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Abstract The Aria cryogenic distillation plant, located in Sardinia, Italy, is a key component of the DarkSide-20k experimental program for WIMP dark matter searches at the INFN Laboratori Nazionali del Gran Sasso, Italy. Aria is designed to purify the argon, extracted from underground wells in Colorado, USA, and used as the DarkSide-20k target material, to detector-grade quality. In this paper, we report the first measurement of argon isotopic separation by distillation with the 26 m tall Aria prototype. We discuss the measurement of the operating parameters of the column and the observation of the simultaneous separation of the three stable argon isotopes: $${}^{36}\hbox {Ar}$$ 36 Ar , $${}^{38}\textrm{Ar}$$ 38 Ar , and $${}^{40}\textrm{Ar}$$ 40 Ar . We also provide a detailed comparison of the experimental results with commercial process simulation software. This measurement of isotopic separation of argon is a significant achievement for the project, building on the success of the initial demonstration of isotopic separation of nitrogen using the same equipment in 2019.

Introduction Acute clinical deterioration in hospital inpatients can be caused by a range of factors including dementia, delirium, substance withdrawal and psychiatric disturbance, creating challenges in diagnosis, often requiring a management plan with input from multiple disciplines. Staff forums and broader literature have confirmed that healthcare staff working in non-mental health settings, may not be as skilled in recognising and managing early signs of emerging and/or escalating clinical agitation. The BoC RRT is a consultation service within the Division of Medicine and CL Psychiatry. Staffed by Medical Registrars and Mental Health Nurses, the collaboration provides a unique healthcare response to acute general wards. The BoC RRT has been implemented to address the rising number of incidences whereby staff and patient safety are compromised. Using evidence-based skills the team aimed to: respond to episodes of clinical agitation that require an internal security response, assist ward referrals by exploring biopsychosocial contributants to behaviour, develop individual patient support plans and review and reduce restrictive intervention practices. Objectives To determine if the rapid response model has influenced: - The impact on staff/patient safety - Frequency of emergency responses for aggression - Frequency of restrictive intervention use Methods This project was approved as a quality assurance project (QA2022018). The patients within scope of the BoC RRT include inpatients in medical and surgical wards. It excludes patients in Emergency Departments, mental health units, outpatient clinics, and visitors. The evaluation of the pilot has used a PDSA (Plan, Do, Study, Act) cycle when implementing new improvements. A mixed methods approach explored the impact of the BoC RRT. Staff consultation will identify challenges in responding to scenarios whereby there is risk of harm to staff and patients. Staff feedback and the emergency response data was monitored. Results In 2021, there was approx. 720 code greys per month, requiring a security response. Since the implementation of BoC RRT, these numbers have reduced to 527. Reviewing restrictive intrvention practices has identified areas for policy review and need for education. Staff consultation found that nurses were confident caring for those patients exhibiting clinical agitation associated with delirium and dementia. However, caring for people with mental health or substance use disorders were more challenging. Conclusions These interim results indicate that BoC RRT has been generally well received by clinical staff. The decline in code grey responses indicates that it is likely having a positive impact in early identification and management of clinical agitation for hospital inpatients. There is support for this response model to continue beyond the pilot phase and further area for research. Disclosure of Interest None Declared

73Ge(n,γ) cross sections were measured at the neutron time-of-flight facility n_TOF at CERN up to neutron energies of 300 keV, providing for the first time experimental data above 8 keV. Results indicate that the stellar cross section at kT=30 keV is 1.5 to 1.7 times higher than most theoretical predictions. The new cross sections result in a substantial decrease of 73Ge produced in stars, which would explain the low isotopic abundance of 73Ge in the solar system. Keywords: Nucleosynthesis, Neutron capture, s process, Germanium, n_TOF

This work reports on accurate, high-resolution measurements of the 25Mg(n,γ)26Mg and 25Mg(n,tot) cross sections in the neutron energy range from thermal to about 300 keV, leading to a significantly improved 25Mg(n,γ)26Mg parametrization. The relevant resonances for n+25Mg were characterized from a combined R-matrix analysis of the experimental data. This resulted in an unambiguous spin/parity assignment of the corresponding excited states in 26Mg. With this information experimental upper limits of the reaction rates for 22Ne(α,n)25Mg and 22Ne(α,γ)26Mg were established, potentially leading to a significantly higher (α,n)/(α,γ) ratio than previously evaluated. The impact of these results has been studied for stellar models in the mass range 2 to 25 M⊙.

