An often-stated public health comment is that "vaccination is a victim of its own success." While the scientific and medical consensus on the benefits of vaccination is clear and unambiguous, an ...increasing number of people are perceiving vaccines as unsafe and unnecessary. The World Health Organization identified "the reluctance or refusal to vaccinate despite availability of vaccines" as one of the 10 threats to global health in 2019. The negative influence of anti-vaccination movements is often named as a cause of increasing vaccine resistance in the public. In this review, we give an overview of the current literature on the topic, beginning by agreeing on terminology and concepts before looking at potential causes, consequences, and impacts of resistance to vaccination.
Objective To compare the long‐term outcomes of tension‐free vaginal tape (TVT) and colposuspension as primary treatment for stress incontinence.
Study design Multicentre randomised controlled ...trial.
Setting Secondary and tertiary care gynaecology, urology and urogynaecology departments in 14 centres in the UK and Eire.
Population Women with urodynamically confirmed stress incontinence and who had previously failed to respond to conservative treatment were invited to participate.
Methods Three hundred and forty‐four women were randomised; 175 to TVT and 169 to colposuspension. This paper reports the 5‐year outcomes.
Main outcome measures The primary outcome at 5 years was a 1‐hour perineal pad test; other outcomes included clinical examination, Short Form‐36 (SF‐36) health status and Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaires.
Results A negative 1‐hour pad test was recorded in 58/72 (81%) women in the TVT group and 44/49 (90%) in the colposuspension group (P= 0.21, Fisher’s exact test) at 5 years. There was an increase in enterocoele and rectocele in the colposuspension group; three late tape complications were seen in the TVT group.
Conclusion This study did not detect a significant difference between TVT and colposuspension for the cure of stress incontinence at 5 years. The effect of both procedures on cure of incontinence and improvement in quality of life is maintained in the long term. Vault and posterior vaginal wall prolapse are seen more commonly after colposuspension. Tape erosion may occur several years after surgery.
This paper explores the effectiveness of sparse representations obtained by learning a set of overcomplete basis (dictionary) in the context of action recognition in videos. Although this work ...concentrates on recognizing human movements-physical actions as well as facial expressions-the proposed approach is fairly general and can be used to address other classification problems. In order to model human actions, three overcomplete dictionary learning frameworks are investigated. An overcomplete dictionary is constructed using a set of spatio-temporal descriptors (extracted from the video sequences) in such a way that each descriptor is represented by some linear combination of a small number of dictionary elements. This leads to a more compact and richer representation of the video sequences compared to the existing methods that involve clustering and vector quantization. For each framework, a novel classification algorithm is proposed. Additionally, this work also presents the idea of a new local spatio-temporal feature that is distinctive, scale invariant, and fast to compute. The proposed approach repeatedly achieves state-of-the-art results on several public data sets containing various physical actions and facial expressions.
Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease and is presumed to be central to the altered responsiveness to recurrent infection in these patients. We examined ...the effects of smoke priming underlying the exacerbated response to viral infection in mice. Lack of interleukin-33 (IL-33) signaling conferred complete protection during exacerbation and prevented enhanced inflammation and exaggerated weight loss. Mechanistically, smoke was required to upregulate epithelial-derived IL-33 and simultaneously alter the distribution of the IL-33 receptor ST2. Specifically, smoke decreased ST2 expression on group 2 innate lymphoid cells (ILC2s) while elevating ST2 expression on macrophages and natural killer (NK) cells, thus altering IL-33 responsiveness within the lung. Consequently, upon infection and release, increased local IL-33 significantly amplified type I proinflammatory responses via synergistic modulation of macrophage and NK cell function. Therefore, in COPD, smoke alters the lung microenvironment to facilitate an alternative IL-33-dependent exaggerated proinflammatory response to infection, exacerbating disease.
•IL-33 is upregulated by cigarette smoke and released in response to virus infection•Smoke dampens ST2 expression on ILC2s but enhances ST2 on NK cells and macrophages•IL-33 drives an exacerbated Th1-cell-like inflammatory response to virus infection•IL-33 might play a critical role in pathogen-induced exacerbations of COPD
Smoking is thought to be central to the altered responsiveness to infection in patients with chronic obstructive pulmonary disease (COPD). Humbles and colleagues show that mice lacking interleukin-33 (IL-33) are protected from smoke-induced exaggerated inflammatory responses to virus infection, suggesting that IL-33 is a critical mediator in acute exacerbations of COPD.
Cytokines related to tumor necrosis factor (TNF) provide a communication network essential for coordinating multiple cell types into an effective host defense system against pathogens and malignant ...cells. The pathways controlled by the TNF superfamily differentiate both innate and adaptive immune cells and modulate stromal cells into microenvironments conducive to host defenses. Members of the TNF receptor superfamily activate diverse cellular functions from the production of type 1 interferons to the modulation of survival of antigen-activated T cells. Here, we focus attention on the subset of TNF superfamily receptors encoded in the immune response locus in chromosomal region 1p36. Recent studies have revealed that these receptors use diverse mechanisms to either co-stimulate or restrict immune responses. Translation of the fundamental mechanisms of TNF superfamily is leading to the design of therapeutics that can alter pathogenic processes in several autoimmune diseases or promote immunity to tumors.
