Population-scale effects of resistant or tolerant crop varieties have received little consideration from epidemiologists. When growers deploy tolerant crop, population-scale disease pressures are ...often unaffected. This only benefits growers using tolerant varieties, selfishly decreasing yields for others. However, resistant crop can reduce disease pressure for all. We coupled an epidemiological model with game theory to understand how this affects uptake of control. Each time a grower plants a new crop, they must decide whether to use an improved (i.e. tolerant/resistant) or unimproved variety. This decision is based on strategic-adaptive expectations in our model, with growers comparing last season’s profit with an estimate of what is expected from the alternative crop. Despite the positive feedback loop promoting use of a tolerant variety whenever it is available, a mixed unimproved- and tolerant-crop equilibrium can persist. Tolerant crop can also induce bistability between a scenario in which all growers use tolerant crop and the disease-free equilibrium, where no growers do. However, due to ‘free-riding’ by growers of unimproved crop, resistant crop nearly always exists in a mixed equilibrium. This work highlights how growers respond to contrasting incentives caused by tolerant and resistant varieties, and the distinct effects on yields and population-scale deployment.
Imaging techniques used to measure hippocampal atrophy are key to understanding the clinical progression of Alzheimer's disease (AD). Various semi-automated hippocampal segmentation techniques are ...available and require human expert input to learn how to accurately segment new data. Our goal was to compare 1) the performance of our automated hippocampal segmentation technique relative to manual segmentations, and 2) the performance of our automated technique when provided with a training set from two different raters. We also explored the ability of hippocampal volumes obtained using manual and automated hippocampal segmentations to predict conversion from MCI to AD.
We analyzed 161 1.5 T T1-weighted brain magnetic resonance images (MRI) from the ADCS Donepezil/Vitamin E clinical study. All subjects carried a diagnosis of mild cognitive impairment (MCI). Three different segmentation outputs (one produced by manual tracing and two produced by a semi-automated algorithm trained with training sets developed by two raters) were compared using single measure intraclass correlation statistics (smICC). The radial distance method was used to assess each segmentation technique's ability to detect hippocampal atrophy in 3D. We then compared how well each segmentation method detected baseline hippocampal differences between MCI subjects who remained stable (MCInc) and those who converted to AD (MCIc) during the trial. Our statistical maps were corrected for multiple comparisons using permutation-based statistics with a threshold of p < .01.
Our smICC analyses showed significant agreement between the manual and automated hippocampal segmentations from rater 1 right smICC = 0.78 (95%CI 0.72–0.84); left smICC = 0.79 (95%CI 0.72–0.85), the manual segmentations from rater 1 versus the automated segmentations from rater 2 right smICC = 0.78 (95%CI 0.7–0.84); left smICC = 0.78 (95%CI 0.71–0.84), and the automated segmentations of rater 1 versus rater 2 right smICC = 0.97 (95%CI 0.96–0.98); left smICC = 0.97 (95%CI 0.96–0.98). All three segmentation methods detected significant CA1 and subicular atrophy in MCIc compared to MCInc at baseline (manual: right pcorrected = 0.0112, left pcorrected = 0.0006; automated rater 1: right pcorrected = 0.0318, left pcorrected = 0.0302; automated rater 2: right pcorrected = 0.0029, left pcorrected = 0.0166).
The hippocampal volumes obtained with a fast semi-automated segmentation method were highly comparable to the ones obtained with the labor-intensive manual segmentation method. The AdaBoost automated hippocampal segmentation technique is highly reliable allowing the efficient analysis of large data sets.
•Manual segmentation of subcortical structures is time and labor intensive.•Reliable automated segmentation techniques can be developed.•AdaBoost volumes favorably compare to manual volumes.•Hippocampal volumetry has limited ability to aid clinical prognosis.
Neighborhood environments may influence the risk for developing type 2 diabetes mellitus (T2DM), but, to our knowledge, no longitudinal study has evaluated specific neighborhood exposures.
To ...determine whether long-term exposures to neighborhood physical and social environments, including the availability of healthy food and physical activity resources and levels of social cohesion and safety, are associated with incident T2DM during a 10-year period.