Sentinel-1A was launched in April 2014, and has been collecting data routinely over more than one year. Sentinel-1B is set for launch on 22 April 2016. The Sentinel-1 constellation has several advantages over previous radar missions for InSAR applications: (1) Data are being acquired systematically for tectonic and volcanic areas, (2) Images cover a wide footprint, 250 km from near to far range in Interferometric Wide Swath (TOPS) mode, (3) Small perpendicular and temporal baselines greatly improve interferometric coherence at C-band, (4) Data are freely available to all users, (5) The mission is planned to be operational for 20 years, with 1C and 1D planned for future launches. These features enable us to map geological processes occurring in any place at anytime using InSAR. We will review progress within COMET towards our ultimate goal of building a fully-automated processing system that provides deformation results and derived products to the wide InSAR and Geophysics communities. In addition to high-resolution-ECMWFbased atmospheric correction model, we will show results of a systematic analysis of interferometric coherence in tectonic and volcanic areas, and discuss the future goals and timeline for the COMET InSAR automated processing system.

Atraumatic splenic rupture is a rare complication of a pancreatic pseudocyst (PP), described in the setting of chronic pancreatitis. There is common understanding, within the literature, that an inflammatory process at the tail of the pancreas may disrupt the spleen and result in such splenic complications. The authors present a case report of a 29-year-old male with a PP, associated with chronic pancreatitis. The patient had a history of excessive alcohol intake and presented to the emergency department with a short history of abdominal pain and vomiting. He denied any significant history of trauma and serum amylase levels were normal. An admission computed tomography (CT) scan of the abdomen confirmed the presence of a PP in direct contact with the spleen. The CT also demonstrated a heterogenous hypodense area of the splenic hilum, along with perisplenic fluid. The patient was admitted for observation. His abdominal pain progressed, and he became haemodynamically unstable. An emergency ultrasound scan (USS) at this time revealed intra-abdominal haemorrhage. A subsequent CT confirmed splenic rupture, which was managed surgically with a full recovery. Few such cases are documented within the literature and more understanding of preempting such events is needed.

ABSTRACT: This work describes a new approach for synthesizing extremely fouling-resistant, zwitterionic membranes with controlled, tunable pore sizes that extend from ion separations (< 1 nm) to the ultrafiltration range (∼2 nm). These membranes are manufactured by the UV treatment of high zwitterion content amphiphilic copolymers with cross-linkable functionality to stabilize the membrane selective layers, preventing excessive swelling and dissolution of copolymers containing as high as 80 wt% zwitterionic repeat units. Zwitterion weight fraction allows the tuning of membrane performance, with effective pore size and permeance both increasing with zwitterion content. The high zwitterion content membranes were remarkably fouling-resistant and demonstrated a salt-responsive behavior not previously observed with self-assembling zwitterionic copolymer membranes.

Background Blood pressure (BP) varies over time within individual patients and across different BP measurement techniques. The effect of different BP targets on concordance between BP measurements is unknown. The goals of this analysis are to evaluate concordance between (1) clinic and ambulatory BP, (2) clinic visit‐to‐visit variability and ambulatory BP variability, and (3) first and second ambulatory BP and to evaluate whether different clinic targets affect these relationships. Methods and Results The SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP monitoring ancillary study obtained ambulatory BP readings in 897 participants at the 27‐month follow‐up visit and obtained a second reading in 203 participants 293±84 days afterward. There was considerable lack of agreement between clinic and daytime ambulatory systolic BP with wide limits of agreement in Bland‐Altman plots of −21 to 34 mm Hg in the intensive‐treatment group and −26 to 32 mm Hg in the standard‐treatment group. Overall, there was poor agreement between clinic visit‐to‐visit variability and ambulatory BP variability with correlation coefficients for systolic and diastolic BP all

BackgroundThe clinical implications of ankle‐brachial index (ABI) cutpoints are not well defined in patients with chronic kidney disease (CKD) despite increased prevalence of high ABI attributed to arterial stiffness. We examined the relationship of ABI with cardiovascular disease (CVD) and all‐cause mortality among CKD patients. Methods and ResultsThree thousand six hundred twenty‐seven participants without clinical peripheral artery disease (PAD) at baseline from the Chronic Renal Insufficiency Cohort Study were included. ABI was obtained per standard protocol and CVD events were confirmed by medical record adjudication. A U‐shaped association of ABI with PAD, myocardial infarction (MI), composite CVD, and all‐cause mortality was observed. Individuals with an ABI between 1.0 and

