Publications by authors named "Susan Weiner"

28 Publications

  • Page 1 of 1

Second Paediatric Strategy Forum for anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies: ACCELERATE in collaboration with the European Medicines Agency with the participation of the Food and Drug Administration.

Eur J Cancer 2021 Nov 15;157:198-213. Epub 2021 Sep 15.

Hospital for Sick Children, Toronto, Canada.

The first (2017) and sixth (2021) multistakeholder Paediatric Strategy Forums focused on anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies. ALK is an important oncogene and target in several paediatric tumours (anaplastic large cell lymphoma [ALCL], inflammatory myofibroblastic tumour [IMT], neuroblastoma and hemispheric gliomas in infants and young children) with unmet therapeutic needs. ALK tyrosine kinase inhibitors have been demonstrated to be active both in ALK fusion-kinase positive ALCL and IMT. ALK alterations differ, with fusions occurring in ALCL, IMT and gliomas, and activating mutations and amplification in neuroblastoma. While there are many ALK inhibitors in development, the number of children diagnosed with ALK driven malignancies is very small. The objectives of this ALK Forum were to (i) Describe current knowledge of ALK biology in childhood cancers; (ii) Provide an overview of the development of ALK inhibitors for children; (iii) Identify the unmet needs taking into account planned or current ongoing trials; (iv) Conclude how second/third-generation inhibitors could be evaluated and prioritised; (v) Identify lessons learnt from the experience with ALK inhibitors to accelerate the paediatric development of other anti-cancer targeted agents in the new regulatory environments. There has been progress over the last four years, with more trials of ALK inhibitors opened in paediatrics and more regulatory submissions. In January 2021, the US Food and Drug Administration approved crizotinib for the treatment of paediatric and young adult patients with relapsed or refractory ALCL and there are paediatric investigation plans (PIPs) for brigatinib and for crizotinib in ALCL and IMT. In ALCL, the current goal is to investigate the inclusion of ALK inhibitors in front-line therapy with the aim of decreasing toxicity with higher/similar efficacy compared to present first-line therapies. For IMT, the focus is to develop a joint prospective trial with one product in children, adolescents and adults, taking advantage of the common biology across the age spectrum. As approximately 50% of IMTs are ALK-positive, molecular analysis is required to identify patients to be treated with an ALK inhibitor. For neuroblastoma, crizotinib has not shown robust anti-tumour activity. A focused and sequential development of ALK inhibitors with very good central nervous system (CNS) penetration in CNS tumours with ALK fusions should be undertaken. The Forum reinforced the strong need for global academic collaboration, very early involvement of regulators with studies seeking possible registration and early academia-multicompany engagement. Innovations in study design and conduct and the use of 'real-world data' supporting development in these rare sub-groups of patients for whom randomised clinical trials are not feasible are important initiatives. A focused and sequenced development strategy, where one product is evaluated first with other products being assessed sequentially, is applicable for ALK inhibitors and other medicinal products in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.08.022DOI Listing
November 2021

A global approach to long-term follow-up of targeted and immune-based therapy in childhood and adolescence.

Pediatr Blood Cancer 2021 Jul 16;68(7):e29047. Epub 2021 Apr 16.

ACCELERATE Platform LTFU Working Group Co-Chair, ACCELERATE, Brussels, Belgium.

While considerable efforts and progress in our understanding of the long-term toxicities of surgery, radiation and chemotherapy in children with cancer have been made over the last 5 decades, there continues to be a wide gap in our knowledge of the long-term health impact of most novel targeted and immunotherapy agents. To address this gap, ACCELERATE, a multi-stakeholder collaboration of clinical and translational academics, regulators from the EMA and FDA, patient/family advocates and members spanning small biotechnology through to large pharmaceutical companies have initiated the development of an international long-term follow-up data registry to collect this important information prospectively. Providing critical safety data on the long-term use of these approved and investigational therapies in children will support the regulatory requirements and labeling information. It will also provide the necessary insight to help guide physicians and families on the appropriateness of a targeted or immune therapy for their child and inform survivorship planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.29047DOI Listing
July 2021

Bromodomain and extra-terminal inhibitors-A consensus prioritisation after the Paediatric Strategy Forum for medicinal product development of epigenetic modifiers in children-ACCELERATE.

