Local Site Research Articles

Seismic mitigation analysis of base-isolated structure with sliding magnetic bearings considering local-site conditions

Base-isolation systems applied in building structures and infrastructures often suffer from damage even failure during strong earthquakes. The adaptability of isolators to local sites is a main concern for the robust design of base-isolation systems. In this study, seismic mitigation analysis of base-isolated structure with newly-developed sliding hydro-magnetic bearing (HMB) and sliding implant-magnetic bearing (IMB) considering local-site conditions is carried out. Extension of modeling of sliding magnetic bearings is first conducted based on the data of shaking-table tests of a reduced-scale base-isolated structure. To assess the instantaneous frequency for quantifying sliding magnetic bearings’ resisting force, the Hilbert–Huang transform (HHT) is applied. The influences of local-site conditions upon mitigation performance of the sliding magnetic bearings are then addressed, including far-field and near-field, ground motions with and without velocity pulses, and hard-soil and soft-soil. For comparison purposes, the seismic mitigation analysis of the base-isolated structure attached with lead rubber bearing (LRB) and curved surface slider (CSS) is carried out as well. Numerical results show that the sliding magnetic bearings outperform the state-of-the-art seismic isolators in both seismic mitigation and deformation constraint, and the IMB has excellent applicability for engineering since its perfect adaptability to local sites. However, the LRB cannot achieve the desired seismic mitigation under near-field pulse-like ground motions.

Peritoneo-Cutaneous Fistula Secondary to Pigtail Catheter Insertion in a Blunt Abdominal Trauma Patient: A Case Report

We hereby present the first case of iatrogenic peritoneal-cutaneous fistula (PCF) formed at the site of removal of the pigtail catheter. The patient was admitted and underwent local site fistulous tract excision under general anaesthesia. Patient was discharged after an uneventful post-op period. Our intervention led to closure of the fistula leading to improved quality of life of the patient. Our case demonstrates that PCF can be created due to epithelialization secondary to chronic inflammation in a previous pigtail catheter tract.

Design of ANCHOR-RA: a multi-national cross-sectional study on screening for interstitial lung disease in patients with rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis (RA) are at risk of developing interstitial lung disease (ILD), which is associated with high mortality. Screening tools based on risk factors are needed to decide which patients with RA should be screened for ILD using high-resolution computed tomography (HRCT). The ANCHOR-RA study is a multi-national cross-sectional study that will develop a multivariable model for prediction of RA-ILD, which can be used to inform screening for RA-ILD in clinical practice.MethodsInvestigators will enrol consecutive patients with RA who have ≥ 2 of the following risk factors for RA-ILD: male; current or previous smoker; age ≥ 60 years at RA diagnosis; high-positive rheumatoid factor and/or anti-cyclic citrullinated peptide (titre > 3 x upper limit of normal); presence or history of certain extra-articular manifestations of RA (vasculitis, Felty’s syndrome, secondary Sjögren’s syndrome, cutaneous rheumatoid nodules, serositis, and/or scleritis/uveitis); high RA disease activity in the prior 12 months. Patients previously identified as having ILD, or who have had a CT scan in the prior 2 years, will not be eligible. Participants will undergo an HRCT scan at their local site, which will be assessed centrally by two expert radiologists. Data will be collected prospectively on demographic and RA-related characteristics, patient-reported outcomes, comorbidities and pulmonary function. The primary outcomes will be the development of a probability score for RA-ILD, based on a multivariable model incorporating potential risk factors commonly assessed in clinical practice, and an estimate of the prevalence of RA-ILD in the study population. It is planned that 1200 participants will be enrolled at approximately 30 sites in the USA, UK, Germany, France, Italy, Spain.DiscussionData from the ANCHOR-RA study will add to the body of evidence to support recommendations for screening for RA-ILD to improve detection of this important complication of RA and enable early intervention.Trial registrationclinicaltrials.gov NCT05855109 (submission date: 3 May 2023).