Background: African American (AA) male survivors of strokes or transient ischemic attacks (TIA) have the highest risk of recurrent stroke when compared to other racial-ethnic men. However, there is a paucity of evidence-based strategies, including organizational, educational, or behavioral interventions, that targets secondary stroke risk reduction in AA men. Methods: Targeted Management for Reducing Stroke Risk (TEAM) is an ongoing, 6-month prospective, randomized controlled trial that will determine whether a curriculum-guided self-management approach, using peer dyads (men who had a stroke or TIA and their care partners) will improve post-stroke care in AA men. Results: The study sample will consist of 160 AA men who have experienced a stroke or TIA within 5 years, randomized to TEAM or Wait-list control group. The primary outcome changes in systolic blood pressure (BP) and high-density lipoprotein (HDL), while secondary outcomes include diastolic BP, total cholesterol, low-density lipoprotein, triglycerides, and glycemic control for diabetics. We hypothesize that AA men in TEAM will have significantly lower systolic BP and higher HDL when compared to AA men in the Wait-list control group at 6-month. Conclusion: Persistent disparities for stroke burden in AA men highlight the need for novel interventions to promote secondary stroke-risk reduction. Building on promising pilot data, TEAM uses a group format, with a nurse and patient co-led intervention focused on AA men and family needs, practice in problem-solving, and attention to emotional and role management. In addition, the TEAM approach may help reduce stroke risk factors and health disparities in AA men. Clinicaltrials.gov Identifier: NCT04402125. [ABSTRACT FROM AUTHOR]

Purpose: Adoption of technology has increased to support self-managing chronic diseases. However, behavioral interventions evaluating such technology have been understudied in African Americans with hypertension. The aim of this study was to explore a community and technology-based intervention for hypertension self-management (COACHMAN) intervention on blood pressure (BP) control and health-related quality of life (HRQoL) in African Americans with hypertension. Methods: Sixty African Americans (mean age 60; 75% females) who were prescribed antihypertensive medications and owning a smartphone were randomized to the COACHMAN (n = 30) or enhanced usual care (n = 30) group for 12 weeks. COACHMAN is comprised of four components: web-based education, home BP monitoring, medication management application, and nurse counseling. Hypertension knowledge, self-efficacy, technology adoption/use, medication adherence, BP, and HRQoL scores were assessed. Results: Mean systolic and diastolic BP at baseline was 150.49 (SD = 13.89) and 86.80 (SD = 13.39), respectively. After completing the 3-month intervention to improve hypertension self-management, the groups did not significantly differ in BP control and HRQoL. Clinically relevant BP reduction was observed in the intervention group. Paired t-test showed that mean medication-taking adherence scores significantly improved in the intervention group (P = 0.023) compared to the control group (P = 0.075). Conclusion: Using technology may have a positive impact on supporting hypertension self-management, particularly in medication-taking adherence. Further research is warranted in a larger sample and should include standardization of medication management to isolate the effects of behavioral interventions on changes in BP. Clinicaltrials.gov Identifier: NCT03722667. [ABSTRACT FROM AUTHOR]

S100A1, a 21-kDa dimeric Ca2+-binding protein, is an enhancer of cardiac Ca2+ release and contractility and a potential therapeutic agent for the treatment of cardiomyopathy. The role of S100A1 in skeletal muscle has been less well defined. Additionally, the precise molecular mechanism underlying S100A1 modulation of sarcoplasmic reticulum Ca2+ release in striated muscle has not been fully elucidated. Here, utilizing a genetic approach to knock out S100A1, we demonstrate a direct physiological role of S100A1 in excitation-contraction coupling in skeletal muscle. We show that the absence of S100A1 leads to decreased global myoplasmic Ca2+ transients following electrical excitation. Using high speed confocal microscopy, we demonstrate with high temporal resolution depressed activation of sarcoplasmic reticulum Ca2+ release in S100A1-/- muscle fibers. Through competition assays with sarcoplasmic reticulum vesicles and through tryptophan fluorescence experiments, we also identify a novel S100A1-binding site on the cytoplasmic face of the intact ryanodine receptor that is conserved throughout striated muscle and corresponds to a previously identified calmodulin-binding site. Using a 12-mer peptide of this putative binding domain, we demonstrate low micromolar binding affinity to S100A1. NMR spectroscopy reveals this peptide binds within the Ca2+-dependent hydrophobic pocket of S100A1. Taken together, these data suggest that S100A1 plays a significant role in skeletal muscle excitation-contraction coupling, primarily through specific interactions with a conserved binding domain of the ryanodine receptor. This warrants further investigation into the use of S100A1 as a therapeutic target for the treatment of both cardiac and skeletal myopathies. [ABSTRACT FROM AUTHOR]

Caulerpa taxifolia is a fast-spreading invasive seaweed that threatens biodiversity in temperate Australian estuaries. To date, little is known about its effects on infauna. In the present study, we describe variation in demographic and life-history traits of the abundant infaunal bivalve, Anadara trapezia, in C. taxifolia and uninvaded habitats (seagrass and unvegetated sediments) at multiple sites across three estuaries in south-eastern New South Wales. Densities of A. trapezia were always lower in C. taxifolia than on unvegetated sediment, and lower in C. taxifolia than in seagrass at three out of four sites where they were compared. Dry tissue weight of A. trapezia was also lower in C. taxifolia than on unvegetated sediment at most sites, but was only lower in C. taxifolia than in seagrass at one of four sites. Populations were dominated by larger individuals (>45 mm length), but smaller individuals (35?45 mm length) were more common in C. taxifolia and seagrass. A. trapezia shell weight and morphology was variable and appeared weakly affected by invasion. Generally, our findings are consistent with the hypothesis that A. trapezia is negatively affected by C. taxifolia. However, C. taxifolia invasion appears complex and, at some places, its effects may not differ from those of native seagrass. There is a need for manipulative studies to understand the mechanisms underlying the effects of C. taxifolia on infauna. [ABSTRACT FROM AUTHOR]

This paper looks at the concepts of entities, identities, identifiers and credentials, their definitions, and how they combine to authenticate an identity to an account, or function, within a service. Credentials can be divided into several different types on the basis of their use, origin and characteristics. In particular, types such as composite, dynamic and derived credentials will be considered, and their applicability within an identity management system. Each credential must be managed through its entire life cycle from initial registration, general use and suspension, to deletion. The notion of public (i.e. freely distributable) and private (i.e. known only to you) aspects of a credential is explored. The bindings, by trusted third parties, of identifiers and public credentials into permits and instruments of proof is explained along with the convenience, but greater exposure, of local information. Several scenarios are analysed in terms of how different types of credentials are employed during the authentication process. [ABSTRACT FROM AUTHOR]

Acute lung injury can be a complication of hemorrhagic shock. Mechanisms of injury include neutrophil-derived inflammatory products that induce necrosis within the lung. Recent data has shown apoptosis, in addition to necrosis, as a pathway leading toward acute lung injury in shock models. This study quantitates apoptotic and necrotic cells in the lung after hemorrhagic shock. Mongrel pigs (20-30 kg) under general anesthesia (with pancuronium and pentobarbital) underwent instrumentation with placement of carotid and external jugular catheters. The animals were randomized to sham hemorrhage (n = 6) and to hemorrhagic shock (n = 7). The hemorrhagic shock group then underwent hemorrhage (40-45% blood volume) to a systolic blood pressure of 40-50 mm Hg for 1 hour. The animals were then resuscitated with shed blood plus crystalloid to normalization of heart rate and blood pressure. The animals were observed under general anesthesia for 6 hours after resuscitation, then sacrificed, and lungs were harvested. Lung injury parameters including histology (H&E stain), apoptosis [terminal deoxynucleotidyl transferasemediated dUTP biotin nick end labeling (TUNEL)], and myeloperioxidase activity (spectrophotometric assay) were assessed. Hemorrhagic shock induced marked loss of lung architecture, neutrophil infiltration, alveolar septal thickening, hemorrhage, and edema in H&E staining. Furthermore, MPO activity, a marker for neutrophil infiltration and activation, was more than doubled as compared to controls (44.0 vs 20.0 Crisham units activity/g). Apoptosis (cell shrinkage, membrane blebbing, apoptotic bodies) and necrosis (cellular swelling, membrane lysis) in neutrophils, macrophages, as well as in alveolar cells was demonstrated and quantified by H&E staining use. Apoptosis was confirmed and further quantified by positive TUNEL signaling via digital semiquantitative analysis, which revealed a significant increase in apoptotic cells (16.0 vs 2.5 cells/hpf, sho... [ABSTRACT FROM AUTHOR]

Muscle injuries represent a major part of sports injuries and are a challenging problem in traumatology. Strain injuries are the most common muscle injuries after contusions. These injuries can lead to significant pain and disability causing time to be lost to training and competition. Despite the frequency of strain injuries the treatment available is limited and is generally not sufficient to enhance muscle regeneration efficiently when fast resumption of sport activity is a primary target. A number of growth factors play a specific role in regeneration and it has been proven that a previously described method of physically and chemically stimulating whole blood (to produce autologous conditioned serum) induces concentration increases in FGF-2, HGF, and TGF-β1. A preliminary study was conducted on muscle strain injuries in professional sportsmen receiving either: 1. autologous conditioned serum (ACS) or 2. Actovegin/Traumeel® treatment as control. Assessment of recovery from injury was done by: 1. sport professional's ability to participate to 100 % under competition conditions in their respective sport and 2. MRI analysis. A significant difference in the recovery time from injury was demonstrated: 16.6 ± 0.9 in the ACS treated instead of 22.3 ± 1.2 (mean ± SEM) days in the Actovegin/Traumeel® control group (p = 0.001). MRI analysis supported the observed acceleration of the lesion recovery time. We conclude that ACS injection is a promising approach to reduce the time to recovery from muscle injury. [ABSTRACT FROM AUTHOR]

