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The aim of this study is to compare long-term outcomes (7-10 years) between vaginal hysterectomy with uterosacral ligament suspension (VHUSLS) and sacrospinous hysteropexy with the Uphold™ Lite mesh System (SHU) for management of apical prolapse.Patients undergoing VHUSLS or SHU from 2008 to 2012 at a single tertiary referral center were included. Patients were contacted, asked to return for physical examination, and to complete the Pelvic Floor Distress Inventory (PFDI-20) questionnaire. Our primary outcome was anatomic failure defined as Stage 2 POP or higher of any compartment. The secondary outcome was subjective changes in symptoms based upon PFDI-20 responses.Two-hundred and two women were identified to have undergone the index surgeries from 2008 to 2012. Sixty-three agreed to return for follow up symptom evaluation and examination (30 VHUSLS and 33 SHU). Baseline characteristics were similar between groups. Clinical cure was high for both groups reaching 93.4 % and 94.0 % for the VHUSLS and SHU groups, respectively (p = 0.721). Anatomical success was lower with 44.7 % and 66.7 % of patients in the VHUSLS and SHU groups, respectively, meeting criteria for success (p = 0.138). There were no mesh complications among patients returning for exams. However, two patients who were contacted and were not interested in this study reported mesh complications and need for additional surgeries. Anterior vaginal wall support was noted to be significantly better supported for SHU (Ba -2.03 ± 0.75 vs -1.42 ± 0.92, p = 0.008). There were no differences between groups for overall PFDI-20 scores postoperatively. However, SHU patients reported higher rates of stress urinary incontinence compared to VHUSLS patients.In women with apical prolapse, VHUSLS and SHU afford similar long-term outcomes. SHU patients reported higher rates of stress urinary incontinence.

The SKA PAthfinder Radio Continuum Surveys (SPARCS) are providing deep-field imaging of the faint (sub-mJy) extra-galactic radio source populations through a series of reference surveys. One of the key science goals for SPARCS is to characterize the relative contribution of radio emission associated with AGN from star-formation (SF) in these faint radio source populations, using a combination of high sensitivity and high angular resolution imaging over a range of spatial scales (arcsec to mas). To isolate AGN contribution from SF, we hypothesise that there exists a brightness temperature cut-off point separating pure AGN from SF. We present a multi-resolution (10-100 mas) view of the transition between compact AGN and diffuse SF through a deep wide-field EVN+e-MERLIN, multiple phase centre survey of the centre of the Northern SPARCS (SLOAN) reference field at 1.6 GHz. This is the first (and only) VLBI (+e-MERLIN) milliarcsecond angular resolution observation of this field, and of the wider SPARCS reference field programme. Using these high spatial resolution (9 pc - 0.3 kpc at z ~ 1.25) data, 11 milliarcsecond-scale sources are detected from a targeted sample of 52 known radio sources from previous observations with the e-MERLIN, giving a VLBI detection fraction of ~ 21%. At spatial scales of ~ 9 pc, these sources show little to no jet structure whilst at ~ 0.3 kpc one-sided and two-sided radio jets begin to emerge on the same sources, indicating a possible transition from pure AGN emissions to AGN and star-formation systems., 14 pages, 10 figures

Many studies have shown that biodiversity regulates multiple ecological functions that are needed to maintain the productivity of a variety of ecosystem types. What is unknown is how human activities may alter the ‘multifunctionality’ of ecosystems through both direct impacts on ecosystems and indirect effects mediated by the loss of multifaceted biodiversity. Using an extensive database of 72 lakes spanning four large Neotropical wetlands in Brazil, we demonstrate that species richness and functional diversity across multiple larger (fish and macrophytes) and smaller (microcrustaceans, rotifers, protists and phytoplankton) groups of aquatic organisms are positively associated with ecosystem multifunctionality. Whereas the positive association between smaller organisms and multifunctionality broke down with increasing human pressure, this positive relationship was maintained for larger organisms despite the increase in human pressure. Human pressure impacted multifunctionality both directly and indirectly through reducing species richness and functional diversity of multiple organismal groups. These findings provide further empirical evidence about the importance of aquatic biodiversity for maintaining wetland multifunctionality. Despite the key role of biodiversity, human pressure reduces the diversity of multiple groups of aquatic organisms, eroding their positive impacts on a suite of ecological functions that sustain wetlands.

