Physicochemical Modeling of Electrochemical Impedance in Solid-State Supercapacitors.

Solid-state supercapacitors (SSCs) consist of porous carbon electrodes and gel-polymer electrolytes and are used in novel energy storage applications. The current study aims to simulate the impedance of SSCs using a clearly defined equivalent circuit (EC) model with the ultimate goal of improving their performance. To this end, a conventional mathematical and a physicochemical model were adapted. The impedance was measured by electrochemical impedance spectroscopy (EIS). An EC consisting of electrical elements was introduced for each modeling approach. The mathematical model was purely based on a best-fit method and utilized an EC with intuitive elements. In contrast, the physicochemical model was motivated by advanced theories and allowed meaningful associations with properties at the electrode, the electrolyte, and their interface. The physicochemical model showed a higher approximation ability (relative error of 3.7%) due to the interface impedance integration in a more complex circuit design. However, this model required more modeling and optimization effort. Moreover, the fitted parameters differed from the analytically calculated ones due to uncertainties in the SSC's microscale configuration, which need further investigations. Nevertheless, the results show that the proposed physicochemical model is promising in simulating EIS data of SSCs with the additional advantage of utilizing well-reasoned property-based EC elements.

A mRNA Vaccine Encoding for a RBD 60-mer Nanoparticle Elicits Neutralizing Antibodies and Protective Immunity Against the SARS-CoV-2 Delta Variant in Transgenic K18-hACE2 Mice.

Two years into the COVID-19 pandemic there is still a need for vaccines to effectively control the spread of novel SARS-CoV-2 variants and associated cases of severe disease. Here we report a messenger RNA vaccine directly encoding for a nanoparticle displaying 60 receptor binding domains (RBDs) of SARS-CoV-2 that acts as a highly effective antigen. A construct encoding the RBD of the Delta variant elicits robust neutralizing antibody response, and also provides protective immunity against the Delta variant in a widely used transgenic mouse model. We ultimately find that the proposed mRNA RBD nanoparticle-based vaccine provides a flexible platform for rapid development and will likely be of great value in combatting current and future SARS-CoV-2 variants of concern.

Are residents of downtown Toronto influenced by their urban neighbourhoods? Using concept mapping to examine neighbourhood characteristics and their perceived impact on self-rated mental well-being.

BACKGROUND: There is ample evidence that residential neighbourhoods can influence mental well-being (MWB), with most studies relying on census or similar data to characterize communities. Few studies have actively investigated local residents' perceptions. METHODS: Concept mapping was conducted with residents from five Toronto neighbourhoods representing low income and non-low income socio-economic groups. These residents participated in small groups and attended two sessions per neighbourhood. The first session (brainstorming) generated neighbourhood characteristics that residents felt influenced their MWB. A few weeks later, participants returned to sort these neighbourhood characteristics and rate their relative importance in affecting residents' 'good' and 'poor' MWB. The data from the sorting and rating groups were analyzed to generate conceptual maps of neighbourhood characteristics that influence MWB. RESULTS: While agreement existed on factors influencing poor MWB (regardless of neighbourhood, income, gender and age), perceptions related to factors affecting good MWB were more varied. For example, women were more likely to rank physical beauty of their neighbourhood and range of services available as more important to good MWB, while men were more likely to cite free access to computers/internet and neighbourhood reputation as important. Low-income residents emphasized aesthetic attributes and public transportation as important to good MWB, while non-low-income residents rated crime, negative neighbourhood environment and social concerns as more important contributors to good MWB. CONCLUSION: These findings contribute to the emerging literature on neighbourhoods and MWB, and inform urban planning in a Canadian context.

Standardized observation of neighbourhood disorder: does it work in Canada?