Muscle contusions represent a major part of sports injuries. The suggested treatments are generally sufficient to support muscle healing, but require a relatively long period of time. Given that autologous blood products are safe treatments, we have used a technique which stimulates the release of certain growth factors in the autologous conditioned serum (ACS). Those growth factors are known to improve the proliferative activity of myogenic precursor cells. Mice were subjected to an experimental contusion injury to their gastrocnemius muscle; one group received local injections of ACS at 2 hrs, 24 hrs, and 48 hrs after injury, a control group received saline injections. The histology results showed that satellite cell activation at 30/48 hrs post injury was accelerated and the diameter of the regenerating myofibers was increased compared to the controls within the first week after injury. ELISA results on the ACS have shown that the elevations in FGF-2 (460 %) and TGF-β1 (82 %) could be partly responsible for the accelerating effects on regeneration due to proliferative and chemotactic properties. We conclude that ACS injection is a promising approach to reduce the time of recovery from muscle injury. In terms of clinical targets, this new approach could be used in the treatment of sports injuries and may also be interesting in postoperative situations. [ABSTRACT FROM AUTHOR]

INTRODUCTION:: Surgical options for vascular reconstruction in a contaminated field are limited and include prosthetic reconstruction or ligation with extra-anatomic bypass. With prosthetic insertion, rates of graft infection and failures (pseudoaneurysms and thrombosis) are high. In the emergent situations, extra-anatomic bypass is time-consuming and complex, and it produces marginal long-term results. Small intestinal submucosa (SIS) is a cell-free collagen matrix derived from porcine small intestine. Preliminary studies have demonstrated its ability to be remodeled into host tissue. In this study, we compared SIS to polytetrafluoroethylene (PTFE) as a vascular patch for arterial repair in the presence of massive gastrointestinal contamination to evaluate graft patency, incorporation, infection, and aneurysm formation. METHODS:: Adult mongrel pigs underwent general anesthesia with Isoflurane and were then randomized to 1 of 3 groups: control, contamination (colon puncture with stool contamination of the pelvis), or shock + contamination (40% blood volume for 1 hour, then resuscitation with shed blood and crystalloid, plus contamination). All groups then underwent a left common iliac arteriotomy and further randomized to a 1 '' 3'''cm patch angioplasty with either SIS or PTFE. All received cefotetan for 24 hours. All animals were sacrificed between 2 and 4 weeks, and necropsy was performed. Grafts were cultured, and microscopic analysis with hematoxylin and eosin and trichrome was performed. Outcomes included pulse quality (normal or diminished) compared with opposite side, graft infection, and pseudoaneurysm; all were determined by a blinded investigator. RESULTS:: Forty animals were randomized, and 1 died of abdominal sepsis. All control animals had normal distal pulses, no pseudoaneurysms, and no patch infections. The pseudoaneurysm rate for the contaminated PTFE patches was 25% compared with 0% in the SIS group (P = 0.09). Patch infection occurred in 73% of all PTFE patches compared with 8% of SIS patches (P < 0.03). Organisms present in the infected grafts included Escherichia coli, Bacteroides species, and other Gram-negative enterics. Histopathology demonstrated the presence of neointima in both SIS and PTFE. Only SIS was completely incorporated, with infiltration of collagen fibrils and lymphocytes. CONCLUSIONS:: SIS was associated with improved graft patency, less infection, complete incorporation, and no false aneurysm formation when compared with PTFE. This may be due to its ability to provide a durable scaffold for cellularization and tissue remodeling. This material may offer a superior alternative to more complex vascular reconstruction techniques in contaminated fields. [ABSTRACT FROM AUTHOR]