The present hydrogeological study was carried out in the complex basement zone (Dabakala department, North-Central Côte d'Ivoire). Indeed, in this area, the population faces a real problem with the drinking water supply during the dry season. The aim of this study is to carry out a spatial characterization of groundwater potentialities in order to establish productive boreholes in the division. Ten decision criteria were developed and then aggregated. The methodology consisted in building a database based on these criteria, using remote sensing and GIS techniques. These criteria applied multi-criteria decision analysis (MCDA) using the Hierarchical Analytical Process (HAP) for their weighting. The resulting groundwater potential map was validated using the sensitivity trend curve technique. Ultimately, the results indicate that approximately 35% of the division’s area has strong to very strong groundwater potential.

The empirical research in this article relies on a data set including all national court decisions on recognition, enforcement and setting aside (vacatur) of international commercial arbitration awards available in the Kluwer database that were rendered from 1 January 2010 to 1 June 2020.Within the time parameters of this study, there were 504 vacatur actions and 553 offensive recognition and enforcement actions. Those decisions were rendered by national courts in 74 different jurisdictions. The research coded every argument raised by defendants challenging the recognition and enforcement of awards based on grounds set forth in Article V of the United Nations Convention on the Recognition and Enforcement of Foreign Arbitral Awards, as well as every argument raised by claimants to challenge awards based on the grounds set forth in Article 34 of the United Nations Commission on International Trade Law (UNCITRAL) Model Law on International Commercial Arbitration. In addition to these grounds, several others, outside the two instruments mentioned above, have been identified in the data set. The results of the research are presented in the article below. An overarching conclusion would be that courts overwhelmingly enforce foreign arbitration awards, in 73% of the cases in the data set, without significant variations between courts in various jurisdictions, and, respectively, overwhelmingly refuse to vacate arbitral awards, with courts vacating in only 23% of cases, again without significant variations between courts in various jurisdictions. arbitral award, national court, set aside, vacatur, recognition and enforcement, public policy, UNCITRAL, New York Convention, due process, arbitrationRoger

Light-dependent chloroplast movements are an actin-dependent cellular response to changes in the light environment that help plants maximize photosynthetic potential and reduce photodamage. Over a dozen proteins are known to be required for normal chloroplast movements, but the molecular mechanisms regulating the transformation of light perception into chloroplast motility are not fully understood. Here, we show that in Arabidopsis (Arabidopsis thaliana) the actin-bundling plasma membrane-associated proteins THRUMIN1, PLASTID MOVEMENT IMPAIRED1 (PMI1), and KINESIN-LIKE PROTEIN FOR ACTIN-BASED CHLOROPLAST MOVEMENT1 (KAC1) interact through the 14-3-3 proteins KAPPA and OMEGA. We also show that the interaction of PMI1 with 14-3-3 KAPPA and OMEGA is regulated by blue light activation of the Phototropin2 photoreceptor. Live-cell confocal microscopy revealed light-induced dynamic changes in the cellular localizations of PMI1 and KAC1. In particular, PMI1 was relocated away from irradiated areas of the plasma membrane in less than a minute after blue light exposure, consistent with PMI1 playing a critical role in initiating light-dependent chloroplast movements. We present a modified conceptual model for high light-dependent chloroplast movements in which PMI1 acts as the mobile signal that initiates a coordinated sequence of changes in protein–protein and protein–plasma membrane interactions that initiate the chloroplast movement response and determine where in the cell chloroplasts are able to anchor to the plasma membrane.

Author(s): Alexander, Roger P; Giraldez, MD; Spengler, RM; Etheridge, A; Godoy, PM; Barczak, AJ; Srinivasan, S; De Hoff, PL; Tanriverdi, K; Courtright, A; Lu, S; Khoory, J; Rubio, R; Baxter, D; Driedonks, TAP; Buermans, HPJ; Nolte-t Hoen, ENM; Jiang, H; Wang, K; Ghiran, I; Wang, Y; Van Keuren-Jensen, K; Freedman, JE; Woodruff, PG; Laurent, LC; Erle, DJ; Galas, DJ; Tewari, M

