Unrecognized opportunities: The landscape of pediatric kidney-paired donation in the United States.

BACKGROUND: Pediatric (age < 18 years) kidney transplant (KT) candidates face increasingly complex choices. The 2014 kidney allocation system nearly doubled wait times for pediatric recipients. Given longer wait times and new ways to optimize compatibility, more pediatric candidates may consider kidney-paired donation (KPD). Motivated by this shift and the potential impact of innovations in KPD practice, we studied pediatric KPD procedures in the US from 2008 to 2021. METHODS: We describe the characteristics and outcomes of pediatric KPD recipients with comparison to pediatric non-KPD living donor kidney transplants (LDKT), pediatric LDKT recipients, and pediatric deceased donor (DDKT) recipients. RESULTS: Our study cohort includes 4987 pediatric DDKTs, 3447 pediatric non-KPD LDKTs, and 258 pediatric KPD transplants. Fewer centers conducted at least one pediatric KPD procedure compared to those that conducted at least one pediatric LDKT or DDKT procedure (67, 136, and 155 centers, respectively). Five centers performed 31% of the pediatric KPD transplants. After adjustment, there were no differences in graft failure or mortality comparing KPD recipients to non-KPD LDKT, LDKT, or DDKT recipients. DISCUSSION: We did not observe differences in transplant outcomes comparing pediatric KPD recipients to controls. Considering these results, KPD may be underutilized for pediatric recipients. Pediatric KT centers should consider including KPD in KT candidate education. Further research will be necessary to develop tools that could aid clinicians and families considering the time horizon for future KT procedures, candidate disease and histocompatibility characteristics, and other factors including logistics and donor protections.

Does perinatal exposure to exogenous oxytocin influence child behavioural problems and autistic-like behaviours to 20 years of age?

BACKGROUND: The neuropeptide and hormone oxytocin is known to have a significant impact on social cognition and behaviour in humans. There is growing concern regarding the influence of exogenous oxytocin (OT) administration in early life on later social and emotional development, including autism spectrum disorder (ASD). No study has examined offspring development in relation to the dose of exogenous oxytocin administered during labour. METHODS: Between 1989 and 1992, 2,900 mothers were recruited prior to the 18th week of pregnancy, delivering 2,868 live offspring. The Child Behaviour Checklist was used to measure offspring behavioural difficulties at ages 5, 8, 10, 14 and 17 years. Autism spectrum disorder was formally diagnosed by consensus of a team of specialists. At 20 years, offspring completed a measure of autistic-like traits, the Autism Spectrum Quotient (AQ). Oxytocin exposure prior to birth was analysed using categorical and continuous approaches (maternal oxytocin dose) with univariate and multivariate statistical techniques. RESULTS: Categorical analyses of oxytocin exposure prior to birth demonstrated no group differences in any measures of child behaviour. A small in magnitude dose-response association was observed for clinically significant total behaviour symptoms (adjusted odds ratio 1.03; 95% CI: 1.01-1.06, p < .01). Exogenous oxytocin administration prior to birth was not associated with ASD (OR: 0.64; 95% CI: 0.15-2.12, p = .46) or high levels of autistic-like traits (p = .93), as assessed by the AQ. CONCLUSIONS: This study is the first to investigate longitudinal mental health outcomes associated with the use of oxytocin-based medications during labour. The results do not provide evidence to support the theory that exogenous OT has a clinically significant negative impact on the long-term mental health of children.

Estimating global economic well-being with unlit settlements.

It is well established that nighttime radiance, measured from satellites, correlates with economic prosperity across the globe. In developing countries, areas with low levels of detected radiance generally indicate limited development - with unlit areas typically being disregarded. Here we combine satellite nighttime lights and the world settlement footprint for the year 2015 to show that 19% of the total settlement footprint of the planet had no detectable artificial radiance associated with it. The majority of unlit settlement footprints are found in Africa (39%), rising to 65% if we consider only rural settlement areas, along with numerous countries in the Middle East and Asia. Significant areas of unlit settlements are also located in some developed countries. For 49 countries spread across Africa, Asia and the Americas we are able to predict and map the wealth class obtained from ~2,400,000 geo-located households based upon the percent of unlit settlements, with an overall accuracy of 87%.

Combined activity of oridonin and wogonin in advanced-stage ovarian cancer cells: sensitivity of ovarian cancer cells to phyto-active chemicals.

The initial response rates of advanced-stage epithelial ovarian cancer to the chemotherapeutic agents carboplatin and paclitaxel are high. However, once drug resistance develops, further chemotherapy is less effective. The objective of this study is to investigate the anti-proliferative activity of the phyto-active chemicals (PACs) oridonin and wogonin in chemo-resistant epithelial ovarian cancer cells. Primary cell cultures from the ascitic fluid of three patients at diagnosis, two patients chemo-resistant to carboplatin and paclitaxel, and one patient treated with letrozole for breast cancer were studied and compared to the ovarian cancer cell lines A2780 and PTX10, by cell viability assay (MTS). Effects on cell cycle modulation and apoptosis were examined by flow cytometry and Western blot analysis (WB). WB was further conducted to investigate protein expressions altered by PACs. The results show that IC(50) of the primary cultures ranged from 0.6 to 5.4 µg/ml for oridonin and 0.3-12.7 µg/ml for wogonin. The paclitaxel-resistant cell line PTX10 was more sensitive to each of the PACs than the chemo-sensitive cell line A2780. Of particular interest is that in combination, the two PACs were synergistic in their cytotoxicity to five of six of the primary cultures and to both the cell lines (combination indices of 0.39-0.95). The inhibition is attributable to apoptosis and cell cycle modulation induced by the PACs as demonstrated in A2780 and PTX10. Up-regulation of the functional p53 protein in A2780 and down-regulation of Akt protein in PTX10 have in part contributed to the apoptosis. These findings suggest that oridonin and wogonin may have activity in ovarian cancer following its development of resistance to carboplatin and paclitaxel.

Quality assurance: using the exposure index and the deviation index to monitor radiation exposure for portable chest radiographs in neonates.

BACKGROUND: Many methods are used to track patient exposure during acquisition of plain film radiographs. A uniform international standard would aid this process. OBJECTIVE: To evaluate and describe a new, simple quality-assurance method for monitoring patient exposure. This method uses the "exposure index" and the "deviation index," recently developed by the International Electrotechnical Commission (IEC) and American Association of Physicists in Medicine (AAPM). The deviation index measures variation from an ideal target exposure index value. Our objective was to determine whether the exposure index and the deviation index can be used to monitor and control exposure drift over time. MATERIALS AND METHODS: Our Agfa workstation automatically keeps a record of the exposure index for every patient. The exposure index and deviation index were calculated on 1,884 consecutive neonatal chest images. Exposure of a neonatal chest phantom was performed as a control. RESULTS: Acquisition of the exposure index and calculation of the deviation index was easily achieved. The weekly mean exposure index of the phantom and the patients was stable and showed <10% change during the study, indicating no exposure drift during the study period. CONCLUSION: The exposure index is an excellent tool to monitor the consistency of patient exposures. It does not indicate the exposure value used, but is an index to track compliance with a pre-determined target exposure.

Inherited balanced translocation t(9;17)(q33.2;q25.3) concomitant with a 16p13.1 duplication in a patient with schizophrenia.

We report two rare genetic aberrations in a schizophrenia patient that may act together to confer disease susceptibility. A previously unreported balanced t(9;17)(q33.2;q25.3) translocation was observed in two schizophrenia-affected members of a small family with diverse psychiatric disorders. The proband also carried a 1.5 Mbp microduplication at 16p13.1 that could not be investigated in other family members. The duplication has been reported to predispose to schizophrenia, autism and mental retardation, with incomplete penetrance and variable expressivity. The t(9;17) (q33.2;q25.3) translocation breakpoint occurs within the open reading frames of KIAA1618 on 17q25.3, and TTLL11 (tyrosine tubulin ligase like 11) on 9q33.2, causing no change in the expression level of KIAA1618 but leading to loss of expression of one TTLL11 allele. TTLL11 belongs to a family of enzymes catalyzing polyglutamylation, an unusual neuron-specific post-translational modification of microtubule proteins, which modulates microtubule development and dynamics. The 16p13.1 duplication resulted in increased expression of NDE1, encoding a DISC1 protein partner mediating DISC1 functions in microtubule dynamics. We hypothesize that concomitant TTLL11-NDE1 deregulation may increase mutation load, among others, also on the DISC1 pathway, which could contribute to disease pathogenesis through multiple effects on neuronal development, synaptic plasticity, and neurotransmission. Our data illustrate the difficulties in interpreting the contribution of multiple potentially pathogenic changes likely to emerge in future next-generation sequencing studies, where access to extended families will be increasingly important.

DETECT Schools Study Protocol: A Prospective Observational Cohort Surveillance Study Investigating the Impact of COVID-19 in Western Australian Schools.

