16S sequencing and functional analysis of the fecal microbiome during treatment of newly diagnosed pediatric inflammatory bowel disease

JJA is funded by a National Institute of Health Research Academic Clinical Fellowship and has received an Action Medical Research training fellowship. TC is funded by a Crohn’s in Childhood research association fellowship. CMC received a PhD studentship from SULSA Spirit industrial studentship. The NGS analysis was made possible by the award of a grant from the Source Bioscience 110th year anniversary promotion to CMC. The Rowett Institute receives funding from the Scottish Government (RESAS).Peer reviewedPublisher PD

CHESS Improves Cancer Caregivers\u27 Burden and Mood: Results of an eHealth RCT

OBJECTIVE: Informal caregivers (family and friends) of people with cancer are often unprepared for their caregiving role, leading to increased burden or distress. Comprehensive Health Enhancement Support System (CHESS) is a Web-based lung cancer information, communication, and coaching system for caregivers. This randomized trial reports the impact on caregiver burden, disruptiveness, and mood of providing caregivers access to CHESS versus the Internet with a list of recommended lung cancer websites. METHODS: A total of 285 informal caregivers of patients with advanced nonsmall cell lung cancer were randomly assigned to a comparison group that received Internet or a treatment group that received Internet and CHESS. Caregivers were provided a computer and Internet service if needed. Written surveys were completed at pretest and during the intervention period bimonthly for up to 24 months. Analyses of covariance (ANCOVAs) compared the intervention\u27s effect on caregivers\u27 disruptiveness and burden (CQOLI-C), and negative mood (combined Anxiety, Depression, and Anger scales of the POMS) at 6 months, controlling for blocking variables (site, caregiver\u27s race, and relationship to patient) and the given outcome at pretest. RESULTS: Caregivers randomized to CHESS reported lower burden, t(84) = 2.36, p = .021, d = .39, and negative mood, t(86) = 2.82, p = .006, d = .44, than those in the Internet group. The effect on disruptiveness was not significant. CONCLUSIONS: Although caring for someone with a terminal illness will always exact a toll on caregivers, eHealth interventions like CHESS may improve caregivers\u27 understanding and coping skills and, as a result, ease their burden and mood

Angular position of nodes in the superconducting gap of YBCO

The thermal conductivity of a YBCO single crystal has been studied as a function of the relative orientation of the crystal axes and a magnetic field rotating in the Cu-O planes. Measurements were carried out at several temperatures below T_c and at a fixed field of 30 kOe. A four-fold symmetry characteristic of a superconducting gap with nodes at odd multiples of 45 degrees in k-space was resolved. Experiments were performed to exclude a possible macroscopic origin for such a four-fold symmetry such as sample shape or anisotropic pinning. Our results impose an upper limit of 10% on the weight of the s-wave component of the essentially d-wave superconducting order parameter of YBCO.Comment: 10 pages, 4 figure

Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration

SummaryThe accumulation of amyloid-β (Aβ) as amyloid fibrils and toxic oligomers is an important step in the development of Alzheimer’s disease (AD). However, there are numerous potentially toxic oligomers and little is known about their neurological effects when generated in the living brain. Here we show that Aβ oligomers can be assigned to one of at least two classes (type 1 and type 2) based on their temporal, spatial, and structural relationships to amyloid fibrils. The type 2 oligomers are related to amyloid fibrils and represent the majority of oligomers generated in vivo, but they remain confined to the vicinity of amyloid plaques and do not impair cognition at levels relevant to AD. Type 1 oligomers are unrelated to amyloid fibrils and may have greater potential to cause global neural dysfunction in AD because they are dispersed. These results refine our understanding of the pathogenicity of Aβ oligomers in vivo

Connecting urban food plans to the countryside: leveraging Denver's food vision to explore meaningful rural-urban linkages

