Search

In recent years, leaders in a number of nations have undermined their public sector's capacity to deliver on its core goals. To understand this interference, it is necessary to examine the formal and informal organizational dynamics at play within bureaucracies. Considering a widely applicable generalized organization, a formal model outlines how a leader may augment the career incentives of supervisors and lower-level workers, which shifts the alignment of policy with an organization's central mission. While hierarchy may amplify disruption, organizational culture can coalesce as a norm facilitating resistance to extreme shifts, thereby stabilizing long-term mission compliance. Yet, should disruption lead to an exodus of mission-driven employees, durable reversals of an organization's capacity to fulfill its aims may ensue. The model highlights three trajectories disrupted organizations follow: temporary reversal, erosion, and resistance. Implications are considered for public sector institutions and international organizations as well as for the study of bureaucratic and state capacities. [ABSTRACT FROM AUTHOR]

The text introduces the Data Challenge Expo 2019, an annual event sponsored by the American Statistical Association. The challenge involves analyzing a data set from the New York City Housing and Vacancy Survey. Participants were asked to explore various research questions related to housing conditions, rent control, gentrification, immigrant residency, and the costs and benefits of renting versus owning in New York City. The winners of the challenge were announced at the Joint Statistical Meetings in 2019, and their analyses are described in this special issue of Computational Statistics. Supplementary materials, including data sets and code, are available for reproducibility purposes. [Extracted from the article]

Immune checkpoint inhibitors (ICIs) are approved for the treatment of a variety of cancer types. The doses of these drugs, though approved by the Food and Drug Administration (FDA), have never been optimised, likely leading to significantly higher doses than required for optimal efficacy. Dose optimisation would hypothetically decrease the risk, severity, and duration of immune-related adverse events, as well as provide an opportunity to reduce costs through interventional pharmacoeconomic strategies such as off-label dose reductions or less frequent dosing. We summarise existing evidence for ICI dose optimisation to advocate for the role of interventional pharmacoeconomics. [ABSTRACT FROM AUTHOR]

Importance: Although durable left ventricular assist device (LVAD) therapy has emerged as an important treatment option for patients with advanced heart failure refractory to pharmacological support, outcomes, including survival, beyond 2 years remain poorly characterized.Objective: To report the composite end point of survival to transplant, recovery, or LVAD support free of debilitating stroke (Modified Rankin Scale score >3) or reoperation to replace the pump 5 years after the implant in participants who received the fully magnetically levitated centrifugal-flow HeartMate 3 or axial-flow HeartMate II LVAD in the MOMENTUM 3 randomized trial and were still receiving LVAD therapy at the 2-year follow-up.Design, Setting, and Participants: This observational study was a 5-year follow-up of the MOMENTUM 3 trial, conducted in 69 US centers, that demonstrated superiority of the centrifugal-flow LVAD to the axial-flow pump with respect to survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump at 2 years. A total of 295 patients were enrolled between June 2019 to April 2021 in the extended-phase study, with 5-year follow-up completed in September 2021.Exposures: Of 1020 patients in the investigational device exemption per-protocol population, 536 were still receiving LVAD support at 2 years, of whom 289 received the centrifugal-flow pump and 247 received the axial-flow pump.Main Outcomes and Measures: There were 10 end points evaluated at 5 years in the per-protocol population, including a composite of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump between the centrifugal-flow and axial-flow pump groups and overall survival between the 2 groups.Results: A total of 477 patients (295 enrolled and 182 provided limited data) of 536 patients still receiving LVAD support at 2 years contributed to the extended-phase analysis (median age, 62 y; 86 [18%] women). The 5-year Kaplan-Meier estimate of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump in the centrifugal-flow vs axial-flow group was 54.0% vs 29.7% (hazard ratio, 0.55 [95% CI, 0.45-0.67]; P < .001). Overall Kaplan-Meier survival was 58.4% in the centrifugal-flow group vs 43.7% in the axial-flow group (hazard ratio, 0.72 [95% CI, 0.58-0.89]; P = .003). Serious adverse events of stroke, bleeding, and pump thrombosis were less frequent in the centrifugal-flow pump group.Conclusions and Relevance: In this observational follow-up study of patients from the MOMENTUM 3 randomized trial, per-protocol analyses found that receipt of a fully magnetically levitated centrifugal-flow LVAD vs axial-flow LVAD was associated with a better composite outcome and higher likelihood of overall survival at 5 years. These findings support the use of the fully magnetically levitated LVAD.Trial Registration: ClinicalTrials.gov Identifier: NCT02224755 and NCT03982979. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring (TDM) involves frequent measurements of drug concentrations to ensure levels remain within a therapeutic window, and it is especially useful for drugs with narrow therapeutic indices or extensive interindividual pharmacokinetic variability. This technique has never been applied to immuno‐oncology drugs, but, given recent examinations of clinical data (both exposure and response) on a number of these drugs, further investigations into TDM may be justified to reduce costs as well as potentially reducing the severity and/or duration of immune‐related adverse events. Specifically, all but one of the approved PD‐1 and PD‐L1 inhibitors (pembrolizumab, nivolumab, cemiplimab‐rwlc, atezolizumab, avelumab, durvalumab) have been shown to exhibit a plateaued exposure‐response (E‐R) curve at doses evaluated extensively to date, as well as time‐dependent changes in drug exposure. Furthermore, responders have a greater decrease in drug clearance over time and would, therefore, have supratherapeutic serum concentrations. With frequent trough measurements, it is possible to use pharmacokinetic modelling and simulation to estimate drug clearance via Bayesian methods. Based on patient‐specific estimates for clearance, optimal alternative dosing strategies can be simulated to lower drug and cost burden yet maintain therapeutic levels, especially as the clearance of the drug decreases over time. This review will comprehensively discuss each of the FDA approved PD‐1, PD‐L1/2 and CTLA‐4 inhibitors regarding their indications and current recommended dosing, with evidence supporting the investigation of these types of TDM strategies. [ABSTRACT FROM AUTHOR]