Lipid droplets (LDs), crucial regulators of lipid metabolism, accumulate during oocyte development. However, their roles in fertility remain largely unknown. During Drosophila oogenesis, LD accumulation coincides with actin remodeling necessary for follicle development. Loss of the LD-associated Adipose Triglyceride Lipase (ATGL) disrupts both actin bundle formation and cortical actin integrity, an unusual phenotype also seen when the prostaglandin (PG) synthase Pxt is missing. Dominant genetic interactions and PG treatment of follicles indicate ATGL acts upstream of Pxt to regulate actin remodeling. Our data suggest ATGL releases arachidonic acid (AA) from LDs to serve as the substrate for PG synthesis. Lipidomic analysis detects AA-containing triglycerides in ovaries, and these are increased when ATGL is lost. High levels of exogenous AA block follicle development; this is enhanced by impairing LD formation and suppressed by reducing ATGL. Together these data support the model that AA stored in LD triglycerides is released by ATGL to drive the production of PGs, which promote actin remodeling necessary for follicle development. We speculate this pathway is conserved across organisms to regulate oocyte development and promote fertility.

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community.

Extracellular proton concentration is at 40 nM when pH is 7.4. In disease conditions such as brain ischemia, proton concentration can reach µM range. To respond to this increase in extracellular proton concentration, the mammalian brain expresses at least three classes of proton receptors. Acid-sensing ion channels (ASICs) are the main neuronal cationic proton receptor. The proton-activated chloride channel (PAC), which is also known as (aka) acid-sensitive outwardly rectifying anion channel (ASOR; TMEM206), mediates acid-induced chloride currents. Besides proton-activated channels, GPR4, GPR65 (aka TDAG8, T-cell death-associated gene 8), and GPR68 (aka OGR1, ovarian cancer G protein-coupled receptor 1) function as proton-sensitive G protein-coupled receptors (GPCRs). Though earlier studies on these GPCRs mainly focus on peripheral cells, we and others have recently provided evidence for their functional importance in brain injury. Specifically, GPR4 shows strong expression in brain endothelium, GPR65 is present in a fraction of microglia, while GPR68 exhibits predominant expression in brain neurons. Here, to get a better view of brain acid signaling and its contribution to ischemic injury, we will review the recent findings regarding the differential contribution of proton-sensitive GPCRs to cerebrovascular function, neuroinflammation, and neuronal injury following acidosis and brain ischemia.

Context Wild house mice cause substantial economic damage to grain crops in Australia, particularly during mouse plagues. Populations were monitored to detect changes in abundance, with data from surveys used in models to forecast likely mouse outbreaks. However, it is not always feasible to use live-trapping (the ‘gold standard’) for assessing mouse abundance at a large number of monitoring sites spread across south-eastern Australia. A range of alternative methods was tried to assist the grains industry with strategic decisions to reduce crop damage. Aims The aim of this work was to determine which survey methods could provide useful and effective indexes of mouse abundance across a large area. Methods Monitoring of mouse populations was conducted at representative grain farms by using (1) live-trapping at long-term ‘benchmark’ sites (n = 2), and (2) mouse chew cards and active burrow counts at ‘rapid-assessment’ sites (n = 44 farms across 5 regions). Monitoring was conducted for 22 monitoring sessions over 7.5 years through low, medium and high mouse abundance conditions. Key results Live-trapping provided the most useful, but most resource-intensive, information. There were strong relationships between the index of mouse abundance from live-trapping with mouse chew cards and active burrow counts at a local (explaining 63% and 71% of variation respectively) and regional (explaining 71% and 81% of variation respectively) scales. The same quantitative relationship held between the mouse chew cards and trapping regardless of season and year. However, the relationship between active burrow counts and trapping was best in winter and autumn seasons. There was a strong relationship between mouse abundance from live-trapping and active burrows across 1 ha grids (R2 = 0.88). We determined there were 1.3 ± 0.2 (mean ± s.e.) mice per active burrow. Conclusions Live-trapping supplemented with data from chew cards and active burrows remains sufficient to monitor a wide range of sites to show regional trends. Implications It is likely that live-trapping will need to be used for the foreseeable future to provide useful parameters such as breeding condition and population abundance that are required for the forecast models. Supplementary monitoring at rapid-assessment sites (using chew cards in all seasons and active burrow counts particularly in autumn and winter), that can be collected easily without the need for animal handling, will provide additional indications of region-specific changes in mouse abundance and activity.