Introduction: Amidst the evolving COVID-19 pandemic, understanding the transmission dynamics of the SARS-CoV-2 virus is key to providing peace of mind for the community and informing policy-making decisions. While available data suggest that school-aged children are not significant spreaders of SARS-CoV-2, the possibility of transmission in schools remains an ongoing concern, especially among an aging teaching workforce. Even in low-prevalence settings, communities must balance the potential risk of transmission with the need for students' ongoing education. Through the roll out of high-throughput school-based SARS-CoV-2 testing, enhanced follow-up for individuals exposed to COVID-19 and wellbeing surveys, this study investigates the dynamics of SARS-CoV-2 transmission and the current psychosocial wellbeing impacts of the pandemic in school communities. Methods: The DETECT Schools Study is a prospective observational cohort surveillance study in 79 schools across Western Australia (WA), Australia. To investigate the incidence, transmission and impact of SARS-CoV-2 in schools, the study comprises three "modules": Module 1) Spot-testing in schools to screen for asymptomatic SARS-CoV-2; Module 2) Enhanced surveillance of close contacts following the identification of any COVID-19 case to determine the secondary attack rate of SARS-CoV-2 in a school setting; and Module 3) Survey monitoring of school staff, students and their parents to assess psycho-social wellbeing following the first wave of the COVID-19 pandemic in WA. Clinical Trial Registration: Trial registration number: ACTRN12620000922976.

Estimated impact of the COVID-19 pandemic on cancer services and excess 1-year mortality in people with cancer and multimorbidity: near real-time data on cancer care, cancer deaths and a population-based cohort study.

OBJECTIVES: To estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer. METHODS: We employed near real-time weekly data on cancer care to determine the adverse effect of the pandemic on cancer services. We also used these data, together with national death registrations until June 2020 to model deaths, in excess of background (pre-COVID-19) mortality, in people with cancer. Background mortality risks for 24 cancers with and without COVID-19-relevant comorbidities were obtained from population-based primary care cohort (Clinical Practice Research Datalink) on 3 862 012 adults in England. RESULTS: Declines in urgent referrals (median=-70.4%) and chemotherapy attendances (median=-41.5%) to a nadir (lowest point) in the pandemic were observed. By 31 May, these declines have only partially recovered; urgent referrals (median=-44.5%) and chemotherapy attendances (median=-31.2%). There were short-term excess death registrations for cancer (without COVID-19), with peak relative risk (RR) of 1.17 at week ending on 3 April. The peak RR for all-cause deaths was 2.1 from week ending on 17 April. Based on these findings and recent literature, we modelled 40% and 80% of cancer patients being affected by the pandemic in the long-term. At 40% affected, we estimated 1-year total (direct and indirect) excess deaths in people with cancer as between 7165 and 17 910, using RRs of 1.2 and 1.5, respectively, where 78% of excess deaths occured in patients with ≥1 comorbidity. CONCLUSIONS: Dramatic reductions were detected in the demand for, and supply of, cancer services which have not fully recovered with lockdown easing. These may contribute, over a 1-year time horizon, to substantial excess mortality among people with cancer and multimorbidity. It is urgent to understand how the recovery of general practitioner, oncology and other hospital services might best mitigate these long-term excess mortality risks.

Electrical output of bryophyte microbial fuel cell systems is sufficient to power a radio or an environmental sensor.

Plant microbial fuel cells are a recently developed technology that exploits photosynthesis in vascular plants by harnessing solar energy and generating electrical power. In this study, the model moss species Physcomitrella patens, and other environmental samples of mosses, have been used to develop a non-vascular bryophyte microbial fuel cell (bryoMFC). A novel three-dimensional anodic matrix was successfully created and characterized and was further tested in a bryoMFC to determine the capacity of mosses to generate electrical power. The importance of anodophilic microorganisms in the bryoMFC was also determined. It was found that the non-sterile bryoMFCs operated with P. patens delivered over an order of magnitude higher peak power output (2.6 ± 0.6 µW m-2) than bryoMFCs kept in near-sterile conditions (0.2 ± 0.1 µW m-2). These results confirm the importance of the microbial populations for delivering electrons to the anode in a bryoMFC. When the bryoMFCs were operated with environmental samples of moss (non-sterile) the peak power output reached 6.7 ± 0.6 mW m-2. The bryoMFCs operated with environmental samples of moss were able to power a commercial radio receiver or an environmental sensor (LCD desktop weather station).