The status of power sector decentralisation in Zambia

Decentralisation has been part of the government’s policy in Zambia since the 1960s. However, due to various factors, the actualisation of decentralisation in various sectors, including energy, has been very slow. Given the rising interest in decentralisation, this study was undertaken to understand the status and prospects of decentralised energy planning and provision in Zambia. Our key findings are that there is currently very little decentralised energy planning; there is confusion regarding the role of the state power utility (ZESCO) and that of the councils in municipal electricity service provision going forward; and there is very little local-level coordination of electrification planning in Zambia. However, our study finds that the prevailing political and policy environment provides a good foundation for the decentralisation of the energy sector in Zambia. To actualise decentralised energy planning, the government must finalise and implement the energy sector devolution plan; introduce integrated local energy sector planning; and strengthen the legal and regulatory framework for the use of the CDF in financing off-grid renewable energy projects in the local councils

Epitope-based vaccination against pneumonic tularemia

Francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacterial pathogens known. No vaccine is currently approved for public use. Previously, we identified epitopes recognized specifically by T cells obtained from individuals following infection with F. tularensis. Here, we report that a subunit vaccine constructed based upon these epitopes elicited protective immunity in “humanized” HLA class II (DRB1*0401) transgenic mice. Vaccinated mice challenged intratracheally with a lethal dose of F. tularensis (Live Vaccine Strain) exhibited a rapid increase in pro-inflammatory cytokine production and diminished number of organisms in the lungs, and a concurrent increased rate of survival. These results demonstrate the efficacy of an epitope-based tularemia vaccine and suggest that such an approach might be widely applicable to the development of vaccines specific for intracellular bacterial pathogens

Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression.

Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST

Second-life battery systems for affordable energy access in Kenyan primary schools

As the world transitions to net zero, energy storage is becoming increasingly important for applications such as electric vehicles, mini-grids, and utility-scale grid stability. The growing demand for storage will constrain raw battery materials, reduce the availability of new batteries, and increase the rate of battery retirement. As retired batteries are difficult to recycle into components, to avoid huge amounts of battery waste, reuse and repurposing options are needed. In this research, we explore the feasibility of using second-life batteries (which have been retired from their first intended life) and solar photovoltaics to provide affordable energy access to primary schools in Kenya. Based on interviews with 12 East African schools, realistic system sizes were determined with varying solar photovoltaic sizes (5–10 kW in 2.5 kW increments) and lithium-ion battery capacities (5–20 kWh in 5 kWh increments). Each combination was simulated under four scenarios as a sensitivity analysis of battery transportation costs (i.e., whether they are sourced locally or imported). A techno-economic analysis is undertaken to compare new and second-life batteries in the resulting 48 system scenarios in terms of cost and performance. We find that second-life batteries decrease the levelized cost of electricity by 5.6–35.3% in 97.2% of scenarios compared to similar systems with new batteries, and by 41.9–64.5% compared to the cost of the same energy service provided by the utility grid. The systems with the smallest levelized cost of electricity (i.e., 0.11 USD/kWh) use either 7.5 kW or 10 kW of solar with 20 kWh of storage. Across all cases, the payback period is decreased by 8.2–42.9% using second-life batteries compared to new batteries; the system with the smallest payback period (i.e., 2.9 years) uses 5 kW solar and 5 kWh storage. These results show second-life batteries to be viable and cost-competitive compared to new batteries for school electrification in Kenya, providing the same benefits while reducing waste

Impaired cholecystokinin-induced gallbladder emptying incriminated in spontaneous “black” pigment gallstone formation in germfree Swiss Webster mice