SUMMARY: INTRODUCTION Shock resuscitation leads to visceral edema often precluding abdominal wall closure. We have developed a staged approach encompassing acute management through definitive abdominal wall reconstruction. The purpose of this report is to analyze our experience with this technique applied to the treatment of patients with open abdomen and giant abdominal wall defects.METHODS Our management scheme for giant abdominal wall defects consists of 3 stages: stage I, absorbable mesh insertion for temporary closure (if edema quickly resolves within 3-5 days, the mesh is gradually pleated, allowing delayed fascial closure); stage II, absorbable mesh removal in patients without edema resolution (2-3 weeks after insertion to allow for granulation and fixation of viscera) and formation of the planned ventral hernia with either split thickness skin graft or full thickness skin closure over the viscera; and stage III, definitive reconstruction after 6-12 months (allowing for inflammation and dense adhesion resolution) by using the modified components separation technique. Consecutive patients from 1993 to 2001 at a single institution were evaluated. Outcomes were analyzed by management stage, with emphasis on wound related morbidity and mortality, and fistula and recurrent hernia rates.RESULTS Two hundred seventy four patients (35 with sepsis, 239 with hemorrhagic shock) were managed. There were 212 males (77%), and mean age was 37 (range, 12-88). The average size of the defects was 20 × 30 cm. In the stage I group, 108 died (92% of all deaths) because of shock. The remaining 166 had temporary closure with polyglactin 910 woven absorbable mesh. As visceral edema resolved, bedside pleating of the absorbable mesh allowed delayed fascial closure in 37 patients (22%). In the stage II group, 9 died (8% of all deaths) from multiple organ failure associated with their underlying disease process, and 96% of the remaining 120 had split-thickness skin graft placed over the viscera. No wound related mortality occurred. There were a total of 14 fistulae (5% of total, 8% of survivors). In the stage III group, to date, 73 of the 120 have had definitive abdominal wall reconstruction using the modified components separation technique. There were no deaths. Mean follow-up was 24 months, (range 2-60). Recurrent hernias developed in 4 of these patients (5%).CONCLUSIONS The staged management of patients with giant abdominal wall defects without the use of permanent mesh results in a safe and consistent approach for both initial and definitive management with low morbidity and no technique-related mortality. Absorbable mesh provides effective temporary abdominal wall defect coverage with a low fistula rate. Because of the low recurrent hernia rate and avoidance of permanent mesh, the components separation technique is the procedure of choice for definitive abdominal wall reconstruction. [ABSTRACT FROM AUTHOR]

Recent legislation in the USA and across Europe, such as the Electronic Communications Act 2000 in the UK, and the ESIGN federal bill in the USA, has provided the missing legal aspect to electronic security that is driving the acceptance and utilisation of electronic documentation in high-value commercial and legal domains. Now legal and financial documents, such as contracts or financial records, no longer require handwritten signatures for non-repudiation, and can gain the advantages of electronic indexing, transmission and storage. The resulting growth in both the volume and value of critical electronic documents has caused a surge in digital archiving services, which offer secure storage to protect against media failure, theft and natural disasters, while providing and maintaining the security and integrity that can be built into the data. This paper describes how digital archiving uses PKI-based technologies, including timestamping, and XML structuring to provide controlled access, integrity and legally binding data. Finally, the paper summarises the work in which BT has been involved, from the ETERMS project with the International Chamber of Commerce, to building prototypes offering timestamping and document archiving, enhancing existing uses of digital certificates. [ABSTRACT FROM AUTHOR]

N-alkylated C2-symmetric amino acid amide derivatives were shown to catalyse the Michael addition of 2-hydroxy-1,4-napthoquinone to β-nitrostyrene, achieving a maximum ee of 44%. The corresponding trifluoroacetic acid salts also catalysed the aldol reaction between 4-nitrobenzaldehyde and hydroxyacetone, leading to the formation of predominantly syn-aldol products in up to 55% ee. Aspects of the solvent dependence of the aldol reaction and the H-bonding of the catalyst were investigated.

Abstract Many cellular processes are governed by protein–protein interactions that require tight spatial and temporal regulation. Accordingly, it is necessary to understand the dynamics of these interactions to fully comprehend and elucidate cellular processes and pathological disease states. To map de novo protein–protein interactions with time resolution at an organelle-wide scale, we developed a quantitative mass spectrometry method, time-resolved interactome profiling (TRIP). We apply TRIP to elucidate aberrant protein interaction dynamics that lead to the protein misfolding disease congenital hypothyroidism. We deconvolute altered temporal interactions of the thyroid hormone precursor thyroglobulin with pathways implicated in hypothyroidism pathophysiology, such as Hsp70-/90-assisted folding, disulfide/redox processing, and N-glycosylation. Functional siRNA screening identified VCP and TEX264 as key protein degradation components whose inhibition selectively rescues mutant prohormone secretion. Ultimately, our results provide novel insight into the temporal coordination of protein homeostasis, and our TRIP method should find broad applications in investigating protein-folding diseases and cellular processes.

