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Extracellular chloride is required for efficient platelet aggregation.
Anion channels perform a diverse range of functions and have been implicated in ATP release, volume regulation, and phosphatidylserine exposure. Platelets have been shown to express several anion channels but their function is incompletely understood. Due to a paucity of specific pharmacological blockers, we investigated the effect of extracellular chloride substitution on platelet activation using aggregometry and flow cytometry. In the absence of extracellular chloride, we observed a modest reduction of the maximum aggregation response to thrombin or collagen-related peptide. However, the rate of aggregation was substantially reduced in a manner that was dependent on the extracellular chloride concentration and aggregation in the absence of chloride was noticeably biphasic, indicative of impaired secondary signaling. This was further investigated by targeting secondary agonists with aspirin and apyrase or by blockade of the ADP receptor P2Y12. Under these conditions, the rates of aggregation were comparable to those recorded in the absence of extracellular chloride. Finally, we assessed platelet granule release by flow cytometry and report a chloride-dependent element of alpha, but not dense, granule secretion. Taken together these data support a role for anion channels in the efficient induction of platelet activation, likely via enhancement of secondary signaling pathways
Factors associated with cytomegalovirus serostatus in young people in England:A cross-sectional study
BACKGROUND: Human cytomegalovirus (CMV) is a common herpesvirus which is estimated to infect 83% of the global population. Whilst many infections are asymptomatic, it is an important cause of morbidity and mortality, particularly for immunocompromised people and for infants who are congenitally infected. A vaccine against CMV has been stated as a public health priority, but there are gaps in our understanding of CMV epidemiology. To guide potential future vaccination strategies, our aim was to examine risk factors for CMV seropositivity in young people in England. METHODS: The Health Survey for England (HSE) is an annual, cross-sectional representative survey of households in England during which data are collected through questionnaires, and blood samples are taken. We randomly selected individuals who participated in the HSE 2002, aiming for 25 participants of each sex in each single year age group from 11 to 24 years. Stored samples were tested for CMV antibodies. We undertook descriptive and regression analyses of CMV seroprevalence and risk factors for infection. RESULTS: Demographic data and serostatus were available for 732 individuals, of whom 175 (23.7%) were CMV-seropositive. CMV seroprevalence was associated with age, with 18.3% seropositive at 11-14 years compared to 28.3% at 22-24 years. CMV serostatus was also higher in people of non-white ethnicity (adjusted odds ratio [aOR] 6.22, 95% confidence interval [CI] 3.47-11.14), and in adults who were seropositive for EBV (aOR 2.08 [1.06-4.09]). There was no evidence that smoking status, occupation, body mass index and region of England were associated with CMV serostatus. CONCLUSIONS: CMV seroprevalence is strongly associated with ethnicity, and modestly increases with age in 11-24-year-olds. A greater understanding of the transmission dynamics of CMV, and the impact of this on CMV-associated morbidity and mortality, is necessary to inform effective vaccination strategies when a vaccine for CMV becomes available
Laser Ultrasonic Thermoelastic/Ablation Generation with Laser Interferometric Detection in Graphite/Polymer Composites
Ultrasonic signals have been generated and detected in graphite/polymer composites by optical methods. A Doppler interferometric technique was used for detection. The output voltage of this type of interferometer is proportional to the surface velocity of a sample area which is illuminated by cw laser light. Ultrasonic signals were generated by thermoelastic and ablation processes which occur as a consequence of laser pulses incident on the opposite surface of the sample. The evolution of the magnitude and shape of the detected signals was measured as a function of the pulse energy of the generating laser. Low-energy laser pulses generated ultrasound without causing obvious surface damage. At higher energies surface damage was observable in post inspection but could also be detected by observing (through protective goggles) bright flashes near the illuminated area. The energy at which these processes first occur is qualitatively referred to as the ablation threshold. Changes in the observed waveform were evident at energies above the ablation threshold. The higher-energy waveforms were found to consist of a superposition of a thermoelastic component and an ablatic component, whose relative magnitudes changed with laser power. A delay in the initiation of the ablatic wave relative to the thermoelastic wave was observed to be of the order of 0.3 μs, consistent with observations in pure polymer. [1] Photoelectric detection measurements of the ablation plume also showed a clear threshold and a time scale for growth of the ablation products with a characteristic time scale on the order of 0.3 μs
The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs
The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised
An evaluation of enteral nutrition practices and nutritional provision in children during the entire length of stay in critical care
<b>Background</b>
Provision of optimal nutrition in children in critical care is often challenging. This study evaluated exclusive enteral nutrition (EN) provision practices and explored predictors of energy intake and delay of EN advancement in critically ill children.<p></p>
<b>Methods</b>
Data on intake and EN practices were collected on a daily basis and compared against predefined targets and dietary reference values in a paediatric intensive care unit. Factors associated with intake and advancement of EN were explored.<p></p>
<b>Results</b>
Data were collected from 130 patients and 887 nutritional support days (NSDs). Delay to initiate EN was longer in patients from both the General Surgical and congenital heart defect (CHD) Surgical groups [Median (IQR); CHD Surgical group: 20.3 (16.4) vs General Surgical group: 11.4 (53.5) vs Medical group: 6.5 (10.9) hours; p <= 0.001]. Daily fasting time per patient was significantly longer in patients from the General Surgical and CHD Surgical groups than those from the Medical group [% of 24 h, Median (IQR); CHD Surgical group: 24.0 (29.2) vs General Surgical group: 41.7 (66.7) vs Medical group: 9.4 (21.9); p <= 0.001]. A lower proportion of fluids was delivered as EN per patient (45% vs 73%) or per NSD (56% vs 73%) in those from the CHD Surgical group compared with those with medical conditions. Protein and energy requirements were achieved in 38% and 33% of the NSDs. In a substantial proportion of NSDs, minimum micronutrient recommendations were not met particularly in those patients from the CHD Surgical group. A higher delivery of fluid requirements (p < 0.05) and a greater proportion of these delivered as EN (p < 0.001) were associated with median energy intake during stay and delay of EN advancement. Fasting (31%), fluid restriction (39%) for clinical reasons, procedures requiring feed cessation and establishing EN (22%) were the most common reasons why target energy requirements were not met.<p></p>
<b>Conclusions</b>
Provision of optimal EN support remains challenging and varies during hospitalisation and among patients. Delivery of EN should be prioritized over other "non-nutritional" fluids whenever this is possible.<p></p>
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The impact of anxiety on postural control: CO2 challenge model
Data availability statement: The data that support the findings of this study are openly available in osf.io at https://doi.org/10.17605/OSF.IO/WZS65, reference number WZS65. Appendix S1: Supporting information:
Table S1 Means and Standard deviations of balance data at different time point and different inhalation condition, available at: https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fpsyp.14192&file=psyp14192-sup-0001-supinfo.docx (Word 2007 document , 23.1 KB). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.Copyright © 2022 The Authors. Anxiety and balance and postural control are linked via common neural pathways, such as the parabrachial nucleus network. A laboratory-based model of general anxiety disorder (GAD) using the CO2 challenge, has potential to be used to observe this relationship, potentially mimicking subjective, autonomic, and neuropsychological features of GAD. The current feasibility study used the CO2 challenge to explore postural control changes in healthy adults. It was predicted that during the CO2 condition, participants would show increased postural sway path length and decreased sway stability, compared with a normal air breathing condition. To assess this, heart and breathing rate, quiet standing postural sway path length, sway dynamic stability, and subjective measures of emotion were measured either before and after or during and after the inhalation conditions. Results demonstrated that CO2 inhalation led to both an increase in sway path length and reduced sway stability compared to the air breathing conditions; the effect on sway path lasted after the inhalation of CO2 had ceased. Additionally, replication of HR and subjective measures of emotion were observed when comparing air and CO2 conditions. This provides experimental evidence that CO2 inhalation can affect balance, suggestive of shared mechanisms between anxiety and balance performance, as well as indicating that the CO2 model of GAD is suitable to look at changes in balance performance in healthy adults. Future use of this model to explore factors that can reduce the influence of GAD on balance would be beneficial as would a more detailed exploration of the neural pathways associated with the associated comorbidity
