ABSTRACT
Forest loss and degradation are the greatest threats to biodiversity worldwide. Rising global wood demand threatens further damage to remaining native forests. Contrasting solutions across a ...continuum of options have been proposed, yet which of these offers most promise remains unresolved. Expansion of high‐yielding tree plantations could free up forest land for conservation provided this is implemented in tandem with stronger policies for conserving native forests. Because plantations and other intensively managed forests often support far less biodiversity than native forests, a second approach argues for widespread adoption of extensive management, or ‘ecological forestry’, which better simulates natural forest structure and disturbance regimes – albeit with compromised wood yields and hence a need to harvest over a larger area. A third, hybrid suggestion involves ‘Triad’ zoning where the landscape is divided into three sorts of management (reserve, ecological/extensive management, and intensive plantation). Progress towards resolving which of these approaches holds the most promise has been hampered by the absence of a conceptual framework and of sufficient empirical data formally to identify the most appropriate landscape‐scale proportions of reserves, extensive, and intensive management to minimize biodiversity impacts while meeting a given level of demand for wood. In this review, we argue that this central challenge for sustainable forestry is analogous to that facing food‐production systems, and that the land sharing–sparing framework devised to establish which approach to farming could meet food demand at least cost to wild species can be readily adapted to assess contrasting forest management regimes. We develop this argument in four ways: (i) we set out the relevance of the sharing–sparing framework for forestry and explore the degree to which concepts from agriculture can translate to a forest management context; (ii) we make design recommendations for empirical research on sustainable forestry to enable application of the sharing–sparing framework; (iii) we present overarching hypotheses which such studies could test; and (iv) we discuss potential pitfalls and opportunities in conceptualizing landscape management through a sharing–sparing lens. The framework we propose will enable forest managers worldwide to assess trade‐offs directly between conservation and wood production and to determine the mix of management approaches that best balances these (and other) competing objectives. The results will inform ecologically sustainable forest policy and management, reduce risks of local and global extinctions from forestry, and potentially improve a valuable sector's social license to operate.
As demand for wood products increases in step with global population growth, balancing the potentially competing values of biodiversity conservation, carbon storage and timber production is a major ...challenge. Land sparing involves conserving forest while growing timber in intensively managed areas. On the other hand, land sharing utilizes ecological forestry approaches, but with a larger management footprint due to lower yields. While the sparing‐sharing framework has been widely tested and debated in agricultural settings to balance competing values, such land‐allocation strategies have been rarely studied in forestry.
We examined whether a sparing, sharing or Triad strategy best achieves multiple forest objectives simultaneously. In Triad, management units (stands) in forest landscapes are allocated to one of three treatments: reserve (where conservation is the sole objective), intensive (timber production is the sole objective) and ecological (both objectives are combined). To our knowledge, ours is the first Triad study from the temperate zone to quantify direct measures of biodiversity (e.g. species' abundance).
Using a commonly utilized forest planning tool parameterized with empirical data, we modelled the capacity of a temperate rainforest to provide multiple ecosystem services (biodiversity, carbon storage, timber production and old‐growth forest structure) over 125 years based on 43 different allocation scenarios. We then quantified trade‐offs between scenarios, taking into account the landscape structure, and determined which strategies most consistently balanced ecosystem services.
Sparing strategies were best when the services provided by both old‐growth and early seral (young) forests were prioritized, but at a cost to species associated with mid‐seral stages, which benefitted most from Triad and sharing strategies. Therefore, sparing provides the greatest net benefit, particularly given that old‐growth‐associated species and ecosystem services are currently of the greatest conservation concern.
Synthesis and applications. We found that maximizing multiple elements of biodiversity and ecosystem services simultaneously with a single management strategy was elusive. The strategy that maximized each service and species varied greatly by both the service and the level of timber production. Fortunately, a diversity of management options can produce the same wood supply, providing ample decision space for establishing priorities and evaluating trade‐offs.
We found that maximizing multiple elements of biodiversity and ecosystem services simultaneously with a single management strategy was elusive. The strategy that maximized each service and species varied greatly by both the service and the level of timber production. Fortunately, a diversity of management options can produce the same wood supply, providing ample decision space for establishing priorities and evaluating trade‐offs.
Pediatric residents care for dying children during training. Few educational efforts focus on helping trainees better understand their own grief process and the supports available to them and their ...patients’ families.
This work aims to assess pediatric residents’ needs and preferences for content included in a curriculum on grief and bereavement.
Pediatric residents, at a single institution, completed an electronic survey in Spring 2023 on how they cope with patient deaths and their preferences on content in a proposed grief and bereavement curriculum.
The survey was emailed to 165 current or recent trainees; 71 surveys were fully completed (43% response rate). Most respondents (63/71, 89%) indicated that a formalized bereavement curriculum for pediatric residents is important. The resources most frequently utilized by residents following a pediatric death included peer support (59/71, 83%), attending a debrief coordinated by residency leadership or the supportive care division (38/71, 54%), and reading a patient's obituary (23/71, 32%).
The most desired content areas were institutional services provided to bereaved families (66/71, 93%), unique aspects of healthcare professional grief (58/71, 82%), and experiences of bereaved families hearing from providers after their child's death (56/71, 79%).
Pediatric residents indicate a strong desire for structured curricula on grief and bereavement focusing on resources that exist for families, approaches to grieving as a healthcare professional, and better understanding the experiences of bereaved families. These data may inform educators on priorities in training and support of pediatric residents on grief and bereavement.
Clear cell ovarian carcinoma (CCOC) is an aggressive disease that often demonstrates resistance to standard chemotherapies. Approximately 25% of patients with CCOC show a strong APOBEC mutation ...signature. Here, we determine which APOBEC3 enzymes are expressed in CCOC, establish clinical correlates, and identify a new biomarker for detection and intervention.
APOBEC3 expression was analyzed by IHC and qRT-PCR in a pilot set of CCOC specimens (
= 9 tumors). The IHC analysis of APOBEC3B was extended to a larger cohort to identify clinical correlates (
= 48). Dose-response experiments with platinum-based drugs in CCOC cell lines and carboplatin treatment of patient-derived xenografts (PDXs) were done to address mechanistic linkages.
One DNA deaminase, APOBEC3B, is overexpressed in a formidable subset of CCOC tumors and is low or absent in normal ovarian and fallopian tube epithelial tissues. High APOBEC3B expression associates with improved progression-free survival (
= 0.026) and moderately with overall survival (
= 0.057). Cell-based studies link APOBEC3B activity and subsequent uracil processing to sensitivity to cisplatin and carboplatin. PDX studies extend this mechanistic relationship to CCOC tissues.
These studies demonstrate that APOBEC3B is overexpressed in a subset of CCOC and, contrary to initial expectations, associated with improved (not worse) clinical outcomes. A likely molecular explanation is that APOBEC3B-induced DNA damage sensitizes cells to additional genotoxic stress by cisplatin. Thus, APOBEC3B is a molecular determinant and a candidate predictive biomarker of the therapeutic response to platinum-based chemotherapy. These findings may have broader translational relevance, as APOBEC3B is overexpressed in many different cancer types.
Background
Cancer‐related deaths over the next decade are expected to increase due to cancer screening deficits associated with the coronavirus disease 2019 (COVID‐19) pandemic. Although national ...deficits have been quantified, a structured response to identifying and addressing local deficits has not been widely available. The objectives of this report are to share preliminary data on monthly screening deficits in breast, colorectal, lung, and cervical cancers across diverse settings and to provide online materials from a national quality improvement (QI) study to help other institutions to address local screening deficits.
Methods
This prospective, national QI study on Return‐to‐Screening enrolled 748 accredited cancer programs in the United States from April through June 2021. Local prepandemic and pandemic monthly screening test volumes (MTVs) were used to calculate the relative percent change in MTV to describe the monthly screening gap.
Results
The majority of facilities reported monthly screening deficits (colorectal cancer, 80.6% n = 104/129; cervical cancer, 69.0% n = 20/29; breast cancer, 55.3% n = 241/436; lung cancer, 44.6% n = 98/220). Overall, the median relative percent change in MTV ranged from –17.7% for colorectal cancer (interquartile range IQR, –33.6% to –2.8%), –6.8% for cervical cancer (IQR, –29.4% to 1.7%), –1.6% for breast cancer (IQR, –9.6% to 7.0%), and 1.2% for lung cancer (IQR, –16.9% to 19.0%). Geographic differences were not observed. There were statistically significant differences in the percent change in MTV between institution types for colorectal cancer screening (P = .02).