Eur J Cancer 2021 03 16;146:115-124. Epub 2021 Feb 16.

ACCELERATE, Europe; Gustave Roussy, France.

Based on biology and pre-clinical data, bromodomain and extra-terminal (BET) inhibitors have at least three potential roles in paediatric malignancies: NUT (nuclear protein in testis) carcinomas, MYC/MYCN-driven cancers and fusion-driven malignancies. However, there are now at least 10 BET inhibitors in development, with a limited relevant paediatric population in which to evaluate these medicinal products. Therefore, a meeting was convened with the specific aim to develop a consensus among relevant biopharmaceutical companies, academic researchers, as well as patient and family advocates, about the development of BET inhibitors, including prioritisation and their specific roles in children. Although BET inhibitors have been in clinical trials in adults since 2012, the first-in-child study (BMS-986158) only opened in 2019. In the future, when there is strong mechanistic rationale or pre-clinical activity of a class of medicinal product in paediatrics, early clinical evaluation with embedded correlative studies of a member of the class should be prioritised and rapidly executed in paediatric populations. There is a strong mechanistic and biological rationale to evaluate BET inhibitors in paediatrics, underpinned by substantial, but not universal, pre-clinical data. However, most pan-BET inhibitors have been challenging to administer in adults, since monotherapy results in only modest anti-tumour activity and provides a narrow therapeutic index due to thrombocytopenia. It was concluded that it is neither scientifically justified nor feasible to undertake simultaneously early clinical trials in paediatrics of all pan-BET inhibitors. However, there is a clinical need for global access to BET inhibitors for patients with NUT carcinoma, a very rare malignancy driven by bromodomain fusions, with proof of concept of clinical benefit in a subset of patients treated with BET inhibitors. Development and regulatory pathway in this indication should include children and adolescents as well as adults. Beyond NUT carcinoma, it was proposed that further clinical development of other pan-BET inhibitors in children should await the results of the first paediatric clinical trial of BMS-986158, unless there is compelling rationale based on the specific agent of interest. BDII-selective inhibitors, central nervous system-penetrant BET inhibitors (e.g. CC-90010), and those dual-targeting BET/p300 bromodomain are of particular interest and warrant further pre-clinical investigation. This meeting emphasised the value of a coordinated and integrated strategy to drug development in paediatric oncology. A multi-stakeholder approach with multiple companies developing a consensus with academic investigators early in the development of a class of compounds, and then engaging regulatory agencies would improve efficiency, productivity, conserve resources and maximise potential benefit for children with cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.01.018DOI Listing
March 2021

Paediatric Strategy Forum for medicinal product development of epigenetic modifiers for children: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Eur J Cancer 2020 11 26;139:135-148. Epub 2020 Sep 26.

Solving Kids' Cancer, USA.