When patients with advanced dementia lose capacity to make medical decisions for themselves, a 'best interests' determination is usually made on their behalf by the responsible clinician. Where possible, this should be made in consultation with members of the multiprofessional team and the family, consistent with ethical and legal norms. This paper is about multidisciplinary approaches to education and practice in dementia care, using a framework.At a UK multiprofessional workshop in 2020, delegates discussed ethical and legal issues that arise when making decisions for patients with advanced dementia. After an initial presentation, providing context and background, delegates broke into small groups. They were tasked with responding to questions arising from anonymised cases based on real-life scenarios. During plenary discussion afterwards, feedback was shared, and points of best practice were discussed. The authors took notes, and following positive evaluations after the event, they did further work on the framework with the intention of making it available for other health care professionals and clinical educators.Based on contemporaneous notes summarising the feedback, plus further reflections, the framework was developed into a 12-point plan to assist health care teams and educators address difficulties in making 'best interests' determinations.Promoting understanding of ethics and law pertaining to 'best interests' should benefit patients and families, with the potential to reduce the need for cases to be decided in court. To help promote good clinical practice, educators may want to consider running case-based workshops at their institution, using the framework as a scaffold for learners.

Prenatal exposure to maternal depression increases the risk for onset of emotional and behavioral disorders in children. Here, we investigated the effects of exposure to prenatal depression on white matter microstructural integrity at birth and at 2–3 years, and associated neurodevelopment. Diffusion-weighted images were acquired for children of the Drakenstein Child Health Study at 2–4 weeks postpartum (n = 70, 47% boys) and at 2–3 years of age (n = 60, 58% boys). Tract-Based Spatial Statistics was used to compare diffusion tensor metrics across groups defined by presence (> 19 on Beck’s Depression Inventory and/or > 12 on the Edinburgh Postnatal Depression Scale) or absence (below depression thresholds) of depression, and associations with neurodevelopmental measures at age 2–3 years were determined. We did not detect group differences in white matter integrity at neonatal age in this cohort, but at 2–3 years, children in the exposed group demonstrated higher fractional anisotropy, and lower mean and radial diffusivity in association tracts compared to control children. This was notable in the sagittal stratum (radial diffusivity: p

Supplemental Figure 1: Hypothetical model of peripheral blood TCR-transgenic cell repopulation. Supplemental Figure 2: GLP team organizational chart. Supplemental Figure 3. Bone marrow transplant (BMT) optimization studies in HLA-A2/Kb transgenic mice. Supplemental Figure 4. Body weight and hematology assessment at day 5 and 3 months after BMT. Supplemental Figure 5. Spleen and bone marrow cellularity at day 5 and 3 months after BMT. Supplemental Figure 6. Serum chemistry at 3 months after BMT. Supplemental Figure 7. Flow cytometry gating strategy for bone marrow and splenocytes phenotype characterization. Supplemental Figure 8. Survival and hematology 3 months after BMT with Lin- cells transduced with LV-empty, LV-NY-ESO-1 TCR or LV-NY-ESO-1 TCR/sr39TK. Supplemental Figure 9. Differentiation of NYESO TCR/sr39TK-engineered T cells in ATOs (artificial thymic organoids). Supplemental Table 1. Certificate of Analysis of the GMP-comparable LV-NY-ESO-1 TCR/sr39TK (RRL-MSCV-optNYESO-optsr39TK-WPRE, production volume: 20L). Supplemental Table 2. Certificate of Analysis of the Clinical Grade Lentivirus LV-NY-ESO- 1 TCR/sr39TK (RRL-MSCV-optNYESO-optsr39TK-WPRE, production volume 60L). Supplemental Table 3. Certificate of Analysis of the clinical grade RV-NY-ESO-1 TCR (MSGV1-A2aB-1G4A-LY3H10) (Production volume 18L)*. Supplemental Table 4. Certificate of Analysis of the GMP comparable RV-NY-ESO-1 TCR (MSGV1-A2ab-1G4A-Ly3H10, Production volume: 3L). Supplemental Table 5. Co-Administration of NY-ESO-1 TCR Genetically Modified T cells and Hematopoietic Stem Cells (HSCs) in HLA-A2.1/Kb mice. GLP studies cohort distribution. Supplemental Table 6. Cell manufacturing acceptance criteria. Supplemental Table 7. List of protocol-specific organs. Supplemental Table 8. Manufacturing validation runs. Supplemental Table 9. Comparison between fresh and cryopreserved product at 1, 30, 90 and 180# days.

Purpose:To improve persistence of adoptively transferred T-cell receptor (TCR)–engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application.Experimental Design:HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)–compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)–compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use.Results:TCR genetically modified and ex vivo–cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality.Conclusions:Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471.

