The geographic distribution of un-immunized children in Ontario,Canada: Hotspot detection using Bayesian spatial analysis

BackgroundIn Ontario, Canada, little is currently known about the extent to which un-immunized children may cluster geographically. Our objectives were to: describe the geographic distribution of fully un-immunized children; identify geographic clusters (hotspots) of un-immunized children; and to characterize the contribution of spatial effects and covariates on hotspots, where found.MethodsOur analytic cohort consisted of Ontario students aged 7–17 years in the 2016–2017 school year. We defined students as un-immunized if they had zero doses of any vaccine and a non-medical exemption recorded in Ontario’s registry. We calculated unadjusted proportions of un-immunized students by Census Subdivision (CSD) and then used a sequential approach to identify hotspots starting first with hotspot identification at the CSD level and then probed identified hotspots further by Dissemination Area (DA) and including covariates. Hotspots were identified using the Besag-York-Mollie Bayesian spatial model and were defined as areas with >95% probability of having two times the proportion of un-immunized students, relative to the province overall.ResultsWe identified 15,208 (0.94%) un-immunized children within our cohort consisting of more than 1.61 million students. Unadjusted proportions of un-immunized students varied greatly by geography, ranging from 0% to 21.5% by CSD. We identified 16 hotspot CSDs which clustered in five distinct areas, all of which were located in southern Ontario. The contribution of covariates and spatial effects on the risk of having un-immunized students varied greatly across hotspot areas.ConclusionsAlthough the provincial proportion (0.94%) of un-immunized students is small, geographical clustering of such students is evident in Ontario and in some areas presents an important risk for future outbreaks. Further qualitative work within these hotspot areas would be a helpful next step to better characterize the factors associated with vaccine refusal in these communities.     

Translating clinical and patient-reported data to tailored shared decision reports with predictive analytics for knee and hip arthritis

Quality of Life Research - New informatics tools can transform evidence-based information to individualized predictive reports to serve shared decisions in clinic. We developed a web-based system...     

Towards a Neurotransmitter-Based Retinal Prosthesis Using an Inkjet Print-head

Electronic chips that provide a patterned stimulus to cells in the retina may provide a viable treatment for age-related macular degeneration. A surrogate MEMS device, in the form of a print-head from a desktop printer, has been used to eject a pattern of neurotransmitters (bradykinin) onto living rat pheochromocytoma (PC12) cells. Fluorescent calcium imaging was used to measure the patterned stimulation of individual cells. The chemical stimulation of cells by directed microfluidic delivery may have applications in retinal prosthetic devices, and in other prosthetic implants in the nervous system.     

Association of sleep duration and quality with immunological response after vaccination against severe acute respiratory syndrome coronavirus-2 infection

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer–BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38–54) years and body mass index of 24·84 (22.6–28.51) kg/m² were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6–7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = −0.178, p < 0.001), poor sleep quality (r = −0.094, p < 0.05), insomnia (r = −0.098, p < 0.05), and nap frequency per week (r = −0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination.     

Two-Generation Reproductive Toxicity Study of Dietary Tributyl Phosphate in CD Rats

Tributyl phosphate (TBP) was tested for reproductive toxicityin rats. Thirty weanlings/sex (F0) were exposed to TBP in thediet ad libitum at 0, 200, 700, or 3000 ppm for 10 weeks andthen randomly mated within groups for 3 weeks with continuedexposure. F0 parents and 10 F1 weanlings/sex/dose were necropsied,and adult reproductive organs, urinary bladders (both sexes),kidneys (males), and livers (females) were evaluated histologically.Thirty F1 weanlings/sex/dose continued exposure for 11 weeksand were bred as described above. F1 parents and P2 weanlings,10/sex/dose, were then necropsied as described above. Adulttoxicity was observed in both sexes and generations at 700 and3000 ppm; observations included reduced body weights, weightgain and feed consumption, urinary bladder epithelial hyperplasia(both sexes), renal pelvis epithelial hyperplasia only at 3000ppm (male kidneys), and centrilobular hypertrophy (female livers).At 200 ppm, transient reductions in body weight were observedin F0 and F1 females, with urinary bladder epithelial hyperplasiain F0 males and females and in F1 males. There was no evidenceof reproductive toxicity, of reproductive organ pathology, orof effects on gestation or lactation at any dose tested. Postnataltoxicity was evidenced by consistent reductions in F1 and F2pup body weights at 3000 ppm and by occasional weight reductionsin F2 litters at 700 ppm, and was associated with maternal toxicityobserved at these doses and times. Under the conditions of thisstudy, a NOAEL was not determined for adult toxicity; the NOAELfor reproductive toxicity was at least 3000 ppm and the NOAELfor postnatal toxicity was approximately 200 ppm.     