The fifth multistakeholder Paediatric Strategy Forum focussed on epigenetic modifier therapies for children and adolescents with cancer. As most mutations in paediatric malignancies influence chromatin-associated proteins or transcription and paediatric cancers are driven by developmental gene expression programs, targeting epigenetic mechanisms is predicted to be a very important therapeutic approach in paediatric cancer. The Research to Accelerate Cures and Equity (RACE) for Children Act FDARA amendments to section 505B of the FD&C Act was implemented in August 2020, and as there are many epigenetic targets on the FDA Paediatric Molecular Targets List, clinical evaluation of epigenetic modifiers in paediatric cancers should be considered early in drug development. Companies are also required to submit to the EMA paediatric investigation plans aiming to ensure that the necessary data to support the authorisation of a medicine for children in EU are of high quality and ethically researched. The specific aims of the forum were i) to identify epigenetic targets or mechanisms of action associated with epigenetic modification relevant to paediatric cancers and ii) to define the landscape for paediatric drug development of epigenetic modifier therapies. DNA methyltransferase inhibitors/hypomethylating agents and histone deacetylase inhibitors were largely excluded from discussion as the aim was to discuss those targets for which therapeutic agents are currently in early paediatric and adult development. Epigenetics is an evolving field and could be highly relevant to many paediatric cancers; the biology is multifaceted and new targets are frequently emerging. Targeting epigenetic mechanisms in paediatric malignancy has in most circumstances yet to reach or extend beyond clinical proof of concept, as many targets do not yet have available investigational drugs developed. Eight classes of medicinal products were discussed and prioritised based on the existing level of science to support early evaluation in children: inhibitors of menin, DOT1L, EZH2, EED, BET, PRMT5 and LSD1 and a retinoic acid receptor alpha agonist. Menin inhibitors should be moved rapidly into paediatric development, in view of their biological rationale, strong preclinical activity and ability to fulfil an unmet clinical need. A combination approach is critical for successful utilisation of any epigenetic modifiers (e.g. EZH2 and EED) and exploration of the optimum combination(s) should be supported by preclinical research and, where possible, molecular biomarker validation in advance of clinical translation. A follow-up multistakeholder meeting focussing on BET inhibitors will be held to define how to prioritise the multiple compounds in clinical development that could be evaluated in children with cancer. As epigenetic modifiers are relatively early in development in paediatrics, there is a clear opportunity to shape the landscape of therapies targeting the epigenome in order that efficient and optimum plans for their evaluation in children and adolescents are developed in a timely manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2020.08.014DOI Listing
November 2020

Long weekend sleep is linked to stronger academic performance in male but not female pharmacy students.

Adv Physiol Educ 2020 Sep;44(3):350-357

School of Pharmacy, Duquesne University, Pittsburgh, Pennsylvania.

Poor sleep hygiene portends loss of physical and mental stamina. Therefore, maintaining a regular sleep/wake schedule on both weekdays and weekends is highly recommended. However, this advice runs contrary to the habits of university students who sleep late on weekends. Pharmacy students at Duquesne University sit for frequent examinations, typically commencing at 7:30 AM, and they complain about mental fatigue. Here, we tested the central hypothesis that longer sleep durations on both weekdays and weekends are linked to stronger academic performance in men and women. Students in their first professional year were administered three surveys to collect data on sleep habits and factors that might influence sleep, such as roommates, long commute times, and sleep interruptions. Grade point averages (GPAs) were collected from the Dean's office, with individual permissions from the students. Longer weekend-but not weekday-sleep durations were significantly correlated with higher cumulative GPAs in men and not in women. Women achieved slightly higher cumulative GPAs than men. Students who fell asleep within 15 min of going to bed had higher professional-phase GPAs than those who fell asleep after an hour or more. Our observations cannot establish causal links, but, given the body of prior evidence on the salutary properties of sleep, men may reap more benefit from recovery sleep on weekends. Rather than recommending that students force themselves awake early on weekends in an attempt to maintain a consistent sleep routine, the real-life habits of students should also be given consideration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/advan.00005.2020DOI Listing
September 2020

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients.

Eur J Cancer 2020 03 24;127:52-66. Epub 2020 Jan 24.

BMS, USA.

The third multistakeholder Paediatric Strategy Forum organised by ACCELERATE and the European Medicines Agency focused on immune checkpoint inhibitors for use in combination therapy in children and adolescents. As immune checkpoint inhibitors, both as monotherapy and in combinations have shown impressive success in some adult malignancies and early phase trials in children of single agent checkpoint inhibitors have now been completed, it seemed an appropriate time to consider opportunities for paediatric studies of checkpoint inhibitors used in combination. Among paediatric patients, early clinical studies of checkpoint inhibitors used as monotherapy have demonstrated a high rate of activity, including complete responses, in Hodgkin lymphoma and hypermutant paediatric tumours. Activity has been very limited, however, in more common malignancies of childhood and adolescence. Furthermore, apart from tumour mutational burden, no other predictive biomarker for monotherapy activity in paediatric tumours has been identified. Based on these observations, there is collective agreement that there is no scientific rationale for children to be enrolled in new monotherapy trials of additional checkpoint inhibitors with the same mechanism of action of agents already studied (e.g. anti-PD1, anti-PDL1 anti-CTLA-4) unless additional scientific knowledge supporting a different approach becomes available. This shared perspective, based on scientific evidence and supported by paediatric oncology cooperative groups, should inform companies on whether a paediatric development plan is justified. This could then be proposed to regulators through the available regulatory tools. Generally, an academic-industry consensus on the scientific merits of a proposal before submission of a paediatric investigational plan would be of great benefit to determine which studies have the highest probability of generating new insights. There is already a rationale for the evaluation of combinations of checkpoint inhibitors with other agents in paediatric Hodgkin lymphoma and hypermutated tumours in view of the activity shown as single agents. In paediatric tumours where no single agent activity has been observed in multiple clinical trials of anti-PD1, anti-PDL1 and anti-CTLA-4 agents as monotherapy, combinations of checkpoint inhibitors with other treatment modalities should be explored when a scientific rationale indicates that they could be efficacious in paediatric cancers and not because these combinations are being evaluated in adults. Immunotherapy in the form of engineered proteins (e.g. monoclonal antibodies and T cell engaging agents) and cellular products (e.g. CAR T cells) has great therapeutic potential for benefit in paediatric cancer. The major challenge for developing checkpoint inhibitors for paediatric cancers is the lack of neoantigens (based on mutations) and corresponding antigen-specific T cells. Progress critically depends on understanding the immune macroenvironment and microenvironment and the ability of the adaptive immune system to recognise paediatric cancers in the absence of high neoantigen burden. Future clinical studies of checkpoint inhibitors in children need to build upon strong biological hypotheses that take into account the distinctive immunobiology of childhood cancers in comparison to that of checkpoint inhibitor responsive adult cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2019.12.029DOI Listing
March 2020

Population Health: The Diabetes Educator's Evolving Role.

Diabetes Educ 2019 08 23;45(4):333-348. Epub 2019 Jun 23.

American Association of Diabetes Educators, Chicago, Illinois.

Purpose: The US health care system's focus on high-quality, efficient, and cost-effective care has led payers and provider groups to identify new models with a shift toward value-based care. This perspective on clinical practice describes the population health movement and the opportunities for diabetes educators beyond diabetes self-management education, as well as steps to engage in and drive new care models to demonstrate individual, organizational, and payer value.

Conclusion: Diabetes educators have an opportunity to position themselves as diabetes specialists for diabetes management, education, and population health care delivery. With expertise that extends beyond diabetes self-management education and with a wide variety of skills, diabetes educators recognize that there is a range of personal, social, economic, and environmental factors that influence diabetes health outcomes. Diabetes educators should align with organizational strategic plans and support the population-level performance measures and quality initiatives, thus enhancing the value that diabetes educators bring to health care organizations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0145721719857728DOI Listing
August 2019

Getting Well Again.

Authors:
Susan Weiner

Schizophr Bull 2019 Feb 26. Epub 2019 Feb 26.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbz010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505184PMC
February 2019

ACCELERATE and European Medicine Agency Paediatric Strategy Forum for medicinal product development for mature B-cell malignancies in children.

Eur J Cancer 2019 03 14;110:74-85. Epub 2019 Feb 14.

Janssen Research & Development, NJ, USA.

Paediatric Strategy Forums have been created by the multistakeholder organisation, ACCELERATE, and the European Medicines Agency to facilitate dialogue between all relevant stakeholders and suggest strategies in critical areas of paediatric oncology drug development. As there are many medicines being developed for B-cell malignancies in adults but comparatively few in children with these malignancies, a Paediatric Strategy Forum was held to discuss the best approach to develop these products for children. It was concluded that as current frontline therapy is highly successful, despite associated acute toxicity, de-escalation of this or substitution of presently used drugs with new medicines can only be undertaken when there is an effective salvage regimen, which is currently not available. Therefore priority should be given to developing treatment for patients with relapsed and refractory mature B-cell lymphomas. The consensus of the clinicians attending the meeting was that CAR T-cells, T-cell engagers and antibody drug conjugates (excluding those with a vinca alkaloid-like drug) presently have the greatest probability of providing benefit in relapse in view of their mechanism of action. However, as producing autologous CAR T-cells currently takes at least 4 weeks, they are not products which could be quickly employed initially at relapse in rapidly progressing mature B-cell malignancies but only for the consolidation phase of the treatment. Global, industry-supported, academic-sponsored studies testing compounds from different pharmaceutical companies simultaneously should be considered in rare populations, and it was proposed that an international working group be formed to develop an overarching clinical trials strategy for these disease groups. Future Forums are planned for other relevant paediatric oncologic diseases with a high unmet medical need and relevant molecular targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2019.01.013DOI Listing
March 2019

A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion.

J Cereb Blood Flow Metab 2018 12 7;38(12):2073-2091. Epub 2018 Sep 7.

1 Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Recent advances in stroke reperfusion therapies have led to remarkable improvement in clinical outcomes, but many patients remain severely disabled, due in part to the lack of effective neuroprotective strategies. In this review, we show that 95% of published preclinical studies on "neuroprotectants" (1990-2018) reported positive outcomes in animal models of ischemic stroke, while none translated to successful Phase III trials. There are many complex reasons for this failure in translational research, including that the majority of clinical trials did not test early delivery of neuroprotectants in combination with successful reperfusion. In contrast to the clinical trials, >80% of recent preclinical studies examined the neuroprotectant in animal models of transient ischemia with complete reperfusion. Furthermore, only a small fraction of preclinical studies included long-term functional assessments, aged animals of both genders, and models with stroke comorbidities. Recent clinical trials demonstrate that 70%-80% of patients treated with endovascular thrombectomy achieve successful reperfusion. These successes revive the opportunity to retest previously failed approaches, including cocktail drugs that target multiple injury phases and different cell types. It is our hope that neurovascular protectants can be retested in future stroke research studies with specific criteria outlined in this review to increase translational successes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0271678X18798162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282224PMC
December 2018

WASPnest: a worldwide assessment of social Polistine nesting behavior.

Ecology 2018 10 4;99(10):2405. Epub 2018 Sep 4.

Department of Neurobiology and Behavior, Cornell University, Ithaca, New York, 14853, USA.

Cooperative breeding decreases the direct reproductive output of subordinate individuals, but cooperation can be evolutionarily favored when there are challenges or constraints to breeding independently. Environmental factors, including temperature, precipitation, latitude, high seasonality, and environmental harshness have been hypothesized to correlate with the presence of cooperative breeding. However, to test the relationship between cooperation and ecological constraints requires comparative data on the frequency and variation of cooperative breeding across differing environments, ideally replicated across multiple species. Paper wasps are primitively social species, forming colonies composed of reproductively active dominants and foraging subordinates. Adult female wasps, referred to as foundresses, initiate new colonies. Nests can be formed by a single solitary foundress (noncooperative) or by multiple foundress associations (cooperative). Cooperative behavior varies within and among species, making paper wasps species well suited to disentangling ecological correlates of variation in cooperative behavior. This data set reports the frequency and extent of cooperative nest founding for 87 paper wasp species. Data were assembled from more than 170 published sources, previously unpublished field observations, and photographs contributed by citizen scientists to online natural history repositories. The data set includes 25,872 nest observations and reports the cooperative behavioral decisions for 45,297 foundresses. Species names were updated to reflect modern taxonomic revisions. The type of substrate on which the nest was built is also included, when available. A smaller population-level version of this data set found that the presence or absence of cooperative nesting in paper wasps was correlated with temperature stability and environmental harshness, but these variables did not predict the extent of cooperation within species. This expanded data set contains details about individual nests and further increases the power to address the relationship between the environment and the presence and extent of cooperative breeding. Beyond the ecological drivers of cooperation, these high-resolution data will be useful for future studies examining the evolutionary consequences of variation in social behavior. This data set may be used for research or educational purposes provided that this data paper is cited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ecy.2448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640739PMC
October 2018