Supplementary Video 1. This is a 3D reconstruction of a 250uCi 18F-FHBG PET/CT scan of an ESO/TK mouse 3h after conscious uptake. Notable areas of uptake are the long bones of the arms and legs, sternum, spine, and thymus.

Engineering immunity against cancer by the adoptive transfer of hematopoietic stem cells (HSC) modified to express antigen-specific T-cell receptors (TCR) or chimeric antigen receptors generates a continual supply of effector T cells, potentially providing superior anticancer efficacy compared with the infusion of terminally differentiated T cells. Here, we demonstrate the in vivo generation of functional effector T cells from CD34-enriched human peripheral blood stem cells modified with a lentiviral vector designed for clinical use encoding a TCR recognizing the cancer/testes antigen NY-ESO-1, coexpressing the PET/suicide gene sr39TK. Ex vivo analysis of T cells showed antigen- and HLA-restricted effector function against melanoma. Robust engraftment of gene-modified human cells was demonstrated with PET reporter imaging in hematopoietic niches such as femurs, humeri, vertebrae, and the thymus. Safety was demonstrated by the in vivo ablation of PET signal, NY-ESO-1-TCR–bearing cells, and integrated lentiviral vector genomes upon treatment with ganciclovir, but not with vehicle control. Our study provides support for the efficacy and safety of gene-modified HSCs as a therapeutic modality for engineered cancer immunotherapy. Cancer Res; 74(18); 5173–83. ©2014 AACR.

Maternal perinatal depression is associated with risk of adverse child developmental outcomes and differences in offspring brain structure. Evidence from low- and middle-income countries is lacking as is an investigation of antenatal, postnatal, and persistent depression in the same sample. In a South African birth cohort, we investigated the effect of antenatal and postpartum maternal depressive symptoms on offspring brain structure at 2–3 years of age. Magnetic resonance imaging was performed, extracting cortical thickness and surface areas in frontal cortex regions of interest and subcortical volumes using FreeSurfer software. Maternal depressive symptoms were measured using the Edinburgh Postpartum Depression Scale and the Beck Depression Inventory II antenatally and at 6–10 weeks, 6 months, 12 months, and 18 months postpartum and analyzed dichotomously and continuously. Linear regressions were used controlling for child age, sex, intracranial volume, maternal education, age, smoking, alcohol use and HIV. 146 children were included with 38 (37%) exposed to depressive symptoms antenatally and 44 (35%) exposed postnatally. Of these, 16 (13%) were exposed to both. Postpartum, but not antenatal, depressive symptoms were associated with smaller amygdala volumes in children (B = −74.73, p = 0.01). Persistent maternal depressive symptoms across pregnancy and postpartum were also independently associated with smaller amygdala volumes (B = −78.61, p = 0.047). Differences in amygdala volumes among children exposed to postnatal as well as persistent maternal depressive symptomatology underscore the importance of identifying women at-risk for depression during the entire perinatal period.

Background To describe the correlation between standardized A-scan echography and histopathology in a ciliary body melanocytoma. Case presentation We present a case of a large ciliary body melanocytoma with significant growth, vision loss, and elevated intraocular pressure that was diagnosed clinically as a melanoma, but the standardized A-scan findings correlated to the histopathological description of a melanocytoma with multiple pseudocysts. Conclusions The reflectivity of this melanocytoma by standardized A-scan was consistent with multiple pseudocysts on pathological evaluation. This echographic pattern guided the differential diagnosis. Standardized A-scan is an important diagnostic tool in the differentiation of ciliary body melanocytomas from melanomas.

Lentiviral vectors (LVs) are robust delivery vehicles for gene therapy as they can efficiently integrate transgenes into host cell genomes. However, LVs with lengthy or complex expression cassettes typically are produced at low titers and have reduced gene transfer capacity, creating barriers for clinical and commercial applications. Modifications of the packaging cell line and methods may be able to produce complex vectors at higher titer and infectivity and may improve production of many different LVs. In this study, we identified two host restriction factors in HEK293T packaging cells that impeded LV production, 2′-5′-oligoadenylate synthetase 1 (OAS1) and low-density lipoprotein receptor (LDLR). Knocking out these two genes separately led to ∼2-fold increases in viral titer. We created a monoclonal cell line, CRISPRed HEK293T to Disrupt Antiviral Response (CHEDAR), by successively knocking out OAS1, LDLR, and PKR, a previously identified factor impeding LV titers. Packaging in CHEDAR yielded ∼7-fold increases in physical particles, full-length vector RNA, and vector titers. In addition, overexpressing transcription elongation factors, SPT4 and SPT5, during packaging improved the production of full-length vector RNA, thereby increasing titers by ∼2-fold. Packaging in CHEDAR with over-expression of SPT4 and SPT5 led to ∼11-fold increases of titers. These approaches improved the production of a variety of LVs, especially vectors with low titers or with internal promoters in the reverse orientation, and may be beneficial for multiple gene therapy applications.

