RENAL DEPOSITION OF SOLUBLE IMMUNE COMPLEXES IN MICE BEARING B-16 MELANOMA : CHARACTERIZATION OF COMPLEXES AND RELATIONSHIP TO TUMOR PROGRESS

Histologic and immunofluorescence studies of the kidneys of mice bearing a progressive melanoma show a proliferative glomerulonephritis associated with immune complex deposition in the mesangium and along the glomerular basement membrane This immune complex disease is distinct from the age-associated disease of the C57BL/6J host strain and the complexes can be shown to consist of soluble tumor antigen and antitumor antibody. Furthermore, the intensity of IgG complex deposition correlates directly with tumor progress (size and metastases) and inversely with mononuclear leukocyte infiltration of the tumor. In vitro assays for lymphocyte cytotoxicity and humoral antibody were found to be less reliable indicators of tumor progress. The possible role of circulating soluble tumor antigen in modifying the immune response to tumors is discussed

Tract-Based Spatial Statistics in Preterm-Born Neonates Predicts Cognitive and Motor Outcomes at 18 Months.

BACKGROUND AND PURPOSE: Adverse neurodevelopmental outcome is common in children born preterm. Early sensitive predictors of neurodevelopmental outcome such as MR imaging are needed. Tract-based spatial statistics, a diffusion MR imaging analysis method, performed at term-equivalent age (40 weeks) is a promising predictor of neurodevelopmental outcomes in children born very preterm. We sought to determine the association of tract-based spatial statistics findings before term-equivalent age with neurodevelopmental outcome at 18-months corrected age. MATERIALS AND METHODS: Of 180 neonates (born at 24-32-weeks\u27 gestation) enrolled, 153 had DTI acquired early at 32 weeks\u27 postmenstrual age and 105 had DTI acquired later at 39.6 weeks\u27 postmenstrual age. Voxelwise statistics were calculated by performing tract-based spatial statistics on DTI that was aligned to age-appropriate templates. At 18-month corrected age, 166 neonates underwent neurodevelopmental assessment by using the Bayley Scales of Infant Development, 3rd ed, and the Peabody Developmental Motor Scales, 2nd ed. RESULTS: Tract-based spatial statistics analysis applied to early-acquired scans (postmenstrual age of 30-33 weeks) indicated a limited significant positive association between motor skills and axial diffusivity and radial diffusivity values in the corpus callosum, internal and external/extreme capsules, and midbrain (P \u3c .05, corrected). In contrast, for term scans (postmenstrual age of 37-41 weeks), tract-based spatial statistics analysis showed a significant relationship between both motor and cognitive scores with fractional anisotropy in the corpus callosum and corticospinal tracts (P \u3c .05, corrected). Tract-based spatial statistics in a limited subset of neonates (n = 22) scanned at CONCLUSIONS: The strength of the association between fractional anisotropy values and neurodevelopmental outcome scores increased from early-to-late-acquired scans in preterm-born neonates, consistent with brain dysmaturation in this population

User needs assessment for climate services in Zambia

Between February and April 2021 research was conducted to assess the user needs of selected farmer groups in Zambia for farmer centric agrometeorological information services. Specifically, it aimed to: • Identify the types of weather information and agronomic advice that farmers currently receive, the sources that they use and how satisfied they are with the information they receive; • Better understand the effects of climate variability and change on different agricultural activities and the decisions farmers are able to make; and • Enable farmers to identify what weather and climate information, services and agronomic advice they need and how they would like to access it. The results were then presented to key stakeholders and used in an ideation process to help design potential climate services for implementation at scale. Key findings from the user research are that: • Respondents articulated a demand for information and advice on a range of different weather variables at a range of different timescales to aid both their long-term planning and more immediate decisions. • There is a gap between the climate and weather information and services that are produced (by Zambia Meteorological Department) and those that farmers are accessing. • The complexities of challenges facing respondents, and the variety of different decisions affected, means that addressing these challenges is not simply about the provision of climate information but supporting farmers to contextualise and use this information. Farmers outlined a range of existing practices that they use to address challenges that are related to weather and climate. Many of these practices address multiple challenges and are often proactive rather than reactive options for farmers. • Engaging farmers with climate services requires a range of different and complimentary approaches. Radio is the most commonly used and requested going forward. Extension staff, lead farmers and farmer groups are important sources of information and support in farmer decision making. Climate services products should be designed with the aim to address multiple farmer ‘problems’. For example, information on the amount of rainfall to expect in a season can aid decision making on choice of land preparation and cultivation methods, choice of crop variety, weeding, as well requirements for pest and disease management in cattle

