Human neural stem cell transplantation into the corpus callosum of Alzheimer’s mice

The hippocampus has been the target of stem cell transplantations in preclinical studies focused on Alzheimer’s disease, with results showing improvements in histological and behavioral outcomes. The corpus callosum is another structure that is affected early in Alzheimer’s disease. Therefore, we hypothesize that this structure is a novel target for human neural stem cell transplantation in transgenic Alzheimer’s disease mouse models. This study demonstrates the feasibility of targeting the corpus callosum and identifies an effective immunosuppression regimen for transplanted neural stem cell survival. These results support further preclinical development of the corpus callosum as a therapeutic target in Alzheimer’s disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138852/1/acn3443_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138852/2/acn3443.pd

CYP1B1 copy number variation is not a major contributor to primary congenital glaucoma

This article is published under a Creative Commons Attribution-NonCommercial-NoDerivatives License 3.0, or CC BY-NC-ND 3.0 (see http://creativecommons.org/licenses/by-nc-nd/3.0/ for license terms). The authors retain copyright and grant Molecular Vision an irrevocable, royalty-free, perpetual license to publish and distribute the article, in all formats now known or later developed, and to identify Molecular Vision as the original publisher.Purpose: To evaluate the prevalence and the diagnostic utility of testing for CYP1B1 copy number variation (CNV) in primary congenital glaucoma (PCG) cases unexplained by CYP1B1 point mutations in The Australian and New Zealand Registry of Advanced Glaucoma. Methods: In total, 50 PCG cases either heterozygous for disease-causing variants or with no CYP1B1 sequence variants were included in the study. CYP1B1 CNV was analyzed by Multiplex Ligation-dependent Probe Amplification (MLPA). Results: No deletions or duplications were found in any of the cases. Conclusion: This is the first study to report on CYP1B1 CNV in PCG cases. Our findings show that this mechanism is not a major contributor to the phenotype and is of limited diagnostic utility

BUILDING A SUSTAINABLE NETWORK OF DROUGHT COMMUNITIES

The first step in managing large-scale (national) collaborations and networks is to consider and address how a group and a potential partnership may match up (Luther, 2005). To explore this concept and many other collaborative concepts, the National Integrated Drought Information System (NIDIS) hosted a workshop, “Building a Sustainable Network of Drought Communities,” which was facilitated by the National Drought Mitigation Center (NDMC) in Chicago, IL, June 8-9, 2011. The workshop explored current examples of good communication and lessons learned within the realm of drought planning in order to address a future NIDIS Engaging Preparedness Communities (EPC) working group that is solution-focused and collaborative. With the diversity and experience of the participants at this meeting, a wealth of good practices or lessons learned in drought planning, preparedness, and general stakeholder engagement set the pathway for building a sustainable community of drought practitioners. In his opening remarks, NIDIS Director Roger Pulwarty noted that adaptive institutions can show robustness in the following ways: Levels of alertness—monitoring the external world for early warning signs that key assumptions are likely to verify/fail and a commitment to rigorous monitoring of performance; Agility—the ability to react to early warning signs of problems or opportunities; flow of knowledge across components, and to adjust strategies and tactics rapidly to meet changes in the environment; and Alignment—the ability to align the whole organization (and partners) to its mission-policies and practices that give rise to failures/successes. Through an interactive workshop format that used Appreciative Inquiry (framing breakout sessions on success), the group was able to effectively discuss topics such as: • Integrating Planning Efforts • Planning Under Uncertainty • Evaluating, Assessing, and Updating Drought Plans • Leveraging Resources for Risk Management • Implementing Plans and Planning Information • Synthesizing Success Stories and Lessons Learned • Creating a Sustainable Network of Drought Professionals The most common themes resulting from the workshop included: • Importance of networking and collaboration—this is a necessity. Figuring out how to make it seamless is the main goal that the NIDIS EPC Community should foster. Good communication is the key among the drought practitioners and their stakeholders. • Celebrate success—in this future drought network, successes related to drought efforts should be highlighted within the community and to the public. This will help drive future positive interactions and collaborations. It also gives the community a sense of pride. • “Stakeholder Buy-In”—why should stakeholders stay engaged in an ongoing drought community? Especially when there is no drought? Again, good communication and collaborations with other multi-hazard, sustainability, and natural resources planning efforts will help keep drought a priority. • Economic, environmental, and social aspects of planning for drought—these should always be considered. This was a recurrent theme in the workshop. • Planners should not “reinvent the wheel”—planners involved in climate adaptation work can and should reference the best drought planning resources and case studies to help them incorporate drought in their overall planning efforts. • “Have a plan for the plan”—how and who will make it happen? What kind of leadership is needed within the NIDIS EPC community to track its progress and success? • Sharing of resources—as budgets become slimmer, a central location of available resources and the sharing of resources in the area of drought preparedness and mitigation is necessary. Communication regarding these potential resources should also be integrated into this NIDIS EPC community. Since the occurrence of the workshop, several EPC-related activities have taken place, including a webinar in December 2011. This workshop report and additional EPC updates will be placed on the U.S. Drought portal (www.drought.gov). Currently, the American Planning Association (APA), NIDIS and the NDMC are collaborating to produce a Planning Advisory Service (PAS) Report to connect drought mitigation resources with the planning practices of local, regional, tribal and state governments. This builds on the work of the APA’s Hazard Planning Center, which produced a similar PAS Report (sponsored by FEMA) on how to integrate multi-hazard planning into planning practices. In May 2012: The APA’s drought planning project webpage went live and can be found at: http://www.planning.org/research/drought/index.ht

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

A guide for social science journal editors on easing into open science

Journal editors have a large amount of power to advance open science in their respective fields by incentivising and mandating open policies and practices at their journals. The Data PASS Journal Editors Discussion Interface (JEDI, an online community for social science journal editors: www.dpjedi.org) has collated several resources on embedding open science in journal editing (www.dpjedi.org/resources). However, it can be overwhelming as an editor new to open science practices to know where to start. For this reason, we created a guide for journal editors on how to get started with open science. The guide outlines steps that editors can take to implement open policies and practices within their journal, and goes through the what, why, how, and worries of each policy and practice. This manuscript introduces and summarizes the guide (full guide: https://doi.org/10.31219/osf.io/hstcx)

American Society of Clinical Oncology/College ofAmerican Pathologists guideline recommendations forimmunohistochemical testing of estrogen andprogesterone receptors in breast cancer

Purpose: To develop a guideline to improve theaccuracy of immunohistochemical (IHC) estrogen receptor(ER) and progesterone receptor (PgR) testing in breastcancer and the utility of these receptors as predictivemarkers.Methods: The American Society of Clinical Oncologyand the College of American Pathologists convened aninternational Expert Panel that conducted a systematicreview and evaluation of the literature in partnership withCancer Care Ontario and developed recommendations foroptimal IHC ER/PgR testing performance.Results: Up to 20% of current IHC determinations ofER and PgR testing worldwide may be inaccurate (falsenegative or false positive). Most of the issues with testinghave occurred because of variation in preanalyticvariables, thresholds for positivity, and interpretationcriteria.Recommendations: The Panel recommends that ER andPgR status be determined on all invasive breast cancers andbreast cancer recurrences. A testing algorithm that relieson accurate, reproducible assay performance is proposed.Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be consideredpositive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.(Arch Pathol Lab Med. 2010;134:907–922

How informed is consent in vulnerable populations? Experience using a continuous consent process during the MDP301 vaginal microbicide trial in Mwanza, Tanzania

BACKGROUND: HIV prevention trials conducted among disadvantaged vulnerable at-risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania. METHODS: A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs) conducted immediately after their 4, 24 and 52 week follow-up visits. RESULTS: 99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews). In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy. CONCLUSIONS: Providing information to trial participants in a focussed, locally-appropriate manner, using methods developed in consultation with the community, and within a continuous informed-consent framework resulted in high levels of comprehension and message retention in this setting. This approach may represent a model for researchers conducting HIV prevention trials among other vulnerable populations in resource-poor settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64716212