Background: Intramedullary fixation in distal biceps tendon repair may be a solution to address specific shortcomings of current fixation techniques. Most investigations are limited to biomechanical evaluation. The purpose of this study was to report the short-term outcomes of an intramedullary fixation device. Methods: We evaluated functional and radiographic outcomes at up to 6 months of follow-up. Patients with an acute distal biceps tendon nipture eligible for surgical repair were invited to take part in the study. Ten patients were included in the final analysis. All patients were evaluated both clinically and radiographically at 2 weeks, 6 weeks, 3 months, and 6 months. Outcomes were recorded using a visual analog scale score for pain, the Mayo Elbow Performance Score, and the Disabilities of the Arm, Shoulder and Hand score. Radiographic evaluation comprised radiographic and computed tomography evaluation. Results: There were no failures of fixation in the patient group examined. Elbow mobility was symmetrical for all patients from 3 months onward. Supination strength was 86% of the uninjured side at final follow-up. The mean Disabilities of the Arm, Shoulder and Hand score and Mayo Elbow Performance Score at final follow-up were 0 and 100, respectively. Computed tomography images showed no signs of button migration, cortical thinning due to button pressure, or button breakout. The tendon could be followed to the button in all cases. Conclusions: The intramedullary fixation button technique to repair the distal biceps tendon has excellent functional outcomes at 6 months. No adverse reactions of the button on the bone were seen. As this technique minimizes the risk of posterior interosseous nerve injury and has a sufficient bone tunnel to avoid gap formation, this may be a promising new technique for distal biceps tendon rupture refixation. (C) 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.

Objectives To investigate the effects of long-term use of the lower lingual arch (LLA) on the sagittal and vertical positions of the permanent lower incisors and first molars. Materials and Methods The sample consisted of 98 patients who were treated with an LLA (LLA group) and 39 patients who were treated without an LLA (no-LLA group). The positional changes of the lower incisors and first molars were analyzed after performing mandibular structural superimpositions on lateral cephalometric radiographs taken before treatment (T1) and at the end of LLA therapy (T2). The mean ages at T1 and T2 were 8.5 years and 13.2 years, respectively. Study casts were analyzed to quantify arch dimensional changes. Results Mesial movement of the lower molar cusp was similar between the LLA and no-LLA groups, but the vertical position was slightly greater at T2 in the LLA group. In the LLA group, there was a molar tip-back effect, and the lower incisors were proclined 4.2° more than in the no-LLA group. Arch perimeter decreased 3.6 ± 2.6 mm without an LLA and 0.97 ± 3.7 mm with an LLA. Intercanine and intermolar widths both increased about 1 mm more with an LLA (P < .0001). Conclusions The LLA does not seem to restrict mesial movement and vertical eruption of the lower incisors and molars in the long term. The LLA effectively preserves the arch perimeter at the expense of a slight lower incisor proclination.

SUMMARY The discovery that large landslides dissected the Hawaiian Islands, scattering debris over thousands of square kilometres of seafloor, changed our ideas of island growth and evolution. The evidence is consistent with catastrophic flank collapse during volcano growth, and draws our focus to the currently active island of Hawai'i, the volcanoes Mauna Loa and Kīlauea, and particularly to the actively mobile south flank of Kīlauea. Both the weight distribution and pressure within an extensive magmatic system are perceived to affect stability, but the role of gravitational body forces and island density distribution has not been quantitatively assessed. We use seismic velocities derived from tomography to model the density distribution of the island of Hawai'i and find that olivine-rich melts and rocks in Hawaiian volcanoes result in a close association of seismic velocity and density. The resultant density model reproduces more than 95 per cent of the observed gravity disturbance signal wherever tomographic control exists and provides a basis for evaluating the body forces from gravity. We also find that if the decollement is weak, then gravitational body forces can produce slip that explains most seismo-tectonic and volcano-tectonic structural features of Kīlauea. Where the decollement is in a state of incipient slip from this weight distribution, fluctuations in magma pressure can trigger accelerated slip on the decollement. Yet this is only true of the south flank of Kīlauea. Though weight and magma distributions produce significant forces driving the west flank of Mauna Loa seaward, this flank is relatively stable. Stability over most of the last decade indicates a strong foundation beneath the west flank of Mauna Loa, perhaps as a result of past landslides that scraped clay-rich sediments from the decollement.