THE MISSED DIAGNOSIS OF TYPE 1 DIABETES. When It's Not Just the Stomach Flu.

Diabetes Self Manag 2017 03;34(2):42-4, 47

View Article and Find Full Text PDF

Download full-text PDF

Source
March 2017

THE TRUTH ABOUT DIABULIMIA.

Authors:
Susan Weiner

Diabetes Self Manag 2017 Mar;34(2):32-35

View Article and Find Full Text PDF

Download full-text PDF

Source
March 2017

Reaffirming and Clarifying the American Society of Clinical Oncology's Policy Statement on the Critical Role of Phase I Trials in Cancer Research and Treatment.

J Clin Oncol 2017 01 28;35(2):139-140. Epub 2016 Nov 28.

Jeffrey S. Weber, New York University Langone Medical Center, New York, NY; Laura A. Levit, American Society of Clinical Oncology, Alexandria, VA; Peter C. Adamson, The Children's Hospital of Philadelphia, Philadelphia, PA; Suanna S. Bruinooge, American Society of Clinical Oncology, Alexandria, VA; Howard A. Burris III, Sarah Cannon Research Institute, Nashville, TN; Michael A. Carducci, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Adam P. Dicker, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA; Mithat Gönen, Memorial Sloan Kettering Cancer Center, New York, NY; Stephen M. Keefe, University of Pennsylvania, Philadelphia, PA; Michael A. Postow, Memorial Sloan Kettering Cancer Center, New York, NY; Michael A. Thompson, Aurora Health Care, Milwaukee, WI; David M. Waterhouse, Oncology Hematology Care, Cincinnati, OH; Susan L. Weiner, Children's Cause for Cancer Advocacy, Washington, DC; and Lynn M. Schuchter, University of Pennsylvania, Philadelphia, PA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2016.70.4692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559890PMC
January 2017

KITCHEN DETOX DECLUTTER AND ORGANIZE TO LOSE WEIGHT.

Authors:
Susan Weiner

Diabetes Self Manag 2016 Sep;33(5):74-76

View Article and Find Full Text PDF

Download full-text PDF

Source
September 2016

OPERATION DIABETES ORGANIZATION. Small Self-care Steps for Every Season.

Diabetes Self Manag 2016 Mar-Apr;33(2):44-7

View Article and Find Full Text PDF

Download full-text PDF

Source
July 2016

Different axes of environmental variation explain the presence vs. extent of cooperative nest founding associations in Polistes paper wasps.

Ecol Lett 2015 Oct 6;18(10):1057-67. Epub 2015 Aug 6.

Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI, 48109, USA.

Ecological constraints on independent breeding are recognised as major drivers of cooperative breeding across diverse lineages. How the prevalence and degree of cooperative breeding relates to ecological variation remains unresolved. Using a large data set of cooperative nesting in Polistes wasps we demonstrate that different aspects of cooperative breeding are likely to be driven by different aspects of climate. Whether or not a species forms cooperative groups is associated with greater short-term temperature fluctuations. In contrast, the number of cooperative foundresses increases in more benign environments with warmer, wetter conditions. The same data set reveals that intraspecific responses to climate variation do not mirror genus-wide trends and instead are highly heterogeneous among species. Collectively these data suggest that the ecological drivers that lead to the origin or loss of cooperation are different from those that influence the extent of its expression within populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ele.12488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564336PMC
October 2015

American Society of Clinical Oncology policy statement update: the critical role of phase I trials in cancer research and treatment.

