Collaboration and Community Change in the Children's Futures Initiative

In 2002, The Robert Wood Johnson Foundation launched Children's Futures (CF), a 10-year community change initiative designed to improve the health and well-being of children from birth to age three throughout Trenton, NJ. CF's strategies included efforts to increase residents' access to prenatal and other health services, provide parenting skills education, improve the quality of available childcare and promote preventive healthcare among medical practices. The Foundation engaged P/PV to evaluate the implementation and outcomes of the initiative and to provide ongoing feedback on its progress.This report, and its forthcoming companion, Early Outcomes in a Community Change Effort to Improve Children's Futures, examine the promise of CF strategies. Collaboration and Community Change in the Children's Futures Initiative focuses on program implementation, participant recruitment and collaborations among Trenton's agencies. The second report examines programmatic improvements and early outcomes for CF families. Major findings from both are compiled in Children's Futures' First Five Years

Targeting protein function: the expanding toolkit for conditional disruption

A major objective in biological research is to understand spatial and temporal requirements for any given gene, especially in dynamic processes acting over short periods, such as catalytically driven reactions, subcellular transport, cell division, cell rearrangement and cell migration. The interrogation of such processes requires the use of rapid and flexible methods of interfering with gene function. However, many of the most widely used interventional approaches, such as RNAi or CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated 9), operate at the level of the gene or its transcripts, meaning that the effects of gene perturbation are exhibited over longer time frames than the process under investigation. There has been much activity over the last few years to address this fundamental problem. In the present review, we describe recent advances in disruption technologies acting at the level of the expressed protein, involving inducible methods of protein cleavage, (in)activation, protein sequestration or degradation. Drawing on examples from model organisms we illustrate the utility of fast-acting techniques and discuss how different components of the molecular toolkit can be employed to dissect previously intractable biochemical processes and cellular behaviours.</jats:p

A Network of Multi-Tasking Proteins at the DNA Replication Fork Preserves Genome Stability

To elucidate the network that maintains high fidelity genome replication, we have introduced two conditional mutant alleles of DNA2, an essential DNA replication gene, into each of the approximately 4,700 viable yeast deletion mutants and determined the fitness of the double mutants. Fifty-six DNA2-interacting genes were identified. Clustering analysis of genomic synthetic lethality profiles of each of 43 of the DNA2-interacting genes defines a network (consisting of 322 genes and 876 interactions) whose topology provides clues as to how replication proteins coordinate regulation and repair to protect genome integrity. The results also shed new light on the functions of the query gene DNA2, which, despite many years of study, remain controversial, especially its proposed role in Okazaki fragment processing and the nature of its in vivo substrates. Because of the multifunctional nature of virtually all proteins at the replication fork, the meaning of any single genetic interaction is inherently ambiguous. The multiplexing nature of the current studies, however, combined with follow-up supporting experiments, reveals most if not all of the unique pathways requiring Dna2p. These include not only Okazaki fragment processing and DNA repair but also chromatin dynamics

Aerobic capacity and upper limb strength are reduced in women diagnosed with breast cancer: a systematic review

AbstractQuestion: What are typical values of physical function for women diagnosed with breast cancer and how do these compare to normative data? Design: Systematic review with meta-analysis. Participants: Women diagnosed with breast cancer who were before, during or after treatment. Outcome measures: Physical function was divided into three categories: aerobic capacity, upper and lower extremity muscular fitness, and mobility. Measures of aerobic capacity included field tests (6-minute walk test, 12-minute walk tests, Rockport 1-mile test, and 2-km walk time) and submaximal/maximal exercise tests on a treadmill or cycle ergometer. Measures of upper and lower extremity muscular fitness included grip strength, one repetition maximum (bench, chest or leg press), muscle endurance tests, and chair stands. The only measure of mobility was the Timed Up and Go test. Results: Of the 1978 studies identified, 85 were eligible for inclusion. Wide ranges of values were reported, reflecting the range of ages, disease severity, treatment type and time since treatment of participants. Aerobic fitness values were generally below average, although 6-minute walk time was closer to population norms. Upper and lower extremity strength was lower than population norms for women who were currently receiving cancer treatment. Lower extremity strength was above population norms for women who had completed treatment. Conclusion: Aerobic capacity and upper extremity strength in women diagnosed with breast cancer are generally lower than population norms. Assessment of values for lower extremity strength is less conclusive. As more research is published, expected values for sub-groups by age, treatment, and co-morbidities should be developed. [Neil-Sztramko SE, Kirkham AA, Hung SH, Niksirat N, Nishikawa K Campbell KL (2014) Aerobic capacity and upper limb strength are reduced in women diagnosed with breast cancer: a systematic review. Journal of Physiotherapy 60: 189–200

An Extremely Bright Echo Associated With SN 2002hh

We present new, very late-time optical photometry and spectroscopy of the interesting Type II-P supernova, SN 2002hh, in NGC 6946. Gemini/GMOS-N has been used to acquire visible spectra at six epochs between 2004 August and 2006 July, following the evolution of the SN from age 661 to 1358 days. Few optical spectra of Type II supernovae with ages greater than one year exist. In addition, g'r'i' images were acquired at all six epochs. The spectral and photometric evolution of SN 2002hh has been very unusual. Measures of the brightness of this SN, both in the R and I bands as well as in the H-alpha emission flux, show no significant fading over an interval of nearly two years. The most straightforward explanation for this behavior is that the light being measured comes not only from the SN itself but also from an echo off of nearby dust. Echoes have been detected previously around several SNe but these echoes, at their brightest, were ~8 mag below the maximum brightness of the SN. At V~21 mag, the putative echo dominates the light of SN 2002hh and is only ~4 mag below the outburst's peak brightness. There is an estimated 6 magnitudes of total extinction in V towards SN 2002hh. The proposed explanation of a differential echo/SN absorption is inconsistent with the observed BVRI colors.Comment: 24 pages, 6 figures. Accepted for publication in the Ap

Perfectionism and exam performance: The mediating effect of task-approach goals

Perfectionistic strivings are positively correlated with students’ achievement goals and exam performance. However, so far no study has employed a prospective design investigating whether achievement goals mediate the positive relationship between perfectionistic strivings and exam performance. In the present study, 100 university students completed a measure of self-oriented perfectionism and socially prescribed perfectionism (Hewitt & Flett, 1991) and received a chapter from a textbook to study for 2-4 days. Then they returned to the lab to complete a measure of achievement goals following the 3 x 2 model (Elliot, Murayama, & Pekrun, 2011) and sit a mock exam testing their knowledge of the chapter. Multiple regressions showed that socially prescribed perfectionism negatively predicted exam performance when the overlap with self-oriented perfectionism was controlled for. In contrast, self-oriented perfectionism—a defining indicator of perfectionistic strivings—positively predicted exam performance. Moreover, task-approach goals mediated the positive relationship between self-oriented perfectionism and exam performance. The findings suggest that perfectionistic strivings make students adopt task-approach goals that help them achieve better results on exams

Levetiracetam-loaded biodegradable polymer implants in the tetanus toxin model of temporal lobe epilepsy in rats

Approximately one-third of people with epilepsy receive insufficient benefit from currently available anticonvulsant medication, and some evidence suggests that this may be due to a lack of effective penetration into brain parenchyma. The current study investigated the ability of biodegradable polymer implants loaded with levetiracetam to ameliorate seizures following implantation above the motor cortex in the tetanus toxin model of temporal lobe epilepsy in rats. The implants led to significantly shorter seizures and a trend towards fewer seizures for up to 1 week. The results of this study indicate that drug-eluting polymer implants represent a promising evolving treatment option for intractable epilepsy. Future research is warranted to investigate issues of device longevity and implantation site

The MEDGICarb-Study: Design of a multi-center randomized controlled trial to determine the differential health-promoting effects of low- and high-glycemic index Mediterranean-style eating patterns