Includes bibliographical references (pages 14-18).Cities are increasingly turning to food policy plans to support goals related to food access, food security, the environment, and economic development. This paper investigates ways that rural farmers, communities, and economies can both support and be supported by metropolitan food-focused initiatives. Specifically, our research question asked what opportunities and barriers exist to developing food policies that support urban food goals, particularly related to local procurement, as well as rural economic development. To address this question, we described and analyzed a meeting of urban stakeholders and larger-scale rural producers related to Colorado’s Denver Food Vision and Plan. We documented and explored “findings” gleaned from a supply chain diagraming and data compilation process that were then used to inform an event that brought together diverse supply chain partners. Three findings stand out. First, facilitating dialog between urban food policymakers and rural producers to understand potential tensions, mitigate such tensions, and capitalize on opportunities is essential. Second, perceptions and expectations surrounding “good food” are nuanced—a timely finding given the number of preferred procurement programs emerging across the county. Third, critical evaluation is needed across a diverse set of value chain strategies (e.g., conventional and alternative distribution) if food policy intends to support heterogeneous producers, their communities, and urban food policy goals

Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer

We studied 2332 individuals with monoallelic mutations in MUTYH among 9504 relatives of 264 colorectal cancer (CRC) cases with a MUTYH mutation. We estimated CRC risks through 70 years of age of 7.2% for male carriers of monoallelic mutations (95% confidence interval [CI], 4.6%-11.3%) and 5.6% for female carriers of monoallelic mutations (95% CI, 3.6%-8.8%), irrespective of family history. For monoallelic MUTYH mutation carriers with a first-degree relative with CRC diagnosed by 50 years of age who does not have the MUTYH mutation, risks of CRC were 12.5% for men (95% CI, 8.6%-17.7%) and 10% for women (95% CI, 6.7%-14.4%). Risks of CRC for carriers of monoallelic mutations in MUTYH with a first-degree relative with CRC are sufficiently high to warrant more intensive screening than for the general population

Preclinical testing of the glycogen synthase kinase-3β inhibitor tideglusib for rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma. RMS often arise from myogenic precursors and displays a poorly differentiated skeletal muscle phenotype most closely resembling regenerating muscle. GSK3β is a ubiquitously expressed serine-threonine kinase capable of repressing the terminal myogenic differentiation program in cardiac and skeletal muscle. Recent unbiased chemical screening efforts have prioritized GSK3β inhibitors as inducers of myodifferentiation in RMS, suggesting efficacy as single agents in suppressing growth and promoting self-renewal in zebrafish transgenic embryonal RMS (eRMS) models in vivo. In this study, we tested the irreversible GSK3β-inhibitor, tideglusib for in vivo efficacy in patient-derived xenograft models of both alveolar rhabdomyosarcoma (aRMS) and eRMS. Tideglusib had effective on-target pharmacodynamic efficacy, but as a single agent had no effect on tumor progression or myodifferentiation. These results suggest that as monotherapy, GSK3β inhibitors may not be a viable treatment for aRMS or eRMS

Evolutionary dynamics of tumor-stroma interactions in multiple myeloma

Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts) exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma

COMAP Early Science: VIII. A Joint Stacking Analysis with eBOSS Quasars

We present a new upper limit on the cosmic molecular gas density at z = 2.4 − 3.4 obtained using the first year of observations from the CO Mapping Array Project (COMAP). COMAP data cubes are stacked on the 3D positions of 243 quasars selected from the Extended Baryon Oscillation SpectroscopicSurvey (eBOSS) catalog, yielding a 95% upper limit for flux from CO(1-0) line emission of 0.129 Jykm/s. Depending on the balance of the emission between the quasar host and its environment, this value can be interpreted as an average CO line luminosity L′CO of eBOSS quasars of ≤ 1.26 × 1011 K km pc2s−1, or an average molecular gas density ρH2 in regions of the universe containing a quasar of ≤ 1.52 × 108 M⊙ cMpc−3. The L′ CO upper limit falls among CO line luminosities obtained fromindividually-targeted quasars in the COMAP redshift range, and the ρH2 value is comparable to upper limits obtained from other Line Intensity Mapping (LIM) surveys and their joint analyses. Further, we forecast the values obtainable with the COMAP/eBOSS stack after the full 5-year COMAP Pathfinder survey. We predict that a detection is probable with this method, depending on the CO properties of the quasar sample. Based on the achieved sensitivity, we believe that this technique of stacking LIM data on the positions of traditional galaxy or quasar catalogs is extremely promising, both asa technique for investigating large galaxy catalogs efficiently at high redshift and as a technique for bolstering the sensitivity of LIM experiments, even with a fraction of their total expected survey data