoV-2 cases in elementary and secondary school settings. The aim of this state-wide, retrospective cohort study was to assess the impact of testing programs and immunity on SARS-CoV-2 case rates in elementary and secondary students.MethodsCommunity-level vaccination and cumulative incidence rates were combined with data about participation in and results of in-school testing programs (test-to-stay, pooled surveillance testing). School-level impacts of surveillance testing programs on SARS-CoV-2 cases in students were estimated using generalized estimating equations within a target trial emulation approach stratified by school type (elementary/middle/high). Impacts of immunity and vaccination were estimated using random effects linear regression.ResultsHere we show that among N = 652,353 students at 2141 schools participating in in-school testing programs, surveillance testing is associated with a small but measurable decrease in in-school positivity rates. During delta, pooled testing positivity rates are higher in communities with higher cumulative incidence of infection. During omicron, when immunity from prior infection became more prevalent, the effect reversed, such that communities with lower burden of infection during the earlier phases of the pandemic had higher infection rates.ConclusionsTesting programs are an effective strategy for supporting in-person learning. Fluctuating levels of immunity acquired via natural infection or vaccination are a major determinant of SARS-CoV-2 cases in schools.

Factors Associated with Multimodal Care Practices for Cancer Cachexia among Pharmacists.

Pharmacists' roles in cachexia care are unclear. This study aimed to clarify the knowledge and practice of cachexia care and identify factors related to the practice of cachexia care among pharmacists. Information on the knowledge and practice of cachexia care was obtained. Components of practicing multimodal care were evaluated. Participants were categorized into two groups according to practicing multimodal care levels. Comparisons were made between the groups, and multiple regression analysis was employed. Of the 451 pharmacists, 243 responded. They were categorized into the Practicing group (n = 119) and Not practicing group (n = 124). Significant differences were observed for the number of advanced cancer patients/month, frequency of caring for them, and involvement in training programs on cachexia. The Practicing group had significantly better knowledge about cachexia. The Practicing group used guidelines, items, and symptoms more frequently to detect cachexia. The Practicing group tended to detect cachexia and initiate interventions in earlier phases and in patients with a better status. Multivariate logistic regression analysis showed that the most significant factor was the regular provision of care (odds ratio, 2.07; 95% confidence interval, 1.10-3.92). The regular provision of care was associated with the practice of multimodal care.

Saltford Manor House, Somerset: A Twelfth-Century Chamber Block

This is the first detailed study of Saltford Manor House in Somerset, including both building survey and documentary research. The earliest phase is identified as a chamber block, which has lost its accompanying hall. The ground floor formed a tall undercroft for storage or service use, accessed by a wide stone-arched doorway and lit by slit windows. The single chamber on the first floor was accessed by an external stair and retains two original windows, one of which is among the finest domestic survivals of the period. The first-floor structure was, unusually, formed of heavy, clear-spanning joists. Three of these survive, enabling production of a tree-ring and isotope date of 1170–83. This, with documentary evidence, allows the builder to be identified as a member of the Wyting family, of knightly status and part of the affinity of the Earls of Gloucester. The building is set in the context of nineteen comparable early detached chamber blocks, including several that have been the focus of recent studies. Saltford Manor is the only example with an accurate, scientific date. Early thirteenth-century wall-paintings survive, one of the earliest domestic schemes in England. Alterations including the conversion of the undercroft to a hall took place in 1456-81, as confirmed by isotope dating, and further works were undertaken in 1637.

Sex-Related Variation in Circadian Rhythms in the Bumble Bee Bombus terrestris.

Mating success depends on many factors, but first of all, a male and a female need to meet at the same place and time. The circadian clock is an endogenous system regulating activity and sex-related behaviors in animals. We studied bumble bees (Bombus terrestris) in which the influence of circadian rhythms on sexual behavior has been little explored. We characterized circadian rhythms in adult emergence and locomotor activity under different illumination regimes for males and gynes (unmated queens). We developed a method to monitor adult emergence from the pupal cocoon and found no circadian rhythms in this behavior for either males or gynes. These results are not consistent with the hypothesis that the circadian clock regulates emergence from the pupa in this species. Consistent with this premise, we found that both gynes and males do not show circadian rhythms in locomotor activity during the first 3 days after pupal emergence, but shortly after developed robust circadian rhythms that are readily shifted by a phase delay in illumination regime. We conclude that the bumble bees do not need strong rhythms in adult emergence and during early adult life in their protected and regulated nest environment, but do need strong activity rhythms for timing flights and mating-related behaviors. Next, we tested the hypothesis that the locomotor activity of males and gynes have a similar phase, which may improve mating success. We found that both males and gynes have strong endogenous circadian rhythms that are entrained by the illumination regime, but males show rhythms at an earlier age, their rhythms are stronger, and their phase is slightly advanced relative to that of gynes. An earlier phase may be advantageous to males competing to mate a receptive gyne. Our results are consistent with the hypothesis that sex-related variations in circadian rhythms is shaped by sexual selection.