Two-week joint mobilization intervention improves self-reported function, range of motion, and dynamic balance in those with chronic ankle instability

We examined the effect of a 2-week anterior-to-posterior ankle joint mobilization intervention on weight-bearing dorsiflexion range of motion (ROM), dynamic balance, and self-reported function in subjects with chronic ankle instability (CAI). In this prospective cohort study, subjects received six Maitland Grade III anterior-to-posterior joint mobilization treatments over 2 weeks. Weightbearing dorsiflexion ROM, the anterior, posteromedial, and posterolateral reach directions of the Star Excursion Balance Test (SEBT), and self-reported function on the Foot and Ankle Ability Measure (FAAM) were assessed 1 week before the intervention (baseline), prior to the first treatment (pre-intervention), 24–48 h following the final treatment (post-intervention), and 1 week later (1-week follow-up) in 12 adults (6 males and 6 females) with CAI. The results indicate that dorsiflexion ROM, reach distance in all directions of the SEBT, and the FAAM improved (p < 0.05 for all) in all measures following the intervention compared to those prior to the intervention. No differences were observed in any assessments between the baseline and pre-intervention measures or between the postintervention and 1-week follow-up measures (p > 0.05). These results indicate that the joint mobilization intervention that targeted posterior talar glide was able to improve measures of function in adults with CAI for at least 1 week

Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib

BACKGROUND: Hypertension (HT) and hand-foot skin reactions (HFSR) may be related to the activity of bevacizumab and sorafenib. We hypothesized that these toxicities would correspond to favorable outcome in these drugs, that HT and HFSR would coincide, and that VEGFR2 genotypic variation would be related to toxicity and clinical outcomes. METHODS: Toxicities (≥ grade 2 HT or HFSR), progression-free survival (PFS), and overall survival (OS) following treatment initiation were evaluated. Toxicity incidence and VEGFR2 H472Q and V297I status were compared to clinical outcomes. RESULTS: Individuals experiencing HT had longer PFS following bevacizumab therapy than those without this toxicity in trials utilizing bevacizumab in patients with prostate cancer (31.5 vs 14.9 months, n = 60, P = 0.0009), and bevacizumab and sorafenib in patients with solid tumors (11.9 vs. 3.7 months, n = 27, P = 0.052). HT was also linked to a > 5-fold OS benefit after sorafenib and bevacizumab cotherapy (5.7 versus 29.0 months, P = 0.0068). HFSR was a marker for prolonged PFS during sorafenib therapy (6.1 versus 3.7 months respectively, n = 113, P = 0.0003). HT was a risk factor for HFSR in patients treated with bevacizumab and/or sorafenib (OR(95%CI) = 3.2(1.5-6.8), P = 0.0024). Carriers of variant alleles at VEGFR2 H472Q experienced greater risk of developing HT (OR(95%CI) = 2.3(1.2 - 4.6), n = 170, P = 0.0154) and HFSR (OR(95%CI) = 2.7(1.3 - 5.6), n = 170, P = 0.0136). CONCLUSIONS: This study suggests that HT and HFSR may be markers for favorable clinical outcome, HT development may be a marker for HFSR, and VEGFR2 alleles may be related to the development of toxicities during therapy with bevacizumab and/or sorafenib

Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- but not BRAF+ colorectal cancer.

Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 38,149 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between lifetime alcohol intake and colorectal cancer risk. Heterogeneity in the HRs across subtypes of colorectal cancer was assessed. A positive dose-dependent association between lifetime alcohol intake and overall colorectal cancer risk (mean follow-up = 14.6 years; n = 596 colon and n = 326 rectal cancer) was observed (HR = 1.08, 95% CI: 1.04-1.12 per 10 g/day increment). The risk was greater for rectal than colon cancer (phomogeneity  = 0.02). Alcohol intake was associated with increased risks of KRAS+ (HR = 1.07, 95% CI: 1.00-1.15) and BRAF-/KRAS- (HR = 1.05, 95% CI: 1.00-1.11) but not BRAF+ tumors (HR = 0.89, 95% CI: 0.78-1.01; phomogeneity  = 0.01). Alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- tumors originating via specific molecular pathways including the traditional adenoma-carcinoma pathway but not with BRAF+ tumors originating via the serrated pathway. Therefore, limiting alcohol intake from a young age might reduce colorectal cancer originating via the traditional adenoma-carcinoma pathway