P53 overexpression as an indicator of overall survival and response to treatment in osteosarcomas

The p53 gene located at chromosome 17pl3 is found to be altered (allelic loss or other mutation) in multiple human cancers, including osteosarcomas. The mutated gene produces a protein with a prolonged half-life thus rendering it detectable by conventional immunohistochemistry. We examined the correlation between p53 expression and clinical prognosis as well as response to therapy. Twentyone patients with previously untreated and histologically verified highly malignant osteosarcoma were used for this study. Biopsy material taken both prior to the start of COSS 91 protocol and at the time of surgery (ten weeks later) was examined for alterations in p53 protein expression and drug resistance. Two patients who had strong (+++) p53 protein expression and three others who became positive during the chemotherapy had significantly worse prognosis (all of them died within one year) than those who showed no p53 expression both at biopsy and after chemotherapy (all 11 patients are alive, average follow-up time: 3.5 years). All patients who showed any kind of positive p53 protein expression on initial biopsy were non-respon-ders to chemotherapy. In contrast, 69% (9 out of 13) of those who exhibited no p53 expression on initial biopsy were responders or intermediate responders to chemotherapy. We concluded that p53 expression may be a useful prognostic factor in osteosarcomas. The direct correlation between p53 positive expression and resistance to therapy can help in identifying patients who are in need of a more vigorous or different chemotherapeutical protocol.     

Vascular and electromyographic responses evoked in forearm muscle by isometric contraction of the contralateral forearm

There is controversy over whether isometric contraction of the forearm evokes vasoconstriction or vasodilatation in the muscles of the contralateral forearm. In the present study we have investigated in normal man, the effects of isometric contraction of one arm at 75, 50 and 25% maximum voluntary contraction (MVC) on arterial pressure, heart rate, blood flow and vascular resistance of the contralateral forearm and on electromyographic (EMG) activity recorded from that same arm with sensitive, surface electrodes.When EMG activity was not being recorded from the resting arm, isometric contraction of the contralateral arm for 2 min evoked increases in arterial pressure and heart rate whose magnitudes were graded with % MVC and an increase in forearm blood flow and a decrease in forearm vascular resistance at 75, 50 and 25% MVC, indicating vasodilatation. Further experiments in which EMG activity was recorded from the resting arm demonstrated that the decrease in forearm vascular resistance evoked by 75% MVC was associated with a substantial increase in EMG activity of the extensor and flexor muscles of that arm. By contrast, when forearm contraction was performed at 75% MVC whilst subjects viewed the EMG activity in the resting arm on an oscilloscope and kept EMG activity minimal, vascular resistance increased in that arm, indicating vasoconstriction. Further, when subjects performed contraction at 25% MVC whilst showing minimal EMG activity in the contralateral arm, vascular resistance in that same arm increased (from 78 ± 16 to 124 ± 29 mmHg/ml/min/100 ml tissue). These results are discussed in relation to those of previous studies. We propose, that in normal man, isometric contraction of the forearm evokes primary vasoconstriction in the muscles of the contralateral forearm, but that this response may be overcome by muscle vasodilatation occurring secondary to unintended muscle contraction or as part of the alerting response to acute stress.