Background: Decision‐making regarding adjuvant chemotherapy for early‐stage breast cancer can be guided by genomic assays such as OncotypeDX. The concordance of expected clinical decisions guided by OncotypeDX and prognostication online tools such as PREDICT is unknown. Methods: We performed a retrospective single‐center cohort study comprising all women with estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative, node negative disease, whose tumors were sent for OncotypeDX analysis. Expected decision on adjuvant chemotherapy was evaluated using OncotypeDX and using PREDICT. The concordance between these two tools was calculated. The impact on concordance of prespecified features was assessed, including age, tumor size, intensity of ER and progesterone receptor (PR), grade, Ki67 and perineural and lymphovascular invasion. Results: A total of 445 women were included. Overall concordance was 75% (K = 0.284). The concordance was significantly higher for grade 1 disease compared to grade 2‐3 (93% vs 72%, P <.001), tumor ≤ 1 cm compared to >1 cm (85% vs 72%, P =.009), PR positive compared to PR negative (78% vs 58%, P <.001) and ki67 < 10% compared to ≥10% (92% vs 63%, P <.001). The intensity of ER and the presence of perineural or lymphovascular invasion had no significant impact on concordance. Conclusions: Compared to PREDICT, using OncotypeDx in node negative, ER positive disease is expected to change the clinical decision in a quarter of patients. The concordance between OncotypeDx and PREDICT is influenced by pathological features. In patients with very low risk, treatment decisions may be made based solely on clinical risk assessment. [ABSTRACT FROM AUTHOR]

We are entering 2021 with an expanding and effective COVID-19 vaccine armamentarium. Recent interim results from COVID-19 vaccine trials, including more than 80,000 participants worldwide, demonstrate remarkable efficacy and low rate of serious adverse events. Based on experience with other vaccines in transplant recipients and knowing the risk of severe COVID-19 in this population, we believe that COVID-19 vaccines provide potential benefit with minimal risk. We strongly support and encourage COVID-19 vaccination of our transplant recipients. [ABSTRACT FROM AUTHOR]

A quantitative model of the mobility of ligand-presenting particles at the interface is pivotal to understanding important systems in biology and nanotechnology. In this work, we investigate the emerging dynamics of particles featuring ligands that selectively bind receptors decorating an interface. The formation of a ligand–receptor complex leads to a molecular bridge anchoring the particle to the surface. We consider systems with reversible bridges in which ligand–receptor pairs bind/unbind with finite reaction rates. For a given set of bridges, the particle can explore a tiny fraction of the surface as the extensivity of the bridges is finite. We show how, at timescales longer than the bridges' lifetime, the average position of the particle diffuses away from its initial value. We distill our findings into two analytic equations for the sliding diffusion constant of particles carrying mobile and fixed ligands. We quantitatively validate our theoretical predictions using reaction–diffusion simulations. We compare our findings with results from recent literature studies and discuss the molecular parameters that likely affect the particle's mobility most. Our results, along with recent literature studies, will allow inferring the microscopic parameters at play in complex biological systems from experimental trajectories. [ABSTRACT FROM AUTHOR]

The population pharmacokinetics of atezolizumab demonstrate that the trough concentrations are well above the putative target of 6 µg/ml. Thus, alternative dosing schedules are indeed of interest, focusing on reducing the frequency to allow greater patient convenience and reduced costs. [ABSTRACT FROM AUTHOR]

Background Primary outcomes analysis of the Multicenter Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3 (MOMENTUM 3) trial short-term cohort demonstrated a higher survival rate free of debilitating stroke and reoperation to replace/remove the device (primary end-point) in patients receiving the HeartMate 3 (HM3) compared with the HeartMate (HMII). In this study we sought to evaluate the individual and interactive effects of pre-specified patient subgroups (age, sex, race, therapeutic intent [bridge to transplant/bridge to candidacy/destination therapy] and severity of illness) on primary end-point outcomes in MOMENTUM 3 patients implanted with HM3 and HMII devices. Methods Cox proportional hazard models were used to analyze patients enrolled in the “as-treated cohort” ( n = 289) of the MOMENTUM 3 trial to: (1) determine interaction of various subgroups on primary end-point outcomes; and (2) identify independent variables associated with primary end-point success. Results Baseline characteristics were well balanced among HM3 ( n = 151) and HMII ( n = 138) cohorts. No significant interaction between the sub-groups on primary end-point outcomes was observed. Cox multivariable modeling identified age (≤65 years vs >65 years, hazard ratio 0.42 [95% confidence interval 0.22 to 0.78], p = 0.006]) and pump type (HM3 vs HMII, hazard ratio 0.53 [95% confidence interval 0.30 to 0.96], p = 0.034) to be independent predictors of primary outcomes success. After adjusting for age, no significant impact of sex, race, therapeutic intent and INTERMACS profiles on primary outcomes were observed. Conclusions This analysis of MOMENTUM 3 suggests that younger age (≤65 years) at implant and pump choice are associated with a greater likelihood of primary end-point success. These findings further suggest that characterization of therapeutic intent into discrete bridge-to-transplant and destination therapy categories offers no clear clinical advantage, and should ideally be abandoned. [ABSTRACT FROM AUTHOR]

For each integer t > 0 and each simple Lie algebra g, we determine the least dimension of an irreducible highest weight representation of g whose highest weight has width t. As a consequence, we classify all irreducible modules whose dimension equals a product of two primes. This consequence, which was in fact the driving force behind our paper, answers a question of N. Katz. [ABSTRACT FROM AUTHOR]

The KEYNOTE 024 trial compared the safety and efficacy of pembrolizumab versus chemotherapy in the first line setting of PD‐L1 positive metastatic NSCLC and suggested an impressive survival benefit with pembrolizumab. The high level of censoring in the trial casts considerable uncertainty on the actual magnitude of the benefit provided with this treatment. [ABSTRACT FROM AUTHOR]

New tools to assess the value of cancer drugs are not sufficiently detailed. Economic modeling provides the ideal method with which to assess their value. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been reported to cause euglycemic diabetic ketoacidosis (eDKA), a diagnosis that may be challenging to establish in the emergency department (ED).Case Report: This is a case report of missed eDKA in a 47-year-old male taking empagliflozin (a SGLT2 inhibitor) that presented to the ED with generalized weakness. His past medical history included multiple sclerosis (MS) diagnosed 4 years ago and type 2 diabetes mellitus. The patient attributed his weakness to MS. His neurologist was consulted and agreed with the plan to discharge the patient with diagnoses of asthenia and dehydration and a prescription of prednisone. The patient returned to the ED the next day with similar symptoms and was admitted to the hospital for treatment of eDKA. He was eventually treated per the hospital diabetic ketoacidosis (DKA) protocol and discharged home with instructions to discontinue empagliflozin. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The increasing utilization of SGLT2 inhibitor in patients with type 2 diabetes mellitus will inevitably lead to more cases of eDKA seen in the ED. Emergency physicians need to consider this diagnosis in patients taking these medications that present with symptoms including weakness, nausea, vomiting, abdominal pain, and dehydration. Patients taking these medications should be warned about these symptoms, especially because they may be falsely reassured by relatively low plasma glucose levels on home glucometer readings. [ABSTRACT FROM AUTHOR]

The author discusses the concept of quality-adjusted life-years (QALY) in relation to cost-effectiveness analysis. Topics include the use of the five-dimensional instrument from EuroQol (EQ-5D) to understand quality of life, the need for the assessment of value of medicines through QALYs, and the usage of high-quality economic modeling to answer criticism against cost-effective analysis.