J Clin Oncol 2015 Jan 15;33(3):278-84. Epub 2014 Dec 15.

Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; Laura A. Levit and Suanna Bruinooge, American Society of Clinical Oncology, Alexandria, VA; Peter C. Adamson, Children's Hospital of Philadelphia; Adam P. Dicker, Jefferson Medical College, Thomas Jefferson University; Stephen M. Keefe and Lynn M. Schuchter, University of Pennsylvania, Philadelphia, PA; Howard A. Burris IIII, Sarah Cannon Research Institute, Nashville, TN; Michael A. Carducci, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD; Mithat Gönen and Michael A. Postow, Memorial Sloan-Kettering Cancer Center, New York, NY; Michael A. Thompson, Aurora Health Care, Milwaukee, WI; David M. Waterhouse, Oncology Hematology Care, Cincinnati, OH; and Susan L. Weiner, Children's Cause for Cancer Advocacy, Washington, DC.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2014.58.2635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516884PMC
January 2015

For Wayne S. Fenton, in memoriam.

Authors:
Susan Weiner

Schizophr Bull 2014 Sep 10;40(5):949-51. Epub 2013 Dec 10.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbt175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133673PMC
September 2014

Six Pillars of Health.

Authors:
Susan Weiner

Schizophr Bull 2016 May 5;42(3):535-7. Epub 2013 Jul 5.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbt091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838074PMC
May 2016

A survey of DNA methylation across social insect species, life stages, and castes reveals abundant and caste-associated methylation in a primitively social wasp.

Naturwissenschaften 2013 Aug 21;100(8):795-9. Epub 2013 Jun 21.

Department of Ecology, Evolution, and Organismal Biology, Iowa State University, Ames, IA, USA.

DNA methylation plays an important role in the epigenetic control of developmental and behavioral plasticity, with connections to the generation of striking phenotypic differences between castes (larger, reproductive queens and smaller, non-reproductive workers) in honeybees and ants. Here, we provide the first comparative investigation of caste- and life stage-associated DNA methylation in several species of bees and vespid wasps displaying different levels of social organization. Our results reveal moderate levels of DNA methylation in most bees and wasps, with no clear relationship to the level of sociality. Strikingly, primitively social Polistes dominula paper wasps show unusually high overall DNA methylation and caste-related differences in site-specific methylation. These results suggest DNA methylation may play a role in the regulation of behavioral and physiological differences in primitively social species with more flexible caste differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00114-013-1064-zDOI Listing
August 2013

Epigenetics in social insects: a new direction for understanding the evolution of castes.

Genet Res Int 2012 28;2012:609810. Epub 2012 Mar 28.

Department of Ecology, Evolution, and Organismal Biology, Iowa State University, Ames, IA 50014, USA.

Epigenetic modifications to DNA, such as DNA methylation, can expand a genome's regulatory flexibility, and thus may contribute to the evolution of phenotypic plasticity. Recent work has demonstrated the importance of DNA methylation in alternative queen and worker "castes" in social insects, particularly honeybees. Social insects are an excellent system for addressing questions about epigenetics and evolution because: (1) they have dramatic caste polyphenisms that appear to be tied to differential methylation, (2) DNA methylation is widespread in various groups of social insects, and (3) there are intriguing connections between the social environment and DNA methylation in many species, from insects to mammals. In this article, we review research on honeybees, and, when available, other social insects, on DNA methylation and queen and worker caste differences. We outline a conceptual framework for the effects of methylation on caste determination in honeybees that may help guide studies of epigenetic regulation in other polyphenic taxa. Finally, we suggest future paths of study for social insect epigenetic research, including the importance of comparative studies of DNA methylation on a broader range of species, and highlight some key unanswered mechanistic questions about how DNA methylation affects gene regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2012/609810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335566PMC
August 2012

Pathways to brain tumor advocacy.