BACKGROUND: There is a growing body of evidence that where you live is important to your health. Despite numerous previous studies investigating the relationship between neighbourhood deprivation (and structure) and residents' health, the precise nature of this relationship remains unclear. Relatively few investigations have relied on direct observation of neighbourhoods, while those that have were developed primarily in US settings. Evaluation of the transferability of such tools to other contexts is an important first step before applying such instruments to the investigation of health and well-being. This study evaluated the performance of a systematic social observational (SSO) tool (adapted from previous studies of American and British neighbourhoods) in a Canadian urban context. METHODS: This was a mixed-methods study. Quantitative SSO ratings and qualitative descriptions of 176 block faces were obtained in six Toronto neighbourhoods (4 low-income, and 2 middle/high-income) by trained raters. Exploratory factor analysis was conducted with the quantitative SSO ratings. Content analysis consisted of independent coding of qualitative data by three members of the research team to yield common themes and categories. RESULTS: Factor analysis identified three factors (physical decay/disorder, social accessibility, recreational opportunities), but only 'physical decay/disorder' reflected previous findings in the literature. Qualitative results (based on raters' fieldwork experiences) revealed the tool's shortcomings in capturing important features of the neighbourhoods under study, and informed interpretation of the quantitative findings. CONCLUSIONS: This study tested the performance of an SSO tool in a Canadian context, which is an important initial step before applying it to the study of health and disease. The tool demonstrated important shortcomings when applied to six diverse Toronto neighbourhoods. The study's analyses challenge previously held assumptions (e.g. social 'disorder') regarding neighbourhood social and built environments. For example, neighbourhood 'order' has traditionally been assumed to be synonymous with a certain degree of homogeneity, however the neighbourhoods under study were characterized by high degrees of heterogeneity and low levels of disorder. Heterogeneity was seen as an appealing feature of a block face. Employing qualitative techniques with SSO represents a unique contribution, enhancing both our understanding of the quantitative ratings obtained and of neighbourhood characteristics that are not currently captured by such instruments.

Thresholds for small for gestational age among newborns of East Asian and South Asian ancestry.

OBJECTIVE: To determine the risk that newborn infants of East Asian and South Asian ancestry may be misclassified as small for gestational age (SGA). METHODS: We performed a single-centre, cross-sectional study of a cohort of liveborn infants born to women who had been born in Canada (n = 2362), East Asia (n = 1565) and South Asia (n = 753) and generated smoothed birth weight curves for males and females. We determined the rate of misclassification of infants of East Asian and South Asian maternal origin as SGA, using conventional weight centile cut-offs, rather than those specific to each ethnic group. RESULTS: Infants of Canadian-born mothers had a mean birth weight that was 144 g and 218 g greater than newborns of mothers of East Asian and South Asian origin, respectively. Using the 3rd centile cut-off for infants of Canadian-born mothers, 7 per 1000 female and 14 per 1000 male infants of East Asian maternal origin were potentially miscategorized as SGA at birth. Among female and male infants of mothers of South Asian origin, the corresponding rates were 29 and 46 per 1000. CONCLUSION: Birth weight curves may need to be modified for newborns of East Asian and South Asian parentage to make a more accurate diagnosis of SGA.

Nonsurgical, radiofrequency collagen denaturation for stress urinary incontinence: retrospective 3-year evaluation.

Transurethral radiofrequency collagen denaturation, a nonsurgical treatment for stress urinary incontinence, reduces regional dynamic tissue compliance without causing tissue necrosis or gross tissue shrinkage, unlike transvaginal radiofrequency tissue ablation. This retrospective study evaluated long-term safety and efficacy in 21 patients from a 12-month, randomized controlled trial utilizing 3-day diaries and the Incontinence Quality of Life (I-QOL) survey. Significant increases in overall I-QOL scores 3 years or more post treatment was the primary end point. Secondary end points were reductions in frequency and severity of incontinence episodes. After 3 years, mean overall I-QOL score improvement was 12.7 (+/-26); 56% of patients achieved 50% or more reduction in frequency. No new adverse events occurred. These results indicate that radiofrequency collagen denaturation is safe and provides durable efficacy.

Results of the Recent Immigrant Pregnancy and Perinatal Long-term Evaluation Study (RIPPLES).