We investigate whether beliefs about the income distribution are associated with political positions for or against redistribution. Using a novel elicitation method, we assess individuals' beliefs about the shape of the income distribution in the United States. We find that respondents' beliefs approximate the actual distribution on average. However they tend to overestimate the median income and underestimate the level of inequality. Surprisingly we find that beliefs about overall inequality, measured in terms of income dispersion, play only a marginal role in political positions as well as prospects of future wealth. Political preferences, however, are predicted by first, beliefs about the level of income of the poorest members of society, and second, a belief in an open society with equal opportunities for all. Support for redistribution is lower for people who give higher estimates of the income level of the poorest members of society and for people who perceive that opportunities for upward mobility are available. [ABSTRACT FROM AUTHOR]

In the introduction to this theme section we attempt to disentangle the webs of in/visibility and in/security by tracing out their diverse iterations. We construct a series of conversations between two of the four key terms relevant to this discussion--security and insecurity, visibility and invisibility--as a means of analyzing the different ways in which their various articulations engage meaningfully in the production and reproduction of contemporary security cultures. Ethnographic examples accompany each iteration, drawn from the work of contributors to this theme section, as well as from other contemporary research. These examples not only illustrate the multiple and shifting intersections of in/visibility and in/security in today's security-minded world but also remind us of the unique contributions that anthropology can make to the critical study of security. In the introduction to this theme section we attempt to disentangle the webs of in/visibility and in/security by tracing out their diverse iterations. We construct a series of conversations between two of the four key terms relevant to this discussion--security and insecurity, visibility and invisibility--as a means of analyzing the different ways in which their various articulations engage meaningfully in the production and reproduction of contemporary security cultures. Ethnographic examples accompany each iteration, drawn from the work of contributors to this theme section, as well as from other contemporary research. These examples not only illustrate the multiple and shifting intersections of in/visibility and in/security in today's security-minded world but also remind us of the unique contributions that anthropology can make to the critical study of security. [ABSTRACT FROM AUTHOR]

Diffusively coupled chemical oscillators can exhibit a wide variety of complex spatial patterns. In this paper, we show that a ring of relaxation oscillators diffusively coupled through the inhibitory species leads to remarkable spatiotemporal patterns in the regime where there is a large separation of time scales between the activator and the inhibitor dynamics. The origin of these complex patterns can be traced back to a preponderance of antiphase synchronized states in the space of attractors. We provide an analytical explanation for the existence and stability of the antiphase synchronized states by examining the limit of extreme time scale separation. Numerical results on rings with small numbers of oscillators show that an explosion of patterns occurs for a ring with five oscillators. [ABSTRACT FROM AUTHOR]

The present study examined correlates and program completion rates of Family only violent (FO) versus Generally violent (GV) male perpetrators of intimate partner violence mandated to batterer intervention programs. Probation records of 456 men sentenced to probation in Lake County, Illinois between 2006 and 2008 were examined, and the men were categorized as FO (n= 269) or GV (n= 187) by graduate student raters. GV men were younger, had more extensive criminal histories, greater substance use, and greater demographic risk factors related to education and employment. GV men were less likely to complete a mandated partner abuse intervention program and were deemed by probation officers to be at higher risk to reoffend as compared to FO men, even after controlling for racial differences. These findings highlight the utility of a reliable, easy to administer dichotomous categorization system for probation officers to use to differentiate between FO vs. GV men that had differential correlates and was associated with differential program completion rates. Implications for treatment of partner violent men are discussed. [ABSTRACT FROM AUTHOR]

The article focuses on activist anthropology. The author explains that she has engaged in activist anthropology through her work at an immigrant rights organization in New Jersey, explores the relationship between ethnography and activist work, and discusses a human chain demonstration she took part in on December 10, 2013, International Human Rights Day, in Elizabeth, New Jersey, at an undocumented immigrant deportation center.

