On the possibility of radar echo detection of ultra-high energy cosmic ray- and neutrino-induced extensive air showers

We revisit and extend the analysis supporting a 60 year-old suggestion that cosmic rays air showers resulting from primary particles with energies above 10^{18} eV should be straightforward to detect with radar ranging techniques, where the radar echoes are produced by scattering from the column of ionized air produced by the shower. The idea has remained curiously untested since it was proposed, but if our analysis is correct, such techniques could provide a significant alternative approach to air shower detection in a standalone array with high duty cycle, and might provide highly complementary measurements of air showers detected in existing and planned ground arrays such as the Fly's Eye or the Auger Project. The method should be particularly sensitive to showers that are transverse to and relatively distant from the detector, and is thus effective in characterizing penetrating horizontal showers such as those that might be induced by ultra-high energy neutrino primaries.Comment: 29 pages, 16 figures, uses aas2pp4.sty. Final version, to appear in Astroparticle Physics. Contains new figs, better estimate of angular precision possibl

Long-term high-effort endurance exercise in older adults: diminishing returns for cognitive and brain aging

While there is evidence that age-related changes in cognitive performance and brain structure can be offset by increased exercise, little is known about the impact on these of long-term high-effort endurance exercise. In a cross-sectional design with 12-month follow-up, we recruited older adults engaging in high-effort endurance exercise over at least twenty years, and compared their cognitive performance and brain structure with a non-sedentary control group similar in age, sex, education, IQ, and lifestyle factors. Our findings showed no differences on measures of speed of processing, executive function, incidental memory, episodic memory, working memory, or visual search for older adults participating in long-term high-effort endurance exercise, when compared without confounds to non-sedentary peers. On tasks that engaged significant attentional control, subtle differences emerged. On indices of brain structure, long-term exercisers displayed higher white matter axial diffusivity than their age-matched peers, but this did not correlate with indices of cognitive performance

Analysis of reactive aldehydes in urine and plasma of type-2 diabetes mellitus patients through liquid chromatography-mass spectrometry: Reactive aldehydes as potential markers of diabetic nephropathy

IntroductionDiabetes is a major public health issue that is approaching epidemic proportions globally. Diabetes mortality is increasing in all ethnic groups, irrespective of socio-economic class. Obesity is often seen as the main contributor to an increasing prevalence of diabetes. Oxidative stress has been shown to trigger obesity by stimulating the deposition of white adipose tissue. In this study, we measured reactive aldehydes by liquid chromatography-mass spectrometry (LC-MS), in the urine and plasma of type-2 diabetic mellitus (T2DM) patients, as potential surrogates of oxidative stress. Our hypothesis was that reactive aldehydes play a significant role in the pathophysiology of diabetes, and these reactive species, may present potential drug targets for patient treatment.Materials and methodsStudy participants [N = 86; control n = 26; T2DM n = 32, and diabetic nephropathy (DN) n = 28] were recruited between 2019 and 2020. Urine and blood samples were collected from all participants, including a detailed clinical history, to include patient behaviours, medications, and co-morbidities. Reactive aldehyde concentrations in urine and plasma were measured using pre-column derivatisation and LC-MS, for control, T2DM and DN patients.ResultsReactive aldehydes were measured in the urine and plasma of control subjects and patients with T2DM and DN. In all cases, the reactive aldehydes under investigation; 4-HNE, 4-ONE, 4-HHE, pentanal, methylglyoxal, and glyoxal, were significantly elevated in the urine and serum of the patients with T2DM and DN, compared to controls (p < 0.001) (Kruskal–Wallis). Urine and serum reactive aldehydes were significantly correlated (≥0.7) (p < 0.001) (Spearman rho). The concentrations of the reactive aldehydes were significantly higher in plasma samples, when compared to urine, suggesting that plasma is the optimal matrix for screening T2DM and DN patients for oxidative stress.ConclusionReactive aldehydes are elevated in the urine and plasma of T2DM and DN patients. Reactive aldehydes have been implicated in the pathobiology of T2DM. Therefore, if reactive aldehydes are surrogates of oxidative stress, these reactive aldehyde species could be therapeutic targets for potential drug development

Non-alcoholic fatty liver disease—A pilot study investigating early inflammatory and fibrotic biomarkers of NAFLD with alcoholic liver disease

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a condition where excess fat accumulates in the liver (hepatic steatosis) and there is no history of alcohol abuse or other secondary causes of chronic liver disease. NAFLD is a very common disorder, occurring in 25% of the global population. NAFLD is now the most common chronic liver disorder in Western countries. Liver biopsy is the gold standard for NAFLD diagnosis and staging; however, this is invasive, costly and not without risk. Biomarkers that could diagnose and stage disease would reduce the need for biopsy and allow stratification of patients at risk of progression to non-alcoholic steatohepatitis (NASH).Methods: One hundred and thirty-five patients were involved in the study [N = 135: n = 34 controls; n = 26 simple steatosis; n = 61 NAFLD/NASH, and n = 14 alcoholic liver disease (ALD)]. Clinically diagnosed (ICD-10) patient serum samples were obtained from Discovery Life Sciences (US) along with clinical history. Samples were run in duplicate using high-sensitivity cytokine array I, immunoassays and ELISAs. In total, n = 20 individual biomarkers were investigated in this pilot study.Results: Thirteen/20 (65%) biomarkers were identified as significantly different between groups; IFNγ, EGF, IL-1β, IL-6, IL-8, IL-10, TNFα, FABP-1, PIIINP, ST2/IL-33R, albumin, AST and ALT. Five/20 (25%) biomarker candidates were identified for further investigation; namely, three biomarkers of inflammation, IL-6, IL-8, and TNFα, and two biomarkers of fibrosis, PIIINP and ST2/IL-33R.Discussion: Single biomarkers are unlikely to be diagnostic or predictive at staging NAFLD due to the complex heterogeneity of the disease. However, biomarker combinations may help stratify risk and stage disease where patients are averse to biopsy. Further studies comparing the 5 biomarkers identified in this study with current diagnostic tests and fibrotic deposition in liver tissue are warranted

Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with L-ascorbic acid

Background: Observational studies showed that circulating l-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation. Objectives:We assessed the relation between l-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating l-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-l-ascorbic acid and l-ascorbic acid–outcome associations. Design: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737). Results: With the use of a meta-analysis of observational estimates, inverse associations were shown between l-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (−0.13-SD change; 95% CI: −0.20-, −0.07-SD change; P = 0.0001) per SD increase in l-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10−6) increase in l-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected. Conclusions: The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of l-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between l-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation

The Nordic Subpopulation Research Programme: prediction of treatment outcome in patients with low back pain treated by chiropractors - does the psychological profile matter?

<p>Abstract</p> <p>Background</p> <p>It is clinically important to be able to select patients suitable for treatment and to be able to predict with some certainty the outcome for patients treated for low back pain (LBP). It is not known to what degree outcome among chiropractic patients is affected by psychological factors.</p> <p>Objectives</p> <p>To investigate if some demographic, psychological, and clinical variables can predict outcome with chiropractic care in patients with LBP.</p> <p>Methods</p> <p>A prospective multi-center practice-based study was carried out, in which demographic, clinical and psychological information was collected at base-line. Outcome was established at the 4^thvisit and after three months. The predictive value was studied for all base-line variables, individually and in a multivariable analysis.</p> <p>Results</p> <p>In all, 55 of 99 invited chiropractors collected information on 731 patients. At the 4^thvisit data were available on 626 patients and on 464 patients after 3 months. Fee subsidization (OR 3.2; 95% CI 1.9-5.5), total duration of pain in the past year (OR 1.5; 95% CI 1.0-2.2), and general health (OR 1.2; 95% CI 1.1-1.4) remained in the final model as predictors of treatment outcome at the 4^thvisit. The sensitivity was low (12%), whereas the specificity was high (97%). At the three months follow-up, duration of pain in the past year (OR 2.1; 95% CI 1.4-3.1), and pain in other parts of the spine in the past year (OR1.6; 1.1-2.5) were independently associated with outcome. However, both the sensitivity and specificity were relatively low (60% and 50%). The addition of the psychological variables did not improve the models and none of the psychological variables remained significant in the final analyses. There was a positive gradient in relation to the number of positive predictor variables and outcome, both at the 4^thvisit and after 3 months.</p> <p>Conclusion</p> <p>Psychological factors were not found to be relevant in the prediction of treatment outcome in Swedish chiropractic patients with LBP.</p

Analysis of SARS-CoV-2 antibody seroprevalence in Northern Ireland during 2020–2021

BackgroundWith the spread of SARS-CoV-2 impacting upon public health directly and socioeconomically, further information was required to inform policy decisions designed to limit virus spread during the pandemic. This study sought to contribute to serosurveillance work within Northern Ireland to track SARS-CoV-2 progression and guide health strategy.MethodsSera/plasma samples from clinical biochemistry laboratories were analysed for anti-SARS-CoV-2 antibodies. Samples were assessed using an Elecsys anti-SARS-CoV-2 or anti-SARS-CoV-2 S ECLIA (Roche) on an automated cobas e 801 analyser. Samples were also assessed via an anti-SARS-CoV-2 ELISA (Euroimmun). A subset of samples assessed via the Elecsys anti-SARS-CoV-2 ECLIA were subsequently analysed in an ACE2 pseudoneutralisation assay using a V-PLEX SARS-CoV-2 Panel 7 for IgG and ACE2 (Meso Scale Diagnostics).ResultsAcross three testing rounds (June–July 2020, November–December 2020 and June–July 2021 (rounds 1–3 respectively)), 4844 residual sera/plasma specimens were assayed for anti-SARS-CoV-2 antibodies. Seropositivity rates increased across the study, peaking at 11.6 % (95 % CI 10.4%–13.0 %) during round 3. Varying trends in SARS-CoV-2 seropositivity were noted based on demographic factors. For instance, highest rates of seropositivity shifted from older to younger demographics across the study period. In round 3, Alpha (B.1.1.7) variant neutralising antibodies were most frequently detected across age groups, with median concentration of anti-spike protein antibodies elevated in 50–69 year olds and anti-S1 RBD antibodies elevated in 70+ year olds, relative to other age groups.ConclusionsWith seropositivity rates of &lt;15 % across the assessment period, it can be concluded that the significant proportion of the Northern Ireland population had not yet naturally contracted the virus by mid-2021

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature