Spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord but also may contribute to its repair. Anti-inflammatory treatment of human SCI ...and its timing must be based on knowledge of the types of cells participating in the inflammatory response, the time after injury when they appear and then decrease in number, and the nature of their actions. Using post-mortem spinal cords, we evaluated the time course and distribution of pathological change, infiltrating neutrophils, monocytes/macrophages and lymphocytes, and microglial activation in injured spinal cords from patients who were ‘dead at the scene’ or who survived for intervals up to 1 year after SCI. SCI caused zones of pathological change, including areas of inflammation and necrosis in the acute cases, and cystic cavities with longer survival (Zone 1), mantles of less severe change, including axonal swellings, inflammation and Wallerian degeneration (Zone 2) and histologically intact areas (Zone 3). Zone 1 areas increased in size with time after injury whereas the overall injury (size of the Zones 1 and 2 combined) remained relatively constant from the time (1–3 days) when damage was first visible. The distribution of inflammatory cells correlated well with the location of Zone 1, and sometimes of Zone 2. Neutrophils, visualized by their expression of human neutrophil α-defensins (defensin), entered the spinal cord by haemorrhage or extravasation, were most numerous 1–3 days after SCI, and were detectable for up to 10 days after SCI. Significant numbers of activated CD68-immunoreactive ramified microglia and a few monocytes/macrophages were in injured tissue within 1–3 days of SCI. Activated microglia, a few monocytes/macrophages and numerous phagocytic macrophages were present for weeks to months after SCI. A few CD8+ lymphocytes were in the injured cords throughout the sampling intervals. Expression by the inflammatory cells of the oxidative enzymes myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate oxidase (gp91phox), and of the pro-inflammatory matrix metalloproteinase (MMP)-9, was analysed to determine their potential to cause oxidative and proteolytic damage. Oxidative activity, inferred from MPO and gp91phox immunoreactivity, was primarily associated with neutrophils and activated microglia. Phagocytic macrophages had weak or no expression of MPO or gp91phox. Only neutrophils expressed MMP-9. These data indicate that potentially destructive neutrophils and activated microglia, replete with oxidative and proteolytic enzymes, appear within the first few days of SCI, suggesting that anti-inflammatory ‘neuroprotective’ strategies should be directed at preventing early neutrophil influx and modifying microglial activation.
We report on the highest precision yet achieved in the measurement of the polarization of a low-energy, O(1GeV) , continuous-wave (CW) electron beam, accomplished using a new polarimeter based on ...electron-photon scattering, in Hall C at Jefferson Lab. A number of technical innovations were necessary, including a novel method for precise control of the laser polarization in a cavity and a novel diamond microstrip detector that was able to capture most of the spectrum of scattered electrons. The data analysis technique exploited track finding, the high granularity of the detector, and its large acceptance. The polarization of the 180−μA , 1.16-GeV electron beam was measured with a statistical precision of <1% per hour and a systematic uncertainty of 0.59%. This exceeds the level of precision required by the Qweak experiment, a measurement of the weak vector charge of the proton. Proposed future low-energy experiments require polarization uncertainty <0.4% , and this result represents an important demonstration of that possibility. This measurement is the first use of diamond detectors for particle tracking in an experiment. It demonstrates the stable operation of a diamond-based tracking detector in a high radiation environment, for two years.
Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways for Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In Australia, there is only ...limited evidence of unrelated patients sharing indistinguishable P. aeruginosa strains. We therefore examined the point-prevalence, distribution, diversity and clinical impact of P. aeruginosa strains in Australian CF patients nationally. 983 patients attending 18 Australian CF centres provided 2887 sputum P. aeruginosa isolates for genotyping by enterobacterial repetitive intergenic consensus-PCR assays with confirmation by multilocus sequence typing. Demographic and clinical details were recorded for each participant. Overall, 610 (62%) patients harboured at least one of 38 shared genotypes. Most shared strains were in small patient clusters from a limited number of centres. However, the two predominant genotypes, AUST-01 and AUST-02, were widely dispersed, being detected in 220 (22%) and 173 (18%) patients attending 17 and 16 centres, respectively. AUST-01 was associated with significantly greater treatment requirements than unique P. aeruginosa strains. Multiple clusters of shared P. aeruginosa strains are common in Australian CF centres. At least one of the predominant and widespread genotypes is associated with increased healthcare utilisation. Longitudinal studies are now needed to determine the infection control implications of these findings.
Blood loss and red blood cell (RBC) transfusion in liver surgery are areas of concern for surgeons, anesthesiologists, and patients alike. While various methods are employed to reduce surgical blood ...loss, the evidence base surrounding each intervention is limited. Hypovolemic phlebotomy, the removal of whole blood from the patient without volume replacement during liver transection, has been strongly associated with decreased bleeding and RBC transfusion in observational studies. This trial aims to investigate whether hypovolemic phlebotomy is superior to usual care in reducing RBC transfusions in liver resection.
