Efficacy of a Computerized Sensor System for Evaluation and Training of Dizzy Patients

Patients with vestibular hypofunction often experience dizziness and unsteadiness while moving their heads. Appropriate sensors can effectively detect a patient’s dynamic visual acuity and associated body balance control. Forty-one vestibular-deficit patients and 10 normal individuals were invited to participate in this study. Questionnaires, clinical assessment scales and objective measures were evaluated on participants’ first visits. After 12 sessions of training, all scales were evaluated again on vestibular-deficit patients. The computerized system was composed of sensors, including a gyro and strain gauges, data acquisition accessories and LabVIEW software. Results revealed that the system could effectively distinguish normal subjects from subjects with vestibular deficits. In addition, after a rehabilitation program, subjects’ subjective and objective performances were significantly improved. Based on our results, we concluded that the present system, which uses a gyro and strain gauges, may provide an effective method for assessing and treating vestibular-deficit patients

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

BENCH-SCALE TECHNICAL REPORT

This technical report presents findings from bench-scale tests evaluating the ability of electron beam treatment to kill aquatic algae and zooplankton, specifically examining delayed mortality within 48 hours following treatment. This evaluation was the first attempt to assess the effect of electron beam treatment on hatch rates of Daphnia magna ephippia. Researchers from the Lake Superior Research Institute (LSRI) of the University of Wisconsin-Superior (UWS) in Superior, Wisconsin, USA traveled to the Fermi National Accelerator Laboratory, hereafter Fermilab, to conduct the bench-scale evaluation in May 2022. The test apparatus is a stationary copper electron beam accelerator that supplies a radiation dose expected to cause mortality in standard test organisms. Testing conducted in this evaluation was developed based on findings from earlier tests at Fermilab that demonstrated electron beam treatment was effective at causing complete mortality in E. coli at the lowest dose employed (1 kGy) and was effective at causing immediate mortality in D. magna and Eucyclops spp. at doses between 5 and 10 kGy (Polkinghorne et al., 2022). S. capricornutum was more resistant to immediate effects of electron beam treatment in initial tests (Polkinghorne et al., 2022). All experimental exposures were conducted at Fermilab. The irradiation process was conducted by Fermilab staff in the Illinois Accelerator Research Center’s (IARC’s) Accelerator Applications Development and Demonstration (A2D2) machine. Doses ranged from 1 to 50 kGy. Dose effectiveness testing was completed in lab water only, based on initial tests demonstrating minimal differences in treatment effect between high and low challenge water (i.e., low vs. high organic carbon content, suspended solids, and UV-transmittance). In samples examined 48 hours post-treatment, S. capricornutum had >99% mortality and Eucyclops spp. had 90% mortality at the 2 kGy dose. D. magna had 100% mortality at the lowest dose. No D. magna emerged from ephippia treated at any dose with the electron beam

TESTS EXPOLORING THE EFFECTIVENESS OF ELECTRON BEAM TREATMENT FOR BALLAST WATER MANAGEMENT

This technical report presents findings from bench-scale tests evaluating the ability of electron beam treatment to inactivate aquatic organisms. This evaluation was the first attempt to assess the electron beam treatment as a potential treatment method for ballast water in the Laurentian Great Lakes. Researchers from the Lake Superior Research Institute (LSRI) of the University of Wisconsin-Superior (UWS) in Superior, Wisconsin, USA traveled to the Fermi National Accelerator Laboratory, hereafter Fermilab, to conduct the bench-scale evaluation in January 2022. The test apparatus is a stationary copper particle accelerator that supplies a radiation dose expected to cause mortality in standard test organisms. It has been previously demonstrated that electron beam treatment can cause direct damage by creating either single- or double-strand breaks in the DNA molecule beyond cell repair (Shehata, M.M.K. et al., 2011) or recovery (Lei, J. et al., 2020). All experimental exposures were conducted at Fermilab. The irradiation process was conducted by Fermilab staff in the Illinois Accelerator Research Center’s (IARC’s) Accelerator Applications Development and Demonstration (A2D2) machine. Doses ranged from 1 to 50 kGy. Dose effectiveness testing was completed in two water types using bacteria, algae, and zooplankton—Escherichia coli, Selenastrum capricornutum, Eucyclops spp., and Daphnia magna, respectively. The treatment caused complete mortality for E. coli in both water types at even the lowest dose employed. Eucyclops spp. and Daphnia magna also experienced complete mortality in both water types between 5 and 10 kGy. Selenastrum capricornutum was the most resistant to treatment effect in both water types, but did experience mortality at the highest doses. Algae examined a week after exposure for delayed mortality experienced high mortality rates at all doses

Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water

In West Bengal, India, more than 300,000 arsenic-exposed people are showing symptoms of arsenic toxicity, which include cancers of skin and different internal organs. Since only 15–20% of the exposed population manifest arsenic-induced skin lesions, it is thought that genetic variation might play an important role in arsenic toxicity and carcinogenicity. A total of 422 unrelated arsenic-exposed subjects (244 skin-symptomatic and 178 asymptomatic) were recruited for this study. Cytogenetic damage, as measured by chromosomal aberrations in lymphocytes and micronuclei formation in oral mucosa cells, urothelial cells and binucleated lymphocytes, was studied in unexposed, skin-symptomatic and asymptomatic individuals with similar socioeconomic status. Identification of null mutations in GSTT1 and GSTM1 genes were carried out by PCR amplification. GSTP1 SNPs, implicated in susceptibility mto various cancers, were assessed by PCR-RFLP method. Symptomatic individuals had higher level of cytogenetic damage compared to asymptomatic individuals and asymptomatic individuals had significantly higher genotoxicity than unexposed individuals. No difference in allelic variants in GSTT1 and GSTP1 mwas observed between these 2 groups. Incidence of GSTM1 null gene frequencies was significantly higher in the asymptomatic group. Individuals with GSTM1-positive (at least one allele) had significantly higher risk of arsenic-induced skin lesions (odds ratio, 1.73; 95% confidence interval, 1.24–2.22). These results show a protective role of GSTM1 null in arsenic toxicity. This study also indicates that asymptomatic individuals are sub clinically affected and are also significantly susceptible to arsenicinduced genotoxicity