BACKGROUND: People who immigrate to Western nations may experience fewer chronic health problems than original residents of those countries, which raises concerns about long-term environmental or lifestyle factors in those countries. We tested whether the "healthy immigrant effect" extends to the risk of placental dysfunction during the short interval of pregnancy. METHODS: We conducted a population-based retrospective cohort study of data for 796 105 women who had a first documented obstetric delivery in Ontario between 1995 and 2005. Recency of immigration was determined for each woman as the time from her enrolment in universal health insurance to her date of delivery, classified as less than 3 months, 3-5 months, 6-11 months, 12-23 months, 24-35 months, 36-47 months, 48-59 months and 5 years or more (the referent). The primary composite outcome was maternal placental syndrome (defined as a diagnosis of pre-eclampsia or eclampsia, placental abruption or placental infarction). RESULTS: The mean age of the women was 28.8 years. Maternal placental syndrome occurred in 45 216 women (5.7%). The risk of this outcome was lowest among the women who had immigrated less than 3 months before delivery (3.8%) and highest among those living in Ontario at least 5 years (6.0%), for a crude odds ratio (OR) of 0.62 (95% confidence interval [CI] 0.54-0.71). After adjustment for maternal age, income status, pre-existing hypertension, diabetes mellitus, multiple gestation and receipt of prenatal ultrasonography, the risk of maternal placental syndrome was correlated with the number of months since immigration in a gradient manner (OR, 95% CI): less than 3 months (0.53, 0.47-0.61), 3-5 months (0.68, 0.61-0.76), 6-11 months (0.67, 0.63-0.71), 12-23 months (0.69, 0.66-0.73), 24-35 months (0.75, 0.70-0.79), 36-47 months (0.75, 0.70-0.80) and 48-59 months (0.82, 0.77-0.87). INTERPRETATION: There was a progressively lower risk of maternal placental syndromes associated with recency of immigration. The "healthy immigrant effect" may extend to common placental disorders, diminishes with the duration of residency and underscores the importance of nongenetic determinants of maternal health accrued over a brief period.

Experience of miscarriage in the UK: qualitative findings from the National Women's Health Study.

Miscarriage is the most common adverse outcome in pregnancy. For many women it is a traumatic experience. Previous research has identified shortcomings in the emotional and social support provided for miscarriage sufferers but personal accounts of pregnancy loss remain relatively under-explored. The UK National Women's Health Study (NWHS) is a nationally representative survey of women's reproductive histories. It provided an opportunity to study accounts of miscarriage written in response to an invitation for further comments on the survey questionnaire. In conjunction with quantitative findings from the NWHS, we thematically analysed 172 detailed narratives that facilitated qualitative exploration of a characteristically private event. Analysis of the narratives suggested that few women who had planned their pregnancy were satisfied with fatalistic explanations of miscarriage. Those who were not given medical explanations for their loss engaged in complex searches for meaning, often linked to accounts of their moral deservedness as mothers. The narratives highlighted tensions between biomedical and lay understandings of pregnancy loss. There were reports of inappropriate medicalisation and a perceived lack of emotional support, but also a desire for medical validation of the reality of miscarriage and investigations to identify medical causes. Professionals' reported behaviour played a key role in women's accounts. These findings remind providers that: women do not experience miscarriage as a routine complication; medicalisation is both resisted and desired; and, for some women, more support and information is needed to assist their search for meaning.

Abnormal urinary potassium metabolism in patients with interstitial cystitis.

PURPOSE: If most patients with interstitial cystitis (IC) have epithelial leakage allowing urinary K to penetrate the interstitium and provoke symptoms, urinary K should be lower in untreated patients than in healthy subjects and it should increase with successful heparinoid treatment. This study tested these hypotheses. MATERIALS AND METHODS: Na, K and creatinine (Cr) were determined in spot urine samples from new, symptomatic, untreated patients with IC meeting all National Institute of Diabetes and Digestive and Kidney Diseases clinical diagnostic criteria, returning patients with IC reporting 50% or greater symptom improvement after 4 or greater months of oral heparinoid therapy and control subjects, and in 24-hour urine samples from new untreated patients and controls. RESULTS: In spot urine specimens of 37 new patients with IC K-to-Cr ratios were significantly lower than in 18 controls (0.51 vs 0.88 mg/mg Cr, p = 0.001). A total of 50 successfully treated patients with IC had significantly higher K-to-Cr ratios than those in 37 new patients (0.66 vs 0.51 mg/mg Cr, p = 0.025). Na-to-Cr ratios in the 3 groups were not significantly different. In 24-hour urine specimens 30 new patients had lower average K (31.0 vs 46.2 mEq/l, p = 0.01) and lower K-to-Cr ratios (0.43 vs 0.52 mg K/mg Cr, p = 0.01) than in 47 controls, while Na was not significantly different. CONCLUSIONS: Our finding of lower urinary K in new, untreated patients supports the concept of abnormal epithelial permeability and K absorption in IC. Higher urinary K in successfully treated vs untreated patients may reflect decreasing urinary K absorption due to mucosal repair and a resulting decrease in epithelial permeability. K/mg Cr appears accurate for normalizing urinary K.

Evidence for suboptimal use of periconceptional folic acid supplements globally.

OBJECTIVE: To systematically summarise the available evidence concerning the rate of folic acid supplement use pre- and periconceptionally, to identify those characteristics associated with low rates of use and to assess whether folic acid public awareness campaigns are associated with higher folic acid use. DESIGN: Systematic overview. SETTING: Survey studies. POPULATION: Women of reproductive age, most of whom were currently or recently pregnant. METHODS: Two investigators searched MEDLINE, Embase and Nutriotiongate databases between 1990 and 2003. Bibliographies of retrieved references were scanned for other relevant publications, and authors were contacted if necessary. Studies were included that evaluated the rate of folic acid supplement use either before conception or in early pregnancy. MAIN OUTCOME MEASURES: Rate of preconceptional and/or periconceptional folic acid use, rate of planned pregnancy in each study, as well as significant characteristics differentiating non-users from users of folic acid, including the effect of folic acid awareness campaigns. RESULTS: A total of 52 studies were included. In 34 studies, reported preconceptional folic acid use varied from 0.9% to 50%. In 49 studies, the reported rate of periconceptional supplement use ranged from 0.5% to 52%. Significant predictors of reduced periconceptional folic acid use were a low level of formal education, immigrant status, young maternal age, lack of a partner and an unplanned pregnancy. Four studies examined the effect of mass media campaigns on periconceptional folic acid use; the reported rates increased significantly, by a factor of 1.7 to 7.2, but in no study was the post-campaign rate above 50%. CONCLUSIONS: In many countries, fewer than 50% of women take periconceptional folic acid supplements. Consideration should be given to the practical advantages of folic acid fortification of centrally processed foods, such as wheat, corn and rice flour, while further promoting vitamin tablet supplement use and planned pregnancy.

Randomized, placebo-controlled, double blind, crossover design trial of the efficacy and safety of Zestra for Women in women with and without female sexual arousal disorder.

Zestra for Women is a botanical feminine massage oil formulated to enhance female sexual pleasure and arousal when applied to the vulva. We conducted this randomized, double-blinded, crossover study to evaluate the efficacy and safety of Zestra for Women compared to placebo oil in 10 women with and 10 women without female sexual arousal disorder (FSAD) in conditions of home use in conjunction with sexual activities. Subjects were screened by physical examination, sex therapist interviews, and questionnaires. We randomized qualified subjects to treatment paths and gave them 5 doses of test article and diaries to use at home. At Visit 2, we assessed them by questionnaires and gave them 5 doses of crossover test article and diaries to use at home. At the final visit, we assessed them with questionnaires. We assessed safety by adverse event reports and primary efficacy by responses to a diary question regarding satisfaction with arousal. Secondary efficacy instruments included remaining diary questions, recall-based questionnaires, global assessment questions, and a consumer-testing questionnaire. All 20 subjects completed the study. Three subjects reported single incidences of mild genital burning sensations lasting 5-30 min after use of Zestra for Women. Both normal and FSAD women showed statistically significant improvements, relative to placebo, in level of arousal, level of desire, satisfaction with arousal, genital sensation, ability to have orgasms, and sexual pleasure. Although FSAD women showed greater magnitude of response, the presence of FSAD had no effect on response rates. Zestra for Women was just as effective in women using selective serotonin reuptake inhibitor antidepressants as in women not using antidepressants. Zestra for Women improved sexual function in normal and FSAD women under conditions of home use.