This study is a double-blind multicenter randomized controlled trial. Adult patients undergoing major hepatic resections for any indication will be randomly allocated in a 1:1 ratio to either hypovolemic phlebotomy and usual care or usual care alone. Exclusion criteria will be minor resections, preoperative hemoglobin <100g/L, renal insufficiency, and other contraindication to hypovolemic phlebotomy. The primary outcome will be the proportion of patients receiving at least one allogeneic RBC transfusion unit within 30 days of the onset of surgery. Secondary outcomes will include transfusion of other allogeneic blood products, blood loss, morbidity, mortality, and intraoperative physiologic parameters. The surgical team will be blinded to the intervention. Randomization will occur on the morning of surgery. The sample size will comprise 440 patients. Enrolment will occur at four Canadian academic liver surgery centers over a 4-year period. Ethics approval will be obtained at participating sites before enrolment.
The results of this randomized control trial will provide high-quality evidence regarding the use of hypovolemic phlebotomy in major liver resection and its effects on RBC transfusion. If proven to be effective, this intervention could become standard of care in liver operations internationally and become incorporated within perioperative patient blood management programs.
ClinicalTrials.gov NCT03651154 . Registered on August 29 2018.
We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of ...the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.
Large experimental programmes in the fields of nuclear and particle physics search for evidence of physics beyond that explained by current theories. The observation of the Higgs boson completed the ...set of particles predicted by the standard model, which currently provides the best description of fundamental particles and forces. However, this theory's limitations include a failure to predict fundamental parameters, such as the mass of the Higgs boson, and the inability to account for dark matter and energy, gravity, and the matter-antimatter asymmetry in the Universe, among other phenomena. These limitations have inspired searches for physics beyond the standard model in the post-Higgs era through the direct production of additional particles at high-energy accelerators, which have so far been unsuccessful. Examples include searches for supersymmetric particles, which connect bosons (integer-spin particles) with fermions (half-integer-spin particles), and for leptoquarks, which mix the fundamental quarks with leptons. Alternatively, indirect searches using precise measurements of well predicted standard-model observables allow highly targeted alternative tests for physics beyond the standard model because they can reach mass and energy scales beyond those directly accessible by today's high-energy accelerators. Such an indirect search aims to determine the weak charge of the proton, which defines the strength of the proton's interaction with other particles via the well known neutral electroweak force. Because parity symmetry (invariance under the spatial inversion (x, y, z) → (-x, -y, -z)) is violated only in the weak interaction, it provides a tool with which to isolate the weak interaction and thus to measure the proton's weak charge
. Here we report the value 0.0719 ± 0.0045, where the uncertainty is one standard deviation, derived from our measured parity-violating asymmetry in the scattering of polarized electrons on protons, which is -226.5 ± 9.3 parts per billion (the uncertainty is one standard deviation). Our value for the proton's weak charge is in excellent agreement with the standard model
and sets multi-teraelectronvolt-scale constraints on any semi-leptonic parity-violating physics not described within the standard model. Our results show that precision parity-violating measurements enable searches for physics beyond the standard model that can compete with direct searches at high-energy accelerators and, together with astronomical observations, can provide fertile approaches to probing higher mass scales.
To the Editor: The Protection of Personal Information Act 4 of 20131 (POPIA) was enacted by the South African (SA) parliament in 2013 after a long process of public consultation. To allow all sectors ...of SA society sufficient time to prepare to be compliant with POPIA, the SA government deferred the entering into force of the substantive provisions of POPIA for several years. Throughout this hiatus period, POPIA was widely publicised in the SA media, as is evident from any internet search.
Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such ...studies despite the importance of genetic factors in understanding Africa’s response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA—a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.
The Q(weak) experiment has measured the parity-violating asymmetry in ep elastic scattering at Q(2)=0.025(GeV/c)(2), employing 145 μA of 89% longitudinally polarized electrons on a 34.4 cm long ...liquid hydrogen target at Jefferson Lab. The results of the experiment's commissioning run, constituting approximately 4% of the data collected in the experiment, are reported here. From these initial results, the measured asymmetry is A(ep)=-279±35 (stat) ± 31 (syst) ppb, which is the smallest and most precise asymmetry ever measured in ep scattering. The small Q(2) of this experiment has made possible the first determination of the weak charge of the proton Q(W)(p) by incorporating earlier parity-violating electron scattering (PVES) data at higher Q(2) to constrain hadronic corrections. The value of Q(W)(p) obtained in this way is Q(W)(p)(PVES)=0.064±0.012, which is in good agreement with the standard model prediction of Q(W)(p)(SM)=0.0710±0.0007. When this result is further combined with the Cs atomic parity violation (APV) measurement, significant constraints on the weak charges of the up and down quarks can also be extracted. That PVES+APV analysis reveals the neutron's weak charge to be Q(W)(n)(PVES+APV)=-0.975±0.010.
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