An intervention development study of an mHealth app to manage women’s health and safety while on probation

PurposePreliminary studies have suggested that women are responsive to using technology to manage their health, due to its discreet, convenient, and cost-effective nature. Yet, there are limited mobile health (mHealth) apps specific to women’s needs, particularly those on probation. The purpose of this study was to explore features of 2 existing mHealth applications related to sexual health and safety, specific to interpersonal and sexual violence, to answer research questions related to the usability, barriers, and facilitators of mHealth app use for women on probation.SubjectsWe purposefully sampled from a local adult probation site and utilized snow-ball sampling to recruit 11 women who were on probation and owned iPhones.MethodsWe conducted an exploratory intervention development study using a qualitative design. Social Cognitive Theory was used for data synthesize and organization.FindingsThree themes emerged: (1) It made me take time for myself; (2) It helped me to be more respectful of my body; (3) The connectivity….that was helpful.Major implicationsParticipants expressed mHealth apps to be usable, feasible, accessible and promoted self-efficacy by allowing them track symptoms and patterns of behavior specific to health and safety in a discreet, convenient, and effective manner. This research suggests that a culturally tailored mHealth app may be an appropriate intervention to provide timely gender-responsive feedback, resources, and health care to women on probation.

Deep soil seismic hazard assessment: analyzing the impact of local site effects by stochastic site response analysis—a comparative approach

Deep soil seismic hazard assessment: analyzing the impact of local site effects by stochastic site response analysis—a comparative approach

Clinical Practice Guidelines to Support Capacity Building in Orthopaedic Surgical Outreach: An International Consensus Building Approach.

Surgical outreach to low- and middle-income countries (LMICs) by organizations from high- income countries is on the rise to help address the growing burden of conditions warranting surgery. However, concerns remain about the impact and sustainability of such outreach. Leading organizations (e.g., the World Health Organization) advocate for a capacity-building approach to ensure the safety, quality, and sustainability of the local health-care system. Despite this, to our knowledge, no guidelines exist to inform such efforts. We aimed to develop clinical practice guidelines (CPGs) to support capacity-building in orthopaedic surgical outreach utilizing a multistakeholder and international voting panel. We followed a modified American Academy of Orthopaedic Surgeons (AAOS) CPG development process. We systematically reviewed the existing literature across 7 predefined capacity-building domains (partnership, professional development, governance, community impact, finance, coordination, and culture). A writing panel composed of 6 orthopaedic surgeons with extensive experience in surgical outreach reviewed the existing literature and developed a consensus-based CPG for each domain. We created an international voting panel of orthopaedic surgeons and administrators who have leadership roles in outreach organizations or hospitals with which outreach organizations partner. Members individually reviewed the CPGs and voted to approve or disapprove each guideline. A CPG was considered approved if >80% of panel members voted to approve it. An international voting panel of 14 surgeons and administrators from 6 countries approved all 7 of the CPGs. Each CPG provides recommendations for capacity-building in a specific domain. For example, in the domain of partnership, the CPG recommends the development of a documented plan for ongoing, bidirectional partnership between the outreach organization and the local team. In the domain of professional development, the CPG recommends the development of a needs-based curriculum focused on both surgical and nonsurgical patient care utilizing didactic and hands-on techniques. As orthopaedic surgical outreach grows, best-practice CPGs to inform capacity-building initiatives can help to ensure that resources and efforts are optimized to support the sustainability of care delivery at local sites. These guidelines can be reviewed and updated in the future as evidence that supports capacity-building in LMICs evolves.The global burden of disease warranting surgery is substantial, and morbidity and mortality from otherwise treatable conditions remain disproportionately high in low- and middle-income countries (LMICs)1,2. It is estimated that up to 2 million (about 40%) of injury-related deaths in LMICs could be avoided annually if mortality rates were reduced to the level of those in high-income countries (HICs)3. Despite this, progress toward improved access to safe, timely surgery in resource-poor areas has been slow. Historically, nongovernmental organizations (NGOs) have tried to address unmet surgical needs through short-term outreach trips; however, growing criticism has highlighted the limitations of short-term trips, including limited follow-up, an increased burden on the local workforce, and further depletion of local resources4-6. In light of ongoing concerns, public health priorities have shifted toward models that emphasize long-term capacity-building rather than short-term care delivery. Capacity-building is an approach to health-care development that builds independence through infrastructure development, sustainability, and enhanced problem-solving while taking context into account7,8.