Financial toxicity is now a well established and generally accepted toxicity related to cancer care. While policy makers and politicians continue to debate about system‐wide changes, physicians and patients can seek ways to decrease financial toxicity and to incorporate this issue into every decision‐making process. See also pages 1453‐63. [ABSTRACT FROM AUTHOR]

Steinhaus asked in the 1950s whether there exists a set in ℝ2 meeting every isometric copy of ℤ2 in precisely one point. Such a ‘Steinhaus set’ was constructed by Jackson and Mauldin. What about ℝ3? Is there a subset S of ℝ3 meeting every isometric copy of ℤ3 in exactly one point? We offer heuristic evidence that the answer is ‘no’. [ABSTRACT FROM AUTHOR]

The debate over genetically modified (GM) crops has raged in Europe since 1996, but had barely risen above a whisper in the USA until recent labeling debates raised public attention. This article will explain GM crops and traits discuss safety assessment provide a view on safety from authoritative organizations discuss selected issues of current debate, and provide the author's perspective as to why the public debate has drifted so far from scientific reality. The economic and environmental benefits of GM crops are beyond scope, but references are provided. GM food and feed undergo comprehensive assessments using recognized approaches to assure they are as safe as the conventional congener. Issues of food safety and nutrition, unrelated to the GM process, may arise when GM foods display novel components or composition. Unanticipated genetic effects in GM crops appear to be limited in contrast to existing variations among conventional varieties resulting from breeding, mutation, and natural mobile genetic elements. Allergenic potential is assessed when selecting genes for introduction into GM crops and remains a theoretical risk to date. Emerging weed and insect resistance is not unique to GM technology and will require the use of integrated pest management/best practices for pest control. Gene flow from GM crops to wild relatives is limited by existing biological barriers but can at time be a relevant consideration in gene selection and planting practices. Insect-resistant GM crops have significantly reduced use of chemical insecticides and appear to have reduced the incidence of pesticide poisoning in areas where small scale farming and hand application are common. Changes in herbicide patterns are more complex and are evolving over time in response to weed resistance management needs. Recent public debate is driven by a combination of unfounded allegations about the technology and purveyors, pseudoscience, and attempts to apply a strict precautionary principle. [ABSTRACT FROM AUTHOR]

For A = (ai,j ) a square integer matrix of prime determinant p, set w(A) =∑ i,j ǀai,j ǀ . We are interested in the smallest possible value wp for w(A), and we show that lim p→∞wp/ log2(p) = 5/2. We also show that wp ⩽ 2.5 log2(p) if and only if p = 2, 7, 13, 37 or a Fermat prime. Our results can also be interpreted as being about addition chains or about presentations of finite cyclic groups. [ABSTRACT FROM AUTHOR]

Abstract: We prove that for any odd prime p, there exist infinitely many finite simple groups S containing a Sylow p-subgroup P of S such that there exists a coset of P in S with the property that all elements in the coset have order a multiple of p. This allows us to answer a question of Richard Taylor related to whether certain Galois representations are automorphic. [Copyright &y& Elsevier]

How accurate are laypeople's intuitions about probability distributions of events? The economic and psychological literatures provide opposing answers. A classical economic view assumes that ordinary decision makers consult perfect expectations, while recent psychological research has emphasized biases in perceptions. In this work, we test laypeople's intuitions about probability distributions. To establish a ground truth against which accuracy can be assessed, we control the information seen by each subject to establish unambiguous normative answers. We find that laypeople's statistical intuitions can be highly accurate, and depend strongly upon the elicitation method used. In particular, we find that eliciting an entire distribution from a respondent using a graphical interface, and then computing simple statistics (such as means, fractiles, and confidence intervals) on this distribution, leads to greater accuracy, on both the individual and aggregate level, than the standard method of asking about the same statistics directly. [ABSTRACT FROM AUTHOR]