The precast industry, due to its specific early-age strength requirements for hollowcore (HC) slab products, has been reluctant to introduce alternative cementitious materials such as ground granulated blast-furnace slag (GGBS) due to the slower strength development of such materials. This paper reports on a study undertaken at a precast production facility to examine how to overcome the consequences of strength loss due to the replacement of up to 50% of CEM I (42·5R), as usually used in cold weather conditions, with GGBS, for environmental or durability reasons. The GGBS concrete slabs were activated using thermal, chemical and mechanical means to enhance their early-age strength gain. The results were compared at early ages in terms of the temperature profile during curing, cube compressive strengths, load-carrying capacities for transportability requirements, ultimate load and short-term creep. In addition, 28 d densities and strengths were compared for in situ cubes and cores extracted from HC slab samples. The experimental results showed a favourable potential for replacing CEM I (42·5R) cement with up to 50% GGBS in winter without compromising on factory productivity.

A male patient aged 16 years with a recent history of blunt trauma to the periorbita presented with blurred vision, pain, and proptosis of the right eye. MRI imaging revealed an intraconal mass. What would you do next?

La Clasificación de Chicago v4.0 (CCv4.0) es el esquema actualizado para clasificar las alteraciones de la motilidad esofágica utilizando la métrica de la manometría de alta resolución (HRM). Para desarrollar la CCv4.0, 52 expertos internacionales diversos separados en siete subgrupos de trabajo utilizaron una metodología formalmente validada, en un periodo de dos años. Las actualizaciones claves de la CCv4.0 consisten en un protocolo de HRM más riguroso y expansivo que incorpora las posiciones en decúbito supino y sedestación, así como pruebas provocadoras; una definición refinada de la obstrucción del flujo de salida de la unión esofagogástrica (EGJOO), criterios diagnósticos más estrictos para la motilidad esofágica inefectiva, y descripción de la métrica basal de la EGJ. Adicionalmente, la CCv4.0 se propuso definir el diagnóstico de alteración de la motilidad como conclusivo o no conclusivo con base en los síntomas asociados, los hallazgos en las pruebas provocadoras, y los resultados de los exámenes de apoyo como el esofagograma con tableta de bario y/o la prueba con sonda para imagen endoluminal funcional. Estos cambios buscan minimizar la ambigüedad presente en iteraciones previas de la Clasificación de Chicago; además proveen criterios más estandarizados y rigurosos para los patrones de alteración de la peristalsis y obstrucción de la EGJ.

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the CYBB gene, resulting in the inability of phagocytic cells to eliminate infections. To design a lentiviral vector (LV) capable of recapitulating the endogenous regulation and expression of CYBB, a bioinformatics-guided approach was used to elucidate the cognate enhancer elements regulating the native CYBB gene. Using this approach, we analyzed a 600-kilobase topologically associated domain of the CYBB gene and identified endogenous enhancer elements to supplement the CYBB promoter to develop MyeloVec, a physiologically regulated LV for the treatment of X-CGD. When compared with an LV currently in clinical trials for X-CGD, MyeloVec showed improved expression, superior gene transfer to hematopoietic stem and progenitor cells (HSPCs), corrected an X-CGD mouse model leading to complete protection against Burkholderia cepacia infection, and restored healthy donor levels of antimicrobial oxidase activity in neutrophils derived from HSPCs from patients with X-CGD. Our findings validate the bioinformatics-guided design approach and have yielded a novel LV with clinical promise for the treatment of X-CGD.