Habitat context and functional growth traits explain alien plant invader impacts on native vegetation communities

Examining context-dependency of ecological impacts of alien plant invasions is critical to further understand the mechanisms driving impacts. We examined how different regional and local habitat contexts influence the abundance-impact associations of an invasive ground-creeper, Tradescantia fluminensis, in native forests across eastern New South Wales (NSW), Australia. Invader impacts were assessed using surveys of resident vegetation at 97 monitoring plots (5 m × 2 m) located at 14 sites, representing a gradient of T. fluminensis abundance. We modelled the association of T. fluminensis invasion with native species richness (number per plot) and foliage cover across two different habitat types (remnant vs replanted forests), two vegetation community types (wet sclerophyll vs river oak forests), and two regions (northern vs. southern NSW). We also modelled variation in native species responses amongst different functional growth forms. The negative associations of T. fluminensis and native species communities was more strongly explained by local site variables (i.e., habitat type, community type, plant growth form) than regional scales. Native richness reduced with invasion in river oak but not wet sclerophyll forest. Native richness also declined in remnant forest, although no effect of invasion was observed in replanted forest. Surprisingly, native species growth forms most like T. fluminensis (ground layer herbs, ferns) were more resistant to reductions in native richness compared to divergent forms (shrub, tree and woody vine recruits). This study highlights the need to explicitly consider local community and habitat context and functional representation of resident species when considering invader impacts and site-level management plans.

Site Response in the Walnut Creek–Concord Region of San Francisco Bay, California: Ground-Motion Amplification in a Fault-Bounded Basin

ABSTRACT Thirty-seven portable accelerometers were deployed in the eastern San Francisco Bay communities of Walnut Creek and Concord to study site response in a fault-bounded, urban, sedimentary basin. Local earthquakes were recorded for a period of two years from 2017 to 2019 resulting in 101 well-recorded events. Site response is estimated by two methods: the reference site spectral ratio method and a source-site spectral inversion method. The reference site spectral ratio method allows investigation of the variability of site amplification with source azimuth and frequency. The source-site spectral inversion method yields the best least-squares fit to site response for a database of ground-motion records. Both methods show substantial amplification in the Walnut Creek–Concord basin below 2 Hz indicating strong surface-wave development. Greater amplification is seen for sources aligned along the long axis of the basin. Inversion using close-in sources at short distances yields lower amplification at longer periods than the entire data set due to reduced surface-wave generation for steeper angles of incidence. Inversion of site response spectra for shallow shear-wave velocity using a global search algorithm yields VS30 values consistent with generalized mapping results based on geology and topography but with greater variability due to local site variations. 3D finite-element modeling shows greater amplification in the Walnut Creek–Concord basin with a basin-edge effect likely contributing to higher ground motions. Topography is also seen to lead to increased scattering and shadowing effects.

Myiasis in Percutaneous Transhepatic Biliary Drainage Site

AbstractThe infection of dipterous larvae causes myiasis. It is generally associated with unsanitary conditions. An interventional radiologist rarely comes across myiasis. We report a case of myiasis around a percutaneous transhepatic biliary drainage (PTBD) tube. A 31-year-old man from a rural area underwent left PTBD for cholangiocarcinoma and was discharged with an internal–external drain. Two weeks later, he presented with pain in the local site, pruritus, and bile leakage. He was found to have maggots around the PTBD tube with poor wound hygiene. Treatment included turpentine oil instillation and oral and topical ivermectin, accompanied by manual removal of the larva.

Correlation of rare earth coordination and spectral properties in Er3+ doped Na2O–Al2O3–SiO2 glasses with different Al2O3 concentrations by molecular dynamics simulations

The molecular structure of Er2O3 doped Na2O–Al2O3–SiO2 glasses with varying Na2O/Al2O3 ratios is explored via molecular dynamics (MD) simulations using the so-called inherent structure sampling method, which allows the calculation of a large number of local structures of low concentration, as needed to determine the surrounding of low concentration dopants. General structural parameters, including radial distribution functions, coordination numbers and interatomic distances of all network forming and network modifying ions are reported. However, in this work, special attention is devoted to the effect of Al2O3 concentration on the local surrounding of the doped Er3+ ions. It is shown that the Er atoms coordinate 5–6 oxygen ions in their first coordination sphere in the investigated glasses. The Er–O coordination number increases monotonically with increasing Al2O3 concentration and decreasing Na2O/Al2O3 ratio. It is found that the Er atoms are preferably connected to non-bridging oxygen atoms (NBO) in all glasses, even in the peraluminous composition. Additionally, the MD simulation results are compared to the glasses spectral properties that were already investigated in detail by Tanabe and Hanada. The increasing Er-NBO coordination number derived by MD simulations could be correlated with the increased peak splitting of the Er3+ absorption peaks reported by Tanabe and Hanada. Furthermore, a correlation between the Judd-Ofelt parameters published by Tanabe and Hanada and the Er3+ coordination in the glass structure is discussed. It is shown that the Er–O coordination increases with increasing Ω2 parameter as the Al2O3 concentration increases in the glass composition. A correlation of the average overall Er–O coordination number with the symmetry of the local Er site is proposed.

Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by MF59 and AS03-like Adjuvants.

MF59 and AS03 are squalene emulsion-based vaccine adjuvants with similar compositions and droplet sizes. Despite their broad use in licensed influenza vaccines, few studies compared their adjuvant effects and action mechanisms side by side. Considering the majority of adjuvants act on dendritic cells (DCs) to achieve their adjuvant effects, this study compared MF59 and AS03-like adjuvants (AddaVax and AddaS03, respectively) to enhance antigen uptake, DC maturation, ovalbumin (OVA) and seasonal influenza vaccine-induced immune responses. Considering MF59 was reported to activate MyD88 to mediate its adjuvant effects, this study also investigated whether the above-explored adjuvant effects of AddaVax and AddaS03 depended on MyD88. We found AddaVax more potently enhanced antigen uptake at the local injection site, while AddaS03 more potently enhanced antigen uptake in the draining lymph nodes. AddaS03 but not AddaVax stimulated DC maturation. Adjuvant-enhanced antigen uptake was MyD88 independent, while AddaS03-induced DC maturation was MyD88 dependent. AddaVax and AddaS03 similarly enhanced OVA-induced IgG and subtype IgG1 antibody responses as well as influenza vaccine-induced hemagglutination inhibition antibody titers, whileAddaS03 more potently enhanced OVA-specific IgG2c antibody responses. Both adjuvants depended on MyD88 to enhance vaccine-induced antibody responses, while AddaVax depended more on MyD88 to achieve its adjuvant effects. Our study reveals similarities and differences of the two squalene emulsion-based vaccine adjuvants, contributing to our improved understanding of their action mechanisms.

Targeting TrkB-PSD-95 coupling to mitigate neurological disorders.

Tropomyosin receptor kinase B (TrkB) signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory. The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre- or postsynaptic TrkB resulting in the strengthening of synapses, reflected by long-term potentiation. Postsynaptically, the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca2+/calmodulin-dependent protein kinase II and phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation. In this review, we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders. A reduction of TrkB signaling has been observed in neurodegenerative disorders, such as Alzheimer's disease and Huntington's disease, and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression. Treatment with brain-derived neurotrophic factor is problematic, due to poor pharmacokinetics, low brain penetration, and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform. Although TrkB agonists and antibodies that activate TrkB are being intensively investigated, they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions. Targeting TrkB-postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

Local Ordering, Distortion, and Redox Activity in (La0.75Sr0.25)(Mn0.25Fe0.25Co0.25Al0.25)O3 Investigated by a Computational Workflow for Compositionally Complex Perovskite Oxides.