As we age, the innate immune system becomes dysregulated and is characterized by persistent inflammatory responses that involve multiple immune and non-immune cell types and that vary depending on the cell activation state and tissue context. This ageing-associated basal inflammation, particularly in humans, is thought to be induced by several factors, including the reactivation of latent viral infections and the release of endogenous damage-associated ligands of pattern recognition receptors (PRRs). Innate immune cell functions that are required to respond to pathogens or vaccines, such as cell migration and PRR signalling, are also impaired in aged individuals. This immune dysregulation may affect conditions associated with chronic inflammation, such as atherosclerosis and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] How aging impacts the immune priming capabilities of dendritic cells is complex. [•] Some studies show reduced function, while others show preserved DC priming function with aging. [•] Lack of consensus may reflect subtle differences in the health status of mice and methods employed. [ABSTRACT FROM AUTHOR]

We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the "chemistry on the complex" strategy. The resulting azide-complexes are then used in the copper(I)-catalysed azide-alkyne Huisgen 1,3-dipolar cycloaddition "click chemistry" reaction to from the corresponding triazole-functionalised iridium(III) bisterpyridines. The photophysical characteristics, including lifetimes, of these compounds were also investigated. Interestingly, oxygen appears to have very little effect on the lifetime of these complexes in aqueous solutions. Unexpectedly, sodium ascorbate acid appears to quench the luminescence of triazole-functionalised iridium(III) bisterpyridines, but this effect can be reversed by the addition of copper(II) sulfate, which is known to oxidize ascorbate under aerobic conditions. The results demonstrate that iridium(III) bisterpyridines can be functionalized for use in "click chemistry" facilitating the use of these photophysically interesting complexes in the modification of polymers or surfaces, to highlight just two possible applications. [ABSTRACT FROM AUTHOR]

intravital two-photon microscopy allows for the analysis of single-cell dynamics within intact tissues. As it is well recognized that molecular cues that regulate leukocyte trafficking into inflammatory sites differ between various tissues, it is important to study organ-specific responses. Recently, intravital two-photon microscopy has been expanded to moving organs in the mouse such as beating hearts. unlike previous experimental approaches to image cardiac tissue explants or isolated perfused heart preparations by two-photon microscopy, intravital imaging accounts for the mechanical force transmitted to vessels by the heartbeat and accurately assesses dynamic leukocyte behavior in the coronary vessels and myocardial tissue. intravital two-photon imaging of beating hearts is a promising experimental tool that will help elucidate cellular and molecular immune processes that contribute to a variety of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Pump thrombosis is a dreaded complication of long-term implantable ventricular assist devices. No guidance exists regarding the diagnosis and management of this entity despite its significant morbidity. After considerable thought and deliberation, a group of leading investigators in the field of mechanical support propose an algorithm for the diagnosis and management of this vexing entity based on clinical symptoms and serologic and imaging studies. [ABSTRACT FROM AUTHOR]

Ischemia reperfusion injury (IRI) that occurs with solid organ transplantation activates the innate immune system to induce inflammation. This leads to enhanced acute allograft rejection, impaired transplant tolerance and accelerated progression of chronic rejection. In this review, we discuss the innate immune signaling pathways that have been shown to play a role in organ transplantation. In particular, we focus on Toll-like receptor signaling pathways and how they have influenced outcomes after organ transplantation both experimentally and from clinical studies. Furthermore, we describe the substances that trigger the innate immune system after transplantation and several of the key cellular mediators of inflammation. We specifically point out unique aspects of activation of the innate immune system after lung transplantation. Finally, we discuss the areas that should be investigated in the future to more clearly understand the influence of the innate immune system after organ transplantation. [ABSTRACT FROM AUTHOR]

Background: Although continuous-flow left ventricular assist device (LVAD) support has become standard therapy, the complexities of device and patient management remain a challenge. In particular, percutaneous site infections (PSI) are a serious complication during the post-implant course. We sought to study the incidence, risk factors, and clinical effect of PSI. Methods: Data were obtained from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Registry. All adult patients who received a primary intracorporeal continuous flow LVAD between June 2006 and September 2010 were included. Descriptive statistics, Kaplan-Meier depictions, and multivariable analysis in the parametric hazard domain were used for statistical analysis. Results: A total of 239 PSIs were documented in 197 of 2,006 recipients (9.8%) of a continuous-flow LVAD. Mean follow-up was 8.1 months. Mean time to development of a PSI was 6.6 months. At 1 year after implant, nearly 19% of continuous-flow LVAD recipients developed a PSI. Multivariate analysis showed younger age (hazard ratio, 1.20; p < 0.0001) was the only factor predicting a PSI. Continuous-flow LVAD recipients who did not develop a PSI had improved survival (p = 0.004). Twenty-three patients died after development of a PSI. Sepsis was the most common cause of death (26.1%). Conclusions: PSIs occur in approximately 19% of continuous-flow LVAD recipients by 12 months after implant. Young age is the only predictor of PSI. Importantly, development of a PSI adversely affects survival. Efforts to enhance driveline integration and to develop future totally implantable systems are warranted. [ABSTRACT FROM AUTHOR]

Aging leads to a gradual dysregulation of immune functions, one consequence of which is reduced vaccine efficacy. In this review, we discuss several key contributing factors to the age-related decline in vaccine efficacy, such as alterations within the lymph nodes where germinal center (GC) reactions take place, alterations in the B cell compartment, alterations in the T cell compartment, and dysregulation of innate immune pathways. Additionally, we discuss several methods currently used in vaccine development to bolster vaccine efficacy in older adults. This review highlights the multifactorial defects that impair vaccine responses with aging. The vaccine response, as measured by titers of vaccine-specific antibodies, the duration of measurable vaccine-specific antibodies, and the quality and affinity of the antibody response, is reduced with age. Age-associated alterations in lymph nodes, such as a reduced number of germinal centers (GCs) and the decline in the number of follicular dendritic cells and fibroblastic reticular cells, contribute to the age-associated decline in vaccine efficacy. The reduced production of B cells from bone marrow and impaired affinity maturation of B cells contribute to the age-associated decline in vaccine efficiency. Aging impairs the production and activation of T cells, leading to reduced number and impaired function of T follicular helper cells that provide costimulatory, survival, and differentiation signals to B cells in the GCs. [ABSTRACT FROM AUTHOR]

Background: Cardiac transplantation in many centers is programmatically limited to patients aged younger than 70 years. We investigated the trends and outcomes for cardiac transplantation in recipients aged 70 years and older in the United States. Methods: De-identified data were provided by United Network of Organ Sharing. Transplant recipients were grouped by age 60–69 years and 70 years and older. Univariate comparisons were performed using Student''s t-test or the Pearson chi-square test. Survival was estimated using the Kaplan-Meier technique and compared with the log-rank test. Cox regression was used to determine predictors of death after transplant. Statistical significance was assigned to p < 0.05. Results: Between January 1, 1998, and June 15, 2010, 5,807 sexagenarians and 332 septuagenarians received allografts. The septuagenarian cohort had more men, less diabetes, was less likely to have a ventricular assist device, and more likely to be status II. Donors for septuagenarians were older and died more frequently from intracranial hemorrhage. Median unadjusted survival was 9.8 years for sexagenarians vs 8.5 years for septuagenarians (p = 0.003). There was no difference in the incidence of cerebrovascular accident, length of stay, or pacemaker need between groups. Septuagenarians were less likely to be treated for rejection the first year (p = 0.001). Age was a multivariate predictor of death (hazard ratio, 1.289; 95% confidence interval, 1.039–1.6; p = 0.021). Conclusions: Selected septuagenarians with advanced heart failure can derive great benefit from cardiac transplantation, although survival is inferior to that of an immediately younger sexagenarian cohort. Most of the mortality risk is seen in the first year after transplantation. A reduced incidence of rejection was observed and warrants further study. [Copyright &y& Elsevier]

Older people exhibit increased morbidity and mortality after viral infections than younger people. Additionally, vaccines are less protective in older people than in younger people. As the immune system is critical for host defense to viral infections and for vaccine efficacy, the implications are that aging negatively affects immunity. The immune system is broadly categorized into adaptive and innate systems. The innate immune system acts as a first line of defense to pathogen invasion. In this review, I focus on how aging affects the innate immune response to viral infection. [ABSTRACT FROM PUBLISHER]

lthough our understanding of the immunological mechanisms of transplant tolerance induction has greatly improved, how the innate immune system impacts transplant tolerance has only been recently appreciated. In this review, the involvement of the innate immune receptors, Toll-like receptors (TLRs), in both experimental models of acute allograft rejection and transplant tolerance induction in addition to clinical studies of organ transplantation are described. Several inflammatory cytokines, including IL-6, TNF-α, and type I interferons, which are induced by TLRs and other activators of innate immunity, prevent transplant tolerance induction. Their induction may be provoked by environmental exposures, such as viral or bacterial infections. Further investigation as to the innate inflammatory basis that controls the balance between immune acceptance and allograft rejection may lead us closer to the elusive goal of transplant tolerance acquisition. [ABSTRACT FROM AUTHOR]