“Black” pigment gallstones form in sterile gallbladder bile in the presence of excess bilirubin conjugates (“hyperbilirubinbilia”) from ineffective erythropoiesis, hemolysis, or induced enterohepatic cycling (EHC) of unconjugated bilirubin. Impaired gallbladder motility is a less well-studied risk factor. We evaluated the spontaneous occurrence of gallstones in adult germfree (GF) and conventionally housed specific pathogen-free (SPF) Swiss Webster (SW) mice. GF SW mice were more likely to have gallstones than SPF SW mice, with 75% and 23% prevalence, respectively. In GF SW mice, gallstones were observed predominately in heavier, older females. Gallbladders of GF SW mice were markedly enlarged, contained sterile black gallstones composed of calcium bilirubinate and <1% cholesterol, and had low-grade inflammation, edema, and epithelial hyperplasia. Hemograms were normal, but serum cholesterol was elevated in GF compared with SPF SW mice, and serum glucose levels were positively related to increasing age. Aged GF and SPF SW mice had deficits in gallbladder smooth muscle activity. In response to cholecystokinin (CCK), gallbladders of fasted GF SW mice showed impaired emptying (females: 29%; males: 1% emptying), whereas SPF SW females and males emptied 89% and 53% of volume, respectively. Bilirubin secretion rates of GF SW mice were not greater than SPF SW mice, repudiating an induced EHC. Gallstones likely developed in GF SW mice because of gallbladder hypomotility, enabled by features of GF physiology, including decreased intestinal CCK concentration and delayed intestinal transit, as well as an apparent genetic predisposition of the SW stock. GF SW mice may provide a valuable model to study gallbladder stasis as a cause of black pigment gallstones.National Institutes of Health (U.S.) (Training Grant T32-OD10978-26)National Institutes of Health (U.S.) (Training Grant P30-ES002109)Kinship Foundation. Searle Scholars Progra

No Place Like Home: Examining a Bilingual-Bicultural, Self-Run Substance Abuse Recovery Home for Latinos

Latinos often do not seek substance abuse services, and this might be correlated to the lack of culturally-modified substance abuse treatment approaches. Oxford House is the largest self-help residential recovery program in the U.S., yet few Latinos are among their current residents. In an effort to change this, bilingual-bicultural recovery homes were recently developed for Latinos. This article describes the process in opening these bilingual-bicultural houses and how sociocultural factors such as the family, simpatía, and gender roles impacted the living environment of these houses. In addition, language is highlighted as a key factor to the comfort and success of Latinos living in Oxford Houses. Based on these experiences, the article addresses several obstacles/barriers that impacted this process and possible feasible solutions to these challenges. One challenge is the Latino family system. While this may provide a supportive, cost-effective option for some; it can also perpetuate a cycle of codependence and substance abuse

Longitudinal data reveal strong genetic and weak non-genetic components of ethnicity-dependent blood DNA methylation levels

Epigenetic architecture is influenced by genetic and environmental factors, but little is known about their relative contributions or longitudinal dynamics. Here, we studied DNA methylation (DNAm) at over 750,000 CpG sites in mononuclear blood cells collected at birth and age 7 from 196 children of primarily self-reported Black and Hispanic ethnicities to study race-associated DNAm patterns. We developed a novel Bayesian method for high-dimensional longitudinal data and showed that race-associated DNAm patterns at birth and age 7 are nearly identical. Additionally, we estimated that up to 51% of all self-reported race-associated CpGs had race-dependent DNAm levels that were mediated through local genotype and, quite surprisingly, found that genetic factors explained an overwhelming majority of the variation in DNAm levels at other, previously identified, environmentally-associated CpGs. These results indicate that race-associated blood DNAm patterns in particular, and blood DNAm levels in general, are primarily driven by genetic factors, and are not as sensitive to environmental exposures as previously suggested, at least during the first 7 years of life

64Cu-MM-302 Positron Emission Tomography Quantifies Variability of Enhanced Permeability and Retention of Nanoparticles in Relation to Treatment Response in Patients with Metastatic Breast Cancer

