Objective Lung cancer is the leading cause of cancer death in North America. Low-dose computed tomography screening can reduce lung cancer–specific mortality by 20%. Method The American Association ...for Thoracic Surgery created a multispecialty task force to create screening guidelines for groups at high risk of developing lung cancer and survivors of previous lung cancer. Results The American Association for Thoracic Surgery guidelines call for annual lung cancer screening with low-dose computed tomography screening for North Americans from age 55 to 79 years with a 30 pack-year history of smoking. Long-term lung cancer survivors should have annual low-dose computed tomography to detect second primary lung cancer until the age of 79 years. Annual low-dose computed tomography lung cancer screening should be offered starting at age 50 years with a 20 pack-year history if there is an additional cumulative risk of developing lung cancer of 5% or greater over the following 5 years. Lung cancer screening requires participation by a subspecialty-qualified team. The American Association for Thoracic Surgery will continue engagement with other specialty societies to refine future screening guidelines. Conclusions The American Association for Thoracic Surgery provides specific guidelines for lung cancer screening in North America.
Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide
. The only available vaccine, BCG (Bacillus Calmette-Guérin), is given intradermally and has variable efficacy ...against pulmonary tuberculosis, the major cause of mortality and disease transmission
. Here we show that intravenous administration of BCG profoundly alters the protective outcome of Mtb challenge in non-human primates (Macaca mulatta). Compared with intradermal or aerosol delivery, intravenous immunization induced substantially more antigen-responsive CD4 and CD8 T cell responses in blood, spleen, bronchoalveolar lavage and lung lymph nodes. Moreover, intravenous immunization induced a high frequency of antigen-responsive T cells across all lung parenchymal tissues. Six months after BCG vaccination, macaques were challenged with virulent Mtb. Notably, nine out of ten macaques that received intravenous BCG vaccination were highly protected, with six macaques showing no detectable levels of infection, as determined by positron emission tomography-computed tomography imaging, mycobacterial growth, pathology and granuloma formation. The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis.
The Lax–Wendroff theorem stipulates that a discretely conservative operator is necessary to accurately capture discontinuities. The discrete operator, however, need not be derived from the divergence ...form of the continuous equations. Indeed, conservation law equations that are split into linear combinations of the divergence and product rule form and then discretized using any diagonal-norm skew-symmetric summation-by-parts (SBP) spatial operator, yield discrete operators that are conservative. Furthermore, split-form, discretely conservation operators can be derived for periodic or finite-domain SBP spatial operators of any order. Examples are presented of a fourth-order, SBP finite-difference operator with second-order boundary closures. Sixth- and eighth-order constructions are derived, and are supplied in an accompanying text file.
The threat to biodiversity posed by urban expansion is well researched and supported. Since the late 1990s, the field of urban ecology has been expanding along with the developed landscapes it ...studies. Past reviews have shown unequal publication rates in urban ecology literature for taxonomic groups and research locations. Herein, we explore differences in the publication rate of urban studies by vertebrate groups, but also expand on previous investigations by broadening the scope of the literature searched, exploring trends in subtopics within the urban wildlife literature, identifying geographic patterns of such publications, and comparing the rate at which non‐native and threatened and endangered species are studied in urban settings. We used linear and segmented regression to assess publication rates and Fisher's exact tests for comparisons between groups. All vertebrate groups show an increasing proportion of urban studies through time, with urban avian studies accelerating most sharply and herpetofauna appearing to be understudied. Non‐native mammals are more studied than non‐native birds, and threatened and endangered herpetofauna and mammals are more likely to be studied than threatened and endangered birds in urban areas. The plurality of urban wildlife studies are found in North America, while there is a dearth of studies from Africa, Asia, and South America. Our results can help inform decisions of urban ecologists on how to better fill in knowledge gaps and bring a greater degree of equity into the field.
Since the late 1990s, the field of urban ecology has been expanding along with the developed landscapes it studies. Herein, we explore differences in the publication rate of urban studies by vertebrate groups, but also expand on previous investigations by broadening the scope of the literature searched, exploring trends in subtopics within the urban wildlife literature, identifying geographic patterns of such publications, and comparing the rate at which non‐native and threatened and endangered species are studied in urban settings.
To evaluate the utilization of brachytherapy and duration of treatment on overall survival for locally advanced cervical cancer.
The National Cancer Database (NCDB) was queried to identify stage ...II-IVA cervical cancer patients diagnosed in the United States between 2004 and 2015 who were treated with definitive chemoradiation therapy. We defined standard of care (SOC) treatment as receiving external beam radiation therapy (EBRT) and concurrent chemotherapy, brachytherapy (BT), and completing treatment within 8 weeks, and compared SOC treatment to non-SOC. The primary outcome was overall survival (OS). We also evaluated the effect of sociodemographic and clinical variables on receiving SOC.
We identified 10,172 women with locally advanced cervical cancer primarily treated with chemotherapy and concurrent EBRT of which 6047 (59.4%) patients received brachytherapy, and only 2978 (29.3%) completed treatment within 8 weeks (SOC). Receipt of SOC was associated with significantly improved overall survival (median OS 131.0 mos vs 95.5 mos, 78.1 mos, 49.2 mos; p < 0.0001). Furthemore, in patients whose treatment extended beyond 8 weeks, brachytherapy was still associated with an improved survival (median OS 95.5 vs 49.2 mos, p < 0.0001). More advanced stage, Non-Hispanic Black race, lower income, lack of insurance or government insurance, less education, and rural residence were associated with decreased likelihood of receiving SOC.
