The effect of exogenous glucose infusion on early embryonic development in lactating dairy cows

peer-reviewedThe objective of this study was to examine the effect of intravenous infusion of glucose on early embryonic development in lactating dairy cows. Nonpregnant, lactating dairy cows (n = 12) were enrolled in the study (276 ± 17 d in milk). On d 7 after a synchronized estrus, cows were randomly assigned to receive an intravenous infusion of either 750 g/d of exogenous glucose (GLUC; 78 mL/h of 40% glucose wt/vol) or saline (CTRL; 78 mL/h of 0.9% saline solution). The infusion period lasted 7 d and cows were confined to metabolism stalls for the duration of the study. Coincident with the commencement of the infusion on d 7 after estrus, 15 in vitro-produced grade 1 blastocysts were transferred into the uterine horn ipsilateral to the corpus luteum. All animals were slaughtered on d 14 to recover conceptuses, uterine fluid, and endometrial tissue. Glucose infusion increased circulating glucose concentrations (4.70 ± 0.12 vs. 4.15 ± 0.12 mmol/L) but did not affect milk production or dry matter intake. Circulating β-hydroxybutyrate concentrations were decreased (0.51 ± 0.01 vs. 0.70 ± 0.01 mmol/L for GLUC vs. CTRL, respectively) but plasma fatty acids, progesterone, and insulin concentrations were unaffected by treatment. Treatment did not affect either uterine lumen fluid glucose concentration or the mRNA abundance of specific glucose transporters in the endometrium. Mean conceptus length, width, and area on d 14 were reduced in the GLUC treatment compared with the CTRL treatment. A greater proportion of embryos in the CTRL group had elongated to all length cut-off measurements between 11 and 20 mm (measured in 1-mm increments) compared with the GLUC treatment. In conclusion, infusion of glucose into lactating dairy cows from d 7 to d 14 post-estrus during the critical period of conceptus elongation had an adverse impact on early embryonic development

A proposal for a drug product Manufacturing Classification System (MCS) for oral solid dosage forms

This paper proposes the development of a drug product Manufacturing Classification System (MCS) based on processing route. It summarizes conclusions from a dedicated APS conference and subsequent discussion within APS focus groups and the MCS working party. The MCS is intended as a tool for pharmaceutical scientists to rank the feasibility of different processing routes for the manufacture of oral solid dosage forms, based on selected properties of the API and the needs of the formulation. It has many applications in pharmaceutical development, in particular, it will provide a common understanding of risk by defining what the “right particles” are, enable the selection of the best process, and aid subsequent transfer to manufacturing. The ultimate aim is one of prediction of product developability and processability based upon previous experience. This paper is intended to stimulate contribution from a broad range of stakeholders to develop the MCS concept further and apply it to practice. In particular, opinions are sought on what API properties are important when selecting or modifying materials to enable an efficient and robust pharmaceutical manufacturing process. Feedback can be given by replying to our dedicated e-mail address ([email protected]); completing the survey on our LinkedIn site; or by attending one of our planned conference roundtable sessions

Resorcinol ninhydrin complex: 1,5,9-trihy­droxy-8-oxatetra­cyclo­[7.7.0.02,7.010,15]hexa­deca-2,4,6,10(15),11,13-hexaen-16-one

In the title compound, C15H10O5, the cyclo­penta­none (r.m.s. deviation = 0.049 Å) and oxolane (r.m.s. deviation = 0.048 Å) rings make a dihedral angle of 67.91 (4)°. An intra­molecular O—H⋯O hydrogen bond is observed. In the crystal, mol­ecules associate via O—H⋯O hydrogen bonds, forming a three-dimensional network

Engaging with Indigenous Australian communities for a human papilloma virus and oropharyngeal cancer project; use of the CONSIDER statement

BACKGROUND: The prevalence of oral HPV infection and HPV-related oropharyngeal squamous cell carcinoma (OPSCC) among Indigenous Australians is unknown. This paper outlines the engagement, consultation and recruitment strategies for a study involving investigation of HPV and OPSCC among Indigenous South Australians, based on the consolidated criteria for strengthening the reporting of health research involving Indigenous Peoples (CONSIDER) statement. METHODS: Initial consultations with all interested Aboriginal Community Controlled Health Organisations (ACCHOs) were done throughout 2014 and 2015. This resulted in a funding application submitted that reflected Indigenous community views and inputs in study design and methodology, and which included nine Indigenous investigators. Once funding was received, community consultation was again undertaken, with six ACCHOs providing structures, strategies and recommendations for how recruitment for participants taking part in the study should be undertaken. Staff were hired (n = 6), with non-Indigenous staff (n = 3) undertaking extensive cultural competency training. An Indigenous Reference Group was established to provide oversight and cultural guidance. Recruitment of Indigenous participants by trained field officers occurred between Feb 2018 and Dec 2018, with n = 1011 recruited. Qualitative records summarising research staff contact with ACCHOs and participants were documented. These records, together with field trip notes, key ACCHO stakeholder reflections and research staff comments, were reviewed to summarise the culturally sensitive strategies that appeared to work most successfully to facilitate ACCHO and participant buy-in. RESULTS: Findings were documented against the CONSIDER statement's research reporting framework of governance: relationships, prioritization, methodologies, participation, capacity, analysis and findings, and dissemination. The apparent success of the community engagement processes were then conceptualised into five domains: (1) engaging with ACCHOs as equal partners very early in the research process; (2) having an Indigenous Reference Group; (3) ACCHOs actively promoting the study; (4) having a flexible agenda responsive to broader environment demands and; (5) including Indigenous capacity building. CONCLUSIONS: Consultation and engagement with all sectors of the Indigenous community are essential in any research, especially a project involving HPV and OPSCC. Enabling local Indigenous staff to provide cultural guidance throughout the research process is helpful. Research that is culturally respectful and in partnership with Indigenous groups can be embraced when the research is collaborative and has clear translational benefits. The CONSIDER statement is a useful checklist against which to assess Indigenous health research processes. In future, the findings may be useful to yield important Aboriginal population estimates for both oral HPV infection and OPSCC. This may serve to convince funding bodies to provide health promotion personnel in the field of oral health, specifically OPSCC, in ACCHOs.Joanne Hedges, Gail Garvey, Zell Dodd, Warren Miller, Terry Dunbar ... Lisa Jamieson ... et al