Adults with central adiposity and other features of the metabolic syndrome have a markedly elevated risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD). A Mediterranean-style healthy eating pattern (MED-HEP) and consumption of foods with a lower glycemic index (GI) are potential dietary approaches to curb the T2D and CVD epidemic. However, experimental evidence of the effectiveness of MED-HEP and of the contribution of GI towards improving indices of glucose homeostasis, especially among non-diabetic people, are lacking. Therefore, we developed the MedGI-Carb trial, a multi-center (Italy, Sweden, and United States) intervention in adults with at least two components of the metabolic syndrome (elevated waist circumference + one other component) that aims to improve markers of glucose homeostasis through dietary modification. All participants were randomized to consume an isocaloric high- or low-GI MED-HEP for 12 weeks. We hypothesized that indexes of insulinemia (primary outcome: postprandial insulin and glucose after standardized breakfast and lunch; secondary outcomes: fasting plasma glucose and insulin, HbA1c, 24-h continuous glucose monitoring) would be improved more with the low-GI versus the high-GI MED-HEP. Additionally, we hypothesized that consumption of a MED-HEP would improve other markers of cardiometabolic health and well-being (fasting blood pressure, fasting lipid profile, sleep quality, satiety, global metabolic alterations in the plasma metabolome, changes in the gut microbiota, subjective health and well-being), with no difference between groups. Collectively, the design of MEDGI-Carb allows several different research questions to be explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03410719

Improved physical health in middle-older aged golf caddies following 24-weeks of high-volume physical activity

Background: The physical demands of golf caddying, including walking while carrying a golf bag, may potentially affect body composition, and markers of metabolic, cardiovascular, and musculoskeletal health. Therefore, this study examined the impact of 24 weeks of caddying on physical health in middle-older aged males. Methods: Eleven full-time experienced male caddies (age: 59 [8] y; caddying experience: 14 [12] y) were recruited from a local golf course. The following were assessed at preseason and after 24 weeks of caddying (March–September 2022): body composition, heart rate, blood pressure, blood lipids, and performance tests (static and dynamic balance, strength, and submaximal fitness). Physical activity (PA) levels were assessed at preseason and at the mid-point of the caddying season. Across the caddying season, participants completed a monthly average of 24.0 (3.8) rounds. Results: Following the caddying season, improvements in static balance (Δ = 13.5 s), dynamic balance (Δ = −1.8 s), and lower back absolute strength (Δ = 112.8 N), and muscle quality (Δ = 2.0 N·kg−1) were observed (all P &lt; .05). Additionally, blood lipids, including total cholesterol (Δ = −0.6 mmol·L−1), high-density lipoprotein cholesterol (Δ = 0.1 mmol·L−1), low-density lipoprotein cholesterol (Δ = −0.6 mmol·L−1) (all P &lt; .05), and body composition, including body mass (Δ = −2.7 kg), fat mass (Δ = −1.9 kg), fat percentage (Δ = −1.4%), fat-to-muscle ratio (Δ = −0.03), and body mass index (Δ = −0.9 kg·m−2) (all P &lt; .05) improved. Caddying did not offer beneficial changes to cardiovascular variables or cardiorespiratory fitness (P &gt; .05), while coronary heart disease risk score decreased (Δ = −3.3%) (P &lt; .05). In relation to PA, light- (Δ = 145 min) and moderate-intensity (Δ = 71 min) PA, moderate to vigorous PA (Δ = 73 min), and total PA (Δ = 218 min) between preseason and the mid-point of the caddying season increased, while sedentary time (Δ = −172 min) decreased (all P &lt; .05). Conclusion: Golf caddying can provide several physical health benefits such as improvements in various markers of cardiometabolic health, lower back absolute strength, and static and dynamic balance. The physical health improvements that caddying offers is likely contributed to by increased PA volume and intensity through walking on the golf course. Therefore, caddying may represent a feasible model for increasing PA volume and intensity and achieve physical health–related benefits

SUMSS: A Wide-Field Radio Imaging Survey of the Southern Sky. I. Science goals, survey design and instrumentation

The Molonglo Observatory Synthesis Telescope, operating at 843 MHz with a 5 square degree field of view, is carrying out a radio imaging survey of the sky south of declination -30 deg. This survey (the Sydney University Molonglo Sky Survey, or SUMSS) produces images with a resolution of 43" x 43" cosec(Dec.) and an rms noise level of about 1 mJy/beam. SUMSS is therefore similar in sensitivity and resolution to the northern NRAO VLA Sky Survey (NVSS; Condon et al. 1998). The survey is progressing at a rate of about 1000 square degrees per year, yielding individual and statistical data for many thousands of weak radio sources. This paper describes the main characteristics of the survey, and presents sample images from the first year of observation.Comment: 27 pages, 12 figures (figures 2, 8, 10 in jpg format); AJ, in pres