The incidence of scarring on the dorsum of the hand
When undertaking image comparison of the hand between accused and perpetrator, it is not unusual for scars to be identified on the back of the hand. To investigate the occurrence of scarring in a discreet sample, a database of 238 individuals was examined, and the dorsum of the right and left hands was gridded for each individual. The position, size and type of scar were recorded within each grid. It was found that, in general, males exhibited a higher incidence of scarring than females. However, males were more likely to show scarring on their left hand whereas females were more likely to exhibit scarring on their right hand. Contrary to the literature, scarring was not most prevalent along the borders of the hand but occurred more frequently in association with the index and middle finger corridor regions. Surgical scars were rare as were large scars whereas linear scars smaller than 6 mm were the most frequently identified. Close to half of the sample did not exhibit scarring on one hand. The importance of understanding the pattern of scarring on the back of the hand is discussed in the light of forensic image comparison analysis
Differences in antigen-specific CD4+ responses to opportunistic infections in HIV infection
HIV-infected individuals with severe immunodeficiency are at risk of opportunistic infection (OI). Tuberculosis (TB) may occur without substantial immune suppression suggesting an early and sustained adverse impact of HIV on Mycobacterium tuberculosis (MTB)-specific cell mediated immunity (CMI). This prospective observational cohort study aimed to observe differences in OI-specific and MTB-specific CMI that might underlie this. Using polychromatic flow cytometry, we compared CD4+ responses to MTB, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Candida albicans in individuals with and without HIV infection. MTB-specific CD4+ T-cells were more polyfunctional than virus specific (CMV/EBV) CD4+ T-cells which predominantly secreted IFN-gamma (IFN-γ) only. There was a reduced frequency of IFN-γ and IL-2 (IL-2)-dual-MTB-specific cells in HIV-infected individuals, which was not apparent for the other pathogens. MTB-specific cells were less differentiated especially compared with CMV-specific cells. CD127 expression was relatively less frequent on MTB-specific cells in HIV co-infection. MTB-specific CD4+ T-cells PD-1 expression was infrequent in contrast to EBV-specific CD4+ T-cells. The variation in the inherent quality of these CD4+ T-cell responses and impact of HIV co-infection may contribute to the timing of co-infectious diseases in HIV infection
LHCD and ICRF heating experiments in H-mode plasmas on EAST
An ICRF system with power up to 6.0 MW and a LHCD system up to 4MW have been applied for heating and current drive experiments on EAST. Intensive lithium wall coating was intensively used to reduce particle recycling and Hydrogen concentration in Deuterium plasma, which is needed for effective ICRF and LHCD power absorption in high density plasmas. Significant progress has been made with ICRF heating and LHW current drive for realizing the H-mode plasma operation in EAST. In 2010, H-mode was generated and sustained by LHCD alone, where lithium coating and gas puffing launcher mouth were applied to improve the LHCD power coupling and penetration into the core plasmas at high density of H-modes. During the last two experimental campaigns, ICRF Heating experiments were carried out at the fixed frequency of 27MHz, achieving effective ions and electrons heating with the H Minority Heating (H-MH) mode, where electrons are predominantly heated by collisions with high energy minority ions. The H-MH mode gave the best plasma performance, and realized H-mode alone in 2012. Combination of ICRF and LHW power injection generated the H-mode plasmas with various ELMy characteristics. The first successful application of the ICRF Heating in the D (He3) plasma was also achieved. The progress on ICRF heating, LHCD experiments and their application in achieving H-mode operation from last two years will be discussed in this report
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