High fidelity iodine spectra provide the wavelength and instrument calibration needed to extract precise radial velocities (RVs) from stellar spectral observations taken through iodine cells. Such iodine spectra are usually taken by a Fourier Transform Spectrometer (FTS). In this work, we investigated the reason behind the discrepancy between two FTS spectra of the iodine cell used for precise RV work with the High Resolution Spectrograph (HRS) at the Hobby–Eberly Telescope (HET). We concluded that the discrepancy between the two HRS FTS spectra was due to temperature changes of the iodine cell. Our work demonstrated that the ultra-high resolution spectra taken by the TS12 arm of the Tull Spectrograph One at McDonald Observatory are of similar quality to the FTS spectra and thus can be used to validate the FTS spectra. Using the software IodineSpec5, which computes the iodine absorption lines at different temperatures, we concluded that the HET/HRS cell was most likely not at its nominal operating temperature of 70°C during its FTS scan at National Institute of Standards and Technology or at the TS12 measurement. We found that extremely high resolution echelle spectra (R > 200,000) can validate and diagnose deficiencies in FTS spectra. We also recommend best practices for temperature control and nightly calibration of iodine cells. [ABSTRACT FROM AUTHOR]

We present a computationally tractable implementation of spectro-perfectionism, a method which minimizes error imparted by spectral extraction. We develop our method in conjunction with a full raw reduction pipeline for the MINiature Exoplanet Radial Velocity Array (MINERVA), capable of performing both optimal extraction and spectro-perfectionism. Although spectro-perfectionism remains computationally expensive, our implementation can extract a MINERVA exposure in approximately 30 minutes. We describe our localized extraction procedure and our approach to point-spread function (PSF) fitting. We compare the performance of both extraction methods on a set of 119 exposures on HD 122064, an RV standard star. Both the optimal extraction and spectro-perfectionism pipelines achieve nearly identical RV precision under a six-exposure chronological binning. We discuss the importance of reliable calibration data for PSF fitting and the potential of spectro-perfectionism for future precise radial velocity exoplanet studies. [ABSTRACT FROM AUTHOR]

The MINiature Exoplanet Radial Velocity Array (MINERVA) is a dedicated observatory of four 0.7 m robotic telescopes fiber-fed to a KiwiSpec spectrograph. The MINERVA mission is to discover super-Earths in the habitable zones of nearby stars. This can be accomplished with MINERVA’s unique combination of high precision and high cadence over long time periods. In this work, we detail changes to the MINERVA facility that have occurred since our previous paper. We then describe MINERVA’s robotic control software, the process by which we perform 1D spectral extraction, and our forward modeling Doppler pipeline. In the process of improving our forward modeling procedure, we found that our spectrograph’s intrinsic instrumental profile is stable for at least nine months. Because of that, we characterized our instrumental profile with a time-independent, cubic spline function based on the profile in the cross dispersion direction, with which we achieved a radial velocity precision similar to using a conventional “sum-of-Gaussians” instrumental profile: 1.8 m s−1 over 1.5 months on the RV standard star HD 122064. Therefore, we conclude that the instrumental profile need not be perfectly accurate as long as it is stable. In addition, we observed 51 Peg and our results are consistent with the literature, confirming our spectrograph and Doppler pipeline are producing accurate and precise radial velocities. [ABSTRACT FROM AUTHOR]

SUMMARY: OBJECTIVE This study was designed to determine whether smoking patients have poorer outcomes after endoscopic sinus surgery (ESS) based on a reliable validated rhinosinusitis-specific quality-of-life outcomes test.STUDY DESIGN Retrospective chart and computed tomography (CT) review with telephone and letter questionnaire.METHODS Charts of 230 adult patients undergoing ESS for chronic rhinosinusitis between January 1995 and December 1998 were reviewed. Each participating patient completed a detailed questionnaire, including the Sino-Nasal Outcome Test-16 (SNOT-16), at an average of 52 months after surgery. Preoperative CT scans were reviewed and the findings used to stage the patients' conditions. Multivariate analysis was used to assess these data.RESULTS Eighty-two patients completed the questionnaire, with 26 who smoked at the time of surgery and continued to smoke at the time of answering the questionnaire (Smokers). Average SNOT-16 score in Smokers was 27.5, versus 18.2 in those who did not smoke at the time of surgery (Non-Smokers). There was a statistically significant correlation between elevated SNOT-16 scores and smoking (P < .001) and antibiotic use within the past year (P < .001). There was an association between high SNOT-16 scores and both prior smoking and passive smoke exposure that did not reach statistical significance (P = .055 and P = .267, respectively). CT staging scores and prior ESS were not statistically correlated with SNOT-16 scores.CONCLUSIONS Smoking is associated with statistically worse outcomes after ESS based on average SNOT-16 scores. Although no investigator has proved that the effects of smoking on sinonasal health are reversible, we counsel smoking patients considering ESS about the desirability of smoking cessation (for this and many health reasons), and the possibility of a poorer postsurgery outcome should they continue smoking. [ABSTRACT FROM AUTHOR]