Mixing multiple cations can result in a significant configurational entropy, offer a new compositional space with vast tunability, and introduce new computational challenges. For applications such as the two-step solar thermochemical hydrogen (STCH) generation techniques, we demonstrate that using density functional theory (DFT) combined with Metropolis Monte Carlo method (DFT-MC) can efficiently sample the possible cation configurations in compositionally complex perovskite oxide (CCPO) materials, with (La0.75Sr0.25)(Mn0.25Fe0.25Co0.25Al0.25)O3 as an example. In the presence of oxygen vacancies (VO), DFT-MC simulations reveal a significant increase of the local site preference of the cations (short-range ordering), compared to a more random mixing without VO. Co is found to be the redox-active element and the VO is the preferentially generated next to Co due to the stretched Co-O bonds. A clear definition of the vacancy formation energy (Evf) is proposed for CCPO in an ensemble of structures evolved in parallel from independent DFT-MC paths. By combining the distribution of Evf with VO interactions into a statistical model, the oxygen nonstoichiometry (δ), under the STCH thermal reduction and oxidation conditions, is predicted and compared with the experiments. Similar to the experiments, the predicted δ can be used to extract the enthalpy and entropy of reduction using the van't Hoff method, providing direct comparisons with the experimental results. This procedure provides a full predictive workflow for using DFT-MC to obtain possible local ordering or fully random structures, understand the redox activity of each element, and predict the thermodynamic properties of CCPOs, for computational screening and design of these CCPO materials at STCH conditions.

Sex-specific associations between air pollutants and asthma prevalence in Japanese adults: a population-based study

ABSTRACT This study investigated the association between air pollutants and asthma prevalence in male and female Japanese adults. In this retrospective cross-sectional analysis, annual mean exposure levels of air pollutants, specifically nitrogen dioxide (NO2) and particulate matter with a median aerodynamic diameter ≤2.5 μm (PM2.5), were assessed at a local monitoring site. Multivariable logistic regression models, adjusted for genetic and/or lifestyle factors, were used to explore the association between air pollutants and asthma, with stratification by sex. A total of 1,497 participants aged ≥40 years were included. Their mean age was 65.9 ± 12.4 years, with 847 being women. Overall, 91 participants were diagnosed with asthma. In the multivariable model, ambient exposure levels of NO2 and PM2.5 were significantly associated with asthma in women but not in men. This study highlights sex as a significant determinant of the link between air pollutants and asthma exacerbation, particularly among female Japanese adults.

PHARMACEUTICAL DEVELOPMENT OF AN ADHESIVE GEL BASED ON A BIODEGRADABLE NATURAL COMPLEX

Introduction. One of the most important issues in the development and improvement of pharmacy is the creation of original and increasing the ef-fectiveness of existing dosage forms. At the same time, there is justifiable interest in the group of application dosage forms (ADF), which have many advantages, both biopharmaceutical and technological and economic in nature. At the same time, the most significant and promising within this group are dosage forms such as gels and films. Purpose of the study – development of optimal composition, adhesive gel technology, pharmacological confirmation of effectiveness on a model of intestinal anastomosis. Material and methods. To obtain an adhesive gel, compositions based on Na-CMC (0.5–1.5%), Na-alginate (0.5–1.5%) and chitosan (1–3%) were prepared. The osmotic capacity of the gels was studied using a model of dialysis through a semipermeable membrane. The adhesive properties of the gel were determined on an experimental model of intestinal anastomosis by the time of localization of the film-gel complex at the site of application. The biodegradation properties of the film-gel complex were also studied in in vitro and in vivo experiments. Results. A 1.5% gel based on Na-CMC has a greater capacity compared to other prototypes, capable of absorbing up to 12.56% of moisture from its own weight. Gel based on Na-alginate (1.5%) absorbs up to 10.20%, and chitosan (3.0%) – up to 11.05% moisture. The “film-gel” complex based on chitosan gel (3.0%) did not migrate from the site of application within 128 hours, which indicates its satisfactory adhesive properties, since the time during which the complex was at the site of localization corresponds to the critical time the period during which coronary artery failure most often oc-curs. The film-gel complex biodegraded in the blood plasma of rats within 136 hours, and remained in the abdominal cavity of rats at the site of appli-cation for up to 7 days. Conclusions. Comparative studies of various models of adhesive gels obtained on different bases were carried out: Na-CMC (1.5%), Na-alginate (1.5%) and chitosan (3.0%) and showed the advantages of a gel based on chitosan in relation to its ability to ensure film fixation at the application site.