Conclusion
Cancer screening is still in need of urgent attention, and the screening resources made available online may help facilities to close critical gaps and address screenings missed in 2020.
Lay Summary
Question: How can the effects of the coronavirus disease 2019 pandemic on cancer screening be mitigated?
Findings: When national resources were provided, including methods to calculate local screening deficits, 748 cancer programs promptly enrolled in a national Return‐to‐Screening study, and the majority identified local screening deficits, most notably in colorectal cancer. Using these results, 814 quality improvement projects were initiated with the potential to add 70,000 screening tests in 2021.
Meaning: Cancer screening is still in need of urgent attention, and the online resources that we provide may help to close critical screening deficits.
A national Return‐to‐Screening quality improvement study including 748 cancer facilities has found that the majority have local screening deficits due to the COVID‐19 pandemic, most notably in colorectal cancer. Cancer screening is still in need of urgent attention, and the screening resources made available online may help to close critical gaps and address screenings missed in 2020.
The airway epithelium forms a barrier between the internal and external environments. Epithelial dysfunction is critical in the pathology of many respiratory diseases, including cystic fibrosis. Ets ...homologous factor (EHF) is a key member of the transcription factor network that regulates gene expression in the airway epithelium in response to endogenous and exogenous stimuli. EHF, which has altered expression in inflammatory states, maps to the 5′ end of an intergenic region on Chr11p13 that is implicated as a modifier of cystic fibrosis airway disease. Here we determine the functions of EHF in primary human bronchial epithelial (HBE) cells and relevant airway cell lines. Using EHF ChIP followed by deep sequencing (ChIP-seq) and RNA sequencing after EHF depletion, we show that EHF targets in HBE cells are enriched for genes involved in inflammation and wound repair. Furthermore, changes in gene expression impact cell phenotype because EHF depletion alters epithelial secretion of a neutrophil chemokine and slows wound closure in HBE cells. EHF activates expression of the SAM pointed domain-containing ETS transcription factor, which contributes to goblet cell hyperplasia. Our data reveal a critical role for EHF in regulating epithelial function in lung disease.
IMPORTANCE: Atypical eye gaze is an early-emerging symptom of autism spectrum disorder (ASD) and holds promise for autism screening. Current eye-tracking methods are expensive and require special ...equipment and calibration. There is a need for scalable, feasible methods for measuring eye gaze. OBJECTIVE: Using computational methods based on computer vision analysis, we evaluated whether an app deployed on an iPhone or iPad that displayed strategically designed brief movies could elicit and quantify differences in eye-gaze patterns of toddlers with ASD vs typical development. DESIGN, SETTING, AND PARTICIPANTS: A prospective study in pediatric primary care clinics was conducted from December 2018 to March 2020, comparing toddlers with and without ASD. Caregivers of 1564 toddlers were invited to participate during a well-child visit. A total of 993 toddlers (63%) completed study measures. Enrollment criteria were aged 16 to 38 months, healthy, English- or Spanish-speaking caregiver, and toddler able to sit and view the app. Participants were screened with the Modified Checklist for Autism in Toddlers–Revised With Follow-up during routine care. Children were referred by their pediatrician for diagnostic evaluation based on results of the checklist or if the caregiver or pediatrician was concerned. Forty toddlers subsequently were diagnosed with ASD. EXPOSURES: A mobile app displayed on a smartphone or tablet. MAIN OUTCOMES AND MEASURES: Computer vision analysis quantified eye-gaze patterns elicited by the app, which were compared between toddlers with ASD vs typical development. RESULTS: Mean age of the sample was 21.1 months (range, 17.1-36.9 months), and 50.6% were boys, 59.8% White individuals, 16.5% Black individuals, 23.7% other race, and 16.9% Hispanic/Latino individuals. Distinctive eye-gaze patterns were detected in toddlers with ASD, characterized by reduced gaze to social stimuli and to salient social moments during the movies, and previously unknown deficits in coordination of gaze with speech sounds. The area under the receiver operating characteristic curve discriminating ASD vs non-ASD using multiple gaze features was 0.90 (95% CI, 0.82-0.97). CONCLUSIONS AND RELEVANCE: The app reliably measured both known and new gaze biomarkers that distinguished toddlers with ASD vs typical development. These novel results may have potential for developing scalable autism screening tools, exportable to natural settings, and enabling data sets amenable to machine learning.
