1UCD Conway Institute of Biomolecular and Biomedical Research, UCD School of Medicine and Medical Science (SMMS), Belfield, Dublin 4, Ireland ; Department of Surgery, Mater Misericordiae Hospital, Dublin 7, Ireland.
2UCD Conway Institute of Biomolecular and Biomedical Research, UCD School of Medicine and Medical Science (SMMS), Belfield, Dublin 4, Ireland.
3Department of Oncology, Mater Misericordiae Hospital, Dublin 7, Ireland.
4Department of Pathology, Mater Misericordiae Hospital, Dublin 7, Ireland.
5School of Pharmacy, Queens University Belfast, Belfast BT7 1NN, UK.
6Department of Surgery, Mater Misericordiae Hospital, Dublin 7, Ireland.
Treatment options for women presenting with triplenegative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype.
SCOPE OF REVIEW:
How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed.
Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome.
Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy.
"Libya’s descent into chaos began with a rushed decision to go to war, made in what one top official called a “shadow of uncertainty” as to Colonel Qaddafi’s intentions. The mission inexorably evolved even as Mrs. Clinton foresaw some of the hazards of toppling another Middle Eastern strongman. She pressed for a secret American program that supplied arms to rebel militias, an effort never before confirmed.
Only after Colonel Qaddafi fell and what one American diplomat called “the endorphins of revolution” faded did it become clear that Libya’s new leaders were unequal to the task of unifying the country, and that the elections Mrs. Clinton and President Obama pointed to as proof of success only deepened Libya’s divisions.
Now Libya, with a population smaller than that of Tennessee, poses an outsize security threat to the region and beyond, calling into question whether the intervention prevented a humanitarian catastrophe or merely helped create one of a different kind."
1From the Department of Pathology, Weill Cornell Medical College, New York, New York (Dr Borczuk); and the Department of Pathology, The University of Texas Medical Branch, Galveston (Dr Allen).
The success of immune checkpoint inhibitor therapy in lung cancer, both in squamous and nonsquamous non-small cell carcinoma, has led to US Food and Drug Administration approval for 2 medications that have as part of their prescribing information an associated immunohistochemistry-based companion or complementary diagnostic test for programmed death ligand 1 (PD-L1). The intense interest in drug development in this area has resulted in additional agents with associated diagnostics looming on the horizon in 2016. In the era of precision medicine, the paradigm of paired molecular target and molecular test, which serves a model of oncogenic mutation-driven cancer therapy, is challenged by the proliferation of immunohistochemistry-based tests with different antibodies, instruments, and scoring. The difficulty inherent to targeted therapy aimed at a moving target is discussed, as well as the emerging challenges to pathologists and oncologists who seek to optimize care in this complex therapeutic arena.
1Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York. Electronic address: firstname.lastname@example.org.
2Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York.
3Department of Biology, Yeshiva University, New York, New York.
4Department of Biology, Yeshiva University, New York, New York. Electronic address: email@example.com.
Detection of mutational alterations is important for guiding treatment decisions of lung non-small-cell carcinomas and thyroid nodules with atypical cytologic findings. Inoperable lung tumors requiring further testing for staging and thyroid lesions often are diagnosed using only cytology material.Molecular diagnostic tests of these samples typically are performed on cell blocks; however, insufficient cellularity of cell blocks is a limitation for test performance. In addition, some of the fixatives used while preparing cell blocks often introduces artifacts for mutation detection. Here, we applied qClamp xenonucleic technology and quantitative RT-PCR to cells microdissected directly from stained cytology smears to detect common alterations including mutations and translocations in non-small-cell carcinomas and thyroid lesions. By using this approach, we achieved a 1%molecular alteration detection rate from as few as 50 cells. Ultrasensitive methods of molecular alteration detection similar to the one described here will be increasingly important for the evaluation of molecular alterations in clinical scenarios when only small tissue samples are available.
"Since they are less likely to remember what their last meal consisted of, how much they’ve eaten, as well as when that dining event occurred, they seldom feel satiated enough, and are therefore much more predisposed to consuming more calories than they should.
They are more susceptible to eating frequently or snacking several times per day, without even realizing it, and as a result they end up packing on an even more pounds.
In a way, this is similar to the way people tend to have more meals if they dine while being distracted by the TV, simply because they don’t concentrate enough on the food they’re ingesting."
1Department of Medicine, Penn State College of Medicine, Columbia University; Department of Medicine, Penn State Hershey Medical Center, Columbia University; Department of Public Health Sciences, Penn State College of Medicine, Columbia University. Electronic address: firstname.lastname@example.org.