Purpose: Therapeutic nanoparticles are designed to deliver their drug payloads through enhanced permeability and retention (EPR) in solid tumors. The extent of EPR and its variability in human tumors is highly debated and has been proposed as an explanation for variable responses to therapeutic nanoparticles in clinical studies. Experimental Design: We assessed the EPR effect in patients using a 64Cu-labeled nanoparticle, 64Cu-MM-302 (64Cu-labeled HER2-targeted PEGylated liposomal doxorubicin), and imaging by PET/CT. Nineteen patients with HER2-positive metastatic breast cancer underwent 2 to 3 PET/CT scans postadministration of 64Cu-MM-302 as part of a clinical trial of MM-302 plus trastuzumab with and without cyclophosphamide (NCT01304797). Results: Significant background uptake of 64Cu-MM-302 was observed in liver and spleen. Tumor accumulation of 64Cu-MM-302 at 24 to 48 hours varied 35-fold (0.52–18.5 %ID/kg), including deposition in bone and brain lesions, and was independent of systemic plasma exposure. Computational analysis quantified rates of deposition and washout, indicating peak liposome deposition at 24 to 48 hours. Patients were classified on the basis of 64Cu-MM-302 lesion deposition using a cut-off point that is comparable with a response threshold in preclinical studies. In a retrospective exploratory analysis of patient outcomes relating to drug levels in tumor lesions, high 64Cu-MM-302 deposition was associated with more favorable treatment outcomes (HR = 0.42). Conclusions: These findings provide important evidence and quantification of the EPR effect in human metastatic tumors and support imaging nanoparticle deposition in tumors as a potential means to identify patients well suited for treatment with therapeutic nanoparticles

Feasibility and implementation of a grocery shopping intervention for adults diagnosed with or at-risk for type 2 diabetes

Abstract Objective: To examine the feasibility and implementation of an optimal defaults intervention designed to align grocery purchases with a diet recommended for people with or at-risk for type 2 diabetes. Design: This was a 5-week pilot randomised trial with three groups: in-person grocery shopping, shopping online and shopping online with ‘default’ carts. Participants were asked to shop normally in Week One, according to group assignment in Weeks Two–Four (intervention period), and as preferred in Week Five. All groups received diabetes-friendly recipes via email each intervention week. Setting: Participants grocery shopped in person or online. Grocery receipt forms, enrolment information and exit surveys were collected remotely and used to assess feasibility and implementation. Participants: Sixty-five adults with or at-risk for type 2 diabetes. Results: Sixty-two participants completed the exit survey and fifty-five submitted receipts all 5 weeks. Forty utilised recipes, 95 % of whom indicated recipes were somewhat or very useful. Orange chicken, quesadillas and pork with potato and apples were the most liked recipes. Most Defaults group participants accepted at least some default cart items. Recipes with the highest default acceptance were whole grain pasta and chicken, quesadillas with black beans and chicken with olives. Participants’ primary concerns about the intervention were costs associated with online shopping, inability to select preferred foods and some recipes including ingredients household members would not eat. Conclusions: The study had high retention, data were successfully collected remotely and the intervention was acceptable to most participants. Tailoring recipes to household preferences may be beneficial in future studies

Characteristics and Predictive Value of Blood Transcriptome Signature in Males with Autism Spectrum Disorders

Autism Spectrum Disorders (ASD) is a spectrum of highly heritable neurodevelopmental disorders in which known mutations contribute to disease risk in 20% of cases. Here, we report the results of the largest blood transcriptome study to date that aims to identify differences in 170 ASD cases and 115 age/sex-matched controls and to evaluate the utility of gene expression profiling as a tool to aid in the diagnosis of ASD. The differentially expressed genes were enriched for the neurotrophin signaling, long-term potentiation/depression, and notch signaling pathways. We developed a 55-gene prediction model, using a cross-validation strategy, on a sample cohort of 66 male ASD cases and 33 age-matched male controls (P1). Subsequently, 104 ASD cases and 82 controls were recruited and used as a validation set (P2). This 55-gene expression signature achieved 68% classification accuracy with the validation cohort (area under the receiver operating characteristic curve (AUC): 0.70 [95% confidence interval [CI]: 0.62–0.77]). Not surprisingly, our prediction model that was built and trained with male samples performed well for males (AUC 0.73, 95% CI 0.65–0.82), but not for female samples (AUC 0.51, 95% CI 0.36–0.67). The 55-gene signature also performed robustly when the prediction model was trained with P2 male samples to classify P1 samples (AUC 0.69, 95% CI 0.58–0.80). Our result suggests that the use of blood expression profiling for ASD detection may be feasible. Further study is required to determine the age at which such a test should be deployed, and what genetic characteristics of ASD can be identified