We used data from the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study of adults aged 45 to 84 years at baseline (July 17, 2000, through August 29, 2002). A total of 5124 participants free of T2DM at baseline underwent 5 clinical follow-up examinations from July 17, 2000, through February 4, 2012. Time-varying measurements of neighborhood healthy food and physical activity resources and social environments were linked to individual participant addresses. Neighborhood environments were measured using geographic information system (GIS)- and survey-based methods and combined into a summary score. We estimated hazard ratios (HRs) of incident T2DM associated with cumulative exposure to neighborhood resources using Cox proportional hazards regression models adjusted for age, sex, income, educational level, race/ethnicity, alcohol use, and cigarette smoking. Data were analyzed from December 15, 2013, through September 22, 2014.
Incident T2DM defined as a fasting glucose level of at least 126 mg/dL or use of insulin or oral antihyperglycemics.
During a median follow-up of 8.9 years (37,394 person-years), 616 of 5124 participants (12.0%) developed T2DM (crude incidence rate, 16.47 95% CI, 15.22-17.83 per 1000 person-years). In adjusted models, a lower risk for developing T2DM was associated with greater cumulative exposure to indicators of neighborhood healthy food (12%; HR per interquartile range IQR increase in summary score, 0.88 95% CI, 0.79-0.98) and physical activity resources (21%; HR per IQR increase in summary score, 0.79 95% CI, 0.71-0.88), with associations driven primarily by the survey exposure measures. Neighborhood social environment was not associated with incident T2DM (HR per IQR increase in summary score, 0.96 95% CI, 0.88-1.07).
Long-term exposure to residential environments with greater resources to support physical activity and, to a lesser extent, healthy diets was associated with a lower incidence of T2DM, although results varied by measurement method. Modifying neighborhood environments may represent a complementary, population-based approach to prevention of T2DM, although further intervention studies are needed.
The anophelins are small protein thrombin inhibitors that are produced in the salivary glands of the Anopheles mosquito to fulfill a vital role in blood feeding. A bioinformatic analysis of anophelin ...sequences revealed the presence of conserved tyrosine residues in an acidic environment that were predicted to be post-translationally sulfated in vivo. To test this prediction, insect cell expression of two anophelin proteins, from Anopheles albimanus and Anopheles gambiae, was performed, followed by analysis by mass spectrometry, which showed heterogeneous sulfation at the predicted sites. Homogeneously sulfated variants of the two proteins were subsequently generated by chemical synthesis via a one-pot ligation–desulfurization strategy. Tyrosine sulfation of the anophelins was shown to significantly enhance the thrombin inhibitory activity, with a doubly sulfated variant of the anophelin from A. albimanus exhibiting a 100-fold increase in potency compared with the unmodified homologue. Sulfated anophelins were also shown to exhibit potent in vivo anticoagulant and antithrombotic activity.
Maintaining peace and conserving biodiversity hinge on an international system of cooperation codified in institutions, but Russia’s invasion of Ukraine brings recent progress to a crossroads. ...Against this backdrop, we address some implications of Russia’s invasion of Ukraine for the governance of biodiversity conservation both within and beyond Russia. The Russian invasion of Ukraine threatens the governance system for biodiversity conservation, as it pertains to Russia and beyond, due to three interacting factors: (i) isolation of Russia from the international system, (ii) halt and delay of international cooperation, and (iii) changes in international and domestic policy priorities. We recommend making the existing international system of governance for conserving biodiversity more resilient and adaptable, while aligning security agendas with biodiversity conservation goals.
Mechanisms resulting in abdominal pain include altered neuro-immune interactions in the gastrointestinal tract, but the signaling processes that link immune activation with visceral hypersensitivity ...are unresolved. We hypothesized that enteric glia link the neural and immune systems of the gut and that communication between enteric glia and immune cells modulates the development of visceral hypersensitivity. To this end, we manipulated a major mechanism of glial intercellular communication that requires connexin-43 and assessed the effects on acute and chronic inflammation, visceral hypersensitivity, and immune responses. Deleting connexin-43 in glia protected against the development of visceral hypersensitivity following chronic colitis. Mechanistically, the protective effects of glial manipulation were mediated by disrupting the glial-mediated activation of macrophages through the macrophage colony-stimulating factor. Collectively, our data identified enteric glia as a critical link between gastrointestinal neural and immune systems that could be harnessed by therapies to ameliorate abdominal pain.
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•Enteric glia regulate visceral hypersensitivity during chronic inflammation•Glial mechanisms include connexin-43 and M-CSF production•Glial M-CSF modulates muscularis macrophage activation•Inflammation-induced glial M-CSF production is regulated by Cx43, PKC, and TACE
Grubišić et al. report that enteric glia regulate macrophage activation and visceral sensitivity following intestinal inflammation through mechanisms that require glial connexin-43 (Cx43) and macrophage colony-stimulating factor (M-CSF) production. Proinflammatory signals induce glial Cx43-dependent M-CSF production through protein kinase C (PKC) and tumor necrosis factor (TNF)-alpha converting enzyme (TACE).
Indigenous Peoples’ lands cover over one‐quarter of Earth's surface, a significant proportion of which is still free from industrial‐level human impacts. As a result, Indigenous Peoples and their ...lands are crucial for the long‐term persistence of Earth's biodiversity and ecosystem services. Yet, information on species composition on these lands globally remains largely unknown. We conducted the first comprehensive analysis of terrestrial mammal composition across mapped Indigenous lands based on data on area of habitat (AOH) for 4460 mammal species assessed by the International Union for Conservation of Nature. We overlaid each species’ AOH on a current map of Indigenous lands and found that 2695 species (60% of assessed mammals) had ≥10% of their ranges on Indigenous Peoples’ lands and 1009 species (23%) had >50% of their ranges on these lands. For threatened species, 473 (47%) occurred on Indigenous lands with 26% having >50% of their habitat on these lands. We also found that 935 mammal species (131 categorized as threatened) had ≥ 10% of their range on Indigenous Peoples’ lands that had low human pressure. Our results show how important Indigenous Peoples’ lands are to the successful implementation of conservation and sustainable development agendas worldwide.
La Importancia de las Tierras de los Pueblos Indígenas para la Conservación de los Mamíferos Terrestres
Resumen
Las tierras pertenecientes a pueblos indígenas cubren más de un cuarto de la superficie del planeta, una proporción importante que se encuentra aún libre de impactos humanos a nivel industrial. Como resultado, los pueblos indígenas y sus tierras son cruciales para la persistencia a largo plazo de la biodiversidad en la Tierra y de los servicios ecosistemicos. Sin embargo, la información sobre la composición de especies en estas tierras a nivel mundial todavía permanece desconocida en su mayoría. Realizamos el primer análisis integral de la composición de mamíferos terrestres a lo largo de las tierras indígenas mapeadas con base en los datos sobre el área del hábitat (ADH) de 4,460 especies de mamíferos valorados por la Unión Internacional para la Conservación de la Naturaleza. Sobrepusimos el ADH de cada especie en un mapa actual de tierras indígenas y encontramos que 2,695 especies (60% de los mamíferos valorados) tienen ≥10% de su distribución dentro de tierras de pueblos indígenas y que 1,009 especies (23%) tienen >50% de su distribución dentro de estas tierras. De las especies amenazadas, 473 (47%) ocurrieron en tierras indígenas.También descubrimos que 935 especies de mamíferos (131 categorizadas como amenazadas) tienen ≥ 10% de su distribución dentro de tierras de pueblos indígenas con baja presión humana. Nuestros resultados muestran cuán importantes son las tierras de los pueblos indígenas para la implementación exitosa de la conservación y las agendas globales de desarrollo sustentable.
【摘要】
原住民的土地占地球表面四分之一以上的面积, 其中有很大一部分尚未受到人类工业的影响。因此, 原住民及其土地对地球生物多样性和生态系统服务的长期续存至关重要。然而, 在全球范围内, 关于这些土地上物种组成的信息仍然很有限。我们根据国际自然保护联盟评估的 4460 种哺乳动物栖息地的数据, 首次对原住民土地上陆生哺乳动物的组成进行了全面分析。我们将每个物种的栖息地范围叠加在现有的原住民土地地图上, 发现 2695 个物种 (占已评估哺乳动物的 60%) 有 10% 以上的分布范围与原住民土地重合, 1009 个物种 (占 23%) 在原住民土地上的分布面积超过其栖息地面积的 50% 。受威胁物种中有 473 种 (占 47%) 在原住民土地上有分布。我们还发现, 935 种哺乳动物 (其中 131 种被列为濒危物种) 有超过 10% 的栖息地位于人类压力较低的原住民土地上。我们的研究结果强调了原住民土地对于全球成功实施保护和可持续发展议程的重要性。【翻译:胡怡思;审校:聂永刚】
Article impact statement: Indigenous Peoples’ lands are important for the successful implementation of international conservation and sustainable development agendas.
Cancer transmission is a known risk for recipients of organ transplants. Many people wait a long time for a suitable transplant; some never receive one. Although patients with brain tumors may donate ...their organs, opinions vary on the risks involved.
To determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. Key secondary objectives were to investigate the association that donor brain tumors have with organ usage and posttransplant survival.
This was a cohort study in England and Scotland, conducted from January 1, 2000, to December 31, 2016, with follow-up to December 31, 2020. This study used linked data on deceased donors and solid organ transplant recipients with valid national patient identifier numbers from the UK Transplant Registry, the National Cancer Registration and Analysis Service (England), and the Scottish Cancer Registry. For secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure. Statistical analysis of study data took place from October 1, 2021, to May 31, 2022.
A history of primary brain tumor in the organ donor, identified from all 3 data sources using disease codes.
Transmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes were organ utilization (ie, transplant of an offered organ) and survival of kidney, liver, heart, and lung transplants and their recipients. Key covariates in donors with brain tumors were tumor grade and treatment history.
This study included a total of 282 donors (median IQR age, 42 33-54 years; 154 females 55%) with primary brain tumors and 887 transplants from them, 778 (88%) of which were analyzed for the primary outcome. There were 262 transplants from donors with high-grade tumors and 494 from donors with prior neurosurgical intervention or radiotherapy. Median (IQR) recipient age was 48 (35-58) years, and 476 (61%) were male. Among 83 posttransplant malignancies (excluding NMSC) that occurred over a median (IQR) of 6 (3-9) years in 79 recipients of transplants from donors with brain tumors, none were of a histological type matching the donor brain tumor. Transplant survival was equivalent to that of matched controls. Kidney, liver, and lung utilization were lower in donors with high-grade brain tumors compared with matched controls.
Results of this cohort study suggest that the risk of cancer transmission in transplants from deceased donors with primary brain tumors was lower than previously thought, even in the context of donors that are considered as higher risk. Long-term transplant outcomes are favorable. These results suggest that it may be possible to safely expand organ usage from this donor group.
Disparities in Cardiovascular Medicine Albert, Michelle A; Carnethon, Mercedes R; Watson, Karol E
Circulation (New York, N.Y.),
06/2021, Letnik:
143, Številka:
24
Journal Article
Type 2 diabetes pathophysiology is characterized by dysregulated glucagon secretion. LY2409021, a potent, selective small-molecule glucagon receptor antagonist that lowers glucose was evaluated for ...efficacy and safety in patients with type 2 diabetes.
The efficacy (HbA1c and glucose) and safety (serum aminotransferase) of once-daily oral administration of LY2409021 was assessed in two double-blind studies. Phase 2a study patients were randomized to 10, 30, or 60 mg of LY2409021 or placebo for 12 weeks. Phase 2b study patients were randomized to 2.5, 10, or 20 mg LY2409021 or placebo for 24 weeks.
LY2409021 produced reductions in HbA1c that were significantly different from placebo over both 12 and 24 weeks. After 12 weeks, least squares (LS) mean change from baseline in HbA1c was -0.83% (10 mg), -0.65% (30 mg), and -0.66% (60 mg) (all P < 0.05) vs. placebo, 0.11%. After 24 weeks, LS mean change from baseline in HbA1c was -0.45% (2.5 mg), -0.78% (10 mg, P < 0.05), -0.92% (20 mg, P < 0.05), and -0.15% with placebo. Increases in serum aminotransferase, fasting glucagon, and total fasting glucagon-like peptide-1 (GLP-1) were observed; levels returned to baseline after drug washout. Fasting glucose was also lowered with LY2409021 at doses associated with only modest increases in aminotransferases (mean increase in alanine aminotransferase ALT ≤10 units/L). The incidence of hypoglycemia in the LY2409021 groups was not statistically different from placebo.
In patients with type 2 diabetes, glucagon receptor antagonist treatment significantly lowered HbA1c and glucose levels with good overall tolerability and a low risk for hypoglycemia. Modest, reversible increases in serum aminotransferases were observed.
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