Bespoke Diblock Copolymer Nanoparticles Enable Production of Relatively Stable Oil-in-Water Pickering Nanoemulsions

Sterically-stabilized diblock copolymer nanoparticles with an intensity-average diameter of 25 nm are prepared in the form of a concentrated aqueous dispersion using polymerization-induced self-assembly (PISA). Addition of n-dodecane followed by high-shear homogenization produces n-dodecane-in-water Pickering macroemulsions of 22-46 µm diameter. If the nanoparticles are present in sufficient excess, subsequent processing using a high-pressure microfluidizer leads to formation of Pickering nanoemulsions with a mean droplet diameter below 200 nm. The size of these Pickering nanoemulsions can be tuned by systematically varying the nanoparticle concentration, applied pressure, the number of passes and the oil volume fraction. High internal phase emulsions can also be achieved by increasing the n-dodecane volume fraction up to 0.80. TEM studies of (dried) n-dodecane droplets confirm the presence of intact nanoparticles and suggest a relatively high surface coverage, which is consistent with model packing calculations based on radius ratios. Such Pickering nanoemulsions proved to be remarkably stable with respect to Ostwald ripening, with no significant change in the mean DLS droplet diameter after storage for approximately four months at 20 °C

Making community-supported agriculture accessible to low-income families: Findings from the Farm Fresh Foods for Healthy Kids process evaluation

A randomized trial of Farm Fresh Foods for Healthy Kids (F3HK) was initiated across 4 states and 12 farms to test whether cost-offset community-supported agriculture (CO-CSA) could improve diet quality among children in low-income families. Intervention households purchased a 50% subsidized share of local produce and were invited to nine complimentary nutrition classes. The purpose of this study was to assess F3HK reach, dose, and fidelity via a mixed methods process evaluation. Screening and enrollment records indicated reach; study records and postlesson educator surveys tracked dose delivered; CSA pickup logs, lesson sign-in sheets, postseason participant surveys, and postlesson caregiver surveys assessed dose received; and coordinator audits and educator surveys tracked fidelity. Educator interviews contextualized findings. The results of this study were as follows. Reach: enrolled caregivers (n = 305) were older (p =. 005) than eligible nonenrollees (n = 243) and more likely to be female (p <. 001). Dose: mean CSA season was 21 weeks (interquartile range [IQR]: 19-23). Median CSA pickup was 88% of the weeks (IQR: 40-100). All sites offered each class at least once. Most adults (77%) and children (54%) attended at least one class; few attended all. Eighty-two percent of caregivers indicated that their household consumed most or all produce. Median lesson activity ratings were 5/5 ("very useful"). Fidelity: CSA locations functioned with integrity to project standards. Educators taught 92% of activities but frequently modified lesson order. This study demonstrates the feasibility of pairing a CO-CSA intervention with nutrition education across geographically dispersed sites. Greater integration of intervention elements and clearer allowance for site-level modifications, particularly for educational elements, may improve intervention dose and, ultimately, impact

Reaction rate for two--neutron capture by 4^4He

Recent investigations suggest that the neutrino--heated hot bubble between the nascent neutron star and the overlying stellar mantle of a type--II supernova may be the site of the r--process. In the preceding $\alpha$--process building up the elements to $A \approx 100$, the $^4$He(2n,$\gamma$)$^6$He-- and $^6$He($\alpha$,n)$^9$Be--reactions bridging the instability gap at $A=5$ and $A=8$ could be of relevance. We suggest a mechanism for $^4$He(2n,$\gamma$)$^6$He and calculate the reaction rate within the $\alpha$+n+n approach. The value obtained is about a factor 1.6 smaller than the one obtained recently in the simpler direct--capture model, but is at least three order of magnitude enhanced compared to the previously adopted value. Our calculation confirms the result of the direct--capture calculation that under representative conditions in the $\alpha$--process the reaction path proceeding through $^6$He is negligible compared to $^4$He($\alpha$n,$\gamma$)$^9$Be.Comment: 13 pages, 4 postscript figures, to appear in "Zeitschrift f. Physik A", changed internet address and filename, the uuencoded postscript file including the figures is available at ftp://is1.kph.tuwien.ac.at/pub/ohu/twoneutron.u

Fruit and vegetable intake assessed by repeat 24 h recalls, but not by a dietary screener, is associated with skin carotenoid measurements in children