Abstract: Older people are more susceptible to a variety of viral infections, including those that induce respiratory disease, resulting in higher morbidity and mortality than younger people. Aging impacts both innate and adaptive arms of the immune system to impair control of viral infections. This review will summarize key findings on how aging impacts immunity to viral infection. [ABSTRACT FROM AUTHOR]

Studies of the neural mechanisms of learning, especially of sensitization, have benefitted from extensive research on the model species, Aplysia californica (hereafter Aplysia). Considering this volume of literature on mechanisms, it is surprising that our understanding of the ecological context of sensitization in Aplysia is completely lacking. Indeed, the widespread use of strong electric shock to induce sensitization (an enhancement of withdrawal reflexes following noxious stimulation) is completely unnatural and leaves unanswered the question of whether this simple form of learning has any ecological relevance. We hypothesized that sublethal attack by a co-occurring predator, the spiny lobster, Panulirus interruptus, might be a natural sensitizing stimulus. We tested reflex withdrawal of the tail-mantle and head of individual Aplysia before and after attack by lobsters. Lobster attack significantly increased the amplitude of both reflexes, with a temporal onset that closely matched that observed with electric shock. This result suggests that electric shock may indeed mimic at least one naturally occurring sensitizing stimulus, suggesting, for the first time, an ecological context for this well studied form of learning. [ABSTRACT FROM AUTHOR]

While matters of security have appeared as paramount themes in a post-9/11 world, anthropology has not developed a critical comparative ethnography of security and its contemporary problematics. In this article I call for the emergence of a critical "security anthropology," one that recognizes the significance of security discourses and practices to the global and local contexts in which cultural anthropology operates. Many issues that have historically preoccupied anthropology are today inextricably linked to security themes, and anthropology expresses a characteristic approach to topics that today must be considered within a security rubric. A focus on security is particularly important to an understanding of human rights in contemporary neoliberal society. Drawing on examples from Latin America and my own work in Bolivia, I track the decline of neoliberalism and the rise of the security paradigm as a framework for organizing contemporary social life. I suggest that security, rather than a reaction to a terrorist attack that "changed everything," is characteristic of a neoliberalism that predates the events of 9/11, affecting the subjects of anthropological work and shaping the contexts within which that work is conducted. [ABSTRACT FROM AUTHOR]

What does it mean for anthropology to be relevant in the context of an ongoing global war on terror? This article examines the meanings of “security,” concentrating on the discipline's engagement with the military and the ways in which the anthropological concept of culture has been deployed in post-9/11 security campaigns. It argues that while there are many potential pitfalls awaiting the so-called culture expert in military collaborations, security nevertheless remains an important field to which anthropologists can bring critical scholarly attention and ethical engagement. [ABSTRACT FROM AUTHOR]

Investing for retirement is one of the most consequential yet daunting decisions consumers face. We present a way to both aid and understand consumers as they construct preferences for retirement income. The method enables consumers to build desired probability distributions of wealth constrained by market forces and the amount invested. We collect desired wealth distributions from a sample of working adults, provide evidence of the technique's reliability and predictive validity, characterize individual- and cluster-level differences, and estimate parameters of risk aversion and loss aversion. We discuss how such an interactive method might help people construct more informed preferences. [ABSTRACT FROM AUTHOR]

Abstract: We show that one can find two nonisomorphic curves over a field K that become isomorphic to one another over two finite extensions of K whose degrees over K are coprime to one another. More specifically, let be an arbitrary prime field and let and be integers that are coprime to one another. We show that one can find a finite extension K of , a degree-r extension L of K, a degree-s extension M of K, and two curves C and D over K such that C and D become isomorphic to one another over L and over M, but not over any proper subextensions of or . We show that such C and D can never have genus 0, and that if K is finite, C and D can have genus 1 if and only if and K is an odd-degree extension of . On the other hand, when we show that genus-2 examples occur in every characteristic other than 3. Our detailed analysis of the case shows that over every finite field K there exist nonisomorphic curves C and D that become isomorphic to one another over the quadratic and cubic extensions of K. Most of our proofs rely on Galois cohomology. Without using Galois cohomology, we show that two nonisomorphic genus-0 curves over an arbitrary field remain nonisomorphic over every odd-degree extension of the base field. [Copyright &y& Elsevier]