Cancer Treat Res 2009 ;150:375-88

Children's Brain Tumor Foundation, New York, NY 10016, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/b109924_25DOI Listing
September 2010

The energetic costs of stereotyped behavior in the paper wasp, Polistes dominulus.

Naturwissenschaften 2009 Feb 22;96(2):297-302. Epub 2008 Oct 22.

Department of Biology, Tufts University, Medford, MA 02155, USA.

Polistes wasps engage in many behavioral interactions. Although there has been debate over the meaning of these interactions, these stereotypical behaviors can be used to determine a colony's linear dominance hierarchy. Due to the implicit relationship between behavioral and reproductive dominance, behavioral interactions are commonly used to distinguish the reproductively dominant alpha foundress from the beta foundress. It has been suggested that in order to maintain reproductive control, the alpha foundress is forced to remain at a physiologically constrained activity limit. This, in turn, may allow aggressive interactions to be used as determinants influencing reproductive partitioning between cooperating individuals. Energetic costs can place important limitations on behavior, but the energetic cost of the interactions has not previously been measured. To address this, we measured the CO(2) production of 19 non-nestmate pairs displaying interactive and noninteractive behavior. The rate of energy used during interaction behavior was positively associated with published rankings of aggression. However, our results indicate that interactions are not very energetically costly in Polistes, particularly when compared to the likely cost of foraging. These data suggest that maintaining reproductive dominance is not very energetically expensive for the dominant and that the dominant foundress expends energy at a lower rate than the subordinate foundress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00114-008-0464-yDOI Listing
February 2009

Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: a Pediatric Brain Tumor Consortium report.

Neuro Oncol 2007 Apr 9;9(2):145-60. Epub 2007 Feb 9.

Department of Neurosurgery, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA.

This study estimated the maximum tolerated dose (MTD) of imatinib with irradiation in children with newly diagnosed brainstem gliomas, and those with recurrent malignant intracranial gliomas, stratified according to use of enzyme-inducing anticonvulsant drugs (EIACDs). In the brainstem glioma stratum, imatinib was initially administered twice daily during irradiation, but because of possible association with intratumoral hemorrhage (ITH) was subsequently started two weeks after irradiation. The protocol was also amended to exclude children with prior hemorrhage. Twenty-four evaluable patients received therapy before the amendment, and three of six with a brainstem tumor experienced dose-limiting toxicity (DLT): one had asymptomatic ITH, one had grade 4 neutropenia and, one had renal insufficiency. None of 18 patients with recurrent glioma experienced DLT. After protocol amendment, 3 of 16 patients with brainstem glioma and 2 of 11 patients with recurrent glioma who were not receiving EIACDs experienced ITH DLTs, with three patients being symptomatic. In addition to the six patients with hemorrhages during the DLT monitoring period, 10 experienced ITH (eight patients were symptomatic) thereafter. The recommended phase II dose for brainstem gliomas was 265 mg/m(2). Three of 27 patients with brainstem gliomas with imaging before and after irradiation, prior to receiving imatinib, had new hemorrhage, excluding their receiving imatinib. The MTD for recurrent high-grade gliomas without EIACDs was 465 mg/m(2), but the MTD was not established with EIACDs, with no DLTs at 800 mg/m(2). In summary, recommended phase II imatinib doses were determined for children with newly diagnosed brainstem glioma and recurrent high-grade glioma who were not receiving EIACDs. Imatinib may increase the risk of ITH, although the incidence of spontaneous hemorrhages in brainstem glioma is sufficiently high that this should be considered in studies of agents in which hemorrhage is a concern.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1215/15228517-2006-031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871662PMC
April 2007

Tissue collection for correlative studies in childhood cancer clinical trials: ethical considerations and special imperatives.

J Clin Oncol 2004 Dec;22(23):4846-50

National Cancer Institute, Cancer Therapy Evaluation Program, Rockville, MD 20892-7436, USA.

Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2004.02.138DOI Listing
December 2004
-->