Accurate measurement of fruit and vegetable (FV) intake is important for nutrition surveillance and evaluation of dietary interventions. We compared two tools for reporting FV intake to objective measurement of skin carotenoids among children. FV cups/day was assessed by repeated 24 h dietary recalls (24H FV) and the National Cancer Institute’s All-Day Fruit and Vegetable Screener (NCI FV). Skin carotenoids were measured by repeated resonance Raman spectroscopy (RRS) of the palm. FV cups were regressed on RRS scores in unadjusted, field-based, and research-setting models with covariates feasible in each scenario. Data were baseline values from children aged 2–12 years in low-income households enrolled in a healthy eating randomized trial in four U.S. states (n = 177). Twenty-four-hour FV cups were associated with skin carotenoids in all models (p < 0.001) but NCI FV cups were not. Predicted RRS scores for discrete 24H FV cups provide a guide to interpretation of RRS in children (2 cups FV intake ~36,000 RRS units), with the research-setting scenario generally providing the narrowest prediction range (+/−1924). When self-reported data are required, 24 h recalls are more accurate than NCI FV screener data; and, when limited time, resources, or literacy must be considered, RRS scores can be quickly obtained and easily interpreted

Community supported agriculture plus nutrition education improves skills, self-efficacy, and eating behaviors among low-income caregivers but not their children: a randomized controlled trial

Background: Adults and children in the U.S. consume inadequate quantities of fruit and vegetables (FV), in part, due to poor access among households with lower socioeconomic status. One approach to improving access to FV is community supported agriculture (CSA) in which households purchase a ‘share’ of local farm produce throughout the growing season. This study examined the effects of cost-offset (half-price) CSA plus tailored nutrition education for low-income households with children. Methods: The Farm Fresh Foods for Healthy Kids (F3HK) randomized controlled trial in New York, North Carolina, Vermont, and Washington (2016–2018) assigned caregiver-child dyads (n = 305) into cost-offset CSA plus education intervention or control (delayed intervention) groups. Following one growing season of CSA participation, changes in children’s diet quality, body mass index (BMI), and physical activity; caregivers’ nutrition knowledge, attitudes, behaviors, and diet quality; and household food access and security were examined using multiple linear or logistic regression, with adjustment for baseline value within an intent-to-treat (ITT) framework in which missing data were multiply imputed. Results: No significant net effects on children’s dietary intake, BMI, or physical activity were observed. Statistically significant net improvements were observed after one growing season for caregivers’ cooking attitudes, skills, and self-efficacy; FV intake and skin carotenoid levels; and household food security. Changes in attitudes and self-efficacy remained one-year after baseline, but improvements in caregiver diet and household food security did not. The number of weeks that participants picked up a CSA share (but not number of education sessions attended) was associated with improvements in caregiver FV intake and household food security. Conclusions: Cost-offset CSA plus tailored nutrition education for low-income households improved important caregiver and household outcomes within just one season of participation; most notably, both self-reported and objectively measured caregiver FV intake and household food security improved. Households that picked up more shares also reported larger improvements. However, these changes were not maintained after the CSA season ended. These results suggest that cost-offset CSA is a viable approach to improving adult, but not child, FV intake and household food security for low-income families, but the seasonality of most CSAs may limit their potential to improve year-round dietary behavior and food security. Trial registration: ClinicalTrials.gov. NCT02770196. Registered 5 April 2016. Retrospectively registered

A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study.

A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus &gt;6-12 months) and Gynecologic Oncology Group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression. The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS. The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches. Clinicaltrials.gov, NCT 01666444

Offsetting the cost of community-supported agriculture (CSA) for low-income families: Perceptions and experiences of CSA farmers and members

Community-supported agriculture (CSA) is an alternative food marketing model in which community members subscribe to receive regular shares of a farm's harvest. Although CSA has the potential to improve access to fresh produce, certain features of CSA membership may prohibit low-income families from participating. A 'cost-offset' CSA (CO-CSA) model provides low-income families with purchasing support with the goal of making CSA more affordable. As a first step toward understanding the potential of CO-CSA to improve access to healthy foods among low-income households, we interviewed 24 CSA farmers and 20 full-pay CSA members about their experiences and perceptions of the cost-offset model and specific mechanisms for offsetting the cost of CSA. Audio recordings were transcribed verbatim and coded using a thematic approach. Ensuring that healthy food was accessible to everyone, regardless of income level, was a major theme expressed by both farmers and members. In general, CSA farmers and CSA members favored member donations over other mechanisms for funding the CO-CSA. The potential time burden that could affect CSA farmers when administering a cost-offset was a commonly-mentioned barrier. Future research should investigate various CO-CSA operational models in order to determine which models are most economically viable and sustainable

Safeguarding Female Reproductive Health against Endocrine Disrupting Chemicals : The FREIA Project

Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 825100.Peer reviewedPublisher PD

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes