Dust Lifting Through Surface Albedo Changes at Jezero Crater, Mars

We identify temporal variations in surface albedo at Jezero crater using first-of-their-kind high-cadence in-situ measurements of reflected shortwave radiation during the first 350 sols of the Mars 2020 mission. Simultaneous Mars Environmental Dynamics Analyzer (MEDA) measurements of pressure, radiative fluxes, winds, and sky brightness indicate that these albedo changes are caused by dust devils under typical conditions and by a dust storm at Ls ∼ 155°. The 17% decrease in albedo caused by the dust storm is one order of magnitude larger than the most apparent changes caused during quiescent periods by dust devils. Spectral reflectance measurements from Mastcam-Z images before and after the storm indicate that the decrease in albedo is mainly caused by dust removal. The occurrence of albedo changes is affected by the intensity and proximity of the convective vortex, and the availability and mobility of small particles at the surface. The probability of observing an albedo change increases with the magnitude of the pressure drop (ΔP): changes were detected in 3.5%, 43%, and 100% of the dust devils with ΔP 2.5 Pa and ΔP > 4.5 Pa, respectively. Albedo changes were associated with peak wind speeds above 15 m·s−1. We discuss dust removal estimates, the observed surface temperature changes coincident with albedo changes, and implications for solar-powered missions. These results show synergies between multiple instruments (MEDA, Mastcam-Z, Navcam, and the Supercam microphone) that improve our understanding of aeolian processes on Mars.This research has been funded by the Comunidad de Madrid Project S2018/NMT-4291 (TEC2SPACE-CM), by the Spanish State Research Agency (AEI) Project MDM-2017-0737 Unidad de Excelencia “María de Maeztu”- Centro de Astrobiología (CSIC/INTA), by the Spanish Ministry of Science and Innovation (MCIN)/State Agency of Research (10.13039/501100011033) project RTI2018-098728-B-C31, and by the project PID2021-126719OB-C41, funded by MCIN/AEI/10.13039/501100011033/FEDER, UE. RH, ASL and AM were supported by Grant PID2019-109467GB-I00 funded by MCIN/AEI/10.13039/501100011033/. Part of the research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). We want to thank J. Bell for processing Mastcam-Z projections showing the entire TIRS FOV and to S. Navarro and the entire team for generating the processed wind sensor data

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Protecting Important Sites for Biodiversity Contributes to Meeting Global Conservation Targets

Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as ‘important sites’). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45–1.14% annually since 1950 for IBAs and 0.79–1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends

Genome-Wide Identification of Ampicillin Resistance Determinants in Enterococcus faecium

Enterococcus faecium has become a nosocomial pathogen of major importance, causing infections that are difficult to treat owing to its multi-drug resistance. In particular, resistance to the β-lactam antibiotic ampicillin has become ubiquitous among clinical isolates. Mutations in the low-affinity penicillin binding protein PBP5 have previously been shown to be important for ampicillin resistance in E. faecium, but the existence of additional resistance determinants has been suggested. Here, we constructed a high-density transposon mutant library in E. faecium and developed a transposon mutant tracking approach termed Microarray-based Transposon Mapping (M-TraM), leading to the identification of a compendium of E. faecium genes that contribute to ampicillin resistance. These genes are part of the core genome of E. faecium, indicating a high potential for E. faecium to evolve towards β-lactam resistance. To validate the M-TraM results, we adapted a Cre-lox recombination system to construct targeted, markerless mutants in E. faecium. We confirmed the role of four genes in ampicillin resistance by the generation of targeted mutants and further characterized these mutants regarding their resistance to lysozyme. The results revealed that ddcP, a gene predicted to encode a low-molecular-weight penicillin binding protein with D-alanyl-D-alanine carboxypeptidase activity, was essential for high-level ampicillin resistance. Furthermore, deletion of ddcP sensitized E. faecium to lysozyme and abolished membrane-associated D,D-carboxypeptidase activity. This study has led to the development of a broadly applicable platform for functional genomic-based studies in E. faecium, and it provides a new perspective on the genetic basis of ampicillin resistance in this organism

The Australasian Resuscitation In Sepsis Evaluation : fluids or vasopressors in emergency department sepsis (ARISE FLUIDS), a multi-centre observational study describing current practice in Australia and New Zealand

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30-day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6- and 24-h post-enrolment, time to antimicrobial administration, intensive care admission, organ support and in-hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre-enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in-hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy

Predicting the effects of polychlorinated biphenyls on cetacean populations through impacts on immunity and calf survival

This work was supported by funding from the International Whaling Commission's Pollution 2000+Program, the U.S. NOAA/NFMS Health and Stranding Response Program and the UK's Natural Environment Research Council (Grant Code SMRU 10001).The potential impact of exposure to polychlorinated biphenyls (PCBs) on the health and survival of cetaceans continues to be an issue for conservation and management, yet few quantitative approaches for estimating population level effects have been developed. An individual based model (IBM) for assessing effects on both calf survival and immunity was developed and tested. Three case study species (bottlenose dolphin, humpback whale and killer whale) in four populations were taken as examples and the impact of varying levels of PCB uptake on achievable population growth was assessed. The unique aspect of the model is its ability to evaluate likely effects of immunosuppression in addition to calf survival, enabling consequences of PCB exposure on immune function on all age-classes to be explored. By incorporating quantitative tissue concentration-response functions from laboratory animal model species into an IBM framework, population trajectories were generated. Model outputs included estimated concentrations of PCBs in the blubber of females by age, which were then compared to published empirical data. Achievable population growth rates were more affected by the inclusion of effects of PCBs on immunity than on calf survival, but the magnitude depended on the virulence of any subsequent encounter with a pathogen and the proportion of the population exposed. Since the starting population parameters were from historic studies, which may already be impacted by PCBs, the results should be interpreted on a relative rather than an absolute basis. The framework will assist in providing quantitative risk assessments for populations of concern.PostprintPostprintPeer reviewe

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

A: A randomised controlled trial of senior lay health mentoring in older people with ischaemic heart disease: the Braveheart project. Age Ageing 2004

Abstract Objective: to examine the effects and feasibility of educating and empowering older people with ischaemic heart disease using trained senior lay health mentors. Design: randomised controlled trial with blinded evaluation. Setting: Falkirk and District Royal InWrmary. Participants: inpatients and outpatients aged 60 or over attending secondary care with a diagnosis of angina or acute myocardial infarction. Three-hundred and nineteen entered and 289 completed exit assessments. The intervention group took part in mentoring groups for 1 year, meeting monthly for 2 hours, each led by two trained lay health mentors in addition to standard care. Main outcome measures: primary outcome measures were changes in coronary risk factors, medication usage and actual use of secondary care health services. Secondary outcomes were total and cardiovascular events; changes in medication compliance, non-medical support requirement, health status and psychological functioning, and social inclusion. Results: there were signiWcant improvements in a reported current exercise score (mean +0.33, +0.02 to +0.52), in the average time spent walking per week by 72 minutes (+1 to +137 minutes), and in the SF36 Physical Functioning Score (+6.1, +2.4 to +9.5). There was a 1.0% reduction in total fat (95% CI −3.0% to −0.6%) and a 0.6% reduction in saturated fat (95% CI −1.5% to −0.03%). The intervention group showed reduced outpatient attendance for coronary heart disease (−0.25 appointments, −0.61 to −0.08). Attendance rates were high. Socio-economic grouping did not affect participation. Conclusions: Lay Health Mentoring is feasible, practical and inclusive, positively inXuencing diet, physical activity, and health resource utilisation in older subjects with ischaemic heart disease without causing harm