Local government policymaking environment for Health in All Policies: a case study research investigation

ABSTRACT The local level of government is identified as being well placed to address the determinants of health due to their flatter governance structure and proximity to the community. Research has identified multiple factors that influence local governments to act on these health determinants, although few have applied theories of the policy process to understand the policymaking environment. Using two Australian local government case study sites, we explored the policymaking environment regarding policy decisions to address health determinants using the lens of four theories of the policy process. We conducted 20 interviews and one focus group with elected members and staff in local government, along with an analysis of 12 policy documents and participation in a policy reference group. Following thematic analysis, 13 factors influencing policy addressing health determinants were identified, mostly confirming previous research from within Australia and globally. New themes have emerged regarding the limited range of policy actors involved and the lack of advocacy, particularly by community or media, who have an identified influence over decision-making in a local government context. Applying theories of the policy process also demonstrates how they can be used to add meaning to the interconnectedness of influences in unique local government policymaking environments.

Modification of Local Site Preference for Achieving Tunable Color Emission from Blue to Near-White in Sr3(PO4)2:Dy3+ Phosphor

The color tunability of Sr3(PO4)2:1%Dy3+ phosphor from blue to near white is studied at various annealing conditions. Higher temperature annealing promotes agglomerated rhombohedral (α) phase formation. Experimental and theoretical analysis reveal dopant preference at the low-symmetry Sr(II) site, altering electric (4F9/2→6H13/2) and magnetic (4F9/2→6H15/2) dipole transitions, thereby affecting the yellow-to-blue (Y/B) ratio. The luminescence intensity variation and color tunability are explained based on the local site symmetry and occupation probability of the dopant in the host lattice. An increase in the luminescence intensity up to an annealing temperature of 1200 °C, followed by quenching is observed due to the oxygen vacancies. Commission Internationale d'Eclairage (CIE) color coordinates of (0.31, 0.38), Correlated Color Temperature (CCT) of 6341 K, and color purity of 22.57% confirm the potential of Sr3(PO4)2:1%Dy3+ phosphor annealed at (1200 °C, 6 hrs) for white light generation. A probable photoluminescence mechanism involving 4f→5d→4f transitions in Sr3(PO4)2:1%Dy3+ is proposed.

Phosphorylation in the Ser/Arg-rich region of the nucleocapsid of SARS-CoV-2 regulates phase separation by inhibiting self-association of a distant helix

The nucleocapsid protein (N) of SARS-CoV-2 is essential for virus replication, genome packaging, evading host immunity, and virus maturation. N is a multidomain protein composed of an independently folded monomeric N-terminal domain that is the primary site for RNA binding, and a dimeric C-terminal domain that is essential for efficient phase separation and condensate formation with RNA. The domains are separated by a disordered Ser/Arg-rich region preceding a self-associating Leu-rich helix. Phosphorylation in the Ser/Arg region in infected cells decreases the viscosity of N:RNA condensates promoting viral replication and host immune evasion. The molecular level effect of phosphorylation, however, is missing from our current understanding. Using NMR spectroscopy and analytical ultracentrifugation we show that phosphorylation destabilizes the self-associating Leu-rich helix 30 amino acids distant from the phosphorylation site. NMR and gel shift assays demonstrate that RNA binding by the linker is dampened by phosphorylation, whereas RNA binding to the full-length protein is not significantly affected presumably due to retained strong interactions with the primary RNA binding domain. Introducing a switchable self-associating domain to replace the Leu-rich helix confirms the importance of linker self-association to droplet formation and suggests that phosphorylation not only increases solubility of the positively charged elongated Ser/Arg region as observed in other RNA binding proteins but can also inhibit self-association of the Leu-rich helix. These data highlight the effect of phosphorylation both at local sites and at a distant self-associating hydrophobic helix in regulating liquid-liquid phase separation of the entire protein.