Neonatal Pain-Related Stress Predicts Cortical Thickness at Age 7 Years in Children Born Very Preterm

Background Altered brain development is evident in children born very preterm (24–32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age. Methods 42 right-handed children born very preterm (24–32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling. Results After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes. Conclusions In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors

Long-term Clinical and Cost-effectiveness of Early Endovenous Ablation in Venous Ulceration: A Randomized Clinical Trial

Importance One-year outcomes from the Early Venous Reflux Ablation (EVRA) randomized trial showed accelerated venous leg ulcer healing and greater ulcer-free time for participants who are treated with early endovenous ablation of lower extremity superficial reflux.Objective To evaluate the clinical and cost-effectiveness of early endovenous ablation of superficial venous reflux in patients with venous leg ulceration.Design, Setting, and Participants Between October 24, 2013, and September 27, 2016, the EVRA randomized clinical trial enrolled 450 participants (450 legs) with venous leg ulceration of less than 6 months’ duration and superficial venous reflux. Initially, 6555 patients were assessed for eligibility, and 6105 were excluded for reasons including ulcer duration greater than 6 months, healed ulcer by the time of randomization, deep venous occlusive disease, and insufficient superficial venous reflux to warrant ablation therapy, among others. A total of 426 of 450 participants (94.7%) from the vascular surgery departments of 20 hospitals in the United Kingdom were included in the analysis for ulcer recurrence. Surgeons, participants, and follow-up assessors were not blinded to the treatment group. Data were analyzed from August 11 to November 4, 2019.Interventions Patients were randomly assigned to receive compression therapy with early endovenous ablation within 2 weeks of randomization (early intervention, n = 224) or compression with deferred endovenous treatment of superficial venous reflux (deferred intervention, n = 226). Endovenous modality and strategy were left to the preference of the treating clinical team.Main Outcomes and Measures The primary outcome for the extended phase was time to first ulcer recurrence. Secondary outcomes included ulcer recurrence rate and cost-effectiveness.Results The early-intervention group consisted of 224 participants (mean [SD] age, 67.0 [15.5] years; 127 men [56.7%]; 206 White participants [92%]). The deferred-intervention group consisted of 226 participants (mean [SD] age, 68.9 [14.0] years; 120 men [53.1%]; 208 White participants [92%]). Of the 426 participants whose leg ulcer had healed, 121 (28.4%) experienced at least 1 recurrence during follow-up. There was no clear difference in time to first ulcer recurrence between the 2 groups (hazard ratio, 0.82; 95% CI, 0.57-1.17; P = .28). Ulcers recurred at a lower rate of 0.11 per person-year in the early-intervention group compared with 0.16 per person-year in the deferred-intervention group (incidence rate ratio, 0.658; 95% CI, 0.480-0.898; P = .003). Time to ulcer healing was shorter in the early-intervention group for primary ulcers (hazard ratio, 1.36; 95% CI, 1.12-1.64; P = .002). At 3 years, early intervention was 91.6% likely to be cost-effective at a willingness to pay of £20 000 ($26 283) per quality-adjusted life year and 90.8$45 995) per quality-adjusted life year.Conclusions and Relevance Early endovenous ablation of superficial venous reflux was highly likely to be cost-effective over a 3-year horizon compared with deferred intervention. Early intervention accelerated the healing of venous leg ulcers and reduced the overall incidence of ulcer recurrence