Interactions between distant places are increasingly widespread and influential, often leading to unexpected outcomes with profound implications for sustainability. Numerous sustainability studies ...have been conducted within a particular place with little attention to the impacts of distant interactions on sustainability in multiple places. Although distant forces have been studied, they are usually treated as exogenous variables and feedbacks have rarely been considered. To understand and integrate various distant interactions better, we propose an integrated framework based on telecoupling, an umbrella concept that refers to socioeconomic and environmental interactions over distances. The concept of telecoupling is a logical extension of research on coupled human and natural systems, in which interactions occur within particular geographic locations. The telecoupling framework contains five major interrelated components, i.e., coupled human and natural systems, flows, agents, causes, and effects. We illustrate the framework using two examples of distant interactions associated with trade of agricultural commodities and invasive species, highlight the implications of the framework, and discuss research needs and approaches to move research on telecouplings forward. The framework can help to analyze system components and their interrelationships, identify research gaps, detect hidden costs and untapped benefits, provide a useful means to incorporate feedbacks as well as trade-offs and synergies across multiple systems (sending, receiving, and spillover systems), and improve the understanding of distant interactions and the effectiveness of policies for socioeconomic and environmental sustainability from local to global levels.
How to improve access and quality of social services to respond to cultural diversity is receiving increased attention. Yet no approach to cultural responsiveness has been widely accepted. ...Coproduction has been championed in many service fields for better service outcomes and has the potential to inform practices for cultural responsiveness. This study explored how coproduction can be used to deliver culturally responsive social services. We conducted a qualitative case study and examined how an Australian disability service organisation operated a programme to improve cultural responsiveness with Australian Chinese people with disability and their families. The findings suggested that coproduction enabled the organisation to identify that the people with disability and their families considered services were culturally responsive when the staff were competent and committed to person‐centred services. The coproduction contributed to continuous improvement of the services and revealed the qualities that were valued by the Australian Chinese service users. This study enriches the knowledge on coproduction by demonstrating the influence of the process of coproduction on outcomes for service users and providers. The study also contributes to the knowledge on cultural responsiveness by highlighting the elements of culturally responsive services valued by the service users. Coproduction could be more widely used for service development given its capacity to identify and respond to service needs. Practical implications for culturally responsive social services are that workforce training could focus on the principles of person‐centred services and skills for working effectively with people from culturally diverse backgrounds.
The immune system of some genetically susceptible children can be triggered by certain environmental factors to produce islet autoantibodies (IA) against pancreatic β cells, which greatly increases ...their risk for Type-1 diabetes. An environmental factor under active investigation is the gut microbiome due to its important role in immune system education. Here, we study gut metagenomes that are de-novo-assembled in 887 at-risk children in the Environmental Determinants of Diabetes in the Young (TEDDY) project. Our results reveal a small set of core protein families, present in >50% of the subjects, which account for 64% of the sequencing reads. Time-series binning generates 21,536 high-quality metagenome-assembled genomes (MAGs) from 883 species, including 176 species that hitherto have no MAG representation in previous comprehensive human microbiome surveys. IA seroconversion is positively associated with 2373 MAGs and negatively with 1549 MAGs. Comparative genomics analysis identifies lipopolysaccharides biosynthesis in Bacteroides MAGs and sulfate reduction in Anaerostipes MAGs as functional signatures of MAGs with positive IA-association. The functional signatures in the MAGs with negative IA-association include carbohydrate degradation in lactic acid bacteria MAGs and nitrate reduction in Escherichia MAGs. Overall, our results show a distinct set of gut microorganisms associated with IA seroconversion and uncovered the functional genomics signatures of these IA-associated microorganisms.
Food insecurity is a stressor associated with adverse health outcomes, including the consumption of sugar-sweetened beverages (SSBs). Our study tests the hypothesis that other socioeconomic ...vulnerabilities may magnify this effect using cross-sectional data from the 2017 New York City (NYC) Kids Survey. Households providing an affirmative response to one or both food security screener questions developed by the US Department of Agriculture were coded as households with low food security. The number of sodas plus other SSBs consumed was standardized per day and categorized as 1 = none, 2 = less than one, and 3 = one or more. We tested the joint effect of low food security with chronic hardship, receipt of federal aid, and immigrant head of household on a sample of
= 2362 kids attending kindergarten and beyond using ordinal logistic regression and accounting for the complex survey design. Only having a US-born parent substantially magnified the effect of low household food security on SSB consumption (OR = 4.2, 95%CI: 2.9-6.3,
< 0.001) compared to the reference group of high household food security with an immigrant parent. The effect of low food security on SSB consumption among NYC children warrants intersectional approaches, especially to elucidate US-based SSB norms in low-food-security settings.
Amphibians on the brink Bower, Deborah S.; Lips, Karen R.; Schwarzkopf, Lin ...
Science (American Association for the Advancement of Science),
08/2017, Letnik:
357, Številka:
6350
Journal Article
Recenzirano
Preemptive policies can protect amphibians from devastating fungal diseases
Over the past three decades, the emergence of a globalized pandemic lineage of chytrid fungus (
Batrachochytrium ...dendrobatidis
) has caused declines of amphibian species in Central America, Europe, Australia, and North America (see the figure). By 2004, where documented, 43.2% of amphibian species globally experienced some level of population decrease, and the amphibian chytrid fungus was identified as a major contributing factor for hundreds of species (
1
). The recent discovery of a related but functionally distinct chytrid fungus,
Batrachochytrium salamandrivorans
, that has begun exterminating salamanders in Europe (
2
) fulfills predictions that further infectious fungal pathogens will continue to emerge (
3
). The threat of chytrids and similar fungal pathogens to areas where they have not yet emerged—for example, in New Guinea—is of critical conservation concern.
There is growing evidence supporting an inherited basis for susceptibility to acute lymphoblastic leukemia (ALL) in children. In particular, we and others reported recurrent germline ETV6 variants ...linked to ALL risk, which collectively represent a novel leukemia predisposition syndrome. To understand the influence of ETV6 variation on ALL pathogenesis, we comprehensively characterized a cohort of 32 childhood leukemia cases arising from this rare syndrome. Of 34 nonsynonymous germline ETV6 variants in ALL, we identified 22 variants with impaired transcription repressor activity, loss of DNA binding, and altered nuclear localization. Missense variants retained dimerization with wild-type ETV6 with potentially dominant-negative effects. Whole-transcriptome and whole-genome sequencing of this cohort of leukemia cases revealed a profound influence of germline ETV6 variants on leukemia transcriptional landscape, with distinct ALL subsets invoking unique patterns of somatic cooperating mutations. 70% of ALL cases with damaging germline ETV6 variants exhibited hyperdiploid karyotype with characteristic recurrent mutations in NRAS, KRAS, and PTPN11. In contrast, the remaining 30% cases had a diploid leukemia genome and an exceedingly high frequency of somatic copy-number loss of PAX5 and ETV6, with a gene expression pattern that strikingly mirrored that of ALL with somatic ETV6-RUNX1 fusion. Two ETV6 germline variants gave rise to both acute myeloid leukemia and ALL, with lineage-specific genetic lesions in the leukemia genomes. ETV6 variants compromise its tumor suppressor activity in vitro with specific molecular targets identified by assay for transposase-accessible chromatin sequencing profiling. ETV6-mediated ALL predisposition exemplifies the intricate interactions between inherited and acquired genomic variations in leukemia pathogenesis.
•Leukemia predisposition variants in ETV6 lead to dramatic loss of transcription repressor activity, mainly by disrupting DNA binding.•Germline ETV6 variants influence ALL transcriptional profile with a striking resemblance of ETV6-RUNX1 ALL but unique somatic mutations.
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Background This study aims to compare perfusion dynamics using indocyanine green videoangiography before and after the creation of a second venous anastomosis between the superficial inferior ...epigastric vein and the retrograde internal mammary vein (IMV) in deep inferior epigastric perforator (DIEP) flap breast reconstructions. Methods Indocyanine green videoangiography performed during DIEP flap reconstructions was analyzed prospectively. The areas of interest were above the perforators with the highest intensity (complete perfusion), the most distal lateral edge of the flap (partial perfusion), and the next lowest intensity (ischemic). We compared the zone intensities before and after the second venous anastomosis, assessing venous drainage patency and functionality. Patient characteristics, operative details, and complications were collected. Results Seven patients (10 breasts) underwent DIEP reconstruction. Mean age was 54.5 ± 12.4 years. Mean operative duration was 575.5 ± 172.6 minutes. Donors included DIEV (n = 10, 100.0%), superficial inferior epigastric vein (n = 9, 90.0%), and superficial circumflex epigastric vein (n = 1, 10.0%). All DIEVs were anastomosed to the antegrade IMV (n = 10, 100.0%). Superficial inferior epigastric veins were anastomosed to the retrograde IMV (n = 10, 100.0%). Mean peak intensities of the complete perfusion zone before and after the second venous anastomosis were 160.7 ± 42.1 and 188 ± 42.1, respectively ( P = 0.163). Mean peak intensities of the partial perfusion zone were 100.8 ± 21.5 and 152 ± 31.5, respectively ( P < 0.001). Mean peak intensities of the ischemic zone were 90.4 ± 37.4 and 143.4 ± 45.3, respectively ( P = 0.012). Conclusion These findings highlight the potential benefits of the super drainage technique in enhancing perfusion and reducing complications, emphasizing the need for further investigation and consideration of this technique in clinical practice.