H2B oncohistones cause homologous recombination defect and genomic instability through reducing H2B monoubiquitination in Schizosaccharomyces pombe

Canonical oncohistones are histone H3 mutations in the N-terminal tail associated with tumors and affect gene expression by altering H3 post-translational modifications (PTMs) and the epigenetic landscape. Noncanonical oncohistone mutations occur in both tails and globular domains of all 4 core histones and alter gene expression by perturbing chromatin remodeling. However, the effects and mechanisms of noncanonical oncohistones remain largely unknown. Here we characterized 16 noncanonical H2B oncohistones in the fission yeast Schizosaccharomyces pombe. We found that 7 of them exhibited temperature sensitivities and 11 exhibited genotoxic sensitivities. A detailed study of 2 of these onco-mutants H2BG52D and H2BP102L revealed that they were defective in homologous recombination (HR) repair with compromised histone eviction and Rad51 recruitment. Interestingly, their genotoxic sensitivities and HR defects were rescued by inactivation of the H2BK119 deubiquitination function of Ubp8 in the Spt-Ada-Gcn5-Acetyltransferase (SAGA) complex. The levels of H2BK119 monoubiquitination (H2Bub) in the H2BG52D and H2BP102L mutants are reduced in global and local DNA break sites presumably due to enhanced recruitment of Ubp8 onto nucleosomes, and are recovered upon loss of H2B deubiquitination function of the SAGA complex. Moreover, H2BG52D and H2BP102L heterozygotes exhibit genotoxic sensitivities and reduced H2Bub in cis. We therefore conclude that H2BG52D and H2BP102L oncohistones affect HR repair and genome stability via reduction of H2Bub and propose that other noncanonical oncohistones may also affect histone PTMs to cause diseases.

Efficacy of a Lidocaine-Impregnated Elastrator Band for Castration and Tail Docking in Lambs.

The primary objective of this study was to demonstrate the non-inferiority between lidocaine-impregnated ligation bands (LLBs) and control bands (CBs) with respect to the efficacy of castration and tail docking. Secondary objectives were to compare castration and tail-docking success, evaluate local site reactions, and compare average daily gain (ADG) between the treatment groups. A total of 238 male lambs were enrolled and randomly assigned to receive LLBs or CBs on their tail and scrotum. Lambs were weighed, had a health assessment, and the band site was observed on -3, 7, 14, 21, 28, 35, and 42 days after the bands were applied. A linear regression model was built to assess average daily gain, whereas a repeated measures model was used to evaluate body weight differences at each of the measured timepoints. Furthermore, logistic regression models were used to evaluate associations with casting outcomes. Few differences were noted between treatment groups with respect to casting success for the scrotum and tail and ADG over the entire experimental period. Non-inferiority calculations demonstrated no differences in tail docking and scrotal casting success, with casting occurring for the majority of animals by d 21 and d 42 for castration and tail docking, respectively. However, lambs receiving LLBs gained more weight from d -3 to 7 (+0.03 kg/d; 95% CI: 0 to 0.07), which may be an indication of effective pain control during the first week following band application. Overall, the use of an LLB does not affect the time to successful casting of the tail and could improve short-term growth when compared to a control band. Further studies are needed to compare LLBs to multimodal methods of pain relief.