There is a strong rationale to consider future cell therapeutic approaches for cystic fibrosis (CF) in which autologous proximal airway basal stem cells, corrected for CFTR mutations, are ...transplanted into the patient’s lungs. We assessed the possibility of editing the CFTR locus in these cells using zinc-finger nucleases and have pursued two approaches. The first, mutation-specific correction, is a footprint-free method replacing the CFTR mutation with corrected sequences. We have applied this approach for correction of ΔF508, demonstrating restoration of mature CFTR protein and function in air-liquid interface cultures established from bulk edited basal cells. The second is targeting integration of a partial CFTR cDNA within an intron of the endogenous CFTR gene, providing correction for all CFTR mutations downstream of the integration and exploiting the native CFTR promoter and chromatin architecture for physiologically relevant expression. Without selection, we observed highly efficient, site-specific targeted integration in basal cells carrying various CFTR mutations and demonstrated restored CFTR function at therapeutically relevant levels. Significantly, Omni-ATAC-seq analysis revealed minimal impact on the positions of open chromatin within the native CFTR locus. These results demonstrate efficient functional correction of CFTR and provide a platform for further ex vivo and in vivo editing.
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Suzuki et al. report correction of the CFTR defect in cystic fibrosis airway basal stem cells. They utilized gene-editing strategies either specific for the ΔF508 CFTR mutation or applicable to most CFTR mutations. Both approaches yielded highly efficient correction without selection, restoring CFTR function to therapeutically relevant levels.
The development of new drugs addressing serious mental health and other disorders should avoid the psychedelic experience. Analogs of psychedelic drugs can have clinical utility and are termed ...“psychoplastogens”. These represent promising candidates for treating opioid use disorder to reduce drug dependence, with rarely reported serious adverse effects. This drug abuse cessation is linked to the induction of neuritogenesis and increased neuroplasticity, a hallmark of psychedelic molecules, such as lysergic acid diethylamine. Some, but not all psychoplastogens may act through the G-protein coupled receptor (GPCR) 5HT2A whereas others may display very different polypharmacology making prediction of hallucinogenic potential challenging. In the process of developing tools to help design new psychoplastogens, we have used artificial intelligence in the form of machine learning classification models for predicting psychedelic effects using a published in vitro data set from PsychLight (support vector classification (SVC), area under the curve (AUC) 0.74) and in vivo human data derived from books from Shulgin and Shulgin (SVC, AUC, 0.72) with nested five-fold cross validation. We have also explored conformal predictors with ECFP6 and electrostatic descriptors in an effort to optimize them. These models have been used to predict known 5HT2A agonists to assess their potential to act as psychedelics and induce hallucinations for PsychLight (SVC, AUC 0.97) and Shulgin and Shulgin (random forest, AUC 0.71). We have tested these models with head twitch data from the mouse. This predictive capability is desirable to reliably design new psychoplastogens that lack in vivo hallucinogenic potential and help assess existing and future molecules for this potential. These efforts also provide useful insights into understanding the psychedelic structure activity relationship.
Background
This study is part of a larger research program focused on developing objective, scalable tools for digital behavioral phenotyping. We evaluated whether a digital app delivered on a ...smartphone or tablet using computer vision analysis (CVA) can elicit and accurately measure one of the most common early autism symptoms, namely failure to respond to a name call.
Methods
During a pediatric primary care well‐child visit, 910 toddlers, 17–37 months old, were administered an app on an iPhone or iPad consisting of brief movies during which the child's name was called three times by an examiner standing behind them. Thirty‐seven toddlers were subsequently diagnosed with autism spectrum disorder (ASD). Name calls and children’s behavior were recorded by the camera embedded in the device, and children’s head turns were coded by both CVA and a human.
Results
CVA coding of response to name was found to be comparable to human coding. Based on CVA, children with ASD responded to their name significantly less frequently than children without ASD. CVA also revealed that children with ASD who did orient to their name exhibited a longer latency before turning their head. Combining information about both the frequency and the delay in response to name improved the ability to distinguish toddlers with and without ASD.
Conclusions
A digital app delivered on an iPhone or iPad in real‐world settings using computer vision analysis to quantify behavior can reliably detect a key early autism symptom—failure to respond to name. Moreover, the higher resolution offered by CVA identified a delay in head turn in toddlers with ASD who did respond to their name. Digital phenotyping is a promising methodology for early assessment of ASD symptoms.
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