Completing standard of care concurrent chemoradiation therapy and brachytherapy in the recommended 8 weeks was associated with a superior overall survival. Patients who received brachytherapy boost show superior survival to patients receiving EBRT alone, regardless of treatment duration. Disparities in care for vulnerable populations highlight the challenges and importance of care coordination for patients with cervical cancer.
•Only 29.3% of Americans with locally advanced cervical cancer receive standard of care treatment•Receiving standard of care treatment is associated with improved overall survival•Receiving brachytherapy, even if it prolongs treatment, is associated with improved overall survival•Patients who are Black, publically insured, low income, less educated, or reside in rural areas were less likely to receive standard of care treatment
Emerging infectious diseases have recently increased in wildlife and can result in population declines and the loss of genetic diversity in susceptible populations. As populations of impacted species ...decline, genetic diversity can be lost, with ramifications including reduced effective population size and increased population structuring. For species of conservation concern, which may already have low genetic diversity, the loss of genetic diversity can be especially important. To investigate the impacts of a novel pathogen on genetic diversity in a genetically depauperate endangered species, we assessed the ramifications of a sylvatic plague-induced bottleneck in black-footed ferrets (Mustela nigripes). Following a plague epizootic, we genotyped 184 ferrets from Conata Basin and Badlands National Park, South Dakota, at seven microsatellite loci. We compared our results to pre-plague studies in the same population. We observed population substructuring into three genetic clusters. These clusters reflect founder effects from ferret reintroduction events followed by genetic drift. Compared to the pre-plague population, we observed losses of allelic diversity in all clusters, as well as significantly reduced heterozygosity in one cluster. These results indicate that disease epizootics may reduce population size and also genetic diversity. Our results suggest the importance of early and sustained management in mitigating disease epizootics in naïve populations for the maintenance of genetic diversity.
People commonly believe that they communicate better with close friends than with strangers. We propose, however, that closeness can lead people to overestimate how well they communicate, a ...phenomenon we term the closeness-communication bias. In one experiment, participants who followed direction of a friend were more likely to make egocentric errors—look at and reach for an object only they could see—than were those who followed direction of a stranger. In two additional experiments, participants who attempted to convey particular meanings with ambiguous phrases overestimated their success more when communicating with a friend or spouse than with strangers. We argue that people engage in active monitoring of strangers’ divergent perspectives because they know they must, but that they “let down their guard” and rely more on their own perspective when they communicate with a friend.
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are characterized by cytoplasmic protein aggregates in the brain and spinal cord that include TAR-DNA binding protein ...43 (TDP-43). TDP-43 is normally localized in the nucleus with roles in the regulation of gene expression, and pathological cytoplasmic aggregates are associated with depletion of nuclear protein. Here, we generated transgenic mice expressing human TDP-43 with a defective nuclear localization signal in the forebrain (hTDP-43-ΔNLS), and compared them with mice expressing WT hTDP-43 (hTDP-43-WT) to determine the effects of mislocalized cytoplasmic TDP-43 on neuronal viability. Expression of either hTDP-43-ΔNLS or hTDP-43-WT led to neuron loss in selectively vulnerable forebrain regions, corticospinal tract degeneration, and motor spasticity recapitulating key aspects of FTLD and primary lateral sclerosis. Only rare cytoplasmic phosphorylated and ubiquitinated TDP-43 inclusions were seen in hTDP-43-ΔNLS mice, suggesting that cytoplasmic inclusions were not required to induce neuronal death. Instead, neurodegeneration in hTDP-43 and hTDP-43-ΔNLS-expressing neurons was accompanied by a dramatic downregulation of the endogenous mouse TDP-43. Moreover, mice expressing hTDP-43-ΔNLS exhibited profound changes in gene expression in cortical neurons. Our data suggest that perturbation of endogenous nuclear TDP-43 results in loss of normal TDP-43 function(s) and gene regulatory pathways, culminating in degeneration of selectively vulnerable affected neurons.
The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the ...National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer deaths fell by 20%. The Task Force's Position Statement outlined a number of the major opportunities to further improve the CT screening in lung cancer approach, based on experience with cancer screening from other organ sites.
The IASLC CT Screening Workshop 2011 further developed these discussions, which are summarized in this report. The recommendation from the workshop, and supported by the IASLC Board of Directors, was to set up the Strategic CT Screening Advisory Committee (IASLC-SSAC). The Strategic CT Screening Advisory Committee is currently engaging professional societies and organizations who are stakeholders in lung cancer CT screening implementation across the globe, to focus on delivering guidelines and recommendations in six specific areas: (i) identification of high-risk individuals for lung cancer CT screening programs; (ii) develop radiological guidelines for use in developing national screening programs; (iii) develop guidelines for the clinical work-up of “indeterminate nodules” resulting from CT screening programmers; (iv) guidelines for pathology reporting of nodules from lung cancer CT screening programs; (v) recommendations for surgical and therapeutic interventions of suspicious nodules identified through lung cancer CT screening programs; and (vi) integration of smoking cessation practices into future national lung cancer CT screening programs.
Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration ...(FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC.
We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration.
Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC.
For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.
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