2Department of Medicine, Penn State College of Medicine, Columbia University; Department of Medicine, Penn State Hershey Medical Center, Columbia University; Department of Public Health Sciences, Penn State College of Medicine, Columbia University.
3Department of Medicine, Penn State College of Medicine, Columbia University.
4Department of Medicine, Penn State College of Medicine, Columbia University; Department of Public Health Sciences, Penn State College of Medicine, Columbia University.
5Department of Public Health Sciences, Penn State College of Medicine, Columbia University.
6Department of Medicine, Penn State Hershey Medical Center, Columbia University.
7Department of Applied Physiology, Columbia University.
The relationship between strength training (ST) behavior and mortality remains understudied in large, national samples, although smaller studies have observed that greater amounts of muscle strength are associated with lower risks of death. We aimed to understand the association between meeting ST guidelines and future mortality in an older US adult population.
Data were analyzed from the 1997-2001 National Health Interview Survey (NHIS) linked to death certificate data in the National Death Index. The main independent variable was guideline-concordant ST (i.e. twice each week) and dependent variable was all-cause mortality. Covariates identified in the literature and included in our analysis were demographics, past medical history, and other health behaviors (including other physical activity). Given our aim to understand outcomes in older adults, analyses were limited to adults age 65 years and older. Multivariate analysis was conducted using multiple logistic regression analysis.
During the study period, 9.6% of NHIS adults age 65 and older (N=30,162) reported doing guideline-concordant ST and 31.6% died. Older adults who reported guideline-concordant ST had 46% lower odds of all-cause mortality than those who did not (adjusted odds ratio: 0.64; 95% CI: 0.57, 0.70; p<0.001). The association between ST and death remained after adjustment for past medical history and health behaviors.
Although a minority of older US adults met ST recommendations, guideline-concordant ST is significantly associated with decreased overall mortality. All-cause mortality may be significantly reduced through the identification of and engagement in guideline-concordant ST interventions by older adults.
1Research Applications Laboratory, National Center for Atmospheric Research, Boulder, Colorado; Center for Science and Technology Policy Research, University of Colorado Boulder, Boulder, Colorado; University of Arizona, Tucson, Arizona email@example.com.
2Research Applications Laboratory, National Center for Atmospheric Research, Boulder, Colorado; Center for Science and Technology Policy Research, University of Colorado Boulder, Boulder, Colorado; University of Arizona, Tucson, Arizona.
Mosquito-borne illnesses like WestNile virus (WNV) and dengue are growing threats to the United States. Proactive mosquito control is one strategy to reduce the risk of disease transmission. In 2012, we measured the public's willingness to pay (WTP) for increased mosquito control in two cities: Key West, FL, where there have been recent dengue outbreaks, and Tucson, AZ, where dengue vectors are established and WNV has been circulating for over a decade. Nearly three quarters of respondents in both cities (74% in Tucson and 73% in Key West) would be willing to pay $25 or more annually toward an increase in publicly funded mosquito control efforts. WTP was positively associated with income (both cities), education (Key West), and perceived mosquito abundance (Tucson). Concerns about environmental impacts of mosquito control were associated with lower WTP in Key West. Expanded mosquito control efforts should incorporate public opinion as they respond to evolving disease risks.
I consider the current state of pharmaceutical marketing vis-à-vis ethical and legal standards and advocate measures to improve it. There is abundant evidence of unethical or illicit marketing. It fuels growing concerns about undue corporate influence over pharmaceutical research, education, and consumption. The most extensive evidence of industry transgressions comes from the United States (US), where whistle-blowers are encouraged by financial rewards to help uncover illicit marketing and fraud. Outside the US increasing evidence of transgressions exists. Recently I have observed a range of new measures to align pharmaceutical marketing practices with ethical and legal standards. In the interest of public health, I highlight the need for additional and more profound reforms to ensure that information about medicines supports quality and resource-efficient care.
Starting next week, the city will require chain restaurants to place salt-shaker warnings on menus beside items with 2,300 milligrams of sodium or more.
But perhaps worse yet, the science behind the regulation is inconclusive. A week before the judge’s ruling, the National Restaurant Association received some good news in the form of a paper by two influential Columbia University professors and one former board member of the New York City Department of Health. The study, a meta-analysis of more than three decades of sodium studies, concluded no scientific consensus has coalesced around the hypothesis that lowering one’s salt intake had “population benefits.”
1Personal Social Services Research Unit, London School of Economics and Political Science, London, UK.
2School of Social Work, Michigan State University, East Lansing, Michigan, USA.
It is often asserted that older people's quality of life (QOL) is improved when they adopt information and communication technology (ICT) such as the Internet, mobile phones and computers. Similar assumptions are made about older people's use of ICT-based care such as telecare and telehealth. To examine the evidence around these claims, we conducted a scoping review of the academic and grey literature, coving the period between January 2007 and August 2014. A framework analysis approach, based on six domains of QOL derived from the ASCOT and WHOQOL models, was adopted to deductively code and analyse relevant literature. The review revealed mixed results. Older people's use of ICT in both mainstream and care contexts has been shown to have both positive and negative impacts on several aspects of QOL. Studies which have rigorously assessed the impact of older people's use of ICT on their QOL mostly demonstrate little effect. A number of qualitative studies have reported on the positive effects for older people who use ICT such as email or Skype to keep in touch with family and friends. Overall, the review unearthed several inconsistencies around the effects of older people's ICT use on their QOL, suggesting that implicit agreement is needed on the best research methods and instrumentation to adequately describe older people's experiences in today's digital age. Moreover, the available evidence does not consider the large number of older people who do not use ICT and how non-use affects QOL.
Chris Christie trumped Marco Rubio's big day by endorsing The Donald.
"So what card does Trump play to deflate Rubio-mentum? Christie – Rubio's tormentor, who authored the lowest point of his political career. Christie, whose presumed last act in this race had been what my colleague David Catanese memorably called a political "suicide-bomber" attack on robotic Rubio. Christie, who Trump has unveiled like a presumed dead comic book villain who suddenly appears alive and angry. Christie is Rubio's personal zombie apocalypse."
1From the Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (Drs Romano and Blessing); and the Department of Pathology, University of Texas Medical Branch, Galveston, Texas (Dr Allen).
In the June 2011 edition of CAP Today, then-College of American Pathologists (CAP) President Stephen N. Bauer, MD, authored an article titled “50 Ways to Leave the Basement.”1 In addition to challenging pathologists and laboratory professionals to redefine pathology for our clinical colleagues, patients, and the public, the article provided specific examples of how to do so. One particular line stands out: “To secure our place in the evolving landscape, we must become aggressive intellectual and economic capitalists.”Aggressive, one might say, is too strong or that it connotes adversarial undertones, but aggressive we must become, as we calmly and confidently guide a detailed, well-informed dialogue highlighting our critical role in patient care. We are physicians after all, having been educated alongside colleagues who went on to become internists, neurosurgeons, and radiologists to name a few. However, legislators, clinicians, and patients are often unclear on the role of pathology as a specialty and our ability to direct cost-effective, quality care by merging diagnostic skills with guidance on ancillary testing and patient management. Similarly, as pathologists, we are often unaware of the potential effect we can and should have on the changing face of medicine. We can accomplish our collective goals and take an active stand in the evolution of health care by focusing on 3 primary objectives—that is, to educate, to motivate, and to cultivate. This article will focus on applying those objectives within the arena of health care policy.
"The endorsement by Mr. Christie, a not unblemished but still highly regarded figure within the party’s elite — he is a former chairman of the Republican Governors Association — landed Friday with crippling force. It was by far the most important defection to Mr. Trump’s insurgency: Mr. Christie may give cover to other Republicans tempted to join Mr. Trump rather than trying to beat him. Not just the Stop Trump forces seemed in peril, but also the traditional party establishment itself.
Should Mr. Trump clinch the presidential nomination, it would represent a rout of historic proportions for the institutional Republican Party, and could set off an internal rift unseen in either party for a half-century, since white Southerners abandoned the Democratic Party en masse during the civil rights movement."
Heidegger has powerful adherents in societies as disparate as Russia and Iran. If liberal democracies are to reckon with his followers, they must wrestle with his thought.
"The radical discontent that Heidegger’s followers articulate poses a challenge that transcends the normal limits of Left and Right in the political life of mature liberal democracies. Even the extremes of normal political partisanship fall well within the target of Heidegger’s critique. Liberals should acknowledge the genuine, practical limits to universalism by drawing from the rich tradition of liberalism itself—Tocqueville and Montesquieu, to name only two. They should also draw from the deep wells of classical political rationalism that long predate liberalism in order to respond to the grievances raised by the Heideggerians. The post-Heideggerian political thought and activity of Václav Havel might provide an inspiring model for such a recovery. In doing so, however, liberals must insist on the dignity that derives from our common human nature, which is, indeed, foundational to the liberal order. This common nature is discerned, and its dignity confirmed, by our rational capacities.
Heideggerian challenges to the late-modern, Western political order will have to be met with the courage that liberal democracies have summoned in their own defense in the past. But they must be understood for what they are, and be met with good sense and prudence—hence the need for a reckoning with Heidegger’s thought."
1Medical Image Optimisation and Perception Group (MIOPeG), Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, Room M213, 75 East Street, Lidcombe, Sydney, NSW 2141, Australia. Electronic address: firstname.lastname@example.org.
2Medical Image Optimisation and Perception Group (MIOPeG), Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, Room M213, 75 East Street, Lidcombe, Sydney, NSW 2141, Australia.
3Institute of Physics, London, United Kingdom.
4Chrissie Tomlinson Memorial Hospital, George Town, Cayman Islands; University of Bern, Bern, Switzerland.
RATIONALE AND OBJECTIVES:
This research investigates whether an expectation of abnormality and prior knowledge might potentially influence the decision-making of radiologists, and discusses the implications for radiological expert witness testimony.
MATERIALS AND METHODS:
This study was a web-based perception experiment. A total of 12 board-certified radiologists were asked to interpret 40 adult chest images (20 abnormal) twice and decide if pulmonary lesions were present. Before the first viewing, a general clinical history was given for all images: cough for 3+ weeks. This was called the "defendants read." Two weeks later, the radiologists were asked to view the same dataset (unaware that the dataset was unchanged). For this reading, the radiologists were given the following information for all images: "These images were reported normal but all of these patients have a lung tumour diagnosed on a subsequent radiograph 6 months later." They were also given the lobar location of the newly diagnosed tumor. This was called the "expert witness read."
There was a significant difference in location-based sensitivity (W = -45, P = 0.02) between the two conditions with nodule detection increasing under the second condition. Specificity increased outside the lobe of interest (W = 727, P = < 0.0001) and decreased within the lobe of interest (W = -237, P = 0.03) significantly in the "expert witness" read. Case-based sensitivity and case-based specificity were unaffected.
This study showed evidence that increased clinical information affects the performance of radiologists. This effect may bias expert witnesses in radiological malpractice litigation.
1Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
3Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
The extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA) were evaluated. Participants were 6,899 women from the Swedish Twin Study of Adults: Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the coexpression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN.
1a Gender and Cultural Studies, Simmons College , Boston , Massachusetts , USA.
To illustrate the challenge of political organizing that grapples with identity politics and inclusion, I focus on two women-centered annual events with very different politics of inclusion: the Michigan Womyn's Music Festival and the Boston Dyke March.
(1) arguments made by marginalized people for inclusion into established oppressed identity groups must be constructed with due care to avoid further marginalizing yet other liminal identities; (2) protesting/boycotting other oppressed groups for the purpose of achieving inclusion is often a problematic strategy; (3) the most effective strategy for honoring all people is to support organizations committed to the ideal of inclusion.
1a Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University , North Ryde , Australia.
2b Research Unit for General Practice, Uni Research Health, University of Bergen , Bergen , Norway.
3c Department of Global Public Health and Primary Care , University of Bergen , Bergen , Norway.
4d Department of Thoracic Medicine , Haukeland University Hospital , Bergen , Norway.
5e Regional Centre of Excellence for Palliative Care, Haukeland University Hospital , Bergen , Norway.
6f Department of Clinical Medicine , University of Bergen , Bergen , Norway.
In the end stages of life, drug treatment goals shift to symptom control and quality of life and as such changes in drug utilization are expected. The aim of this paper is to review the extent to which costs are considered in drug utilization research at the end of life, with a particular focus on the outcome measures being used. This systematic review identified seven studies across varied settings studies reporting both drug utilization and medication cost outcome measures. The main factors identified that impacted medication use and cost were the time period considered and the provision of specialist palliative care services. Combining drug utilization and medication cost outcomes is critical for the allocation of healthcare resources and the development of a sound health policy.
1Division of Neonatal-Perinatal Medicine, Yale School of Medicine, New Haven, CT. Electronic address: email@example.com.
Pregnancy in an early adolescent carries with it specific ethical considerations, in some ways different from pregnancy in an adult and from medical care of a non-pregnant adolescent. Obstetrical ethics emphasizes the right of the patient to autonomy and bodily integrity, including the right to refuse medical intervention. Pediatric ethics recognizes the right of parents, within limits, to make medical decisions for their children, and the right of a child to receive medical or surgical interventions likely to be of benefit to her, sometimes over her own objections. As the child gets older, and particularly during the years of adolescence, there is also a recognition of the right to an increasingly prominent role in decisions about her own healthcare. Pediatric obstetrical ethics, referring to ethical decisions made by, with, and for pregnant early adolescents, represents the intersection of these different cultures. Principles and approaches from both obstetrical and pediatric ethics, as well as a unified understanding of rights, obligations, and practical considerations, will be needed.