A deeper understanding of the network of cellular and molecular pathways initiated by the TNF superfamily of cytokines is emerging from fundamental research and human clinical trials. Selective modulation of these cytokines could achieve the goal of limiting cancer without autoimmune disease as a restricting consequence.
An increase in retrogressive thaw slump (RTS) activity has been observed in the Arctic in recent decades. However, a gap exists between observations in high Arctic polar desert regions where mean ...annual ground temperatures are as cold as −16.5 °C and vegetation coverage is sparse. In this study, we present a ∼30 year record of annual RTS observations (frequency and distribution) from 1989 to 2018 within the Eureka Sound Lowlands, Ellesmere and Axel Heiberg Islands. Record summer warmth in 2011 and 2012 promoted rapid RTS initialization, increasing active slumps from 100 in a given year or less to over 200 regionally and promoting RTS initiation in previously unaffected terrain. Differential GPS and remote sensing observations of 12 RTSs initiated during this period (2011-2018) provided a mean headwall retreat rate for all RTSs of 6.2 m yr−1 and for specific RTSs up to 26.7 m yr−1. To better understand the dynamics of climate and terrain factors controlling RTS headwall retreat rates we explored RTS interactions by correlating headwall retreat with climate factors (thawing degree days, annual rainfall and annual snowfall) and terrain factors (aspect and slope). Our findings indicate a sensitivity of cold permafrost in the high Arctic to climate-driven thermokarst initiation, but the decoupling of RTS dynamics from climate appears to occur over time for individual RTS as terrain factors take on a greater role controlling headwall retreat. Detailed observations of thermokarst development in a high Arctic polar desert permafrost setting are important as it demonstrates the sensitivity of this system to changes in summer temperatures and highlight differences to changes occurring in other Arctic permafrost regions.
Substance-use disorders are a public health crisis globally and carry with them significant morbidity and mortality. Stigma toward people who abuse these substances, as well as the internalization of ...that stigma by substance users, is widespread. In this review, we synthesized the available evidence for the role of perceived social stigma and self-stigma in people's willingness to seek treatment. While stigma may be frequently cited as a barrier to treatment in some samples, the degree of its impact on decision-making regarding treatment varied widely. More research needs to be done to standardize the definition and measurement of self- and perceived social stigma to fully determine the magnitude of their effect on treatment-seeking decisions.
Fine particle pollution, PM
, is associated with increased risk of death from cardiorespiratory diseases. A multidecadal shift in the United States (U.S.) PM
composition towards organic aerosol as ...well as advances in predictive algorithms for secondary organic aerosol (SOA) allows for novel examinations of the role of PM
components on mortality. Here we show SOA is strongly associated with county-level cardiorespiratory death rates in the U.S. independent of the total PM
mass association with the largest associations located in the southeastern U.S. Compared to PM
, county-level variability in SOA across the U.S. is associated with 3.5× greater per capita county-level cardiorespiratory mortality. On a per mass basis, SOA is associated with a 6.5× higher rate of mortality than PM
, and biogenic and anthropogenic carbon sources both play a role in the overall SOA association with mortality. Our results suggest reducing the health impacts of PM
requires consideration of SOA.
Electricity market models are widely employed to study the role, impacts and economic viability of new technologies. Sources of arbitrage, such as storage and transmission, are increasingly seen as ...essential for integrating higher shares of variable renewables. Understanding their operation and business case requires models which accurately represent time-series of wholesale electricity prices.
We show that the prevailing assumption of generators bidding short-run marginal cost, such as in the merit order stack, substantially underestimates the spread and volatility of hourly wholesale prices. To compound this, the lack of transparent outputs from previous electricity market modelling studies makes it impossible to scrutinise the prevailing methods or provide a detailed inter-comparison.
We demonstrate a simple modification to the short-run marginal cost approach that delivers improved variability in modelled prices: allowing generators to make a spread of bids, below cost for their first megawatts of capacity, above for their last. Using this model we demonstrate the impact of price variability on the operation and profitability of storage, highlighting the urgent need for greater awareness of this aspect of market model performance.
•Energy modelling needs to recognise the value of full model validation.•Price variability is inaccurately represented in electricity market models.•Accurate arbitrage calculations require prices with realistic variability.•Allowing modelled plant bid away from SRMC improves model skill.•Supply curve-based models cannot give accurate price variability.
Most of the world's crops depend on pollinators, so declines in both managed and wild bees raise concerns about food security. However, the degree to which insect pollination is actually limiting ...current crop production is poorly understood, as is the role of wild species (as opposed to managed honeybees) in pollinating crops, particularly in intensive production areas. We established a nationwide study to assess the extent of pollinator limitation in seven crops at 131 locations situated across major crop-producing areas of the USA. We found that five out of seven crops showed evidence of pollinator limitation. Wild bees and honeybees provided comparable amounts of pollination for most crops, even in agriculturally intensive regions. We estimated the nationwide annual production value of wild pollinators to the seven crops we studied at over $1.5 billion; the value of wild bee pollination of all pollinator-dependent crops would be much greater. Our findings show that pollinator declines could translate directly into decreased yields or production for most of the crops studied, and that wild species contribute substantially to pollination of most study crops in major crop-producing regions.
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