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Acknowledgements: The authors thank the expert group for their time and effort in this priority–setting exercise, and the contribution of anonymous reviewers to the final version of this report. We acknowledge inputs from Dr Diane Morof from Centers for Disease Control and Prevention, USA. Funding: This work was supported by Save the Children.Peer reviewedPublisher PD

Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies

Expansion microscopy (ExM) enables imaging of preserved specimens with nanoscale precision on diffraction-limited instead of specialized super-resolution microscopes. ExM works by physically separating fluorescent probes after anchoring them to a swellable gel. The first ExM method did not result in the retention of native proteins in the gel and relied on custom-made reagents that are not widely available. Here we describe protein retention ExM (proExM), a variant of ExM in which proteins are anchored to the swellable gel, allowing the use of conventional fluorescently labeled antibodies and streptavidin, and fluorescent proteins. We validated and demonstrated the utility of proExM for multicolor super-resolution (~70 nm) imaging of cells and mammalian tissues on conventional microscopes.United States. National Institutes of Health (1R01GM104948)United States. National Institutes of Health (1DP1NS087724)United States. National Institutes of Health ( NIH 1R01EY023173)United States. National Institutes of Health (1U01MH106011

Designing the climate observing system of the future

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Earth's Future 6 (2018): 80–102, doi:10.1002/2017EF000627.Climate observations are needed to address a large range of important societal issues including sea level rise, droughts, floods, extreme heat events, food security, and freshwater availability in the coming decades. Past, targeted investments in specific climate questions have resulted in tremendous improvements in issues important to human health, security, and infrastructure. However, the current climate observing system was not planned in a comprehensive, focused manner required to adequately address the full range of climate needs. A potential approach to planning the observing system of the future is presented in this article. First, this article proposes that priority be given to the most critical needs as identified within the World Climate Research Program as Grand Challenges. These currently include seven important topics: melting ice and global consequences; clouds, circulation and climate sensitivity; carbon feedbacks in the climate system; understanding and predicting weather and climate extremes; water for the food baskets of the world; regional sea-level change and coastal impacts; and near-term climate prediction. For each Grand Challenge, observations are needed for long-term monitoring, process studies and forecasting capabilities. Second, objective evaluations of proposed observing systems, including satellites, ground-based and in situ observations as well as potentially new, unidentified observational approaches, can quantify the ability to address these climate priorities. And third, investments in effective climate observations will be economically important as they will offer a magnified return on investment that justifies a far greater development of observations to serve society's needs

The Relationship between Pitching Volume and Arm Soreness in Collegiate Baseball Pitchers

Background: Excessive baseball pitch volume has been associated with increased risk of injury in adolescents. However, many collegiate athletes report non-time loss injuries over the course of the season. It is unknown how pitch volume throughout a collegiate baseball season affects arm soreness. Purpose: The primary purpose of this study was to determine the relationship between pitch volume and self-reported arm soreness. A secondary purpose was to determine the relationship between change in pitch volume and change in arm soreness over the course of the season for collegiate baseball pitchers. Study Design: Prospective Cohort. Methods: Seven collegiate baseball pitchers volunteered to participate in a yearlong prospective study. The seven pitchers reported daily pitch volume and level of soreness from the fall through spring collegiate baseball season during practices and games. The athletic trainer, a member of the research team, tracked athletic exposures and injuries for the entire season. Frequency counts of athletic exposures were categorized by game, practice, conditioning and injury status. Frequency counts of pitch volume was categorized by game, game bullpen, practice bullpen, flat ground, long toss and warm-up pitches. The pitch volume and soreness levels for each athlete were used to determine the relationship between these two variables using a Pearson correlation. Results: The seven pitchers were involved with 1,256 athletic exposures and a total of 54,151 throws, averaging 7,735 throws per player for the entire season. The pitch volume and self-reported arm soreness for the entire season revealed a correlation of r = .72 (p = .004). The relationship between change in pitch volume and change in arm soreness was r = .635 (p = .001) over the season. Conclusion: There was a moderate significant correlation between arm soreness and pitch volume across the whole season. This relationship was maintained when evaluating weekly changes. Level of Evidence: 4

1980 Missouri beef cattle pesticide use survey

"Miscellaneous Publication 520, January 1981, 1M

Setting research priorities to improve global newborn health and prevent stillbirths by 2025.

BACKGROUND: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. METHODS: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. RESULTS: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. CONCLUSION: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed