Declaration of medical writing assistance in international peer-reviewed publications

Medical researchers have an ethical and scientific obligation to publish, but between one third and two thirds of research may remain unpublished. A major reason for nonpublication is lack of time, which may lead researchers to seek medical writing assistance. Guidelines from journal editors and medical writers encourage authors to acknowledge medical writers. We quantified the proportion of articles from international, peer-reviewed, high-ranking journals that reported medical writing assistance

Impact assessment of the Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery

Background: Research impact is an emerging measure of research achievement alongside traditional academic outputs such as publications. We present the results of applying the Framework to Assess the Impact from Translational health research (FAIT) to the Centre for Research Excellence (CRE) in Stroke Rehabilitation and Brain Recovery (CRE-Stroke, 2014–2019) and report on the feasibility and lessons from the application of FAIT to a CRE rather than a discrete research project. Methods: Data were gathered via online surveys, in-depth interviews, document analysis and review of relevant websites/databases to report on the three major FAIT methods: the modified Payback Framework, an assessment of costs against monetized consequences, and a narrative account of the impact generated from CRE-Stroke activities. FAIT was applied during the last 4 years of CRE-Stroke operation. Results: With an economic investment of AU$3.9 million over 5 years, CRE-Stroke delivered a return on investment that included AU$ 18.8 million in leveraged grants, fellowships and consultancies. Collectively, CRE-Stroke members produced 354 publications that were accessed 470,000 times and cited over 7220 times. CRE-Stroke supported 26 PhDs, 39 postdocs and seven novice clinician researchers. There were 59 capacity-building events benefiting 744 individuals including policy-makers and consumers. CRE-Stroke created research infrastructure (including a research register of stroke survivors and a brain biobank), and its global leadership produced international consensus recommendations to influence the stroke research landscape worldwide. Members contributed to the Australian Living Stroke Guidelines: four researchers’ outputs were directly referenced. Based only on the consequences that could be monetized, CRE-Stroke returned AU$ 4.82 for every dollar invested in the CRE. Conclusion: This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstrate and report the impact of and returns on research investment. The prospective application of FAIT by a dedicated research impact team demonstrated impact in broad categories of knowledge-gain, capacity-building, new infrastructure, input to policy and economic benefits. The methods can be used by other research teams to provide comprehensive evidence to governments and other research funders about what has been generated from their research investment but requires dedicated resources to complete

Preventing and controlling nonnative species invasions to bend the curve of global freshwater biodiversity loss

The Emergency Recovery Plan for freshwater biodiversity recognizes that addressing nonnative species is one of six principal actions needed to bend the curve in freshwater biodiversity loss. This is because introduction rates of nonnative species continue to accelerate globally and where these species develop invasive populations, they can have severe impacts on freshwater biodiversity. The most effective management measure to protect freshwater biodiversity is to prevent introductions of nonnative species. Should a nonnative species be introduced, however, then its early detection and the implementation of rapid reaction measures can avoid it establishing and dispersing. If these measures are unsuccessful and the species becomes invasive, then control and containment measures can minimize its further spread and impact. Minimizing further spread and impact includes control methods to reduce invader abundance and containment methods such as screening of invaded sites and strict biosecurity to avoid the invader dispersing to neighbouring basins. Thesemanagement actions have benefitted from developments in invasion risk assessment that can prioritize species according to their invasion risk and, for species already invasive, ensure that management actions are commensurate with assessed risk. The successful management of freshwater nonnative species still requires the overcoming of some implementation challenges, including nonnative species often being a symptom of degraded habitats rather than the main driver of ecological change, and eradication methods often being non-species specific. Given the multiple anthropogenic stressors in freshwaters, nonnative species management must work with other restoration strategies if it is to deliver the Emergency Recovery Plan for freshwater biodiversity

Endogenous Syngap1 Alpha Splice Forms Promote Cognitive Function and Seizure Protection

Altres ajuts: NIH grants from the National Institute of Mental Health (MH096847, MH108408, MH115005, MH113949, MH105400); National Institute for Neurological Disorders and Stroke (NS064079); Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD089491); National Institute for Drug Abuse (DA034116, DA036376); Autism Speaks Weatherstone Pre-Doctoral fellowship (10646); Training fellowship from the Leon and Friends Charitable Foundation.Loss-of-function variants in SYNGAP1 cause a developmental encephalopathy defined by cognitive impairment, autistic features, and epilepsy. SYNGAP1 splicing leads to expression of distinct functional protein isoforms. Splicing imparts multiple cellular functions of SynGAP proteins through coding of distinct C-terminal motifs. However, it remains unknown how these different splice sequences function in vivo to regulate neuronal function and behavior. Reduced expression of SynGAP-α1/2 C-terminal splice variants in mice caused severe phenotypes, including reduced survival, impaired learning, and reduced seizure latency. In contrast, upregulation of α1/2 expression improved learning and increased seizure latency. Mice expressing α1-specific mutations, which disrupted SynGAP cellular functions without altering protein expression, promoted seizure, disrupted synapse plasticity, and impaired learning. These findings demonstrate that endogenous SynGAP isoforms with α1/2 spliced sequences promote cognitive function and impart seizure protection. Regulation of SynGAP-α expression or function may be a viable therapeutic strategy to broadly improve cognitive function and mitigate seizure

Agent orange exposure and prostate cancer risk in the million veteran program

BackgroundThe US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk.Patients and methodsParticipants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models.Results and interpretationOn univariable analysis, exposure to Agent Orange was not associated with increased PCa (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.06), metastatic PCa (HR: 0.98, 95% CI: 0.91-1.05, p = 0.55), or fatal PCa (HR: 0.94, 95% CI: 0.79-1.09, p = 0.41). When accounting for race/ethnicity and family history, Agent Orange exposure was independently associated with slightly increased risk of PCa (HR: 1.06, 95% CI: 1.04-1.09, <10-6) but not with metastatic PCa (HR: 1.07, 95% CI: 0.98-1.15, p = 0.10) or PCa death (HR: 1.02, 95% CI: 0.83-1.23, p = 0.09). Similar results were found when accounting for genetic risk. Agent Orange exposure history may not improve modern PCa risk stratification

Trends in utilization and costs of BRCA testing among women aged 18–64 years in the United States, 2003–2014

Purpose We examined 12-year trends in BRCA testing rates and costs in the context of clinical guidelines, national policies, and other factors. Methods We estimated trends in BRCA testing rates and costs from 2003 to 2014 for women aged 18–64 years using private claims data and publicly reported revenues from the primary BRCA testing provider. Results The percentage of women with zero out-of-pocket payments for BRCA testing increased during 2013–2014, after 7 years of general decline, coinciding with a clarification of Affordable Care Act coverage of BRCA genetic testing. Beginning in 2007, family history accounted for an increasing proportion of women with BRCA tests compared with personal history, coinciding with BRCA testing guidelines for primary care settings and direct-to-consumer advertising campaigns. During 2013–2014, BRCA testing rates based on claims grew at a faster rate than revenues, following 3 years of similar growth, consistent with increased marketplace competition. In 2013, BRCA testing rates based on claims increased 57%, compared with 11% average annual increases over the preceding 3 years, coinciding with celebrity publicity. Conclusion The observed trends in BRCA testing rates and costs are consistent with possible effects of several factors, including the Affordable Care Act, clinical guidelines and celebrity publicity

Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT

Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT