Dendritic cells (DCs) develop in the bone marrow from haematopoietic progenitors that have numerous shared characteristics between mice and humans. Human counterparts of mouse DC progenitors have ...been identified by their shared transcriptional signatures and developmental potential. New findings continue to revise models of DC ontogeny but it is well accepted that DCs can be divided into two main functional groups. Classical DCs include type 1 and type 2 subsets, which can detect different pathogens, produce specific cytokines and present antigens to polarize mainly naive CD8
or CD4
T cells, respectively. By contrast, the function of plasmacytoid DCs is largely innate and restricted to the detection of viral infections and the production of type I interferon. Here, we discuss genetic models of mouse DC development and function that have aided in correlating ontogeny with function, as well as how these findings can be translated to human DCs and their progenitors.
Acute Myocardial Infarction Anderson, Jeffrey L; Morrow, David A
The New England journal of medicine,
05/2017, Volume:
376, Issue:
21
Journal Article
Peer reviewed
This review focuses on the initial presentation and in-hospital management of acute myocardial infarction, including selection of a management strategy and options for antithrombotic therapy.
Acute ...myocardial infarction with or without ST-segment elevation (STEMI or non-STEMI) is a common cardiac emergency, with the potential for substantial morbidity and mortality. The management of acute myocardial infarction has improved dramatically over the past three decades and continues to evolve. This review focuses on the initial presentation and in-hospital management of type 1 acute myocardial infarction.
Definition and Types
Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.
1
In practice, the disorder is diagnosed and assessed on the basis of clinical evaluation, the electrocardiogram (ECG), biochemical testing, invasive and noninvasive imaging, and . . .
Summary
Sleep reactivity is the trait‐like degree to which stress exposure disrupts sleep, resulting in difficulty falling and staying asleep. Individuals with highly reactive sleep systems ...experience drastic deterioration of sleep when stressed, whereas those with low sleep reactivity proceed largely unperturbed during stress. Research shows that genetics, familial history of insomnia, female gender and environmental stress influence how the sleep system responds to stress. Further work has identified neurobiological underpinnings for sleep reactivity involving disrupted cortical networks and dysregulation in the autonomic nervous system and hypothalamic‐pituitary‐adrenal axis. Sleep reactivity is most pathologically and clinically pertinent when in excess, such that high sleep reactivity predicts risk for future insomnia disorder, with early evidence suggesting high sleep reactivity corresponds to severe insomnia phenotypes (sleep onset insomnia and short sleep insomnia). High sleep reactivity is also linked to risk of shift‐work disorder, depression and anxiety. Importantly, stress‐related worry and rumination may exploit sensitive sleep systems, thereby augmenting the pathogenicity of sleep reactivity. With the development of cost‐effective assessment of sleep reactivity, we can now identify individuals at risk of future insomnia, shift‐work disorder and mental illness, thus identifying a target population for preventive intervention. Given that insomniacs with high sleep reactivity tend to present with severe insomnia phenotypes, patient sleep reactivity may inform triaging to different levels of treatment. Future research on sleep reactivity is needed to clarify its neurobiology, characterize its long‐term prospective associations with insomnia and shift‐work disorder phenotypes, and establish its prognostic value for mental illness and other non‐sleep disorders.
The most comprehensive history of Canadian military
intelligence and its influence on key military
operations
Canadian intelligence has become increasingly central to the
operations of the Canadian ...Armed Forces (CAF). Canadian
Military Intelligence: Operations and Evolution from the October
Crisis to the War in Afghanistan is the first comprehensive
history that examines the impact of tactical, operational, and
strategic intelligence on the Canadian military.
Drawing upon a wide range of original documents and interviews
with participants in specific operations, author David A. Charters
provides an inside perspective on the development of military
intelligence since the Second World War. He shows how intelligence
influenced key military operations, from domestic internal security
to peacekeeping efforts to high-intensity air campaigns-including
the October Crisis of 1970, the Oka Crisis, the Gulf War,
peacekeeping and enforcement operations in the Balkans, and the war
in Afghanistan. He describes how decades of experience, innovation,
and increasingly close cooperation with its Five Eyes and NATO
allies allowed Canada's military intelligence to punch above its
weight. Its tactical effectiveness and ability to overcome
challenges reshaped the outlook of military commanders, and
intelligence emerged from the margins to become a central feature
of military and defense operations.
Canadian Military Intelligence offers lessons from the
past and critical implications for future intelligence support with
the creation of the Canadian Forces Intelligence Command. This book
will be essential to both intelligence history and military history
readers and collections.
The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and ...T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2, but not Th17, cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite (HDM) challenge without affecting cytotoxic T lymphocyte (CTL), Th1 cell, or Th17 cell responses to herpes simplex virus, Toxoplasma gondii, and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity.
Display omitted
•Klf4 is required for the development of a subset of IRF4-expressing cDCs•Klf4 deletion results in reduced pre-cDCs•A specific Klf4-dependent subset can be identified in several tissues•Klf4fl/flItgax-cre mice have selectively impaired Th2 cell immunity
The IRF4-expressing cDCs subset is highly heterogeneous and has been implicated in priming Th17, as well as Th2 cell immunity. Murphy and colleagues dissect this heterogeneity showing a developmental requirement for Klf4 on specific subsets across several tissues. Moreover, Klf4 guides a transcriptional program necessary for Th2 cell immunity.
Estimates of crime’s burden inform public and private decisions about
crime-prevention measures. More than counts of criminal offenses, the aggregate
cost of crime conveys the scale of problems from ...crime and the value of
deterrence. This article offers an estimate of the total annual cost of crime in
the United States, including the direct costs of law enforcement, criminal
justice, and victims’ losses and the indirect costs of private deterrence, fear
and agony, and time lost to avoidance and recovery. The findings update
crime-cost estimates of past decades while expanding the scope of coverage to
include categories missing from past studies. The estimated annual cost of crime
is $4.71–$5.76 trillion including transfers from victims to criminals and
$2.86–$3.92 trillion net of transfers.
In a prospective 5-year study of women with breast cancer, pre-chemotherapy anti-Müllerian hormone concentration predicted long-term ovarian function.
Context:
Administration of chemotherapy to ...premenopausal women shortens their reproductive lifespan by depleting nonrenewable oocytes. Preservation of fertility is a priority for many such women, and identification of women at risk of infertility is therefore important. However, age is the only patient characteristic currently recognized to be predictive of long-term ovarian function after chemotherapy.
Objective:
Our objective was to assess markers of ovarian reserve and age as long-term predictors of ovarian function after chemotherapy.
Design and Setting:
We conducted a prospective, longitudinal study at a university hospital and research institute.
Patients:
Patients included women who were premenopausal at the time of diagnosis of early breast cancer.
Main Outcome Measures:
Ovarian function was assessed at 5 yr follow-up in relation to pretreatment hormonal and ultrasound markers of ovarian reserve.
Results:
Forty-two women received (neo-)adjuvant chemotherapy. Continuing menses 4–5 yr after diagnosis closely reflected ovarian activity as assessed by a range of serum markers, including estradiol, inhibin B, FSH, and anti-Müllerian hormone (AMH). Pretreatment serum AMH, FSH, antral follicle count, and age predicted late ovarian activity by univariate analysis. However, only AMH was predictive in a multivariate logistic regression (odds ratio = 13.0; 95% confidence interval = 2.5–66.7); 0.71 ng/ml gave peak likelihood ratio of 7.0 with 54% sensitivity and 92% specificity. Bone mineral density fell over the 4–5 yr after diagnosis with greater loss in women with lower ovarian activity. Higher pretreatment AMH was associated with lower bone mineral density at both lumbar spine and hip at 5 yr (P < 0.02).
Conclusion:
Measurement of AMH at cancer diagnosis predicts long-term ovarian function after chemotherapy. Use of this in clinical practice may allow better prediction of chemotherapy-related risk to future fertility.
Abstract
Background
The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries provide annual ...updates on cancer occurrence and trends by cancer type, sex, race, ethnicity, and age in the United States. This year’s report highlights the cancer burden among men and women age 20–49 years.
Methods
Incidence data for the years 1999 to 2015 from the Centers for Disease Control and Prevention- and National Cancer Institute–funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries and death data for the years 1999 to 2016 from the National Vital Statistics System were used. Trends in age-standardized incidence and death rates, estimated by joinpoint, were expressed as average annual percent change.
Results
Overall cancer incidence rates (per 100 000) for all ages during 2011–2015 were 494.3 among male patients and 420.5 among female patients; during the same time period, incidence rates decreased 2.1% (95% confidence interval CI = −2.6% to −1.6%) per year in men and were stable in females. Overall cancer death rates (per 100 000) for all ages during 2012–2016 were 193.1 among male patients and 137.7 among female patients. During 2012–2016, overall cancer death rates for all ages decreased 1.8% (95% CI = −1.8% to −1.8%) per year in male patients and 1.4% (95% CI = −1.4% to −1.4%) per year in females. Important changes in trends were stabilization of thyroid cancer incidence rates in women and rapid declines in death rates for melanoma of the skin (both sexes). Among adults age 20–49 years, overall cancer incidence rates were substantially lower among men (115.3 per 100 000) than among women (203.3 per 100 000); cancers with the highest incidence rates (per 100 000) among men were colon and rectum (13.1), testis (10.7), and melanoma of the skin (9.8), and among women were breast (73.2), thyroid (28.4), and melanoma of the skin (14.1). During 2011 to 2015, the incidence of all invasive cancers combined among adults age 20–49 years decreased −0.7% (95% CI = −1.0% to −0.4%) among men and increased among women (1.3%, 95% CI = 0.7% to 1.9%). The death rate for (per 100 000) adults age 20–49 years for all cancer sites combined during 2012 to 2016 was 22.8 among men and 27.1 among women; during the same time period, death rates decreased 2.3% (95% CI = −2.4% to −2.2%) per year among men and 1.7% (95% CI = −1.8% to −1.6%) per year among women.
Conclusions
Among people of all ages and ages 20–49 years, favorable as well as unfavorable trends in site-specific cancer incidence were observed, whereas trends in death rates were generally favorable. Characterizing the cancer burden may inform research and cancer-control efforts.
The study of murine dendritic cell (DC) development has been integral to the identification of specialized DC subsets that have unique requirements for their form and function. Advances in the field ...have also provided a framework for the identification of human DC counterparts, which appear to have conserved mechanisms of development and function. Multiple transcription factors are expressed in unique combinations that direct the development of classical DCs (cDCs), which include two major subsets known as cDC1s and cDC2s, and plasmacytoid DCs (pDCs). pDCs are potent producers of type I interferons and thus these cells are implicated in immune responses that depend on this cytokine. Mouse models deficient in the cDC1 lineage have revealed their importance in directing immune responses to intracellular bacteria, viruses, and cancer through the cross-presentation of cell-associated antigen. Models of transcription factor deficiency have been used to identify subsets of cDC2 that are required for T helper (Th)2 and Th17 responses to certain pathogens; however, no single factor is known to be absolutely required for the development of the complete cDC2 lineage. In this review, we will discuss the current state of knowledge of mouse and human DC development and function and highlight areas in the field that remain unresolved.
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