Immunogenicity of a plasmid DNA vaccine encoding chimeric idiotype in patients with B-cell lymphoma.

B-cell lymphomas express tumor-specific immunoglobulin, the variable regions of which [idiotype (Id)] can serve as a target for active immunotherapy. Promising results have been obtained in clinical studies of Id vaccination using Id proteins.However, Id protein is laborious and time-consuming to produce. DNA vaccination is an attractive alternative for delivering Id vaccines, because Id DNA can be rapidly isolated by PCR techniques. DNA coding for lymphoma Id can provide protective immunity in murine models. In the present study, we performed a Phase I/II clinical trial to study the safety and immunogenicity of naked DNA Id vaccines in 12 patients with follicular B-cell lymphoma. The DNA encoded a chimeric immunoglobulin molecule containing variable heavy and light chain immunoglobulin sequences derived from each patient's tumor, linked to the IgG2a and kappa mouse immunoglobulin (MsIg) heavy- and light-chain constant regions chains, respectively. Patients in remission after chemotherapy received three monthly i.m. injections of the DNA in three dose escalation cohorts of four patients each (200, 600, and 1800 micro g). After vaccination, 7 of 12 patients mounted either humoral (n = 4) or T-cell-proliferative (n = 4) responses to the MsIg component of the vaccine. In one patient, a T-cell response specific to autologous Id was also measured. Anti-Id antibodies were not detectable in any patient. A second series of vaccinations was then administered using a needle-free injection device (Biojector) to deliver 1800 micro g both i.m. and intradermally (i.d.); 9 of 12 patients had humoral (n = 6) and/or T-cell (n = 4) responses to MsIg. Six of 12 patients exhibited humoral and/or T-cell anti-Id responses; yet, these were cross-reactive with Id proteins from other patient's tumors. Subsequently, a third series of vaccinations was carried out using 500 micro g of human granulocyte-macrophage colony-stimulating factor DNA mixed with 1800 micro g of Id DNA. The proportion of patients responding to MsIg remained essentially unchanged (8 of 12), although humoral or T-cell responses were boosted in some cases. Throughout the study, no significant side effects or toxicities were observed. Despite the modest level of antitumor immune responses in this study, DNA vaccine technology retains potential advantages in developing anti-Id immunotherapies. Additional studies are warranted to optimize vaccine dose, routes of administration, vector designs, and prime-boost strategies. These results will help guide the design of such future DNA vaccine trials.

The development of a bicistronic plasmid DNA vaccine for B-cell lymphoma.

Tumor vaccines are a promising alternative to chemotherapy for the treatment of metastatic cancer. To be effective and safe, a therapeutic cancer vaccine should specifically target antigens expressed only on metastatic tumor cells. A vaccine directed against the unique surface immunoglobulin or idiotype expressed on non-Hodgkin's B-cell lymphoma fulfills these criteria, as both primary and metastatic tumor cells express tumor specific immunoglobulins. Using the murine 38C13 B-cell lymphoma tumor as a model system, a plasmid DNA vaccine was designed to express a bicistronic mRNA encoding both the light and heavy tumor immunoglobulin (idiotype) proteins expressed on the surface of the 38C13 tumor. To increase the immunogenicity of the plasmid DNA vaccine, each of the murine variable domains (light and heavy) were fused to their respective human immunoglobulin constant domains. In addition, a eukaryotic expression cassette was constructed to effect both high-level expression of the mouse/human chimeric immunoglobulin, and to elicit a protective immune response in vivo. Unique Sfi I restriction sites were used for the rapid cloning of any tumor specific immunoglobulin idiotype domains and a series of plasmid constructs were made to test changes to the J domain and/or the human C domain to insert the Sfi I restriction sites. Such changes were found to have significant effects on both expression and immunogenicity. Vaccination of mice with prototype idiotype vaccines was found to generate a protective immune response to the 38C13 tumor. This study indicates that a novel bicistronic plasmid DNA-based vaccine can be used to develop a tumor specific vaccine against B-cell lymphoma.