Abstract Eukaryotes produce a large number of cytochrome P450s that mediate the synthesis and degradation of diverse endogenous and exogenous metabolites. Yet, most of these P450s are uncharacterized and global tools to study these challenging, membrane-resident enzymes remain to be exploited. Here, we applied activity profiling of plant, mouse and fungal P450s with chemical probes that become reactive when oxidized by P450 enzymes. Identification by mass spectrometry revealed labeling of a wide range of active P450s, including six plant P450s, 40 mouse P450s and 13 P450s of the fungal wheat pathogen Zymoseptoria tritici. We next used transient expression of GFP-tagged P450s by agroinfiltration to show ER-targeting and NADPH-dependent, activity-based labeling of plant, mouse and fungal P450s. Both global profiling and transient expression can be used to detect a broad range of active P450s to study e.g. their regulation and discover selective inhibitors.

Abstract Record high temperatures were documented in the McMurdo Dry Valleys, Antarctica, on 18 March 2022, exceeding average temperatures for that day by nearly 30°C. Satellite imagery and stream gage measurements indicate that surface wetting coincided with this warming more than 2 months after peak summer thaw and likely exceeded thresholds for rehydration and activation of resident organisms that typically survive the cold and dry conditions of the polar fall in a freeze‐dried state. This weather event is notable in both the timing and magnitude of the warming and wetting when temperatures exceeded 0°C at a time when biological communities and streams have typically entered a persistent frozen state. Such events may be a harbinger of future climate conditions characterized by warmer temperatures and greater thaw in this region of Antarctica, which could influence the distribution, activity, and abundance of sentinel taxa. Here we describe the ecosystem responses to this weather anomaly reporting on meteorological and hydrological measurements across the region and on later biological observations from Canada Stream, one of the most diverse and productive ecosystems within the McMurdo Dry Valleys.

Clostridioides difficile is an important human pathogen, for which there are very limited treatment options, primarily the glycopeptide antibiotic vancomycin. In recent years, vancomycin resistance has emerged as a serious problem in several gram-positive pathogens, but high-level resistance has yet to be reported for C. difficile, although it is not known if this is due to constraints upon resistance evolution in this species. Here, we show that resistance to vancomycin can evolve rapidly under ramping selection but is accompanied by fitness costs and pleiotropic trade-offs, including sporulation defects that would be expected to severely impact transmission. We identified 2 distinct pathways to resistance, both of which are predicted to result in changes to the muropeptide terminal D-Ala-D-Ala that is the primary target of vancomycin. One of these pathways involves a previously uncharacterised D,D-carboxypeptidase, expression of which is controlled by a dedicated two-component signal transduction system. Our findings suggest that while C. difficile is capable of evolving high-level vancomycin resistance, this outcome may be limited clinically due to pleiotropic effects on key pathogenicity traits. Moreover, our data identify potential mutational routes to resistance that should be considered in genomic surveillance.

Abstract Pseudomonas aeruginosa is a major nosocomial pathogen that causes severe disease including sepsis. Carbapenem-resistant P. aeruginosa is recognised by the World Health Organisation as a priority 1 pathogen, with urgent need for new therapeutics. As such, there is renewed interest in using bacteriophages as a therapeutic. However, the dynamics of treating pan-resistant P. aeruginosa with phage in vivo are poorly understood. Using a pan-resistant P. aeruginosa in vivo infection model, phage therapy displays strong therapeutic potential, clearing infection from the blood, kidneys, and spleen. Remaining bacteria in the lungs and liver displays phage resistance due to limiting phage adsorption. Yet, resistance to phage results in re-sensitisation to a wide range of antibiotics. In this work, we use phage steering in vivo, pre-exposing a pan resistant P. aeruginosa infection with a phage cocktail to re-sensitise bacteria to antibiotics, clearing the infection from all organs.

We describe techniques for performing photolithography and electron beam lithography in succession on the same resist-covered substrate. Larger openings are defined in the resist film through photolithography whereas smaller openings are defined through conventional electron beam lithography. The two processes are carried out one after the other and without an intermediate wet development step. At the conclusion of the two exposures, the resist film is developed once to reveal both large and small openings. Interestingly, these techniques are applicable to both positive and negative tone lithographies with both optical and electron beam exposure. Polymethyl methacrylate, by itself or mixed with a photocatalytic cross-linking agent, is used for this purpose. We demonstrate that such resists are sensitive to both ultraviolet and electron beam irradiation. All four possible combinations, consisting of optical and electron beam lithographies, carried out in positive and negative tone modes have been described. Demonstration grating structures have been shown and process conditions have been described for all four cases. [ABSTRACT FROM AUTHOR]