Les Houches 2011: Physics at TeV Colliders New Physics Working Group Report

We present the activities of the "New Physics" working group for the "Physics at TeV Colliders" workshop (Les Houches, France, 30 May-17 June, 2011). Our report includes new agreements on formats for interfaces between computational tools, new tool developments, important signatures for searches at the LHC, recommendations for presentation of LHC search results, as well as additional phenomenological studies.Comment: 243 pages, report of the Les Houches 2011 New Physics Group; fix three figure

Supporting Aboriginal and Torres Strait Islander Families to Stay Together from the Start (SAFeST Start): Urgent call to action to address crisis in infant removals

Reducing the rate of over-representation of Aboriginal and Torres Strait Islander children in out-of-home care (OOHC) is a key Closing the Gap target committed to by all Australian governments. Current strategies are failing. The “gap” is widening, with the rate of Aboriginal and Torres Strait Islander children in OOHC at 30 June 2020 being 11 times that of non-Indigenous children. Approximately, one in five Aboriginal and Torres Strait Islander children entering OOHC each year are younger than one year. These figures represent compounding intergenerational trauma and institutional harm to Aboriginal and Torres Strait Islander families and communities. This article outlines systemic failures to address the needs of Aboriginal and Torres Strait Islander parents during pregnancy and following birth, causing cumulative harm and trauma to families, communities and cultures. Major reform to child and family notification and service systems, and significant investment to address this crisis, is urgently needed. The Family Matters Building Blocks and five elements of the Aboriginal and Torres Strait Islander Child Placement Principle (Prevention, Participation, Partnerships, Placement and Connection) provide a transformative foundation to address historical, institutional, well-being and socioeconomic drivers of current catastrophic trajectories. The time for action is now

Human papillomavirus and oropharyngeal cancer among Indigenous Australians: protocol for a prevalence study of oral-related human papillomavirus and cost-effectiveness of prevention

Background: Oropharyngeal cancer is an important, understudied cancer affecting Aboriginal and Torres Strait Islander Australians. The human papillomavirus (HPV) is a significant risk factor for oropharyngeal cancer. Current generation HPV vaccines are effective against the 2 most common types of high-risk HPVs in cancer (hrHPVs 16/18). Objectives: This study aims (1) to yield population estimates of oncogenic genotypes of HPV in the mouth and oropharynx of defined Aboriginal and Torres Strait Islander populations; (2) to estimate the proportion of oropharyngeal cancer attributable to HPV among these Australian citizens; (3) to estimate the impact of HPV vaccination as currently implemented on rates of oropharyngeal cancer among Aboriginal and Torres Strait Islander Australians; and (4) taking into account impact on oropharyngeal as well as cervical cancer, to evaluate efficacy and cost-effectiveness of targeted extended HPV vaccination to older ages, among our study population. Methods: Our study design and operation is straightforward, with minimal impost on participants. It involves testing for carriage of hrHPV in the mouth and oropharynx among 1000 Aboriginal South Australians by simple saliva collection and with follow-up at 12 and 24 months, collection of sexual history at baseline, collection of information for estimating health state (quality-of-life) utilities at baseline, genotyping of viruses, predictive outcome and cost-effectiveness modeling, data interpretation and development of vaccination, and follow-up management strategies driven by the Aboriginal community. Results: Participant recruitment for this study commenced in February 2018 and enrollment is ongoing. The first results are expected to be submitted for publication in 2019. Conclusions: The project will have a number of important outcomes. Synthesis of evidence will enable generation of estimates of the burden of oropharyngeal cancer among Aboriginal and Torres Strait Islander Australians and indicate the likely effectiveness and cost-effectiveness of prevention. This will be important for health services planning, and for Aboriginal health worker and patient education. The results will also point to important areas where research efforts should be focused to improve outcomes in Aboriginal and Torres Strait Islander Australians with oropharyngeal cancer. There will be a strong focus on community engagement and accounting for the preferences of individuals and the community in control of HPV-related cancers. The project has international relevance in that it will be the first to systematically evaluate prevention of both cervical and oropharyngeal cancer in a high-risk Indigenous population taking into account all population, testing, and surveillance options.Lisa Jamieson, Gail Garvey, Joanne Hedges, Amanda Mitchell, Terry Dunbar, Cathy Leane, Isaac Hill, Kate Warren, Alex Brown, Xiangqun Ju, David Roder, Richard Logan, Newell Johnson, Megan Smith, Annika Antonsson, Karen Canfel