Thiopurines (eg, 6-mercaptopurine MP) are highly efficacious antileukemic agents, but they are also associated with dose-limiting toxicities. Recent studies by us and others have identified inherited ...NUDT15 deficiency as a novel genetic cause of thiopurine toxicity, and there is a strong rationale for NUDT15-guided dose individualization to preemptively mitigate adverse effects of these drugs. Using CRISPR-Cas9 genome editing, we established a Nudt15−/− mouse model to evaluate the effectiveness of this strategy in vivo. Across MP dosages, Nudt15−/− mice experienced severe leukopenia, rapid weight loss, earlier death resulting from toxicity, and more bone marrow hypocellularity compared with wild-type mice. Nudt15−/− mice also showed excessive accumulation of a thiopurine active metabolite (ie, DNA-incorporated thioguanine nucleotides DNA-TG) in an MP dose–dependent fashion, as a plausible cause of increased toxicity. MP dose reduction effectively normalized systemic exposure to DNA-TG in Nudt15−/− mice and largely eliminated Nudt15 deficiency–mediated toxicity. In 95 children with acute lymphoblastic leukemia, MP dose adjustment also directly led to alteration in DNA-TG levels, the effects of which were proportional to the degree of NUDT15 deficiency. Using leukemia-bearing mice with concordant Nudt15 genotype in leukemia and host, we also confirmed that therapeutic efficacy was preserved in Nudt15−/− mice receiving a reduced MP dose compared with Nudt15+/+ counterparts exposed to a standard dose. In conclusion, we demonstrated that NUDT15 genotype–guided MP dose individualization can preemptively mitigate toxicity without compromising therapeutic efficacy.
•We established a Nudt15 knockout mouse model with which to evaluate individualized thiopurine therapy.•Preemptive NUDT15 genotype–guided thiopurine dosing can effectively prevent drug toxicity without compromising antileukemic efficacy.
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Complex surgical back wounds represent significant morbidity in patients who have undergone spinal procedures requiring closure or revision by plastic surgeons. This study aimed to assess the utility ...of bacterial wound culture data for predicting surgical outcomes of wound management.
This study is a single-institution retrospective review of consecutive patients who required plastic surgery intervention for wound infection following spinal procedures between the years 2010 and 2021 (n = 70). Statistical analysis was performed for demographics, comorbidities, perioperative laboratory studies, and treatment methods. The primary outcomes of interest were rate of postoperative complications after soft tissue reconstruction and reconstructive failure. The secondary outcome of interest was time to healing in number of days.
The overall complication rate after wound closure was 31.4%, with wound infection in 12.9%, seroma in 10%, dehiscence in 12.9%, and hematoma in 1.4%. Increasing number of debridements before wound closure increased the likelihood of a surgical complication of any kind (odds ratio OR, 1.772; 95% confidence interval CI, 1.045-3.002). Positive wound cultures before reconstruction were associated with development of seroma only (OR, 0.265; 95% CI, 0.078-0.893). Use of incisional vacuum-assisted closure devices significantly decreased the odds of postoperative wound dehiscence (OR, 0.179; 95% CI, 0.034-0.904) and increased odds of healing (hazard ratio, 3.638; 95% CI, 1.547-8.613).
Positive wound cultures were not significantly associated with negative outcomes after complex closure or reconstruction of infected spinal surgical wounds. This finding emphasizes the importance of clinical judgment with a multidisciplinary approach to complex surgical back wounds over culture data for wound closure timing.
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