We used dynamic pelvic floor ultrasound to investigate the relationship between obstructed defecation symptom (ODS) severity and the degree of rectal hypermobility/folding. In this retrospective study, women who presented with ODS from October 2017 to January 2019 and underwent an interview, pelvic examination, and pelvic floor ultrasound were recruited. Patients were diagnosed with abdominal constipation, dyssynergia, or pelvic constipation. Pelvic constipation patients were categorized based on their reported frequency of incomplete emptying of stool (

Concrete median barriers are designed to mitigate serious cross-median crashes by preventing penetration of errant vehicles into oncoming traffic. When implemented in flood-prone areas, however, solid concrete median barriers can act as a dam to floodwaters, as recently seen in the U.S. in Texas during Hurricane Harvey, or in Louisiana and Pennsylvania following severe storms. This raises the height of the floodwaters and increases the severity of flooding on highways and surrounding roads and communities. To reduce flooding, new median barrier options with openings were investigated. Finite element simulations were used to aid investigation and evaluation of the designs, and laboratory testing was performed to evaluate the hydraulic efficiency of barrier designs in a variety of simulated flood conditions. A concrete single-slope profile median barrier with a large scupper was selected for crash testing following Manual for Assessing Safety Hardware (MASH) Test Level 4 (TL-4) impact conditions and evaluation criteria. The median barrier design was deemed MASH compliant and is ready for implementation in areas susceptible to flooding, with the goal of reducing flooding severity, decreasing associated risk to motorists, and reducing the level of flood damage to both highways and surrounding areas.

Fecal incontinence (FI) has two primary subtypes: urgency fecal incontinence (UFI) and passive fecal leakage (PFL). The pathophysiology underlying the subtypes is incompletely understood. To compare the bowel habits, physical examinations and pelvic floor anatomical defects in patients with UFI-dominant FI versus patients with PFL-dominant FI. This is a retrospective cross-sectional study of female patients who presented with fecal incontinence symptoms to our tertiary urogynecology center. All subjects underwent a comprehensive history, physical examination, 3D-static pelvic floor ultrasound, and 2D-dynamic ultrasound of the posterior compartment. Patients with UFI-dominant FI were compared to patients with PFL-dominant FI. One hundred forty-five patients were included in the analysis; 57 categorized as UFI-dominant FI, 69 PFL-dominant FI and 19 categorized as having “both” leakage patterns. In comparing bowel habits, patient with UFI-dominant FI had more frequent bowel movements (15.5 ± SD 13.0/week vs. 10.9 ± SD 7.6 /week, p = 0.022) and were more likely to have loose stools (48.2% vs. 26.1%, p = 0.01). No statistically significant differences were observed in the prevalence of external anal sphincter defect (11.3% vs. 17.2%, p = 0.38) or internal anal sphincter defect (11.3% vs. 19%, p = 0.26) between groups. Finally, patients with UFI-dominant FI had a higher incidence of rectal hypermobility (loss of rectal support on Valsalva) (58% vs. 36.9%, p = 0.025). Patients with urge-predominant FI have increased frequency of bowel movements, looser stools, and increased rectal folding diagnosed via dynamic ultrasound as compared to patients with passive-dominant FI.

The objective was to find an alternative treatment to a low-dose antibiotic for the prevention of recurrent urinary tract infections (UTI) and to evaluate the difference in rates of reinfection within 1 year when treated with methenamine hippurate for prophylaxis compared with trimethoprim. We present a non-blinded randomized trial comparing methenamine hippurate with trimethoprim for the prevention of recurrent UTI at 12 months after starting treatment. Women over 18 who had at least two culture-positive UTI in the prior 6 months or three in the prior year were included. Ninety-two patients met enrollment criteria and were randomized to receive daily prophylaxis with methenamine hippurate or trimethoprim for a minimum of 6 months. Both intent-to-treat and per-protocol analyses if patients received the alternative drug after randomization were analyzed using Student’s t test, Mann–Whitney U test, Kaplan–Meier curves, log-rank test, and a logistic and multivariate regression model. The primary outcome of this study was culture-proven UTI recurrence by 12 months after initiating prophylaxis. In the intent-to-treat analysis, we found no difference between groups in recurrent UTI, with a 65% (28 out of 43) recurrence in the trimethoprim group versus 65% (28 out of 43) in the methenamine hippurate group (p = 1.00). In the per-protocol analysis, 65% (26 out of 40) versus 65% (30 out of 46) of patients had UTI recurrences in the trimethoprim group versus the methenamine hippurate group (p = 0.98). Methenamine hippurate may be an alternative for the prevention of recurrent UTI, with similar rates of recurrence and adverse effects to trimethoprim.